Nursing Level III

Module Title:- Administer and Monitor

Range of Medication
Module Code:- HLT NUR3 M07 0122
MODULE TITLE: ADMINISTERING AND MONITORING RANGE OF MEDICATION
MODULE DESCRIPTION :
This module aims to describe the knowledge, skills and attitude required of
enrolled nurses to administer, monitor and evaluate medications and their
effectiveness for clients within a heath environment.
LEARNING OUTCOMES: - At the end of the module the learner will be able

to:
LO1. Apply pharmacology in the field of nursing practice.
LO2. Minimize potential risk to the safe administration of
medications
LO3. Prepare medications
LO4. Perform medications administration
LO5. Monitor and evaluate client response to administered

medication
MODULE CONTENT
LO1. Applying pharmacology in the field of nursing practice
 Basic concept of pharmacology
 Pharmaco-dynamics
 Pharmacokinetics
 Classification of drugs
 Adverse reactions of drug
 Pharmaceutical dosage forms and system of measurement
 Dosage calculations
 Drugs standards and nursing management
 Drugs affecting the gastrointestinal system
 Anti - inflammatory drugs
 Drugs act on respiratory system
 Drugs act on cardiovascular system
 Drugs act on the renal system
  Drugs act on endocrine system
 Drugs act on the nervous system
 Drugs act on the musculoskeletal system
 Drug that act on integumentary system
 Drug that act on EENT system
 Chemotherapy of infectious diseases
 Cancer chemotherapy
 Pregnancy drug category and classification
 Describing fluids and minerals
 Essential drugs list in Ethiopia
LO2.Minimize potential risk to the safe administration of medications
 Checking expiate date
 Medication chart
 Common contraindications and adverse reactions
 Checking allergies
LO3. Preparing medications.
 Common terminology associated with drug, fluid and electrolytes
 Medication preparation
 Forms of medication
 Site of injections
 Route of administration
 Principles of medication administration
 Potential risk related with medication administration
 Storing & handling of medication
 Delivery of drug doses
LO4. Performing medication administration
 Ten rights of medication administration
 Administering Oral medication
 Administering intra-dermal medication
 Administering subcutaneous medication
 Administering intravenous medication
  Administering intravenous infusion
 Administering blood transfusion
 Applying topical medication
 Medication errors
Assessment method
Exam (mid & final) 60%
Assignment (20%)
Class activity (10%)
Attendance (10%)
LO I Applying pharmacology in the field of nursing practice
By the end of this unit the student will be able to:
▫Discuss the nurse’s legal responsibilities in medication prescription and administration▫Diff
erentiate toxic, idiosyncratic, allergic, and side effects of medications
▫Describe physiologic mechanisms of medication actions including: absorption, distribution,
metabolism, and excretion
▫Identify properties of pharmacokinetics▫Describe factors to consider when choosing routes o
f medication administration
▫Correctly calculate a prescribed medication dosage
▫Discuss factors to include in assessing a patient’s needs for and response to medication thera
py▫List the six rights of medication administration

Information Sheet I:- Basic concept of pharmacology

Pharmacology is an experimental science dealing with the properties of drugs & their effects
on living systems. It includes;
 Pharmacodynamics; response to drug action.
 Pharmacokinetics; the mathematical description of temporal changes in
concentration of drug & their metabolites within the body.
 Therapeutics; the treatment of disease in general using drugs , surgery, radiation,
behavioral modification & other modalities.
 Pharmacotherapy; use of drugs in the treatment of disease.
 Chemotherapy; a branch of pharmacology dealing with drugs that selectively inhibit
or destroy specific agents of disease such as bacteria , viruses, fungi, &other
parasites. Term has been extended to the use of drugs in treatment of neoplastic
diseases. Selective toxicity ia a notion central to chemotherapy. Drugs that are useful
as chemotherapeutics affect the pathogen or abnormal cell more adversely than
normal cells.
 Toxicology; concerned with the adverse effects of xenobiotics. Its scope includes
drugs, chemicals responsible for household, industrial waste, food additives,
 radioactive substances. & pesticides. Toxicology is the science that defines the limits
of safety of chemical agents.
Drugs
The word is derived from the Old French drogue which meant herb.
Drugs have been defined as articles intended to be used in the diagnosis, mitigation,
treatment or diagnosis of diseases in humans or other animals; & articles other than food
intended to affect the structure or function of the body.
Nutraceuticals
Are nutritional products which allegedly have some therapeutic value in addition to their
scientifically recognized nutritional contents.
Sources of drugs;
1- Plants; most of the old remedies were derived from plants & included
all plant structures; roots; park; seeds; leaves etc. Active principals
included alkaloids, glycosides, oils, saponines, tanines & resins.
2- Animals; many useful old medicines were prepared from animals.
Modern drugs of animal origin can be exemplified by
i) hormones: insulin, gonadotrophins& the anabolic steroids.
ii) vitamins: cod liver oil contains vitamins A&D. iii) sera & antisera.
3- Micro-organisms; i) the penicillins.
ii) bacteria are now being genetically modified to produce certain
substances.
4- Mineral origin; including many simple compounds of medicinal
value ; Epson salt; MgSO4&NaCl.
5- Synthetic compounds.
The classification of drugs
1- Anatomic site of action; atropine classified as a gastrointestinal drug.
2- Therapeutic effect; atropineclassified as an anti-spasmodic.
3- Mechanism of action;atropineclassified as an anti-cholinergic.
4- Source or pharmaceutical properties;atropineclassified as a saponaceous
alkaloid.
The nomenclature of drugs
 1- Approved or official name; is given by an approved body such as The British
Pharmacopoeial commission. The advantages of using official names are that
i) They are informative e.g. Diazepam&Nitrozepamhave the commercial names
Valium &Mogaden respectively.
ii) The patient is given better choice regarding availability and price of the drug.
An approved name indicating the establishment of a drug is usually entered into
an official publication commonly known as a Pharmacopoeia e.g. The British
Pharmacopoeia (BP) or The United States Pharmacopoeia (USP). Additional
information about monographs on actions & uses of drugs plus their toxicities &
antidotal measures are given in the so cold Pharmaceutical Codex e.g. The
British Codex.
2- Commercial or propriety names; are coined by pharmaceutical manufacturers on
their drugs & get registered as trade marks. The advantages of using a
commercial drug name in prescribing are; i) The confidence of
the prescription writer. ii) The psychological preference of the
patient or iii) The actual superiority of the trade mark.
3- Chemical names; which correspond to the formula of the drug & are usually not
practical in prescribing being very long, detailed & complex.
The posology of drugs
1- Posology is the study of medicine dosage, the effect of the drug & individual
tolerance or susceptibility. Metrology is the study of weights & measures as
applied to preparation & administration of drugs.
2- A dose is the quantity of medication to be administered at one time. Dosage refers
to determination & regulation of multiple doses. An effective dose is that amount
of a drug necessary to elicit the desired therapeutic response in the patient.
Targets for drug action
Protein targets for drug action on mammalian cells can be divided into 4 categories;
1- Receptors.
2- Ion channels.
3- Enzymes.
4- Carrier-molecules.
 Other types of protein targets for specific classes of drugs are also known & include;
I- Certain structural proteins such as tubulin, the target for colchicine.
II- Intracellular immunophillins which are targeted by cyclosporine& other
immunosuppressive agents.
DNA, RNA, cell wall constituents & other proteins , of microorganisms & cancer cells are
targeted by chemotherapeutic agents.

Routes of drug administration;

Drugs are administered in prepared dosage form, the product contains a certain
amount of pharmacologically-active drug substances. The dosage form & route of
administration can influence the selectivity of a drug product & thereafter its clinical
indication.
A- Enteral administration;
1. Oral; weak acidic drugs absorption is optimal in the acidic environment of the
stomach, wherein weak basic drug absorption is optimal in the relatively-alkaline
small intestine.
Factors that accelerate gastric emptying into intestine are likely to increase the rate
of absorption.
Drugs destroyed by gastric juice or cause gastric irritation are coated, with the
possibility of failure of dissolution.
Advantages are; convenience, safety & economy.
Disadvantages; requires cooperative patients, affects bioavailability, slow &
unpredictable.
2. Sublingual; specific non-ionic high lipid-soluble drugs e.g. nitroglycerine are
readily-absorbed. Mouth is drained to superior vena cava, so the drug is protected
from 1st pass metabolism by the liver (completely destroyed).
3. Rectal; useful in patients that are unconscious or vomiting. 50% of the medication is
approximately bio-available. Absorption is incomplete, irregular & irritation to rectal
mucosa is not uncommon.
B- Parenteral injection; is either vascular including i/v & intera-arteriorly, or extra-vascular
including I/m & S/c . Absorption is determined by the area of the capillary membrane in I/m
& S/c thro large aqueous channels in the endothelial membrane by indiscriminate diffusion
of molecules regardless of lipid-solubility. Larger molecules e.g. proteins, slowly gain access
to circulation by way of lymphatics, parenterally-given drugs are subjected to 1 st pass in the
lungs.
1- I/v;
Advantages;
1. Drug attains immediate predictable systemic conc. useful in emergency.
2. The entire dose is almost bio-available.
3. By controlling the rate of infusion the effects can be titrated e.g. surgical
anaesthesia with pentobarbitone.
4. Certain irritating hypertonic solutions can only be given I/v.
5. Continuous-infusion maintaining steady-state conc.
Disadvantages;
1. Potentially the most dangerous route, rapid high conc. enhances the
likelihood of toxicity particularly in CNS.
2. Drugs in oily vehicles or suspensions are contra-indicated.
3. Drugs that precipitate blood components or hemolyse RBCs are also
contra-indicated.
4. Anti-septic measures should be taken carefully & the administration
performed slowly, except in the case of i/v bolus in the induction of rapid
anaesthesia with thiopentone.
2- Subcutaneous administration;
 Rate of absorption is often adequately constant & slow to provide
sustained effects that may be varied intentionally e.g. the soluble &
insoluble forms of insulin.
 Solid pellets (e.g. hormones) are implanted under the skin to
produce effects over weeks & months.
 Disadvantages in certain irritating drugs that may cause severe
pain & necrosis.
3- I/m administration;
 Rapid absorption depending on the blood flow to the area.
  Aqueous solutions absorbed more rapidly.
 Deltoid more than gluteus particularly in females.
 Very obese & very emaciated subjects show unusual patterns of s/c & i/m absorption.
 Penecillinis often administered I/M, irritant drugs can be administered i/m.
4- Intra-arterial administration;
 Localizes the response to the particular organ or tissue.
 1st pass is not evident.
 Diagnostic agents are sometimes administered I/arteriorly.
5- Intrathecal;
Used once rapid local effects are needed on the meninges & cerebrospinal axis e.g. spinal
anaesthesia & CNS infections.
6- Intra-peritonial;
 Large surface.
 Drug absorbed via portal circulation, 1st pass thro the liver.
 Lab. procedure.
 Infections & adhesions.
C- Pulmonary absorption;
Advantages;
 Gases & volatile drugs may be inhaled.
 Rapid (large surface).
 1st pass thro liver avoided.
 Useful in pulmonary disease e.g. bronchial asthma.
Disadvantages;
 Poor ability to regulate dose.
 Cumbersomeness of methods of administration.
 Many drugs & gases irritate pulmonary epithelium.
D- Topical application;
I- Mucus membranes; conjunctiva, nasopharynx, oropharynx, vagina,
colon, & urethra. Aim is local effects, however, sometimes
generalized effects are achieved e.g. ADH is applied to the nasal
mucosa.
 II- Skin ; few drug penetrate intact skin, surface area & lipid-
solubility being the determinant factors, as well as oily vehicles &
rubbing (innunction). Occlusive dressings of polyethylene enhance
absorption. Dimethylsulfoxide, skin irritant & sorption promoter
vehicle, enhances penetration of the stratum cornium. Controlled-
release topical patches e.g. scopolamine(behind the ear) for motion
sickness, & trans-dermal oestrogen replacement therapy.
III- Eye; local effects, requires absorption thro the cornea.
Disadvantages include corneal infection or trauma.

Information Sheet II:- Pharmaco-dynamics

Pharmacodynamic terms;
(1) Receptor is the macromolecule component of the body tissue with which the
drug interacts to initiate its pharmacologic effects.
(2) Agonist is a drug that possesses affinity for a particular receptor & causes a
change in the receptor that results in an observable effect. A full agonist
produces a maximum response when it occupies all or a fraction of the
receptors, a partial agonist produces a sub-maximal response even if it
occupies all the receptors.
(3) Affinity describes the tendency of a drug to combine with a particular kind of
receptors.
(4) Efficacy (intrinsic activity) refers to the maximal effect a drug can produce.
(5) Potency refers to the dose that must be administered to produce a particular
effect of given intensity & is influenced by; i- affinity; ii- pharmacokinetic
processes that determine the drug concentration in the vicinity of its site of
action. Potency varies inversely with dose, the lower the dose required to
produce a stated response, the more potent the drug.
(6) Antagonist is a drug that blocks the response produced by an agonist by
interaction with the receptor or other component of the effector mechanism,
competitive antagonism is reversible & surmountable eg. atropine or
propranolol. A non-competitive antagonist conceptually removes the
receptor, or response mechanism, from the system eg. the platelet inhibiting
action of aspirin.
(7) Selectivity of a drug depends on its capacity to preferentially produce a
particular effect. The characteristic action of a drug is produced at lower
doses than those required to produce other actions. A truly selective drug
produces only one single effect, e.g. heparin.
(8) Specificity when all the effects produced by a drug are due to a single
mechanism of action the drug is said to be specific. A specific drug acts at
only one type of receptors but may produce multiple pharmacologic effects
because of location of receptors in various organs, e.g. acepromazine, with
actions that include sedation (increased dopamine turnover rate in the brain) ;
antiemetic (depress CTZ); hypotension (alpha-adrenergic
blockade) ;antispasmodic (anticholinergic action in the smooth muscles of the
GIT) ; & hypothermia (interference with the hypothalamic control of
temperature regulation). In the other hand atropine is a specific drug wherein
all its varied effects can be attributed to its antimuscarinic action.
(9) Desensitization, tachyphylaxis, tolerance & resistance are synonymous terms
used to describe the gradual diminishing of drug effects when it is given
continuously or repeatedly. Mechanisms that give rise to the phenomena
include ;
1- Change in receptors.
 2- Loss of receptors.
3- Exhaustion of mediators.
4- Increased metabolic degradation.
5- Physiological adaptation.
6- Active extrusion of the drug from cells (mainly chemotherapeutics).
Tolerance ensues when the condition gets aggravated while resistance is a term conserved for
microorganisms.

Information Sheet III:- Pharmacokinetics

Are defined as the mathematical description of drug conc. changes in the body.
Biologic membranes may be viewed as fluid mosaics of functional units composed of
lipoprotein complexes, with a bi-layer of amphipathic lipids, their hydrocarbon chains
oriented inwards to form a continuous hydrophobic phase & their hydrophilic heads oriented
outwards, individual lipid molecules move laterally endowing the membrane with fluidity,
flexibility, high electric resistance & relative impermeability to high-polar molecules.
Membrane proteins embedded in the bi-layer serve as receptors signaling electrical or
chemical pathways.

Transfer of drugs across membranes;

A- Passive processes; Diffusion;
1- Along a conc. gradient by virtue of lipid solubility (water-lipid partition
coefficient of the drug) until steady-state equilibrium is reached.
2- For ionic compounds equilibrium is dependant on; pH-differences across the
membrane, & on electro-chemical gradient for ions.
3- Most membranes are relatively-permeable to water & small water soluble
molecules by; diffusion, hydrostatic pressure or osmotic differences.
4- The conc. gradient for many ions is determined by active-transport e.g. Na &
K,, the trans-membrane potential determines the distribution of other ions e.g.
chloride.
5- Channels with selectivity for individual ions exist.
6- In terms of drug distribution, penetration of drugs into extra-cellular fluid of
the brain & CSF is similar to diffusion into intracellular fluid elsewhere in the
body. Passage of a drug from cerebral circulation into brain extra-cellular
fluid can take place only by diffusion thro capillary endothelial cells (blood-
brain barrier).
7- A drug enters CSF from systemic circulation only by diffusion thro the
choroidal epithelial cells (blood-CSF barrier).
8- The penetration of drugs into aqueous-humor of the eye involves diffusion
thro the blood-aqueous barrier.
9- Blood-sertoli cells & blood-tunica albogenia barriers are the most efficient
barriers.
10- Fever & certain inflammatory conditions increase the capacity of drugs to
cross these barriers.
The influence of pH
 Most drugs are weak acids or bases present in solution as both ionized & non-ionized
species. The non-ionized species are usually lipid-soluble & readily diffuse across the
membrane to achieve equilibrium on both sides. The ionized moiety is often virtually
excluded from trans-membrane diffusion because of its low lipid solubility.
The degree of ionization of an organic electrolyte is dependant on;
1- Its pKa value (-ve logarithm of the acidic-ionization, or dissociation, constant).
2- pH of the medium.
E.g. 1) weak organic acids such as aspirin (pKa 3.5), phenylbutazone (pKa 4.4),
sulphadiazine(pKa 6.4) &phenobarbitone(pKa 7.4) are well-absorbed from the
stomach (pH 1.4) into plasma (pH 7.4).
E.g. 2) the acidic reaction of urine promotes passive re-absorption of acidic drugs
(pKa between 3- 7.2) from the distal portion of the nephron. Urinary alkalinization
will promote their excretion, a technique that may has clinical application in
management of overdose (provided that the drug is excreted unchanged).
E.g. 3) basic drugs (narcotic analgesics, phenothiazines,
ketamine, diazepam&antiarrhythmic agents) tend to concentrate in fluids that are
acidic relative to plasma e.g. intracellular fluid (pH 7).
B- Carrier-mediated transport;
 Sites; neuronal membranes, choroid plexus, renal tubules & hepatocytes.
 Characteristics; selectivity, competitive inhibition, saturability, requirement for
energy & movement against electrochemical gradient.
 Types ;
1- Active transport; requires a direct expenditure of energy e.g. transfer into bile &
urine of strongly acidic or basic drugs & drug-metabolites, also the removal of
drugs e.g. penicillinfrom CNS.
2- Facilitated diffusion; not energy-dependant nor does it move substances against
gradient e.g. uptake of glucose into cell facilitated by insulin.
Absorption;
 Bioavailability; is a term used to indicate the extent to which a drug
reaches its site of action.
  1st pass effect; defines the effect of passage of drugs thro the liver before
reaching the systemic circulation.
Factors that modify absorption;
1. Solubility; aqueous more rapidly absorbed than oily.
2. Rate of dissolution.
3. Local conditions at site of absorption; deltoid better than gluteus.
4. Drug conc. in the dosage form (GIT in particular).
5. Circulation to the site of administration; (+) massage & heat, (-)
vasoconstrictors & shock.
6. Area of the absorbing surface to which the drug is exposed.

The Distribution of Drugs

Drugs are conveyed thro-out the body in the circulating blood & reach the tissues of every
organ in an amount determined by blood flow & conc. to the organ. The conc. attained in the
tissues depends on the capacity of the drug to;
1. Penetrate capillary endothelium (influenced mainly by plasma-protein binding).
2. Diffuse across cell membrane.
CNS & CSF;
A- Entry of drugs into CSF is restricted by;
1. Absence of intercellular pores & pinocytic vesicles & predomination of tight-
junctions.
2. The unique arrangement of glial cells contributes to the slow diffusion of organic
acids & basesinto the CNS.
B- Strongly-ionized agents such as quaternary amines are normally unable to enter CNS.
C- Organic ions are extruded from CSF into blood at choroids plexus by transport processes
similar to those of renal tubules.
D- The barrier is neither absolute nor invariable;
1. Large doses of penicillin may produce seizures.
2. Meningeal or encephalic inflammation increases permeability.
 3. Maneuvers to increase permeability of the barrier are important to enhance efficiency
of chemotherapeutics in treatment of local infections & tumors.
Drug Reservoirs;
Are body compartments in which a drug accumulates, if a reservoir has a large capacity
& fills rapidly, then larger quantities are initially required to provide a therapeutically-
effective conc. in the target organ.
I- Plasma proteins binding;
Sulfadimethoxine 81 % Thiopentone 75 %
Sulfisoxazole 68 % Sulfadiazine 17 %
Clorpromazine 94 % Chloramphinicol 39 %
Propranolol 97 % Amphetamine 27 %
Morphine 12 %

1. Acidic drugs extensively bind albumin, basic drugs bind alpha 1-glycoprotein
& beta-globulin, binding is reversible.
2. Binding to plasma proteins limits drug conc. in tissues & at locus of action
since only the free drug equiliberates across membranes.
3. Although binding limits glomerular filteration it does not generally limit
tubular secretion or hepatic metabolism, so it is a transport mechanism that
fosters the delivery of drugs to sites of elimination.
4. Binding is rather non-selective. Many drugs with physico-chemical
similarities compete for binding sites e.g. displacement of bilirubin from
albumin by sulfonamidesincreasing the risk of encephalopathy in the
newborn, this could be of concern in drugs with narrow therapeutic indices
e.g. warfarin displacement by phenylbutazone.
5. Alteration of molecular structure can influence the % of drug binding e.g.
digoxin (27 %) &digitoxin (89 %) wherein these complex molecules differ
only in a hydroxyl group.
6. Certain diseases such as hypoalbuminaemia (nephrotic syndrome) or
chronic renal failure cause an increase in the % of free drug in plasma & site
of action.
II- Cellular Reservoirs;
Quinacrine(anti-malarial) after long term therapy, attains a conc. in the liver several
thousands times that of plasma.
1- Tissue binding of drugs occurs to proteins, phospholipids & nucleoproteins, it
is generally reversible.
2- Neutral fat (10 ~ 50 % of body wt.) accumulates many lipid soluble drugs
e.g. thiopentone. It is a stable reservoir (low blood flow).
3- Bone is a reservoir for tetracyclines& other metal ion chelating agents, it can
become a reservoir for release of toxic agents such as leador radiumlong
after exposure has ceased.
4- The GIT is the major trans-cellular reservoir in the case of slowly-absorbed
oral drugs & particularly those agents undergoing entero-hepatic circulation.
III- Re-distribution;
Terminates drug effects primarily when a highly lipid soluble drug acting on the
brain or the cardiovascular system is rapidly administered I/v or inhaled e.g. thiopentone.
IV- Placental transfer of drugs;
 Drugs may cause congenital anomalies or adverse effects in the newborn.
 Drugs cross the placenta primarily by simple diffusion in rates variable from early
to late pregnancy.
 It would be inaccurate to view the placenta as a barrier, the fetus is, at least to
some extent, exposed to essentially all the drugs taken by the mother.
Special drug delivery systems;
1. Biologically-errodable micro-spheres of polymers; engineered to adhere to mucosal
epithelium of gut, such micro-spheres can be loaded with drugs as a means of
improving absorption e.g. insulin&polymers of fumaric acid.
2. Pro-drugs ; Zidovudine is phosphorelated to its active tri-phosphate metabolite only
in cells containing appropriate reverse transcriptase hence conferring selective
toxicity towards cells infected with HIV. The cytotoxic drug
Cyclophosphamidebecomes active only after metabolism in the liver therefore
causing no GIT damage when taken orally.
 3. Antibody-drug conjugates; e.g. attachment of a cytotoxic drug to an antibody
directed towards a tumor-specific antigen.
4. Packaging in liposomes; liposomes are vehicles produced from certain aqueous
phospholipids & can be filled with non lipid soluble drugs released after disruption in
the reticulo-endothelial cells particularly in the liver. Liposomes are also
concentrated in malignant tumors achieving selective delivery of cytotoxic agents
e.g. Amphotericin(an antifungal used in the treatment of systemic mycosis) is
available in a liposomal formulation that is less nephrotoxic than the regular one.
Drug Elimination
Mechanisms of drug elimination are bio-transformation (metabolism) & excretion. Although
it is usual for one process to predominate, both hepatic-metabolism & renal-excretion are
involved in the elimination of most drugs.
1. Lipid solubility is prerequisite for bio-transformation by hepatic microsomal enzyme
system.
2. Polar drugs & drug metabolites are excreted by the kidneys.
3. Wide extra-vascular distribution & selective tissue-binding e.g. the localization of
thiopentalin body fat reduces the rate of elimination of a drug by limiting its
accessibility to eliminating-organs.
4. It is common for a drug to be metabolized along 2, or more, pathways
simultaneously.
Drug Bio-transformation
Drugs undergo metabolic changes in the body that are directed primarily towards
formation of metabolites that have physico-chemical properties favorable to their excretion,
metabolites are generally less lipid soluble & more polar in nature rendering them suitable
for carrier-mediated excretion processes & more likely to be partitioned into fluids of the
body such as the blood stream.
PhaseI reactions;
Usually unmask or expose or introduce to the drug molecule polar groups such as –OH, -
SH, -COOH & -NH. These functional groups enable the compound to undergo conjugation.
A- Oxidation; liver microsomal enzymes are mixed-function oxidases of the ER that have
specific requirement for reduced NADPH & molecular oxygen.
 1. NADPH reduces cytochrome P-450(which is the oxidizing enzyme of the
microsome) as follows; NADPH + A + H+ AH2 + NADP+.
2. Reduced cytochrome P-450 reacts with molecular oxygen to form an active oxygen
intermediate; AH2 + O2 “active oxygen complex”.
3. The interaction between this complex & a lipid soluble drug or steroid substrate
yields a hydroxylated substrate, oxidized P-450 & an equivalent molar fraction of
water; “active
oxygen complex” + Drug Oxidized Drug + A + H2O.

Oxidative reaction Drug Metabolite

Aromatic hydroxylation - Phenobarbital - p-hydroxyphenobarbital
- Penylbutazone - Oxyphenbutazone*
Aliphatic oxidation Pentobarbital Pentobarbital alcohol
N-dealkylation Diazepam N-desmethyl diazepam*
O-dealkylation Phenacetin Acetaminophen*
Oxidative de-amination Amphetamine Phenylacetone

B- Reduction ; hepatic microsomes reduce azo & nitro compounds to corresponding amines
in anaerobic conditions & the requirement for NADPH mediated by enzymes that contain
flavine adenine dinucleotide FAD e.g. prontosil(azo dye) is reduced to
sulfanilamide(antibacterial), e.g. inactivation of chloramphinicol, & the reductive
dehalogenation of halothane &methoxyflurane.
C- Hydrolysis; is an important pathway for compounds with an ester linkage (-coo-) or an
amide bond (-coNH-) e.g. suxamethonium, atropine, pethedine&hydrocortisone. Most
amines are hydrolyzed more slowly than the corresponding esters. Use of procainamideas an
anti-arrhythmic is based on its slow rate of hydrolysis, compared with that of procaine, with
the ultimate formation of the active metabolite N-acetyl procainamide*.
Phase II reactions (conjugation);
A drug or, phase I metabolite, containing a suitable functional group is combined to
endogenous substances that include glucouronic acid, glutathione, glycine, cysteine,
methionine, sulfate & acetate.
 1. These processes utilize energy.
2. Catalysis by an enzyme is required.
3. The activated form of the endogenous substance undergoes conjugation e.g. acetyl-
coA for acetate & uridine diphosphate glucouronic acid (UDPGA) for glucouronic
acid.
4. The total pool of sulfate in the body can be exhausted so that glucourinidation
predominates.
5. Acetylation decreases water solubility as-well-as lipid solubility of
sulfonamidesincreasing the risk of crystalluria.
Metabolic- transformations mediated by GI microflora;
1. GI microflora mediate metabolic transformations especially hydrolytic & reductive
reactions.
2. Enteric sulfonamides e.g. phthalylsulfathiazole&succinylsulfathiazole depend on
microfloral release of sulfathiazolefor their antibacterial activity.
3. Microfloral hydrolysis is also responsible for activation of anthraquinone glycosides.
4. The hydrolytic enzyme responsible, beta-glucourinidase, is principally found in E.
coli.
5. The release of bile acids from their conjugates leads to the entero-hepatic circulation
of drugs & the function of bile acids in fat absorption.

Drug Phase II reaction

- Morphine Glucourinidation
- Salicylates
- Acetaminophen
- Chloramphinicol
- Steroid hormones*
- Thyroxin
- Bilirubin
- Phenol Sulfate conjugation
- Acetaminophen
- Morphine
 - Isoproterenol (CA)
- Ascorbic acid
Sulfonamides Acetylation

Factors affecting drug metabolism;

I- Genetic; wide inter-individual differences in drug bio-transformation is due to inherited
autosomally-recessive traits, polymorphism, this may include the rapidity & the metabolic
pathway & thereafter the metabolic end-products.
II- Physiologic;
1. Age & gender E.g. i- Cytochrome
P450, CYP3A7 is expressed exclusively in the fetus (although drug metabolism is
generally active at low levels in feti).
E.g. ii- newborns are able to catalyze most phase I reactions (at slow rates) & there
is impairment of bilirubin glucourinidation during the 1 st 2 weeks.
E.g. iii- the age-related decrease in hepatic mass, enzymes (particularly CP450) &
blood flow  decreased metabolic capacity.
E.g. iv- clinical reports of decreased oestrogen&benzodiazepinesoxidation in
females suggest gender-related metabolic variations.
2. Disease: hepatitis, alcoholic liver disease, fatty liver disease, biliary cirrhosis,
hepatic carcinoma & cardiac insufficiency.
E.g. diazepam&morphinein hepatic disease &lidocaine&propranololin decreased
hepatic blood flow.
3. State.
III- Metabolic drug interactions;
1. Induction; an increased synthesis of de novo cytochrome P450 associated with
exposure to certain drugs & environmental agents e.g. rifampinliver & gut induction
on; corticosteroids, cyclosporine, diazepam, quinidine, digoxin &oral
contraceptives. Auto-induction occurs with the anticonvulsant carbamazepine.
2. Inhibition ; competition between 2 or more drugs for the active site of the same
enzyme e.g. cimetidine& the antifungal ketoconazoleinhibit oxidative drug
 metabolism by forming tight complexes with CP450 , a metabolite of
erythromycinhas the same effect.
Drug excretion
Renal excretion is the principal process of drug elimination. Drugs eliminated
unchanged include;
1. Many antibiotics (most penicillins, cephalosporins such as
cephradin&cephalexin, aminoglycosidessuch as gentamycin / neomycin /
apramycin, &oxytetracycline).
2. Most diuretics (excluding ethacrynic acid).
3. Neuromuscular blockers (d-tubocurarine&gallamine).
Metabolites are usually cleared more rapidly than the parent compounds. 3 renal
processes are involved;
I- Glomerular filteration;
 Glomerular capillaries allow drugs of molecular wt < 20 000 to pass into the filterate.
 Plasma protein-bound drugs are completely held back.
II- Tubular secretion & re-absorption;
 80 % of the renal blood flow is delivered at the tubules.
 2 independent & rather non-selective carrier systems deliver drugs to tubular lumen;
one for acidic drugs e.g. acetyl salicylic acid, furosemide, acetazolamide, thiazides,
penicillins&probenecid,& the other for organic bases e.g. narcotic analgesics such
as morphine&pethidine, amines such as 5HT, histamine&dopamine, &quinine.
 Carriers can transport drugs against electro-chemical gradient reducing plasma levels
to zero.
 Secretion is not influenced by P.P.B. e.g. penicillin ( 80% protein-bound ) is
completely removed via proximal-tubular secretion , cloxacillin( 80% ppb )
&ampicillin( 20% ppb ) have the same plasma t1/2e . This indicates the dissociation of
the drug-albumin complex after the removal of the free spp.
 Competition occurs between drugs sharing the transporter e.g.
penicillin&probenecid (ceftiofur)R
III- Diffusion across the renal tubule
 pH & pKadependant.
  Drug in the filterate & plasma equiliberates.
 Highly lipid-soluble drugs are passively re-absorbed & slowly cleared.
 Highly polar drugs e.g. digoxin&aminoglycosidesachieve urine levels 100 folds
times that of plasma.
 Alkalinization of urine can overcome overdose of acidic drugs.
Biliary excretion
 Hepatocytes transfer substances, including drugs, from plasma to bile.
 Enterohepatic circulation creates a reservoir wherein 20% of the total drug recycles
e.g. morphine&ethinylestradiol. De-acetylated rifampicin & intact vecuroniumare
excreted in feces.
Excretion by other routes
 pH- determined simple- diffusion of non- ionized spp. into saliva, sweat & tears,
attaining levels parallel to plasma.
 The better part of alkaline drugs is partitioned to milk being more acidic relative to
plasma. Non-electrolytes such as ethanol &ureaequiliberate.
 Sensitive methods for detection of toxic metals in hair & skin have forensic
significance.
Information Sheet IV:- Adverse reactions of drug

Adverse drug reaction (ADR)

It is unintended harm by drug used, at normal dose, in prevention or therapy of disease.
It may;
1. Require discontinuation of therapy.
2. Require treatment change, dose modification or supportive therapy.
3. Necessitate or prolong hospitalization.
4. Negatively affect prognosis.
5. Induce temporary or permanent disability or death.
6. Withdrawal, abuse, accidental poisoning & overdose complications are excluded
from ADR.
Side effect
Are defined as known, expected reactions resulting in little or no change in patient
management e.g. nausea due to neoplastic medication or sedation due to antihistamines. The
frequency is predictable, intensity is related dose size.
Classification of ADR
1. Lack of efficacy; provided that the drug is given at the proper dose, route, interval
& duration to treat a condition for which efficacy had, previously, been instituted.
2. Allergy ;
 Cannot be anticipated.
 Are not dose dependant.
 Clinical presentation ranges from mild rash to anaphylaxis.
 Mechanism, usually, involves a drug or its metabolite(s) forming covalent
bonds with an endogenous substance resulting in an antigen.
  Cross-reactivity may develop i.e. a subject allergic to a drug develops
similar reactions to drugs belonging to the same formulation. 100% of
humans allergic to penicillinare equally allergic to other penicillins, 20%
react to cephalosporins.
3. Semi-allergy ;
 Similar clinical presentation.
 Underlying mechanism is not immunologic.
 Haematologic reactions similar to autoimmune haemolytic anaemia e.g.
following I/v dimethyl sulfoxide(conc.> 20%).
 Cardio-pulmonary reactions e.g. following I/v drugs dissolved in
polyethylene glycol vehicle.
 Hyperpyrexia (drug fever) e.g. aspirin (due to uncoupling of oxidative -
phosphorylation).
4. Organ damage ;
 Complex mechanisms.
 Not related to drug pharmacodynamics.
 Aminoglycoside&tetracyclinenephro-toxicity is not explained by the
binding of these antibiotics to bacterial ribosomal subunits & inhibition of
protein synthesis.
 Acetaminophenreactive metabolites causing hepatotoxicity not related to
the analgesic antipyretic actions of the drug.
5. Idiosyncratic (individual);
 Not described by 1— 4.
 Not dose dependant.
 Often genetically determined.
Characteristics of ADR;
 Diagnosis of certain ADR s is challenging especially when resembling conditions
they are supposed to treat e.g. drug fever associated with aspirin, however, there
often is a temporal definable relationship between administration & the offset of
manifestation.
 Manifestations improve with discontinuing therapy.
  ADR initially present as a mild rash may, on subsequent use, result in a severe fatal
reaction.

Information Sheet v:- Pharmaceutical dosage forms and system of measurement

What is Pharmaceutical Dosage Forms?

A dosage form is a pharmaceutical preparation consisting of drug and excipients to facilitate

dosing, administration, and delivery of the content to the drug product.
The design, materials, manufacturing, and testing of all dosage forms target drug product
quality.

A testing protocol must consider not only the physical, chemical, microbiological, and
biological properties of the dosage form as appropriate, but also the administration route and
desired dosing regimen.

List of official dosage forms

 Aerosols
 Capsules
 Creams
 Emulsions
 Films
 Foams
 Gases
 Gels
 Granules
 Gums
 Implants
 njections
 Inserts
 Shampoos
 Soaps
 Solutions
 Sprays
 Strips
 Suppositories
 Suspensions
 Tablets
 Liquids
 Lotions
 Ointments
 Pastes
 Pills
 Powders

system of measurement
Consistency in dosing for a patient or consumer requires that the variation in the drug
substance content of each dosage unit be accurately controlled throughout the manufactured
batch or compounded lot of drug product.
Uniformity of dosage units typically is demonstrated by one of two procedures: content
uniformity or weight variation.
Drug product stability involves the evaluation of chemical stability, physical stability, and
performance over time.
For tablets, capsules, oral suspensions, and implants, in vitro release test procedures such as
dissolution and disintegration provide a measure of continuing consistency in performance
over time.

Bioavailability is influenced by factors such as the method of manufacture or compounding,

particle size, crystal form (polymorph) of the drug substance, the properties of the excipients
used to formulate the dosage form, and physical changes as the drug product ages.
With proper justification, in vitro release testing (e.g., disintegration and dissolution) may be
used as a surrogate to demonstrate consistent availability of the drug substance from the
formulated dosage.

Dosage Form/ Drug Delivery System by route of administration

Oral
 Tablets
 Capsules
 Solutions
 Syrups
 Elixirs
 Suspensions
 Gels
 Powders

Sublingual
 Tablets
 Lozenges
Parenteral
 Solutions
 Suspensions
Conjunctival
 Contact lens inserts
 Ointments

Epicutaneous / transdermal
 Ointments
 Creams
 Infusion pumps
 Pastes
 Plasters
 Powders
 Aerosols
 Lotions
Intraocular
 Solutions
 Suspensions
Intranasal
 Solutions
 Sprays
 Inhalers
 Ointments
Intrarespiratory
 Aerosols
Vaginal
 Solutions
 Ointments
 Emulsion foams
 Gels
 Tablets
 Inserts, suppositories
Rectal
 Solutions
 Ointments
 Suppositories
Urethral
 Solutions
 Suppositories
Information Sheet VII:- Dosage calculations

– It is one of nursing skill

– Used to determine 24 hrs of drug need of a patient
– Used to bring therapeutic effect
– To avoid toxic effect of medication
– Calculated by using different methods
To calculate an adult dose, a formula

This formula is used to calculate an adult dose, a formula used to calculate dose of
 Tablets
 Capsules
 Ampoules
 Vials
 Suspensions
 Syrups
 Example 1: Erythromycin 500mg is ordered. It is applied in a liquid form containing
250mg in 5 ml to calculate the dose.
 Given
– Desired dose= 500 mg
– Dose at hand = 250 mg
– Quantity at hand =5ml
– Desired quantity =X?

Example 1

= 250 mg = 500mg

5ml X

X = 500mg*5ml

250 mg
 X= 2*5Ml

X= 10 Ml is needed

Dosage calculation for children

– Unlike adult dosages children dosages are not always standard
– Body size significantly affects dosages
– There are some formulas for calculation of child dose (1-12 years)
Drug Measurement System
– Metric system
– Apothecary’s system
– Household system
Metric system
– Drug measurement system is the most widely accepted and convenient/suitable
method.
– Basic units of measurement are meter (linear), liter (volume) & gram (weight).
– Is the decimal system in which each unit can be divided into multiples of 10.
Drug calculation
Conversions
● 1 liter =1000 ml
● 1 kg = 1000g
● 1g = 1000 mgs =1000,000g
● 1 mg = 1000 g
● 1 tsp = 5 ml
● 1 tbs = 15 ml
● 2% = 2g/100ml
● 40% = 40g/100ml
● 1:1000 =1g/1000ml =1mg/ml
● 1:10,000=1g/10,000ml=0.1mg/ml
• Apothecary system
– Less convenient & precise than the metric system and infrequently used.
– Basic unit of weight is the grain. The minim, dram, ounce, pint, & quart are
used for volume.
– Roman numerals are used to express numbers (grain x )and quantities less
than one are written in fraction form (grain ¼)
• Household system: -
– Used when accurate systems of measurements are not required,
– Because it is the least accurate one.
– Units of measurement is drops, teaspoon, tablespoon, teacup, cups, glasses,
etc.
IV Fluids

• Fluids or solutions administered through blood vessel

• They are used to replace body fluid either intracellular or extra cellular
• They are composed of blood or non-blood products
• Are classified as colloid & crystalloids

Reasons to administer
– To provide water, electrolytes, and nutrients to meet daily requirements
– To replace water and correct electrolyte deficits
– To administer medications and blood products
Information Sheet IIX:- Drugs standards and nursing management
 A desire to take medicine is, perhaps, a great feature which distinguishes people from
other animals.
 The Code of Hammurabi described penalties for malpractice by practitioners.
 The oldest record of Egyptian drug codification is the Kahun papyrus written about
2000 BC. It deals with veterinary medicine & uterine disease of women.
 The Ebers papyrus (1550 BC) is a compilation of a No. of disease conditions & 829
prescriptions for medicaments employed in Egyptian medicine.
 The foremost Greek physician Hippocrates (460-375 BC) had little use for drugs after
recognizing that sick people usually tended to get well regardless of treatment. This
concept of the healing power of nature became known as The Vis Medicatrix
Naturae .
 A precept from the Hippocratic school which still provides an ethical basis for the
practice of therapeutics is “ Above all, do not harm”.
 Works of Galen (131-201) dealing with physiology & materia medica were
authoritative for the next 1400 years & consist of preparations of plants by soaking or
boiling & classification of medicinal plants.
 Muslims distilled wines & beers to obtain ethanol for preparing tinctures. Geber Ibn
Hajar (702-765) classified drugs & poisons of his time & recognized that “The
difference between a drug & a poison was a matter of dosage. Any drug can be toxic
if given in large enough amounts”.

Proficiency at writing a prescription order accurately & speedily requires practice. The order
should be written legibly. It is convenient & the accepted form to have one`s name, address,
telephone No., office hours & registration No. printed on the order blank. Orders should be
written in ink & a doctor should keep a copy for the files, this protects the physician & serves
to complete the record of treatment.
Choice of drug name
 Use the official name.
 Use the official name followed by the manufacturer`s name between parenthesis if the
product has distinct advantages. Some pts exhibit dramatic changes in response when
switched from one product to another on subsequent refills, this is of particular
concern in drugs with low therapeutic indices e.g. anti-epileptic drugs.
 Write “dispense as written” or verbally communicate the pharmacist if need be.
Choice of a system of wts & measures
 Always write in the metric system.
 Designate the amount of drugs by numbers & indicate the desired metric wt or
volume.
Construction of the prescription order
1. Date.
2. Name, age, sex of patient.
Address of patient.
3. Rx
4. Ampicillin Oral suspension 250mg/5ml.
5. Dispense 200 ml (with oral syringe).
6. Label: Take 5ml orally at 8AM; 12noon, 4PM; &8PM daily for 10days for infection.
Ampicillin 250mg/5ml, 200ml.
7. Do not refill.
8. Signature.
 Rxis abbreviation for recipe the Latin for “Take thou”.
 (4) drug, strength & inert additives, (5) directions to the pharmacist, (6) directions to
the patient, (7) refill informations.
1. The physician, & or pharmacist, should demonstrate how the drug is used.
2. Expressions such as “Take as desired”or “Take as necessary”or “Take every
8hrs”should be avoided (i.e. specify).
 3. To avoid possible error, the 1st word of the directions to the pt. should serve as a
reminder of the correct route of administration; Take for internal use; Apply for
ointment or lotion; Insertfor suppositories; &Place for drops of the conjunctival sac,
external auditory canal or nostril.
4. The directions to the pt should also include a reminder of the intended purpose of the
prescription e.g. “for relief of pain”, “for relief of headache” or “to relief itching”.
5. If it is desirable to administer a drug in a larger amount than is customarily
employed, underline the dose or write ”Correct amount” or “Correct dose” with
your initials at the side.
6. Indicate the No. of refills on each original prescription order, irrespective of whether
the substance is controlled or not.
7. Dosage should include the no. of days for which medication is contemplated, no. of
doses per day & size of each dose.
8. The max. limit is indicated for most prescriptions depending on stability & cost of
the drug & the possible necessity for alternation of the ttt.
9. If the pt is depressed or potentially suicidal do not prescribe total amounts of drug
that would prove lethal if taken all at one time.
10. Storage of unused portions of a prescription & sharing of prescriptions with others
should be discussed with any pt who receives an important medication.
11. Usual doseis intended to serve only as a guide to the physician who very frequently
must give more or less than what is usual in order to optimize therapy.

Abbreviations commonly used in prescribing

Abbreviation Latin Meaning
ad. lib. ad libitum Freely as wanted
aa ana Of each
A ante Before
a.c. anti cibum Before meals
aq. aqua Water
b.i.d.(BID) bis in die Twice a day
Cap. capula Capsule
C cum With
dos. dosis A dose
eq.pts equalis partis Equal parts
gtt gutta A drop
H hora Hour
M. misce Mix
n.r. non repetatur Not to be repeated
o.d. omne die Everyday
p.c. post cibum After meals
p.r.n. pro re nata As occasion requires
q.i.d.(QID) quarter in die 4 times a day
s.i.d.(SID) semel in die Once a day
Sig.S. Signa Write on the label
S.O.S. Si opus sit If necessary
Sol. solutio Solution
Stat. statim Immediately
Tab. tabella a tablet
t.i.d. ter in die 3 times a day
Information Sheet IX:- Drugs affecting the gastrointestinal system
(1) Salivary Stimulants
 Watery saliva is governed by parasympathetic NS.
 Viscous saliva is governed by sympathetic NS.
Indication
To improve appetite & digestibility.
1- Locally-acting agents are known as bitters e.g. nux vomica&strychnine, act by
stimulation of taste buds on the tongue.
2- Centrally-acting agents e.g. cabachol act by general stimulation of the
parasympathetic NS.

(2) Salivary Inhibitors (antisialagogues)

Indication
Surgery of the mouth.
Agent used is atropine.
Action
Mainly inhibition of bronchial secretions.
(3) Appetite Stimulants
Mechanisms & receptors
A- Appetite is primarily (not exclusively) controlled by ventral & lateral nuclei of the
hypothalamus.
B- Stimulatory mediators include noradrenaline (α2-receptors), dopamine (D1 –receptors)
& GABA. The inhibitory mediator is 5HT.
 C- Neuropeptides control appetite by controlling the neurotransmitter release; opiates &
pancreatic polypeptides increase appetite, calcitonin, cholecytokinin &
corticotrophin-RF inhibit appetite.
Indications
Cachexia, anorexia & weight-loss associated with cancer.
Agents
1- Drugs that inhibit gluconeogenesis e.g. hydrazine sulphate.
2- Drugs that promote gastric emptying e.g. metclopramide.
3- Steroids e.g. megestrol (less adverse effects than anabolic steroids).
4- Benzodiazepines e.g. I/v or oral diazepam or oral oxazepam through GABA-induced
effects & inhibition of satiety centre of hypothalamus.
5- Cyproheptadine the antihistaminic with antiserotonin properties.
6- Others include serotonin agonists, glucocorticoids, B-vitamins & the anti-
depressants; TCA&lithium.

Emesis
A complex protective reflex controlled by the emetic centre located in the lateral reticular
formation protected by the BBB.
Afferent pathways
1- Higher centres (cerebrum), mediators ACh & histamine, psychogenic stimuli.
2- Elevated CSF, CNS disorders & head injury, mediators ACh & histamine H1.
3- Vestibular apparatus, H1& ACh e.g. in motion sickness.
4- Peripheral receptor via 9th cranial nerve to emetic centre, abdominal& thoracic organs
irritation, distention, hyperosmolarity & inflammation, ACh.
The CTZ in area postrema outside BBB is stimulated by blood-bourn chemical substances
e.g. drugs, toxins, uremia, pyometra, liver disease, endotoxemia, radiation sickness disease,
digitalis, apomorphine, narcotic analgesics & oestrogen. Initiators are dopamine receptors,
5HT & H1.
(4) Emetics
Indications
Intoxication, accidental ingestion of drugs by children & emergency operations.
 1- Central emetics S/c apomorphine stimulates CTZ.
2- Peripheral emetics act by local irritation of gastric mucosa
 Rapidly acting as salts of heavy metals, hypertonic solutions or mustard in
warm water.
 Slowly acting which are used as nauseating expectorants e.g. tincture
ipecacuanha, tincture senega&ammonium chloride&carbonate.

(5) Anti-emetic drugs

1- Antihistaminics (H1-blockers) diphenylhydramine, dimenhydinate,
chlorpheniramine maleate, meclizine, cyclizine & promethazine. They act by
inhibiting the vomiting centre, used in motion sickness.
2- Phenothazines chlorpromazine, trifluoperazine & thioethylperazine. Act by
blocking dopaminergic receptors in CTZ, effective against all types of vomiting
except motion sickness.
3- Butyrophenones droperidol&haloperidol, block D2-receptor in CTZ.
4- Thioxanthenes flupenthioxol, block D2-receptor in CTZ.
5- Metclopramide (primperan)R,
Actions
I. Antiemetic action by blocking D2 in CTZ.
II. Prokinetic action stimulating motility especially in proximal gut but unlike
cholinergic agonists does not stimulate gastric or pancreatic secretions.
III. It releases ACh from cholinergic neurons in myenteric plexus of enteric NS &
may sensitize the intestinal smooth muscles to its action.
IV. Its action is mediated by blocking dopamineric receptor D 2, & modulating
serotonin receptor.
Uses;
1. Antiemetic especially in cancer chemotherapy, radiation sickness, post-
operative vomiting & hiccough.
2. Facilitates small bowel intubation, increases gastric emptying after vagotomy
or in diabetic gastroparesis, in reflux oesophagitis & in emergency operation
or labor to prevent aspiration of gastric contents.
 Adverse effects;
Parkinsonism, hyperprolactinaemia, galactorrhea & menstrual disturbances.
6- Domperidone ( Motilium)R dopamineric antagonist which crosses BBB to a limited
extent so has less side effects.
7- Ondasteron, gransteron are 5HT antagonists used in vomiting indused by cancer
chemotherapy.
8- Hyoscine act by inhibiting the vomiting centre.
9- Pyridoxine (B6) in vomiting of pregnancy.
10- Glucocorticoids as dexamethasone can be combined with pyridoxine.

(5) Prokinetic drugs

1- Metclopramide, domperidone & cisapride. Both metclopramide & cisapride are
serotonine-R modulators.
2- Parasympathomimetics, as bethanechol, increase motility & secretions.
3- Motilin-like agents e.g. erythromycin ( motilin is a peptide hormone which has
prokinetic effect in upper gut by acting in specific motilin-R). Eyrthromycin acts on
these R so can be used in diabetic gastroparesis.

(6) Laxatives & Purgatives

Are drugs which evacuate the bowel by increasing frequency of defecation or fecal
volume or consistency.
 Laxatives (or aperients) promote the elimination of soft formed stools.
 Purgatives (or cathartics) produce a more fluid evacuation.
(A) Luminally-active agents (bulk purgatives)
1- Hydrophilic colloids & undigestible fibres as agar, psyllium (plantago) seed, methyl
cellulose&bran, by increasing bulk they stimulate peristalsis.
2- Osmotic agents absorb water & swell forming emollient gel.
 Cellulose&hemicellulose fermented by gut bacteria to volatile fatty acids that exert
osmotic effects.
 Saline purgatives as Mg-sulphate (Epsom salt), Na-sulphate (Glauber`s salt), K-
Na-tartrate (Rochelle salt), Mg-oxide (Milk of magnesia) &Mg-citrate. They are
 poorly absorbed from gut so retain water increasing bulk. Act after 1-2 hours. Given
before breakfast on empty stomach in isotonic solution. Contraindicated in
pregnancy & chronic constipation.
 Non-digestible sugar-alcohols lactulose, sorbitol &manitol are hydrolyzed in the
intestine to organic acids which acidify luminal contents & draw water stimulating
colonic motility. By saccharolytic microflora acetic acid, lactic acid, etc. are formed
lowering pH.
 Lactulose used for treatment of hepatic encephalopathy by acidification of large
intestine favors the formation of the non-absorbable ammonium ion than the readily-
absorbable ammonia molecule, which requires detoxification in the liver by the urea
cycle, hyperammonemia is thus prevented, other toxic amines absorption also is
reduced.
3- Emollients & wetting agents (lubricant purgatives)
 Liquid paraffin; mineral oil; produce softening of the stools & easier evacuation,
act in 10 hours so given overnight, used in chronic habitual constipation wherein
saline agents are contraindicated.
Side effects
I. Interference with absorption of fat-soluble vitamins & interaction with oral
anticoagulants.
II. Foreign-body reaction if absorbed.
III. Lipid pneumonia if reach lungs.
IV. Anal polypi on prolonged use.
V. Delay healing of ano-rectal wounds. vi- leakage from anus & pruritis ani.
 Wetting agents as dioctyl-Na sulphosuccinate which lowers surface tension &
facilitates penetration of water into stools.
(B) Irritant; Stimulant; Contact Purgatives Stimulate motility & secretion.
1- Mild irritant
 Figs&prunes (bulk & irritant).
 Castor oil which when taken orally is transformed by pancreatic lipase into glycerol
& the hi-irritant ricinoleic acid which increases intestinal motility yielding complete
 evacuation of the gut. Act in 2~6 hours at dose range of 15~ 60 & is inactive in
obstructive jaundice & contraindicated during pregnancy.
 Linseed oil&olive oil are less irritant & act by the respective formation of linoleates
& oliveates (the Na & K salts of the released fatty acids) which are irritant soaps.
2- Moderate irritant
 Anthracene (senna, cascara, aloe&rhubarb) release active compounds ( emodin?)
which stimulate colonic motility.
Untoward effects include secretion into milk affecting suckling babies, & into urine
producing yellowish-brown discoloration of acidic urine & reddish-brown in alkaline
urine. Colic & pigmentation of
colonic mucosa are not uncommon.
 Derivatives of diphenylmethane; Phenolphthalein&bisacodyl are dissolved by
alkalinity in intestine, little is absorbed & excreted in urine & bile. Directly stimulate
colon for a period made long by their entero-hepatic circulation. Redden alkaline
urine & may trigger skin rash.
3- Severe purgatives as croton oil are not clinically used.
(C) Neuromuscular purgatives
Neostigmine, physostigmine, bethanechol, &carbachol. Other substances that stimulate
visceral smooth muscle contraction include vasopressin, oxytocin, PGF2α& other PGs.
Indications of purgatives
1- Constipation.
2- Drug & food poisoning.
3- Before operation or radiography.
4- In treatment of helminthes.
5- To prevent straining as in heart failure or hernia.
(7) Enemata
 Evacuant enema; large volume given rapidly at hi-pressure & 38ºC.
 Retention enema; nutrition, basal narcotic, MgSO4& in treatment of some
parasitic diseases. Small volume slowly given at low head pressure.
(8) Treatment of constipation
 Proper diet; dietary fibres.
  Bowl training; conditioned reflux.
 Treat cause.
 Mild laxative.
(9) Treatment of food or drug poisoning
 Water or milk intake.
 Charcoal.
 Tincture ipecacuanha.
 Saline purgative.
(10) Treatment of diarrhea
1. Oral rehydration therapy.
2. Specific treatment of cause.
3. Symptomatic treatment;
 Adsorbants & absorbants; bismuth carbonate&subgallate, chalk &Kaolin.
 Astringents ppt. surface proteins; tincture krameria&catecho which release
tannic acid.
 Opium derivatives; diphenoxylate (lomotil)R, loperamide (imodium)R which
have no CNS actions & are not addictive.
 Mebeverin direct action on musculature & used also in irritable bowel
syndrome.
 Atropine& other anticholinergic agents.
(11) Treatment of inflammatory bowel syndrome
1. Steroids.
2. Sulphasalazine, sulphapyridine& 5-amino-salicylic acid which act to inhibit
leukotriene synthesis.
3. Azathioprine.
(12) Uses of Magnesium sulphate
Dependency of pharmacologic action on the route of drug administration;
1. Cholagogue, small oral dose.
2. Bulk purgative, large oral dose.
3. A dehydrating agent, rectally.
4. Anticonvulsant (in eclampsia); hypotensive & calcium antagonist, parenterally.
(13) Drugs used in hepatic encephalopathy
 Neomycin sterilizes colon inhibiting ammonia producing organisms.
 Lactulose.
(14) Hepatotoxic drugs
 Heavy metals, alcohol, chloroform& tetracyclines inflict direct injury.
 Chloroform, hydrazine, MAO&halothane induce lesions similar to viral hepatitis.

 Methyl testosterone, phenothiazines (chlorpromazine), chlorpropamide& anti-

thyroid drugs (thiouracil) produce a cholestatic injury.

 Methyl dopa may cause allergic chronic hepatitis.

(15) Cholagogues

Are evacuants of the gallbladder.

 Mg-sulphate acts by the relaxation of the sphincter of Oddi.

 Cholcystokinin acts by the contraction of the wall.

(16) Choleretics

Stimulants of bile- secretion by liver cells.

(17) Hydrocholeretics

Increase volume but not total solids of bile, salicylates or benzoates, contraindicated
in acute hepatitis.

(18) Spasmolytics

Parasympatholytics or direct spasmolytics e.g. volatile oils, papaverine, nitrites,

khellin & aminophylline.

(19) Chenodeoxycholic acid & ursodeoxycholic acid

 Are used to dissolve cholesterol gallstones.

(20) Octreotide

 A synthetic analog of somatostatin given parenterally.

 Inhibits gastric acid secretion, gastrin, secretin, VIP, & smooth muscle contraction.
 Used to treat symptoms of gut tumors; carcinoid, insulinoma, & gastrinoma, & in
refractory diarrhea.

(21) Peptic ulcer

It is a non-malignant injury of mucosal barrier that result in diffusion of H+ and ulceration
in part of the digestive tract which is exposed to gastric secretion.

a) Acute Ulceration and Erosions:

1. Related to acute gastritis due to predisposition to aspirin, excess alcohol

&bile reflux.

2. Related to shock: severe pain, major trauma, cerebrovascular accident,

septicemia, ACTH or corticosteroid therapy.
 3. Ulceration is usually multiple and asymptomatic.

b) Chronic Peptic Ulcers; usually single and penetrate muscularis mucosa.

c) Pathophysiology: ↑ aggressive forces or factors including HCL, pepsin &
Helicobacter pylori &/or ↓ protective or defense mechanisms including
prostaglandins, mucus &bicarbonates.
d) In gastriculcer the acid secretion is normal or reduced suggesting an impaired
mucosal resistance. The pain is less regular (½-1hr) after meal.
e) In duodenal ulcer there are excess acid and pepsin secretions with tendency to
nocturnal hyper-secretion. Typically pain relieved by taking food.
f) Goals of therapy: 1- relief of pain. 2- promotion of healing . 3- prevention of
recurrence.

(22) Treatment of Peptic ulcer

a) Measures to relief pain

 General measures.

 Antacids.

 Anticholinergics.

b) Measures to promote healing:

 General measures.

 Drugs:

1- Large doses of antacids.

2-Antisecretory (drugs which inhibit acid secretion): H 2 blockers, proton
pump inhibitors, anticholinergics, gastrin antagonist (proglumide) and
prostaglandins (misoprostol) .
3- Mucosal protective agents: sucralfate, colloidal bismuth cpd,
carbenoxolone, prostaglandins.
 c) Measures to prevent recurrence:

 General measures.

 Sedation if indicated by diazepam.

 Maintenance treatment (eradication of Helicobacter pylori)

General Measures

1) Rest and sedation; can heal gastric ulcer and may spontaneously improve duodenal
ulcer.

2) Stop smoking; smoking lowers the rate of ulcer healing and tends to increase the
relapse.

3) Diet; avoiding spices and taking regular meals in order to buffer intra-gastric
acidity.

4) Avoidance of Irritants such as caffeine, alcohol, NSAIDs, corticosteroids,

reserpine…etc.

Drugs to relief pain

a) Antacids: small, usual doses relief pain.

Mechanism of Action:
 Neutralize gastric acidity → relief of pain.

Increase pH of the stomach → ↓ proteolytic activity of pepsin .

Some (in large doses) →↑PGs and eradicate H. pylori.

Classification :

Are classified as chemical or physical anti-acids .

1- chemical anti-acids :

a- Systemic antacids: soluble and absorbable; can produce systemic alkalosis

e.g. NaHCO3.

b- Non-systemic (insoluble and non-absorbable); like salts of Al +++, Mg++ and

Ca++ .

Uses:

1- Peptic ulcer→ relief of pain.

2- Gastro-esophageal reflux and heart burn.

3- Gastritis.
4- To ↑ urinary excretion of weak acidic drugs e.g.

salicylates and barbiturates.

5- To ↑ urinary excretion of uric acid → treat gout.

Adverse actions:

1. Changes in bowel habits (Ca++ and Al+++ cause constipation, and Mg++ causes
diarrhea)

2. High Na+ content can harm cardiac, renal or hepatic patients.

3. Systemic alkalosis with large doses of systemic antacids.

4. Ca-based may cause rebound hyper-secretion

5. Milk-alkali syndrome with high Ca++ intake

6. Mg++ or Al+++ may be retained in renal failure

 7. Al+++ salts (not phosphate) leads to phosphate depletion

Contraindications:

1. Ca, Mg and Al decrease tetracycline absorption

2. Al(OH)3 decreases absorption of digoxin, phenytoin, warfarin, etc

3. Antacids decrease absorption of anticholinergics, phenothiazine&iron

preparations.

4. Systemic antacids increase excretion of acidic drugs and decreases excretion of

basic drugs.

Drug interactions:

a) affect bioavalability of other drugs e.g. Ca, Mg and Al↓absorption of

tetracyclines; Mg and Al ↓absorption of warfarin,digoxin, iron,
theophyline, ketoconazole and quinolones
b) change pH of bowel contents
c) adsorption or chelation
d) change gastric emptying or transit time

Preparations:

 NaHCO3: is the only useful water-soluble antacid. It acts rapidly but has a
transient action (short duration) and absorbed bicarbonate in higher doses may
cause

1. systemic alkalosis,
2. CO2 release→ abd.distention→ discomfort, dissolve mucus,
3. alkalinization of urine: a- precipitates phosphate stones . b- ↓excretion
of weak basic drugs e.g. ephedrine.
4. hypernatremia which is contraindicated in heart failure and
hypertension.

 Al(OH)3: has a relatively slower action. Al +3 ions form complex with certain drugs
like tetracycline& constipation, a mixture of Al(OH)3 and Mg(OH)2 may be used
to minimize the effect on motility.
 Mg(OH)2: insoluble in water and has a fairly rapid action. Mg ++ has a laxative
effect → diarrhea.

 GavisonR: (alginic acid, Mg tri-silicate, Al(OH) 3 gel, NaHCO3). The alginic acid
in presence of saliva reacts with NaHCO3 to produce a high viscous foaming
solution of Na alginate in which librated CO 2 is trapped. This material swells and
floats on gastric contents as a chaff which usually prevents gastric reflux.
 b) Anticholinergics:

 Their unwanted effects (dry mouth, constipation, urinary retention, tachycardia,

excitement, glaucoma, etc) limit their uses.
 They also decrease the lower esophageal sphincter (LES) pressure, increase the
gastro-esophageal and delay the gastric emptying.

Mechanism of action:

1. ↓ gastric acid secretion

2. ↓motility and spasm by blocking muscarinic receptors in gut.
3. Are less effective alone but may be useful when combined with H 2-blockers or
antacids.

They are of two types:

1) Non selective: Oxyphenonium (5mg tds) and propantheline (15mg qid)

Dicyclomine.
 2) Selective M1-blockers: Pirenzepine (50mg bid orally for 4~6 weeks) and
telenzepine which are selective blockers of peripheral muscarinic receptors near
gastric parietal cells. They selectively inhibit gastric acid secretion with minimal
side effects.

Measures to promote healing

Antacids in high doses (patient compliance is poor)

Anticholinergics with H2-blockers or antacids.

Mucosal protective agents:

1) Liquorice Derivatives (carbenoxoloneR):

These are derivatives of glycyrrhizinic acid and have steroid-like molecules.

Mechanism of Action:

I. ↑ mucosal resistance as they slow down gastric epithelial turnover.

II. ↑secretion.
III. Alter its chemical composition decrease back diffusion of H+ ions into mucosa.

Preparations:

I. Bio-gastrone for gastric ulcer

II. Duo-gastrone for duodenal ulcer (enteric caps act topically)

Side Effects:

Mineralcorticoid actions (↑Na, hypertension, edema, ↓K).

2) Sucralfate:

 It is an aluminum salt of sulfate sucrose.

 It promotes healing of duodenal ulcer and may also be used in gastric ulcer.

Mechanism of Action:

 Acts topically by forming a complex with protein in ulcer to form a protective barrier
against the acid, pepsin and bile salts.
 Stimulates the release of prostaglandins (PGs).
  Requires an acidic pH to be activated and should be administrated simultaneously
with H2-blockers or antacids.

Dose:

1gm QID on an empty stomach or 1hour before meals.

Side Effects:

 Not absorbed systemically, it has few side effects like constipation.

 It decreases the bioavailability of tetracycline, digoxin and phenytoin.

4) Colloidal Bismuth Compound(de-nolR):

It promotes healing of gastric and duodenal ulcers.

Mechanism of Action:

Acts locally combining with exudate and mucosa in the base of the ulcer providing a
protective coat.
Stimulates mucus secretion & inhibits Helicobacter pylori.

Dose:

As suspension 15mg or tablets 120mg QID before meals.

Side Effects:

Unpleasant ammoniacal odor, black stools and teeth discoloration.

In cases of chronic treatment, there may be encephalopathy especially in renal failure.

4) Prostaglandin synthetic analogs (misoprostolR200mg tablets):

a. Provide mucosal cytoprotection.

b. Increase mucus and HCO3 secretion.
c. Maintain gastric blood flow.
d. Stimulate mucosal cellular renewal and regeneration.
e. A mild inhibitory effect on gastric acid secretion.

5) Histamine (H2 receptor) Antagonists:

 Reduce both daytime and nocturnal gastric acid secretion.

 Block acid secretion induced by histamine, gastrin, cholinergic drugs and vagal
stimulation.

Mechanism of Action:

Competitively inhibit histamine at H2-receptor of parietal cells.

1) Cimetidine (tagametR):

Rapidly absorbed from upper small intestine.

Excreted by kidney.
Adverse effects:

1) Diarrhea, nausea, vomiting, fatigue and skin rash.

2) CNS: headache, dizziness, elderly mental confusion and delirium.

3) Endocrine: hyperprolactinemia, galactorrhea and infertility in females and

gynecomastia in males.

4) Anti-androgenic action: loss of libido, impotence and decreased sperm count.

5) ↑ serum transaminases, hepatitis, cardiac arrhythmias, bone marrow depression &

blood dyscrasias.

6) Slow metabolism of some drugs due to inhibition of cytochrome P-450 leading to

↑level & effect of warfarin, β-blockers, phenytoin, diazepam &theophylline.

2) Ranitidine (zantacR):

Differs from Cimetidine in the following:

1) Chemically it is not an imidazole but a substituted furan.

2) 5~10 times more potent and more selective H2-blocker.

3) A slightly longer duration of action.

4) Less side effects and drug interactions.

5) Doesn’t inhibit CP-450 or block androgen receptors.

6) No evidence of CNS effect.

Dose: 300mg BID.

3) Famotidine (pepcidR): Is 8~10 times more potent.

4) Nizatidine (AxidR):Stronger than ranitidine, 100% bioavilable.

6) Proton Pump Inhibitors (omeprazole):

They are activated at acidic pH to sulfonamide derivatives that binds irreversibly to

H+-K+ATPase (an enzyme found at the secretory surface of the parietal cells).
So, they inhibit the final transport of H+ via exchange with K+ ion in gastric lumen.
They inhibit both basal and stimulated acid secretion.
Use & dose:

Peptic ulcer and Zollinger-Ellison’s syndrome.

20~40mg /day, orally.

Side Effects:

1) GIT: diarrhea & colic.

2) CNS: headache & dizziness.

3) Skin rash, leucopenia & transient ↑ in liver enzymes.

4) ↑ gastric pH leads to ↓ absorption of ampicillin, iron preparation, ketoconazole, etc

5) Pronounced acid inhibition at extremely high doses leads to feedback elevation of

gastrin and subsequent enterochromaffin-like-cells change of the stomach.

Preparations:

1. Omeprazole (losecR)20~40mg od .orally and I.V.

2. Lansopprazole (lanzorR):15~30mg od. Orally for 4 weeks(duodenal ulcer)
3. Pantoprazole (controlocR) : 20-40mg od. Po and 8 weeks(gastric ulcer)
4. Rabeprazole (parietR): 20mg p.o.

Metoclopramide:

 It is a pro-kinetic drug.
 The main action is to prevent enterogastric reflux.
 More effective in gastric than duodenal ulcer.
 Prevents gastroesophageal reflux- in reflux esophagitis.

(23) Standard treatment regimen for peptic ulcer:

 Drugs used to treat infections caused by H. pylori.

 The most frequently prescribed agent is (1) amoxicillin or tetracycline or
clarithromycine plus (2) metronidazole or tinidazole in combinantion with (3)
bismuth .
  This triple-therapy for 10~14 days is effective but gives rise to frequent side effects
like nausea, diarrhea, etc. This regimen eradicates H. pylori in about 70-80% of
patients.
 Omeprazole, erythromycin or clarithromycine and metronidazole eradicate H.
pylori in 95-100% of patients in one week with fewer side effects.
 Metronidazole resistance may be a problem.

Action of combinations of antibiotic ulcer therapy that must be used

• Clarithromycin – inhibits protein synthesis

• Amoxicillin – disrupts cell wall

• Tetracycline – inhibits protein synthesis

• Metronidazole – used often due to bacterial resistance to amoxicillin and

tetracycline, or due to intolerance by the patient

• Bismuth (Pepto-Bismol®) – disrupts cell wall of H. pylori

(24) Gastroesophageal reflux disease (GERD):

– Backflow of stomach acid into the esophagus

– Esophagus is not equipped to handle stomach acid => scaring.

 – Usual symptoms are heartburn, an uncomfortable burning sensation behind
the sternum (MI often mistaken for GERD).

– More severe symptoms: difficulty swallowing, chest pain.

– Reflux into the throat can cause sore throat.

– Complications include esophageal erosions, esophageal ulcer and narrowing

of the esophagus (esophageal stricture).

– In some patients, the normal esophageal lining or epithelium may be replaced

with abnormal (Barrett's) epithelium. This condition
(Barrett's esophagus) has been linked to cancer of
the esophagus.

– Primary treatment option are proton pump inhibitors.

Information Sheet X:- Anti - inflammatory drugs

Autacoids & Related Drugs
1. Autacoids:
 Are diverse substances produced by wide variety of cells in the body having intense
biological activity, but generally locally at the site of synthesis & release
 Involved in a number of physiological & pathological processes, especially reaction
in injury & immunological disorders
 A number of useful drugs act by modifying their action or metabolism
 Classical autacoids include: Histamine, prostaglandins, leukotrienes & serotonin
Histamine & Antihistamines
 Is a basic amine formed from histidine by histidine decrboxylase and major portion is
stored in mast cells and basophils
 present mostly with in storage granules of mast cells
 Tissue rich in histamine: - skin, gastrointestinal mucosa, lungs, liver & placenta.
 Stimuli causing the release of histamines include:-
1. The destruction of cells because of cold, bacterial toxins, beesting venom or
trauma
2. Allergies
 The released histamine act by binding with two types of receptors: H1 and H2
H1-receptors:-smooth muscle contraction, increases capillary permeability, vasodilatation
H2- receptor: - gastric acid secretion increase (secretion of HCL in stomach)
H1-Antagonists:-
 Competitively antagonize action of histamine at H1-receptors
 block histamine induced bronchoconstriction, contraction of intestinal & other
smooth muscles, whealflare and itching,
 Depending on the ability to pass BBB-produce sedation (histamine involved in
manitaing wakefulless)
 Prevent motion sickness by anti-muscarinic activity & CNS effects
1st Generation:
 Diphenhydramine, Dimenhydrinate,promethazine,chloropheneramine
 Most of them produce CNS depression: sedation, drowsiness, inability to concentrate,
disturbance of coordination
 Diphenhydramine,promethazine and dimenhydrinate have antimotion sickness action
2nd Generation:
 Loratadine,cetrzine
 higher H1 -selectivity, no anticholinergic effects
 Absence of CNS depressant property
 Additional antiallergic mechanism (by acting on leukotrienes)
Therapeutic use
 Antiallergies: allergic rhinitis, (hay fever), urticaria, insect bites, drug allergy
  Anti-emetics: prevention of motion sickness or vomiting due to other causes.
 Treatment of insomnia -for sedation(1st-generation)
H2- Antagonists:
 Cimetidine,Ranitidine,Famotidine
 Indicated for peptic ulcer & gastric hyper secretory states
Eicosanoids
 Unlike histamine are not found preformed in the tissue
 The main source of eicosanoids is arachidonic acid which is metabolized mainly by
two ways
1. Cyclooxygenase (Cox) pathway
 produces prostaglandins & thromboxane
 Cox 1- found in most cells as a constitutive enzyme
 Cox 2-induced in inflammatory cells by inflammatory stimulus
2. Lipoxygenase path way
 produces leucotrines
1. Prostaglandins (PGS)
 PGS(PGE, PGI, and PGF) differ in potency to produce a given action & sometimes
have opposite effects
 All cells are capable of forming PGS

 Biosynthesis
Essential fatty acids

Cell membrane phospholipids

Arachidonic acid
5-lipooxygenase Cyclooxygenase
Leucotrines PG (PGE2, PGF2, thromboxane, PGI)

 Physiological action of PGS:-

 Blood Vessel: - Vasodilatation
 Uterus: - Contraction
 Stomach: - decrease acid secretion & increase mucus secretion
 CNS: - Mediated marked rise in body temperature.PGE is a potent pyrogenic
substance (↑ fever)
 PGI (prostacyclin) is a potent inhibitor of platelet aggregation and vasodilator
 PGI (prostacyclin) is a potent inhibitor of platelet aggregation and vasodilator
2. Thromboxane: causes platelet aggregation and vasoconstriction
3. Leucotrines[reading assignment]

Non- Steroidal Anti-inflammatory drugs (NSAIDS)

Inflammation
 Is the body's effect to inactivate or destroy invading organisms, remove irritants and set
the stage of tissue repair.
 Is always accompanied by the release of PGs
 Is triggered by the release of chemical mediators from injured cells-histamine, 5-HT-
PGS, bradykinin & inter lukin.
NSAIDs
 Inhibit the formation of both COX-1 and COX-2 though they vary in the degree of
inhibition
 Many of them act by inhibiting the synthesis of prostaglandins
 The anti-inflammatory action is mainly due to inhibition of COX-2
 Their unwanted effects particularly those affecting the GIT are results of their
inhibition of COX-1
Aspirin (Acetyl salicylic acid) (ASA)
 Is a weak organic acid
 Is deacetylated in the body to salicylic acid, which also has anti-inflammatory, antipyretic
& analgesic effect
 Mechanism of action:-
 Inhibit the synthesis of prostaglandins, important mediators of inflammation.
 Inhibition of platelet aggregation is attributable to the inhibition of platelet synthesis
of thromboxane A2, a potent vasoconstrictor and inducer of platelet aggregation.
This effect occurs at low doses and lasts for the life of the platelet (8 days).
 Higher doses inhibit the synthesis of prostacyclin, a potent vasodilator and inhibitor
of platelet aggregation.
 Action:-
 Anti-inflammatory analgesic & antipyretic action
 ASA block PG synthesis so inhibits the formation and maintainance of gastric mucosa
leading to direct damage due to acidity - epigastric distress, ulceration and bleeding
 Effects on platelets- Low dose ASA block synthesis of TXA2
 Anti-coagulant effect.
 Delays labor if given during the time of labor.
 Therapeutic uses:-
 Antipyretic, analgesic & anti-inflammatory; rheumatism, rheumatic arthritis &
headache
 Cardiovascular application: inhibitor of platelet aggregation and thrombus formation
 Adverse effects:-
 GI-ulceration & bleeding
 Contraindicated in gout patients
 Toxicity:-
 At fairly high doses, it causes salycilism (mental confusion, tinnitus, vertigo,
decrease hearing, nausea and vomiting).
 Asprine may cause Rey’s syndrome (Liver disorder and encephalopathy) when
given to children with viral infections.So it is best avoided in children under 12
years of age.
  Drug interaction:-
Aspirin increases the effect of warfarin by displacing it from plasma protein
binding and also due to its effect on platelets
Aspirin interferes with the effects of uricosuric drugs such as probenicid and
sulphinpyrazone
Ibuprofen
 Less GIT effect than aspirin
 Therapeutic use: - Analgesic, antipyretic & anti-inflammatory
Indomethacin
 is more potent anti-inflammatory agent than aspirin but toxicity limits its use
 Analgesic, antipyretic & anti-inflammatory
 Adverseeffects:nausea,Vomiting , anorexia , diarrhea , abdominal pain
ulceration,perforation,hemorrhage,dizziness,mentalconfusion,aplasticanemia
rashes ,itching.
Diclofenac Sodium
 A Cyclo oxygenase inhibitor
 Therapeutic use: - Analgesic, antipyretic & anti-inflammatory agent
 Use for Rheumatoid arthritis, Osteo arthritis, dysmenorrhea.
 Is among the most extensively used NSAIDs
 Adverse effects: - Generally mild epigastric distress, nausea, head ache, dizziness,
rashes.*Gastric ulceration & bleeding is less common.
Acetaminophen (paracetamol)
 Does not belong to the NSAIDs, Unlike the NSAIDs has little or no anti-inflammatory
activity.
 Act by inhibiting PG synthesis in CNS & less effect on peripheral tissue (antipyretic &
analgesic but weak anti-inflammatory properties),
 Lack many of the side effects of NSAIDs.
 Therapeutic use- analgesic and antipyretic
 Is the analgesic & antipyretic of choice for children
 Adverse effects:-
 At therapeutic dose: - free of any significant side effects
  At large doses: - Very serious hepatic toxicity
Others: Phenyl butazone, Pyroxicam, Sulindac [reading assignment]

Drugs for the treatment of Gout

 Gout: - is a metabolic disorder in which plasma urate concentration is raised because of
overproduction or impaired excretion of purines.
 Sodium urate is an end product of purine metabolism in humans
 Sodium urate crystals will accumulate in joints, cartilages and kidneys.→ initiate
inflammatory process.
DNA
RNA Purines hypoxanthin xanthin XO uric acid
XO= Xanthine oxidase
 Treatment of gout is directed at:
 ↑ Excretion of uric acid
 ↓ Synthesis of uric acid
 Alter the inflammatory process
Uricosuric drugs:
 Increase uric acid excretion by direct action on the renal tubule.e.g.Probenicid,
Sulphinpyrazone.
 Drugs which inhibit migration of leucocytese.g Colchicine
 NSAIDs modify the inflammatory response
 Drugs which inhibit the synthesis of uric acid.eg. Allopurinol
 Allopurinol reduces the synthesis of uric acid by inhibiting xanthine oxidase
Information Sheet XI:- Drugs act on respiratory system

Drugs acting on the Respiratory system

Anatomy and Physiology of Respiratory system
Organs and Structures of the Respiratory System
 The major organs of the respiratory system function primarily to provide oxygen to body
tissues for cellular respiration, remove the waste product carbon dioxide, and help to
maintain acid-base balance.
 Portions of the respiratory system are also used for non-vital functions , such as sensing
odors, speech production, and for straining, such as during child birth or coughing
Figure; Major Respiratory Structures The major respiratory structures span the nasal cavity to the
diaphragm
 Functionally, the respiratory system can be divided into aconducting zone and
arespiratoryzone.
 The conducting zone of the respiratory system includes the organs and structures not
directly involved in gas exchange.
 The gas exchange occurs in the respiratory zone.
Conducting Zone
The major functions of the conducting zone are to provide a route for incoming and
outgoing air, remove debris and
pathogens from the incoming air, and warm and humidify the incoming air. Several
structures within the conducting zone perform other functions as well.
 The epithelium of the nasal passages, for example, is essential to sensing odors, and the
bronchial epithelium that lines the lungs can metabolize some airborne carcinogens
Respiratory Zone
 In contrast to the conducting zone, the respiratory zone includes structures that are
directly involved in gas exchange.
 The respiratory zone begins where the terminal bronchioles join a respiratory
bronchiole , the smallest type of bronchiole , which then leads to an alveolar duct,
opening into a cluster of alveoli.
Drugs used to treat asthma
 Bronchial Asthma: -Is a disease characterized by increased responsiveness of trachea
and bronchi to various stimuli and wide spread narrowing of the air ways.
 Mediated by IGE antibodies bound to mast cells in the air way mucosa. Allergen
interaction with mast cell fixed IGE release histamine and leucotriens which cause
bronchial spasm.
 In bronchial asthma, air flow is impaired by:
 Contraction of smooth muscle
 Thickening of bronchial mucosa from edema and cellular infiltration.
 Abnormally thick mucus plug on the air ways.
 The goal of therapy is to relive symptoms and to prevent recurrence.
Pharmacotherapy of asthma
1. Broncho dilators
β- Adrenergic Agonists
Non selective eg. Epinephrine, Ephedrine
Selective β2 agonist eg.Salbutamol
Adrenaline (Epinephrine)
 Non selective stimulant of both α & β receptors.
 Relax bronchial smooth muscles by interacting with β2 receptors.
 Cause more cardiac stimulation.
 It has fast onset and short duration of action.
 Used in acute attack of bronchial asthma.
 Administered by inhalation or subcutaneously but not orally.
  If there is no response,additional dose of adrenaline should be considered after 20
minutes.If there is no response after two doses of injection or if the attack worsenes after
the first injection, aminophyline should be given intravenously.
Salbutamol
 Is a selective β2 agonist.
 Used for the sympthomatic treatment of bronchial asthma.
Ephedrine
 Longer duration of action.
 More pronounced central effect
 Lower potency.
Methyl xanthines
Three pharmacologically active methyl xanthines:
 Theophylline (Employed in clinical medicine).
 Theobromine
 caffeine
 Theophyline is available in combination with Ephedrine,”Theoephedrine”.
 Theophyline can also be used as theophyline ethylene diammine (Aminophyline).
 Theophyline has bronchodilator action though it is rather less effective than the
β2receptor agonists.
Mechanism of action:
 It competitively inhibits the action of adenosine on adenosine receptors; adenosine causes
contraction of smooth muscles and provokes release of histamine.
Adverse effects
 anorexia, nausea, vomiting, abdominal discomfort, insomnia, anxiety.
CNS effects
 stimulant effect causing nervousness, interferes with sleep, tremor.
CVS
 +ve inotropic and chronotropic effects, vasodilation in most blood vessels but
vasoconstriction in the CNS.
Renal system
 weak diuretic effect.
Clinical uses
 antiasthmatic in patients who do not respond to β2 agonists
Aminophyline is used intravenously in acute severe asthma.
 NB. Theophyline is a drug with narrow therapeutic index.

2) Corticosteroids
Asthma is associated with air way inflammation.
Glucocorticoids decreases the inflammatory components in chronic asthma.They do not
relax air way smooth muscle.
Mechanism of action
Corticosteroids decrease the formation and activation of cytokines, eosinophills,
leucotrines and other inflammatory chemicals.
Inhaled glucocorticoids are used prophylactically to control asthma rather than to acutely
reverse asthma sympthoms.eg. Beclomethasone
Systemic side effects are rare but oropharyngeal candidiasis may occur.
Systemic steroidis: -sever asthma may require intravenous administration of methyl
predinsolone, triamicilonone or oral predinsolone.
7.2 Drugs used to treat cough:-
Cough: - is protective reflex mechanism that removes foreign material and secretions from the
bronchi and bronchiols.It can be inappropriately stimulated by inflammation in the respiratory
system.
Expectorants
o Render the cough more productive by stimulating the flow of respiratory tract secretions
o Guaifenesin is most commonly used
o Available alone & as an ingredient in many combination cough & cold remedies
o Dosage
Guaifenesin
 100-400 mg q4h po
Ammonia & Ipecacuaha Mixture
 10-20 ml three to four times daily po
Mucolytics
 o Reacts directly with mucus to make it more watery. This should help make the
cough more productive
o Dosage
o Acetylcysteine
 100 mg two to four times daily
 200 mg two to three times daily
 600 mg once daily
o Bromhexine
 8-16 mg three times daily po
o Carbocisteine
 750 mg three times daily, then 1.5 g daily in divided doses
Nasal Decongestants
 Sympathomimetics are used to reduce nasal congestion
 Stimulate alpha1-adrenergic receptors on nasal blood vessels, which causes
vasoconstriction & hence shrinkage of swollen membranes
 Topical administration:
 Response is rapid & intense
 Oral administration:
 Response are delayed, moderate & prolonged
Includes
 Oxymetazoline
 Phenylephrine
 Xylometazoline
Adverse effects:
o Rebound congestion develops with topical agents when used for more than a few
days
o CNS stimulation (such as restlessness, irritability, anxiety and insomnia) occurs
with oral sympathomimetics
o Sympathomimetics can cause vasoconstriction by stimulating α-1 adrenergic
receptors. More common with oral agents
 o Sympathomimetics cause CNS stimulation, and can produce effects similar to
amphetamine. Hence, these drugs are subject to abuse
Nursing alerts:
o Overuse of topical nasal decongestants can cause rebound congestion, meaning
that the congestion can be worse with the use of drug. To minimise this, drug
therapy should be discontinued gradually.
o The use of topical agents is limited to no more than 3 to 5 days
o The patient’s blood pressure and pulse should be assessed before a decongestant
is administered
o Inform the patient that nasal burning and stinging may occur with topical
decongestants

Antitussives (Cough suppressants)

o Drugs that suppress cough
o Used only for dry (unproductive) cough.
o can cause harmful sputum thickening and retention. for the cough associated with asthma.
o Some act within the CNS, some act peripherally
o Indicated in dry, hacking, nonproductive cough that interfere with rest & sleep
o Include:
 Opoids -codeine.
 Non Opoids-Dextrometorphan
 Adverse effects:
o Drowsiness
o Respiratory depression (for opioid antitussives)
o Constipation (for opioid antitussives)
o Preparations containing codeine or similar analgesics are not generally
recommended in children & should be avoided altogether in those under 1
year of age
  Nursing Alerts:
o Observe for excessive suppression of the cough reflex (inability to cough
effectively when secretions are present). This is a potentially serious adverse
effect because retained secretions may lead to lungs collapse, pneumonia,
hypoxia, hypercarbia, and respiratory failure

Antihistamines
Cough mixtures may also contain Antihistamines –Chloroapheneramine, diphenhydramine

 H1 receptor antagonists
 Inhibit smooth muscle constriction in blood vessels & respiratory & GI tracts
 Decrease capillary permeability
 Decrease salivation & tear formation
 Used for variety of allergic disorders to prevent or reverse target organ inflammation
 All antihistamines are of potential value in the treatment of nasal allergies, particularly
seasonal allergic rhinitis (hay fever)
 Reduce rhinorrhoea & sneezing but are usually less effective for nasal congestion
 Are also used topically in the eye, in the nose, & on the skin
 First-generation H1 receptor antagonists
 Non-selective/sedating
 Bind to both central & peripheral H1 receptors
 Usually cause CNS depression (drowsiness, sedation) but may cause CNS
stimulation (anxiety, agitation), especially in children
 Also have substantial anticholinergic effects
 Adverse effects:
 Sedation
 Dry mouth
 Blurred vision
 GI disturbances
 Headache
 Urinary retention
  Hydroxyzine is not recommended for pregnancy & breast-feeding
 Second-generation H1 receptor antagonists
 Selective/non-sedating
 Cause less CNS depression because they are selective for peripheral H 1 receptors
& do not cross blood-brain barrier
 Longer-acting compared to first-generation antihistamines
 Adverse effects:
 May cause slight sedation
 Some antihistamines may interact with antifungal, e.g. ketoconazole; antibiotics,
e.g. erythromycin; prokinetic drug-- cisapride or grapefruit juice, leading to
potentially serious ECG changes e.g. Terfenadine

Information Sheet XII:- Drugs act on cardiovascular system

DRUGS AFFECTING THE CARDIOVASCULAR SYSTEM

3.1 Anatomy and Physiology of cardiovascular system and Renal system

 The human heart is located within the thoracic cavity , medially between the lungs in the
space known as the mediastinum
 Within the mediastinum, the heart is separated from the other mediastinal structures by a
tough membrane known as the pericardium, or pericardial sac, and sits in its own space
called the pericardial cavity.
 The human heart consists of four chambers: The left side and the right side each have one
atrium and one ventricle. Each of the upper chambers, the right atrium (plural = atria) and
 the left atrium, acts as a receiving chamber and contracts to push blood into the lower
chambers , the right ventricle and the left ventricle. The ventricles serve as the primary
pumping chambers of the heart, propelling blood to the lungs or to the rest of the body
 There are two distinct but linked circuits in the human circulation called the pulmonary
and systemic circuits. Although both circuits transport blood and everything it carries, we
can initially view the circuits from the point of view of gases.
 The pulmonary circuit transports blood to and from the lungs, where it picks up oxygen
and delivers carbondioxide for exhalation.
 The systemic circuit transports oxygenated blood to virtually all of the tissues of the body
and returns relatively deoxygenated blood and carbon dioxide to the heart to be sent back
to the pulmonary circulation.
 The blood exiting the systemic capillaries is lower in oxygen concentration than when it
entered. The capillaries will ultimately unite to form venules, joining to form ever-larger
veins, flowing into the two major systemic veins, the superior vena cava and the inferior
vena cava, which return blood to the right atrium.
 The blood in the superior and inferior venae cavae flows into the right atrium, which
pumps blood into the right ventricle. This process of blood circulation continues as long
as the individual remains alive
Membranes
The membrane that directly surrounds the heart and defines the pericardial cavity is
called the pericardium or pericardial sac.
It also surrounds the“roots”of the major vessels ,or the areas of closest proximity to
the heart.
The pericardium,which literally translates as “around the heart,” consists of two
distinct sublayers: the sturdy outer fibrous pericardium and the inner serous
pericardium.
The fibrous pericardium is made of tough, dense connective tissue that protects the
heart and maintains its position in the thorax.
The more delicate serous pericardium consists of two layers: the parietal
pericardium, which is fused to the fibrous pericardium, and an inner visceral
 pericardium, or epicardium, which is fused to the heart and I s part of the heart
wall.
The pericardial cavity , filled with lubricating serous fluid, lies between the
epicardium and the pericardium.

The heart as a pump

The heart functions as a pump, which together with the vascular system supplies the
tissues with blood containing oxygen and nutrients, and removes waste products
Deoxygenated blood from body tissues reaches the right atrium through the systemic
veins (the superior and inferior venae cavae).
Blood flows into the right ventricle, which then pumps the deoxygenated blood via the
pulmonary circulation to the lungs, where the blood becomes oxygenated before reaching
the left atrium.
Blood flows from the left atrium into the left ventricle, from where it is pumped into the
systemic circulation via the aorta, to supply the tissues of the body.
Cardiac rate and rhythm
  The sinoatrial node (SAN), located in the roof of the right atrium near the entrance of the
superior vena cava, and the atrioventricular node (AVN), located at the base of the right
atrium, possess a spontaneous intrinsic rhythm. The SAN discharges at a frequency
higher than other regions of the heart(80 impulses/minute). Thus it is the pacemaker
forthe heart, and as such determines the heart rate.
 The action potential generated by the SAN spreadsthroughout both atria, reaching the
AVN, from whichit enters the interventricular septum by means of thebundle of His. The
bundle of His splits into left andright branches making contact with the Purkinjefibres,
which conduct the impulse throughout theventricles, causing them to contract
Autonomic control of the heart
 Both the parasympathetic and sympathetic nervoussystems influence the heart, though
parasympatheticactivity predominates and explains why the heart rate is lower than the
inherent firing frequency ofthe SAN.The sympathetic nervous system mediates itseffects
through the cardiac nerve, and activation of b1adrenoceptors. These are linked to adenylyl
cyclase and their activation causes increased levels of cyclic adenosine monophosphate
(cAMP), and a subsequent increase in intracellular calcium levels.
Effects of the sympathetic and parasympathetic systems on the heart

Structure and Function of Blood Vessels

◊ Blood is carried through the body via blood vessels. An artery is a blood vessel that
carries blood away from the heart, where it branches into ever-smaller vessels.
Eventually, the smallest arteries, vessels called arterioles, further branch into tiny
capillaries , where nutrients and wastes are exchanged , and then combine with
 other vessels that exit capillaries to form venules , small blood vessels that carry
blood to a vein, a larger blood vessel that returns blood to the heart
◊ Arteries and veins transport blood in two distinct circuits: the systemic circuit and
the pulmonary circuit (Fig 2).Systemic arteries provide blood rich in oxygen to the
body’s tissues. The blood returned to the heart through systemic veins has less
oxygen, since much of the oxygen carried by the arteries has been delivered to the
cells.Incontrast,in the pulmonary circuit , arteries carry blood low in oxygen
exclusively to the lungs for gas exchange.Pulmonary veins then return freshly
oxygenated blood from the lungs to the heart to be pumped back out into systemic
circulation. Although arteries and veins differ structurally and functionally, they
share certain features

3.1 ANTIHYPERTENSIVE DRUGS

Hyprtention
 Normal blood pressure is generally regarded as 120/80 mmHg (systolic pressure/diastolic
pressure)
 HTN is defined as sustained diastolic pressure >90mmHg accompanied by an elevated
systolic blood pressure >140mmHg.
 The condition can be fatal if left untreated, as it greatly increases the risk of thrombosis,
stroke and renal failure
 Three factors determine blood pressure:
 Blood volume
 Cardiac output
 Peripheral vascular resistance.
Arterial pressure is the product of cardiac output and peripheral vascular resistance.
BP = COP Ẋ PR
Heart rate Filling Pressure
Contractility Blood volume
Venous tone

 ‘Primary’ or ‘essential’ hypertension accounts for 90–95% of all cases of hypertension. This
has no known cause, but is associated with:
 Age (40+)
 Obesity
 Physical inactivity
 Smoking and alcohol consumption
 Genetic predisposition.
 ‘Secondary hypertension’ accounts for the remaining 5–10% of cases of hypertension. The
cause is usually one of the following:
 Renal disease, which activates the RAS
 Endocrine disease, e.g. phaeochromocytoma, steroid-secreting tumour of the adrenal
cortex, adrenaline-secreting tumour of the adrenal medulla.
 Arterial BP is controlled mainly by two overlapping mechanisms:
1. Baroreflex mediated by the sympathetic nervous system for moment to moment control of BP.
 Baroreceptors sense droped blood pressure in the CNS which leads to increased
sympathetic activity and decreased parasympathetic activity.This leads to
vasoconstriction and increased cardiac output which again leads to rise in blood pressure.
2. Renin angiotensin aldosterone axis - for long term control of BP.
Angiotensinogen --------Renin----------> Angiotensin I ---ACE--------> Angiotensin II
  Angiotensin II causes vasoconstriction and release of Aldosterone which increases blood
volume and BP.
 Blood pressure in both normal and a hypertensive patient is controlled by the same
mechanism.
 Sustained arterial hypertention damages blood vessels in the kidney, heart and brain and
leads to an increased insidence of renal failure,heart failure,cerebrovascular accidents
(stroke).
Antihypertensive therapy
1. Non pharmacological therapy
2. Pharmacological therapy
The non pharmacollogical methods include;
 low sodium chloride diet
 Weight reduction
 Exercise
 Cessation of smoking
 Decrease consumption of alcohol
 Psychological relaxation
 Dietary decrease in saturated fat
Pharmacollogic Therapy
 Based on the primary site or mechanism of action, anti-hypertensive drugs may be classified
as follows
Diuretics
1. Thiazide diuretics eg. Hydrochlorothiazide
2. Loop diuretics eg. Furosemide
3. K+ sparing diuretics eg. Spironelactone
Sympatholytic drugs
1. Centrally acting agents eg. α-methyl dopa
2. Adrenergic neurone blocking agents eg reserpine
3. B-adrenergic antagonists eg. Propranolol,Atenolol
4. α - adrenergic antagonists eg Prazocine,Terazocine
Vasodilators
 1. Arterial vasodilators eg. hydralazine, minoxidil,diazoxide
2. Arterial and venous dilators eg. Nitropruside
Ca++ channel blockers eg, Verapamil, Nifedipine
ACE inhibitors eg. Captopril,Enalapril, Lisinopril
Angiotensin II receptor antagonists - Losartan, Valsartan

Pharmacology of Individual drugs

I) Diuretics

Hydrochlorothiazide -

Site of action - distal convulated tubule.

Mechanism of action
 they decrease active reabsorbtion of Na + and accompanying Cl-.
 Increase sodium and water excretion ------> Reduce blood volume and cardiac output ---->
reduce BP.

Pharmacokinetics:
 Well absorbed from the GIT, excreted in the urine mainly by tubular secretion.( competes
with uric acid for tubular secretion).
Clinical uses:
 Hypertension
 Mild heart failure
 Oedema
Unwanted effects
 Hypokalemia, increase plasma uric acid, hyperglycemia, increased plasma cholesterole.

Furosemide
  A loop diuretic which acts primarly on the thick segment of the ascending loop of
Henle.It acts by inhibiting the reabsorbtion of NaCl.
 Loop diuretics are more potent than thiazide diuretics.The antihypertensive effect is
mainly due to reduction of blood volume.
Clinical uses
 Hypertention ( thiazides are usually prefered)
 Acute pulmonary oedema
 Chronic heart failure
 Cirhosis of the liver
 Nephrotic syndrome and renal failure
Unwanted effects
 Potassium loss --> hypokalemia (usually corrected by using potassium supplement or
potassium sparing diuretics).
 Hypovolemia and hypotension.
Drug interaction: Ototoxicity may result when furosemide is taken along with aminoglycosides.
Spironolactone
A potassium sparing diuretic with limited diuretic action so often used along with thiazide or
loop diuretics
Mechanism of action:
 Spironolactone is an aldosterone antagonist which competes for intracellular aldosterone
receptors in the cells of the distal tubule.
N.B. Aldosterone is a hormone secreted by the adrenal cortex that enhances Na + reabsorption and
K+ secretion by the kidney.
Clinical uses
 Along with thiazide or loop diuretics to prevent potassium loss. In hypertention or heart
failure along with other drugs.
 In hyperaldostronism
Unwanted effects
 GI upset, hyperkalemia,gynaecomastia,menstrual disorders and impotence.
II) Centrally acting antihypertensive agents
Methyl dopa
Methyl dopa is an α - agonist which is converted to methyl norepinephrine centrally to diminish
the adrenergic output from the CNS.
The decrease in sympathetic out flow from the medula results either in decrease of peripheral
resistance or cardiac output.
N.B. Methyldopa is a prodrug and must be converted in the CNS to active α - methyl
norepinephrine to exert the effect on blood pressure.
Uses: Mild to moderate hypertention.
Side effects:
CNS - Sedation,headache, dizzyness
GIT - dry mouth,nausea,vomiting
Others - Postural hypotention, impotence,allergic reactions.

III) Beta adrenergic antagonists

 β-blockers antagonize β-receptors located on the myocardium and prevent the
cardioacceleration which follows sympathetic stimulation.The rate and force of myocardial
contraction is diminished,decreasing cardiac output and thus lowering blood pressure.
 Renin release is also mediated by β- receptors and receptor blockade prevents angiotensin II
formation and associated aldosterone secretion,resulting in decrease in total peripheral
resistance and blood volume.
There are two groups of β -blockers
1. Non selective β1 and β2 adrenergic -blockers: Propranolol, Timolol
2. Selective β1 adrenergic blockers: Atenolol

Propranolol
 Competitively blocks beta-adrenergic receptors in the heart and juxtoglomerular
apparatus, decreasing the influence of the sympathetic nervous system on these tissues.
Actions
I. Cardiovascular:- Diminishes cardiac output , having both negative inotropic and
chronotropic effects by blocking β1 receptors.The reduction in cardiac output leads to
decreased blood pressure.
 II. Bronchoconstriction: - blocking β2 receptors in the lungs of susceptible patients causes
contraction of the bronchial smooth muscles.Therefore it is contraindicated in patients
with asthma.
III. Increased Na+ retention: - Reduced blood pressure causes a decrease in renal perfussion
resulting in an increase in Na + retaintion and plasma volume which may elevate blood
pressure. Therefore β-blockers are often combined with a diuretic to prevent Na +
retention..
IV. Disturbance in glucose metabolism :- β -blockade leads to decreased glycogenolysis and
decreased glucagon secretion.Therefore if an insuline dependent diabetic patient is to be
given propranolol, pronounced hypoglycemia may occur after insuline injection.
Therapeutic uses
 Hypertention- lowers B.P. by decreasing cardiac output.
 Angina pectoris -decreases oxygen requirement of heart muscle.
 Cardiac arrhythmias (tachyarrhythmias).
 Prophylaxis for migraine headache.
Adverse effects
 Bronchoconstriction in susceptible patients
 Arrhythmia
 Disturbance in metabolism
Drug interactions
 Cimetidine, furosemide, Chloropromazine inhibit the metabolism of propranolol which
may potentiate its antihypertensive effect. Barbiturates, Phenytoin & Refampicin
stimulate metabolism of propranolol and can mitigate its effects.

Timolol
 Timolol is a non-selective β -adrenergic blocker which has similar pharmacollogic effects
with propranolol.
 It reduces the production of aqueous humor in the eye and is used topically in the
treatment of chronic glaucoma.
Atenolol
 Selective β1 antagonist.
  Eliminate the unwanted bronchoconstrictor effect of propranolol seen among asthmatic
patients.
Therapeutic use
 Useful for hypertensive patients with impaired pulmonary function.
 Useful in diabetic hypertensive patients who are receiving insuline or oral hypoglycemic
agents.
 Treatment of angina pectoris
Sideffects- Bradycardia, Crdiac arrhythmia.

IV) Alpha adrenergic antagonists

 The principal action of alpha adrenergic blocking agents is to produce peripheral
vasodilation.
 Prazosine, Doxazocine and Terazosine are selective α1 blockers.
 Prazosine was the first α1 blocking agent but doxazosine and Terazosine have a longer
plasma half life allowing once daily dossing.
 α1 adrenergic blocking agents also cause relaxation of the smooth muscles of the bladder
neck and prostate capsule so are useful in patients with urinary retention associated with
benighn prostatic hypertrophy.
 The main side effects of this group of drugs is postural hypotention, nasal stuffiness,
failure of ejaculation in males.

V) Vasodilators
1. Arterial vasodilators eg. hydralazine, minoxidil,diazoxide
2. Arterial and venous dilators eg. Nitropruside
Hydralazine
 It dilates arterioles but not veins.
 The most common adverse effects are headache, nausea, anorexia, palpitations, sweating
and flushing which are typical to vasodilators.

Sodium nitroprusside
  It is a powerful vasodilator that is used in treating hypertensive emergencies as well as
severe heart failure.
 It dilates both arterial and venous vessels, resulting in reduced peripheral vascular
resistance and venous return.
 It rapidly reduces venous return and may result in excessive hypotention.
VI) Angiotensin converting enzyme (ACE) inhibitors
 These drugs inhibit ACE that hydrolyzes angiotensin I (Inactive) to Angiotensin II
(Active) a potent vasoconstrictor which additionally stimulates the secretion of
aldosterone.It lowers B.P. principally by decreasing peripheral resistance.
 Drugs: Captopril, Enalepril, Lisinopril.
Advantages:
 Metabolic side effects are not encountered during long term therapy.
 The drugs do not alter plasma concentration of uric acid.
 Improve insulin sensitivity in patients with insulin resistance
 Decrease cholesterol levels
 Serious untoward effects are rare.
Clinical uses:
 Hypertension
 Heart failure
 Ventricular dysfunction following myocardial dysfunction.
Untoward effects: rash, cough, granulocytopenia, diminished sense of taste.

VII) Angiotensin II receptor antagonists

 These drugs inhibit the vasoconstrictor effect of angiotensin II by blocking the receptors.
 They are selective blockers and preffered when some of the sideeffects of ACE inhibitors
(like dry cough due to the accumulation of bradykinins in the lung) are intolerable.
 Drugs: Losartan, Valsartan

VIII) Calcium channel blockers

 These drugs block the entry of calcium in to the heart and vascular smooth muscles. This
results in reduction of contractility of the cardiac as well as vascular smooth muscles.
Actions: Decrease cardiac output and then blood pressure.
Drugs: Nifedipine, Verapamil, Diltiazem.
Selectivity between heart and smooth muscle varies: Nifedipine has little effect on the heart and
is a potent vasodilator.
Verapamil has greater effect on the heart than on blood vessels.
Clinical uses:
Hypertention
 Angina pectoris
 Dysrhythmia (Verapamil - to slow ventricular rate)
Unwanted effects:
 Most of the unwanted effects of calcium antagonists are extensions of their main
pharmacollogic actions.
 Nifedipine causes flushing, ankle swelling and headache because of its vasodilator action.
 Verapamil can cause constipation (because of calcium channel blocking effect on the
gastrointestinal smooth muscle), worsening of heart failure

3.2 Drugs used in heart failure

Congestive heart failure is a condition in which the heart is unable to pump sufficient
blood to meet the needs of the body due to impaired ability of cardiac muscle to contract
or increased work load imposed on the heart.
Causes of heart failure
 Ischaemic heart disease
 Hypertention
 Heart muscle disorders
 Valvular heart disease
Therapeutic strategies in heart failure includes:
 Reduction in physical activity
 Low dietary intake of sodium
 Treatment with drugs.
 The current approach to therapy for CHF involves preload reduction, afterload reduction, and
enhancement of inotropic state.
There are two classes of drugs:
a. Drugs with positive inotropic effect
b. Drugs without positive inotropic effect
Drugs with positive inotropic effect
 Positive inotropic agents enhance cardiac muscle contractility and thus increase cardiac
output.
i) Cardiac glycosides: Digoxine, Digitoxine
 Cardiac glycosides come from fox gloves (Digitalis spp.) and related plants.
Mechanism of action
 Glycosides inhibit Na+/K+ ATPase transport system.
 Inhibition of Na+/K+ ATPase inhibits outflux of Na+ and increase intracellular Na+
concentration.
 Increased Na+ concentration slows extrusion of Ca++ via the Na+/Ca++ exchange
transporter.It also facilitates release of Ca++ from the sarcoplasmic reticulum.The overall
effect is increased intracellular calcium level.
 Digitalis glycosides increase the force of myocardial contraction.
Therapeutic uses
 Congestive heart failure
 Cardiac arrhythmias
 Adverse effects
 Digitalis glycosides have a low therapeutic index.Digitalis toxicity includes, anorexia,
nausea, vomiting, visual disturbance and arrhythmia.
ii) Beta- adrenergic agonists;
o Increase the force of myocardial contractility and then increase cardiac output.
o Improve cardiac performance by possitive inotropic effects.
o The +ve chronotropic effect of these agents minimizes their use.
 Dobutamine has greater inotropic effect than chronotropic effect.Dobutamine IV infusion is
used in treatment of acute heart failure.
Drugs without positive inotropic effecrs
i) Vasodilators:
o The vasodilators are effective in acute heart failure because they provide a reduction in
preload or after load.
o Dilation of venules decrease cardiac preload.
o Dilation of arteries decreases cardiac after load.
 Hydralazine has a direct vasodilator effect on arteries.A decrease in vascular resistance
improves in cardiac output.
 Sodium nitropruside dilates both the arteries and veins.As with most vasodilators, the
most common adverse effect of nitroprusside is hypotension. In general, nitroprusside
initiation in patients with severe heart failure results in increased cardiac output and a
parallel increase in renal blood flow, improving both glomerular filtration and diuretic
effectiveness.
ii) Angiotensin converting enzyme inhibitors:
 ACEIs, by blocking the formation of angiotensinII, reduce the vascular
resistance,improve tissue perfussion and reduce cardiac after load.They also cause
natriuresis (excretion of sodium through the urine in large amounts) by inhibiting
secretion of aldosterone.
iii) Diuretics
 Diuretics are important in increasing salt and water excretion, especially if there is
edema.
 They decrease preload and after load.

3.3 ANTIANGINAL DRUGS

 Angina pectoris is a clinical syndrome characterized by paroxyms of pain or a feeling of
pressure in the anterior chest.It is caused by coronary blood flow that is insufficient to
meet the oxygen demands of myocardium.
 It is usually caused by atheriosclerotic heart disease, and almost invariably associated
with a significant obstruction of a major artery.

Angina is managed by using drugs that either improve perfusion of the myocardium or reduce its
metabolic demand, or both.
ANTIANGINAL DRUGS
1. Organic nitrates: Isosorbide dinitrate, Glyceryl trinitrate (nitroglycerine).
2. Beta blockers: Propranolol, Atenolol
3. Ca++ channel blockers: Verapamil, Nifedipine

Organic nitrates
o Isosorbide dinitrate, Glyceryl trinitrate (nitroglycerine).
Mechanism of action: -
o Dilitation of veins ----> decrease preload -----> decrease work load on the heart------>
decrease oxygen demand.
Dilitation of coronary artery ----------> Increase blood supply to heart muscle.
Clinical uses
o Treatment or prophylaxis of angina pectoris.
o Heart failure
o Hypertention
Unwanted effects
o The main adverse effects of nitrates are a direct consequence of their main
pharmacollogical actions and includes postural hypotention and headache.
N.B. Tolerance may occur to the antianginal effects or the side effects of Organic nitrates.
Beta Adrenergic Blockers
o Supress the activation of heart by blocking beta receptors.
o They are important in prophylaxis of angina.They act by reducing cardiac oxygen
consumption.
Calcium channel blockers
o Inhibit the entrance of calcium in to cardiac and smooth muscle cells of blood vessels.
Nifedipine
o Functions mainly as arteriolar vasodilator.
o Has minimal effect on cardiac tissue.
Verapamil
 o Slows cardiac contraction directly and thus decrease heart rate and oxygen demand.
o Causes greater negative inotropic effect than nifedipine.

3.4 Anti arrhythmic drugs

o Cardiac muscle possesses the properties of excitability, automaticity, conductivity and

contractility.
o The heart contains specialized cells that can intrinsically generate action potentials in the
absence of external stimuliwhich are called pacemaker cells.
o The impulse generated from the SA node is conducted through the heart in the following
path;
SA node -------> Atrium-------> AV node --------> Purkinje fiber -------> Ventricle
o Dysfunction in impulse generation or conduction can cause abnormality in cardiac
rhythm.
o Cardiac arrhythmia is a problem which occurs when the rate, rhythm or both of the heart
are affected.
Classification of arrhythmia
 Based on the the site of origion of the abnormality: Atrial,junctional,ventricular
 Whether the rate is increased or decreased: tachycardia, bradycardia.
Classification of anti arrhythmic drugs
There are four classes of antiarrhythmic drugs:
1) Class I - Na+ channel blockers: Lidocain, Procainamide, Quinidine.Class I drugs block
sodium channels.Their characterstic effect on the action potential is to reduce the
maximum rate of depolarization during phase 0.
2) Class II - Beta adrenoceptor antagonists: Propranolol, AtenololAdrenaline (Epinephrine)
can cause dysrrhthmia by its effect on phase IV (the pacemaker potential) and on the
plateau potential (slow inward Ca++ currents).Beta adrenoceptor antagonists block this
effect.
3) Class III - K+ channel blockers: Amiodarone, Brethilium These drugs block potassium
channel and prolong the cardiac action potential.
 4) Class IV - Ca++ channel blockers: verapamil These drugs block voltage sensitive Ca++
channel and slow conduction in the SA and AV nodes where action potential propagation
depends on slow inward Ca current.Decreased calcium entry reduces after depolarization
and supresses premature ectopic beats.

3.5 Antihyperlipidemic drugs

 Hyperlipidemia (Dyslipidemia) is a complex group of diseases caused by an increased
level of plasma cholesterole and /or triglycerole containing lipoprotein particles due to
environmental causes such as diet or by inherited genetic deffects in the appropriate
synthesis or degradation of these compounds.
 Drugs used in the treatment of dyslipidemia are generally targeted to:
 Decrease production of lipoproteines by tissues: HMG-CoA reductase inhibitors
(statins) eg. Lovastatine,Atrovastatine inhibit the synthesis of cholesterole in the liver
 Increase the removal of cholesterole from the body Bile acid binding resins e.g
Cholestyramine,colestipol, inhance fecal elimination of cholesterole and bile acids.

Information Sheet XIIV:- Drugs act on the renal system

NORMAL REGULATION OF FLUIDS & ELECTROLYIES BY THE KIDNEYS

 16-20% of the blood plasma entering the kidney is filtered
 The filtrate is free of proteins & blood cells but contains low molecular weight plasma
components in the same concentration as plasma; include;- glucose, sodium bicarbonates,
amino acids, electrolytes such as Na+ K+ and Cl-
 The kidney regulates the ionic composition and volume of urine by the reabsorption or
secretion of ions and /or water by acting on nephroin’s proximal convoluted tubule, the
descending loop of henle the, ascending loop of Henle, the distal convoluted tubule &
collecting duct
1. PROXIMAL CONVOLUTED TUBULE
 Almost all of the glucose, bicarbonate, amino acids and other metabolites are reabsorbed
 Two third of Na+ reabsorbed – Chloride & water passively re absorbed to maintain
electrical and osmotic equality.
 Site of organic acid & base secretary system; secrete such as uric acid from the blood
stream to proximal tubule.
 Most of the diuretic drugs compete with secretion of organic acid may leads to
hyperuricemia (Furosemide or chlorothizide)
2. DESCENDING LOOP OF HENLE (DLH)
 The filtrate, which is isotonic with blood, enters the DLH
 Counter current Mechanism increase salt cocentration in three folds
3. ASCENDING LOOP OF HENLE
 Impermeable to water
 Active reabsorption of Na+, K+& Cl- by Na+/k+/Cl -co- transport system
 25-30 % of tubular NaCl reabsorbed
 Mg++& Ca++ are also reabsorbed
 Diluting region of the nephrons
 Major site of self-reabsorption
 Loop diuretics the most efficacious of all the diuretics because they affect this site
4. DISTAL CONVOLUTED TUBULE
o impermeable to water
o 10% of the filtered NaCl reabsorbed
o Ca++ excretion is regulated by parathyroid hormone at this site
5. COLLECTING TUBULE & DUCT
  Responsible for Na+ /K+ exchange & for H+ secretion
 Stimulation of aldosterone receptors – Na+ re absorption and K+ secretion
 ADH receptors promote reabsorption of water at this site
Diuretic drugs:
 Are drug which induce a state of increased urine flow
 Are ion transport inhibitors that decrease reabsorption of Na + at different sites in the
nephron
 Cl- and water enter in the urine passively to maintain osmotic and electrical equilibrium
 Increase volume of the urine and change its PH as the ionic composition of the urine &
blood
A.Carbonic-anhydrate inhibitors
Acetazolamide:-
 Inhibit the enzyme carbonic anhydrase in proximal tubular epithelium
 Carbonic anhydrase catalyze
H2O + CO2 Carbonic anhydrase H2 CO3

Epithelide cell of renal tubule blood

Lumen
H O+
2 CO2H2O+CO2 CO2

Acetazolamide
H2CO3
H2CO3

Acetazolamide

HCO3- H+ H+ HCO3
Na+ Na+

 Decrease the exchange of Na+ for H+ produce mild diuresis.

 HCO3 is retained in lumen - marked elevation of urinary PH
Therapeutic uses:-
 - Treatment of glaucoma: - decrease the production of aqueous humor by blocking
carbonic anhydrase in the cilary body of the eye.
B.Loop or high ceiling diuretics (Loop diuretics)
(Bumetanide, Furosemide, Torsemide & ethacrynic acid)
 Major action on the ascending limb of loop of henle
 They are the most efficacious.
 Diuresis increased secretion of urine
 Calcemia – the presence of an abnormally large amount of calcium in the blood
 Mechanism of action
- Inhibit Na+/K+/Cl- transport system; so inhibit reabsorption of Na + (the ascending
loop of Henle accounts for the reabsorption of 25-30% of filtered Nacl)
- Increase Ca++ content of the urine; leads to decrease renal vascular resistance &
increase blood flow (Useful for patients with poor renal function)
 Therapeutic use:-
 Because of their rapid onset of action useful in emergency – acute pulmonary
edema of congestive heart failure
 Hyper calcemia
 Adverse effects:-
- Ototoxicity – when used in conjunction with aminglycosides.
- Hyperuricmia – compete with uric acid tubular secretion – exacerbate gout attack
- Acute hypovolemia – hypotension, shock & cardiac arrhythmia
- Hypokalemia – At collecting duct, high Na + reach leads to increase exchange of Na +
for K+
C.Thiziade & related drugs
(Chlorothizide, Hydrochlorothiazide, chlorothzlidone)
 The most widely used – inexpensive and well tolerated
 Greater diuretic activity than acetazolamide
 Mechanism of action:-
- Act mainly on the distal tubule.
- Decreased the reabsorption of Na+& Cl- by inhibiting the Na+ /Cl- Co- transport
system
 - Cause loss of k+ prolonged use leads to activation of the rennin – angiotensin –
aldosterone system by the decrease intravascular volume
- KCl supplement or k+ sparing diuretics, spirolactone is used in conjunction
- Cause decrease urinary calcium excretion (opposite to loop diuretics)
 Therapeutic Uses:-
 Hypertension
 Congestive heart failure
 Hypercalciuria useful patients (Excess of calcium in the urine) calcium oxalate
stones in the urinary tract
 Adverse effects:-
- Potassium depletion:-
- Hyperuricmea increase serum uric acid by inhibiting (computing) with active
tubular secretion – exacerbate gouty attack
- Hypecalcemia
- Hyper sensitivity
D.Potassium sparing direutics
Spirolactone (Aldactone)
 act in the collecting tubule to inhibit Na+ absorption K+ secretion and H+ secretion
 Mechanism of action: - aldosterone antagonist that compete with aldosterone receptor site
 Therapeutic use:-
- Given with thiazide or loop diuretics to prevent hypokalemia
- Secondary hyper aldasteronism

NB

 Aldesterone – the principle electrolyte regulating steroid secreted by the adrenal

cortex
  Aldosteronism- an abnormality of electrolyte metabolism produced by excessive
secretion of aldasterone
E.Osmotic diuretics (Mannitol & Urea)
 Hydrophillic chemical substances filtered through the glomerulus's and carry water with
them leads to diuretics
 Therapeutic use: - toxic ingestion, drug toxicity

Information Sheet XIV:- Drugs act on endocrine system

Drugs used in diabetes mellitus

Diabetes mellitus occurs due to lack of insulin or resistance to its actions.
 Type 1 diabetes (IDDM) occurs due to deficiency of insulin following autoimmune
destruction of pancreatic beta cells, patients require adminsteration of insulin.
 Type 2 diabetes (NIDDM) occurs due to decreased insulin secretion or peripheral
resistance to its actions (or both), patients require adminstration of oral antidiabetic drugs
or insulin (or both).

Insulin
Therapeutic indications
1. Diabetic ketoacidosis (DKA).
2. Rapid onset of symptoms.
3. Substantial loss of weight.
4. Weakness.
5. Ketonuria.
 6. A 1st degree relative who have type 1 diabetes.
7. All children with diabetes.
8. For type 2 diabetes when other methods have failed to achieve control.
9. For type 2 diabetes temporarily in the presence of intercurrent illness or peri-operatively.
10. For type- 2 diabetes during pregnancy.

Therapeutic goals
1. To alleviate symptoms.
2. To avoid complications of therapy mainly hypoglycemia.
3. To maintain a normoglycemic status of 4- 9 mmol/l for most of the time (4- 7 mmol/l
before meals and less than 9 mmol/l postprandially) or glycosylated hemoglobin (HbA 1C)
concentration of 6.5- 7.5% (reference range 4- 6%).
4. To prevent complications of the disease.

Pharmacokinetics
1. Insulin is inactivated by gastro-intestinal enzymes and must therefore be given by
injection.
2. It is commonly administered S/C using the conventional syringe, injection device `pen`,
or by continuous S/C infusion using a portable infusion pump which delivers a contiuous
basal short acting insulin infusion and and a patient- activated pollus at meal time.
3. It is commonly administered S/C in the upper arms, thighs, buttocks or abdomen.
4. Although S/C absorption is slow and fairly regular, absorption from a limb site may be
increased if the limb is used in strenuous exercise after the injection.
5. I/V infusion peri-operational, and during diabetic emergencies via a syringe pump. If a
syringe pump is not available soluble insulin 16 units/l is added to the I/V infusion of
glucose 5 or 10% containing K. The infusion is run at a rate appropriate to the patient
fluid requirements, depending on the volume of depletion, cardiac function, age and other
factors.
6. The duration of action of I/V insulin is only a few minutes. The infusion should be
stopped for 30 minutes is the patient becomes overtly hypoglycemic (≤ 3mmol/l).
7. K levels should be regularly monitored with other plasma electrolytes.
8. NaCl 9% should replace 5% glucose if high blood glucose level persists (≥ 15mmol/l).
Side effects
1. Hypoglycemia.
2. All insulin preparations including porcine, bovine and recombinant insulin are
immunogenic, immunological resistance to insulin actions is not uncommon.
Preparations of human sequence insulin, by enzymatic modification of porcine insulin,
should theoretically be less immunogenic, but no evidence supports this in the clinical
trials.
3. Fat hypertrophy at recurrent site of injection. Can be minimized by using different
injection sites in rotation.
4. Local allergic reactions (rare).
5. Weight gain.
6. Large babies that might develop postpartum hypoglycemia.

Insulin preparations
1. Short- acting insulins
Insulin Preparation Use Duration Notes
Soluble(Neutral) Highly-purified DM Rapid onset All routes of
e.g. Hypurin® porcine or DKA (30- 60min). adminstration.
bovine Surgery Peak 2- 4hrs.
Duration 8hrs.
Soluble(Neutral) Human- DM Rapid onset Not indicated
e.g. Humulin® sequence DKA (30- 60min). for use in S/C
Insuman® modified porcine Surgery Peak 2- 4hrs. infusion.
Duration 8hrs
Aspart Recombinant DM Faster onset. Less
human insulin Shorter hypoglycemic
analogue duration. events.
Glulisine Recombinant DM Faster onset. Less
human insulin Shorter hypoglycemic
analogue duration events.
Lispro Recombinant DM Faster onset. Less
human insulin hypoglycemic
 analogue Shorter events.
duration

2. Intermediate- and long- acting insulins

Insulin Preparation Use Duration Notes
Detemir Recombinant DM Long- acting. Should not be
e.g. Levemir® human insulin Delayed onset mixed with
analogue 1- 2 hrs. soluble insulin
Peak 4- 12hrs. in the same
Duration 16- syringe.
35hrs. OD or BID
with soluble
insulin.
Glargine Recombinant DM Long- acting. Should not be
e.g. Lantus® human insulin Delayed onset mixed with
analogue 1- 2 hrs. soluble insulin
Peak 4- 12hrs. in the same
Duration 16- syringe.
35hrs. OD or BID
with soluble
insulin.
Insulin zinc Human-sequence DM Long- acting.
suspension or porcine and/or Delayed onset
(Mixed) bovine insulin 1- 2 hrs.
e.g. Hypurin® complexed with Peak 4- 12hrs.
Bovine Lente a suitable zinc Duration 16-
salt 35hrs.
Isophane Porcine or DM Intermediate-
insulin bovine insulin or acting
(Isophane Human-sequence
protamine suspension
 insulin complexed with
injection) a suitable
protamine
Protamine Zinc Soluble insulin DM Long- acting. Blunts the
Insulin complexed with initial effect of
protamine and soluble
zinc chloride insulins.

3. Biphasic insulins
Insulin Preparation Use Duration
Biphasic 25% insulin DM Intermediate-
insulin Lispro Lispro , 75% acting
e.g. insulin Lispro
Humalog®Mix protamine
Biphasic 30% Insulin DM Intermediate-
insulin Aspart Aspart, 70% acting
e.g. Novomix® Insulin Aspart
protamine
Biphasic Porcine or DM Intermediate-
Isophane human insulin acting
insulin complexed
e.g. Mixtard® with protamine
sulphate in a
solution of
insulin of the
same species.

Oral antidiabetic drugs

Sulphonylureas
Drugs in the class include the long- acting Glibenclamide and Chlorpropamide associated with a
greater risk of hypoglycemia particularly in the elderly, and the short- acting Gliclazide,
Glipizide, Glimepiride and Tolbutamide.
Mechanism of action
Act by augmenting insulin secretion by increasing depolarization of pancreatic β- cells through
K- channels. They are effective only when some residual β- cells activity is present.
Therapeutic indications
1. Type 2 DM after the patient fails to respond to a 3 month restriction of carbohydrate and
energy intake and increased exercise.
2. Type 2 DM in patients who are not overweight and did not respond to or tolerate
Metformin.

Contra- indications
1. Severe hepatic impairment.
2. Pregnancy and breast- feeding.
3. DKA.
4. Caution with obesity, renal impairment, and elderly.

Side effects
1. Hypoglycemia.
2. GIT disturbances.
3. Chlorpropamide due to prolonged duration causes hypoglycemia more frequently and
face flushing so no longer recommended.
4. Occasional alteration of liver function and cholestatic jaundice.
5. Initial allergic reactions which may proceed to erythema multiform and exfoliative
dermatitis or photosensitivity.
6. Blood disorders including pancytopenia.

Biguanides
Metformin (GlucophageR)
Mechanism of action
Act by decreasing gluconeogenesis and by increasing peripheral glucose utilization. Its actions
depend on the presence of endogenous insulin so it is effective only when some residual β- cells
activity is present.
Therapeutic indications
1. Type 2 DM, the drug of choice in obese patients not controlled by diet restriction alone.
2. Combined with sulphonylureas in patients not controlled by sulphonylureas alone.
3. Increased insulin sensitivity aids in weight reduction.
4. Symptomatic management in polycystic ovary syndrome.
5. Normalization of menstrual cycle by increasing the rate of spontaneous ovulation.
6. Improves hirsutism.

Contra- indications
1. DKA, lactic acidosis and renal impairment.
2. General anaesthesia.
3. Pregnancy and breast- feeding.

Side effects
1. GIT disturbances and taste disturbances.
2. Rare lactic acidosis.
3. Decreased B12 absorption.
4. Allergy.

Other antidiabetic drugs

Acarbose (GlucobayR)
Mechanism of action
Act by inhibiting intestinal α- glucosidases, it delays the digestion and absorption of starch and
sucrose thereby significantly lowering blood glucose.
Therapeutic indications
1. Type 2 DM, reserved for use in patients when other oral hypoglycemic drugs are
contraindicated or are not tolerated.
2. Postprandial hyperglycemia in type 1 DM.

Contra- indications
 1. IBD, predisposition to partial intestinal obstruction, hernia, previous abdominal surgery.
2. Hepatic or renal impairment.
3. Pregnancy and breast- feeding.

Side effects
1. GIT disturbances associated with flatulence and diarrhoea.
2. Allergy.

Nateglinide and Repaglinide

Mechanism of action
1. Stimulate insulin secretion.
2. Rapid onset and short duration of action.

Therapeutic indications
1. Type 2 DM, administered shortly after each main meal.
2. Repaglinide is indicated as monotherapy in patients who are not overweight or in whom
Metformin is not indicated, or it may be given combined with Metformin.
3. Nateglinide is licensed only for use with Metformin.

Contra- indications
1. DKA.
2. Hepatic impairment.
3. Pregnancy and breast- feeding.

Side effects
1. Hypoglycemia.
2. GIT disturbances associated with flatulence and diarrhoea.
3. Allergy.

Thiazolidinediones
Pioglitazone and Rosiglitazone
Mechanism of action
Act by reducing peripheral insulin resistance. Their actions depend on the presence of
endogenous insulin so they are effective only when some residual β- cells activity is present.
Therapeutic indications
Type 2 DM alone or with:
1. Sulphonylureas if Metformin is not indicated.
2. Metformin in risk of hypoglycemia.
3. Sulphonylureas and Metformin if Insulin is not indicated or if the patient is obese or has a
metabolic syndrome.

Contra- indications
1. Cardiovascular disease.
2. Hepatic impairment.
3. Pregnancy and breast- feeding.

Side effects
1. GIT disturbances.
2. Weight gain and oedema.
3. Headache dizziness, vertigo and visual disturbances.
4. Arthralgia and hypoaesthesia.
5. Insomnia and sweating.

Thyroid hormones

THYROXI LEVOTHYROXINE-Na LIOTHYROXINE- Na

NE
(Thyroxine Na) (L- Tri- iodothyronine Na)
Indications 1. Hypothyroidism o Severe hypothyroid states
(myxoedem). where rapid response is
2. Diffuse non- toxic goiter. required.
3. Hashimoto`s thyroiditis. o IV injection is the TFC in
4. Thyroid carcinoma. hypothyroid coma.
5. Neonatal congenital o Adjunct. T. include fluids,
hypothyroidism. hydrocortisone, anti-
6. Juvenile myxoedema. infection and assisted
ventilation.
 Potency 1 4
(25 microgms are equivalent to
100 microgms of levothyroxine).
Onset of Slow but sustained suitable for Rapid in a few hrs and disappear
action & maintenance therapy. within 24- 48 hrs.
T1/2E
Pregnancy o Crosses placenta. o Does not cross placenta.
& lactation o Hi- doses detrimental to o Too small amounts to
foetus. affect tests for neonatal
o Too small amounts to hypothyroidism.
affect tests for neonatal
hypothyroidism.
Side effects Mimic symptoms of Mimic symptoms of
hyperthyroidism hyperthyroidism

Antithyroid drugs
Carbimazole
Mechanism of action
Acts primarily by interfering with the synthesis of thyroid hormones.
Indications
1. Hyperthyroidism.
2. Preparation of thyroidectomy patients for surgery.

Contra- indications
1. Severe hepatic impairment.
2. Pregnancy, risk of afflicting neonatal goiter and hypothyroidism and congenital defects
including aplasia cutis.
3. Breast- feeding, may affect neonatal thyroid function.

Side effects
1. Hypothyroidism with over- treatment.
 2. BM- suppression leading to neutropenia and agranulocytosis, patients should be
counseled to report immediately sore throat, mouth ulcers, bruising, fever, malaise or non
specific illness.
3. Rash and pruritus commonly treated with antihistamines without discontinuing therapy.

Blocking- replacement therapy

Is the use of carbimazole with levothyroxine OD usually for 18 months, this regimen is not
suitable during pregnancy.
Propylthiouracil
Mechanism of action
Acts primarily by interfering with the synthesis of thyroid hormones.
Indications
1. Hyperthyroidism.
2. Reserved for patients who are intolerant of carbimazole or who experience sensitivity
reaction and other treatments are not appropriate.

Contra- indications and side effects are similar to carbimazole.

Iodine
Indications
1. Adjunct to antithyroid drugs.
2. Radioactive Na- iodide (131I) is indicated for thyrotoxicosis in all ages, in patients with
heart disease and in those who relapse after thyroidectomy.

Contra- indication
1. Long- term treatment due to development of tolerance.
2. Pregnancy.

Propranolol and nadolol

Indications
1. Thyrotoxic symptoms.
2. Adjunct to antithyroid drugs and iodine.
3. Neonatal thyrotoxicosis.
4. Supraventricular arrhythmias due to hyperthyroidism.
Treatment of thyrotoxic crisis (thyroid storm)
1. Emergency IV fluids.
2. Propranolol.
3. Hydrocortisone Na- succinate.
4. Oral iodine solution with carbimazole or propylthiouracil by NG- tube.

Information Sheet XV:- .Drugs act on the nervous system

ntroduction to Nervous system

Nervous System:
 The two nervous system are;
1. the central nervous system(brain & spinal cord) and
2. the peripheral nervous systems (nervous located outside the CNS & enter or leave
the CNS )
The peripheral nervous system(PNS)
Divided into two:
A. Efferent division: neurous carry signal away from the brain & the spinal cord to
peripheral tissue
 The somatic efferent are involved in voluntarily controlled functions such as
contraction of skeletal muscles in locomotion
 The autonomic efferent functions are involved in involuntary activity and
innervates smooth muscle of the visceral, cardiac muscle, vasculature & the
exocrine gland
 B. Afferent division: nervous bringing information from the periphery to the CNS
Anatomy of the Autonomic Nervous System
Efferent neurons:-
 carries nerve impulses from the CNS to the effector organ by way of two types of
efferent neurons pregnanlionic neurons & postganglionic neurons
 Preganglionic neuron has its cell body located within the CNS and make a synaptic
connection in ganglia with the post ganglionic neuron.
 Postganglionic neuron has a cell body originated in the ganglion & terminates on
effector organ
 The efferent A.N.S is divided in to
 sympathetic and
 parasympathetic neurons
Sympathetic neurons:
 the pregnanglionic neurons arise from thoracic & lumbar regions of the spinal cord
 The adrenal medulla receives preganglionic fibers from the sympathetic system
Parasympathetic neurons:
 the pregnanglionic neurons arise from the cranial & sacral regions of the spinal cord
 In both symp & parasymp systems the post ganglionic fibers extend from the ganglia to
the effector organs
Afferent neurons: - important for reflex regulation of the system
Functions of sympathetic & parasympathetic neurons:-
Sympathetic division:
 Has the property of adjusting in response to stressful situation (fight or flight response).
 Adrenal medulla, kidney, pilomotor muscles & sweat glands, receive innervations only
from the sympathetic system.
Parasympathetic division:
 Maintains essential bodily functions (rest & digest)
 Most organs in the body are innervated by both systems

Table 2:11 functions of sympathetic and parasympathetic system

Organ Sympathetic systems Parasympathetic system
Eye Contraction of iris radial muscle (pupil Contraction of iris sphincter
dilates) muscle (pupil contracts)
Ureters & bladder Relaxes detrusor & contract sphincter Contraction of detrusor &
relaxation of sphincter
Genitals male Stimulates ejaculation Stimulate erection
Lacrimal glands Stimulate tear
Heart Increased rate & contraction Decreased rate & contraction
Gastro intestinal Decrease in muscle motility and tone, Increase muscle motility and
contraction of sphincter tone
Genitals female Relaxation of uterus
Bloodvessels (skeletal Dilatation
muscle)
Bloodvessels(skin Constriction
&mucusmembrane)

Neurotransmitters
communication between nerve cells & b/n nerve cells & effectors organs occur through the
release of specific chemical signals called neurotransmitters (from the nerve terminals)
 Fifty chemical signal molecules are identified in the nervous systems. Six signal cpds
(nor-epinephrine (closely related epinephrine), acetylcholine, dopamine, serotonin,
histamine and α-aminobutyric acid are most commonly involved in the actions of
therapeutically useful drugs.
Cholinergic system and drugs
Cholinergic neurons:-
 If transmission is mediated by acetylcholine, the neuron is termed as cholinergic while If
epinephrine or nor-epinephrine is the transmitter, the fiber is called adrenergic
(adrenaline is another name of epinephrine)
 Fiber to the adrenal medulla
 The autonomic ganglia (symp & para)
 Post ganglion fiber of parasymp.
  Neurons innervate voluntary muscles of somatic systems
Step in neurotransmission at cholinergic neurons:-
Synthesis of acetylcholine from choline and acetyl CoA which catalyzed by choline
acetyl transferase
I. Up take to storage vesicle
II. Release of acetyl choline by exocytosis
III. Binding to receptor
IV. Degradation of acetyl choline by cholinesterase to acetate & choline
V. Recycling of choline
Cholinergic receptors:

1. Muscarinic receptors: -
 Bind acetyl choline( Ach)
 Also recognize muscarine-alkaloid present in certain poisonous mush rooms
 show a weak affinity for nicotine
 For specific reception, several subclasses are M1, M2, M3, M4 & M5.
2. Nicotinic receptors:-
 Bind acetyl choline( Ach)
 also recognize nicotine
 Show only a weak affinity for muscarine.

Cholinergic drugs (Cholinomimetic, parasympathomimetic)

 are drugs which produce actions similar to that of Ach, either by
 directly interacting with cholinergic receptors (cholinergic agonists) or
 by increasing availability of Ach at these sites (anticholine esterases)
Actions of acetylcholine: -
 Its actions classified as muscarinic or nicotinic
Muscarinic

 Heart: - bradycardia (rate & force of contraction decreased)

 Blood vessels (skin of face & neck) :- Dilation – fall in blood pressure
  Smooth muscles:-
 In most organs – contraction
 Tone & peristalsis in GIT is increased and sphincters relaxed – abdominal
cramp & evacuation of bowel
 Peristalsis in ureter is increased – muscle contracts & sphincter relaxes –
voiding of bladder
 Bronchial muscles constrict – dysponoea, precipitation of an attack of
bronchial asthma.
 Glands:-Secretion is increased:- sweating, salivation, lacrymation, tracheobronchial and
gastric secretion
 Eye:-
o Contraction of iris sphincter muscle – miosis (constriction of pupil)
o Contraction of ciliary muscle – spasm of accommodation, increased out flow
facility – reduction in ocular tension
Nicotinic
 Autonomic ganglia:- both sympathetic & parasympathetic ganglia are stimulated (effect
is manifested at higher doses)
 Skeletal muscles :-Contraction
 CNS:- Stimulation followed by depression
NB. Ach therapeutically of no importance because of multiplicity of actions & its rapid
inactivation by acetyl cholinesterase
Cholinergic agonists
A. Choline esters
1. Bethanechol
 not hydrolyzed by acetyl choline esterase
 has no or little nicotinic actions but does have strong muscarinic activity
 It’s major actions are on the smooth musculature of the bladder and GI
 Therapeutic application:
 in post-operative urinary retention
 post-operative abdominal distention
  Side effects: sweating, salivation, flushing, decreased blood pressure, abdominal pain,
diarrhea and bronchospasm.

2. Carbachol
 Has both muscarinic & nicotinic actions
 Not destroyed by acetyl cholinesterase→long duration of action
 Has more pronounced effect in the intestine and urinary bladder
 Can be given orally or instilled in to the eye
 Therapeutic use:
 Rarely used, except in the eyes as a miotic agent to cause contraction of pupil and
a decrease in intraocular pressure.
 Atony of bladder, Paralytic ileus
3. Methacholine
 Metabolised by acetyl cholinesterase but at a slower rate
 Has intermediate duration of action b/n Ach and carbachol.
Carbachol > Metacholine > Ach
 Acts mainly on muscarinic receptors
 Actions on CVS are more marked

B. Alkaloids
1. Pilocarpine:-
 Exhibits muscarinic activity and is primarily used in ophthalmology
 Actions: rapid miosis and contraction of the ciliary muscle (vision is fixed at some
particular distance making it impossible to focus)
 Therapeutic use:
 Is the drug of choice in the emergency lowering of intraocular pressure
(glaucoma)
 Effective in opening the trabecular meshwork, causing an immediate drop in
intraocular pressure as a result of the increased drainage of aqueous humor.
 Action lasts up to 1 day
 available as 0.5-4% eye drops
2. Muscarine and Arecoline:-
 Only useful for toxicologic purposes
 Sympthoms of muscarine toxicity are similar to cholera. (Vomiting, diarrhea, vasomotor
collapse, jaundice)
Anti-Cholinesterases (Anti-ChEs)
 are agents which inhibits ChEs, protect Ach from hydrolysis
 This results in the accumulation of acetylcholine in the synaptic cleft
 These drugs can thus provoke a response at all cholinoceptros in the body, including both
muscarinic and nicotinic receptors of the autonomic nervous system as well as the
neuromuscular junction & the brain
 Classified in to two groups:-
1. Reversible
Carbamates
Physostigmine
Neostigmine
Pyridostigmine
Edrophoniuim
Rivastigmine
2. Irreversible:-
Organophosphates
Dyflos (DFP) – diisoproyl fluorophosphates
Echothiophate
Parathion
Malathion
Diazinon (Tlk-20)
Tabun
Sarin - Nerve gases for chemical warfarin
Soman

1. Reversible anticholinesterases
Physostigmine:-
 Is a substrate for acetylcholine esterase, reversibly inactivates the enzyme
 Actions:-
 stimulates both muscarinic & nicotinic sites of the ANS & nicotinic receptor of
neuromuscular junction
 Duration of action: 2-4 hours
 Therapeutic use:-
 Increase intestinal & bladder motility (in atony of either organ)
 Used as nicotinic agent for the treatment of glaucoma
 Treatment of overdose of drugs with anticholinergic drugs such as atropine,
phenothiazine & tricyclic anti-depressants
 Adverse effect:-
 Effect on CNS may lead to convulsions with high doses
 Bradycardia
 Paralysis of skeletal muscle however, these affects are rarely seen with
therapeutic doses
Neostigmine:-
 Is more polar & therefore does not enter the CNS
 Its effect on skeletal muscle is greater than that of physostigmine
  used to stimulate the bladder and GI tract
 Antidotes for tubocurarine and other competitive neuromuscular blocking agent
 Used in symptomatic treatment of myasthenia gravis (weakening of muscle caused by
antibodies to the nicotinic receptor)
 Duration of action 2-4 hours
 Adverse effect:-Generalized cholinergic stimulation such as salivation, flushing,
decreased blood pressure, nausea, abdominal pain, diarrhea and bronchospasm
Pyridostigmine:-
 Similar to neostigmine but slower onset and longer duration of action.
 Used in the chronic management of myasthenia gravis (weakening of muscle caused by
antibodies to the nicotinic receptor)
 Duration of action 3-6 hours
2. Irreversible anticholinesterases
 Bind covalently to acetyl cholinesterase which is extremely stable,leads to long lasting
increase in Ach act all sites where it is released
 Extremely toxic & used as nerve agents in military & insecticides
 Easily available and extensively used as agricultural and household insecticides
 Accidental as well as suicidal and homicidal poisoning:-
 Initially: miosis, salivation, sweating, vomiting, diarrhea and bronchial
constriction, followed by involvement of nervous systems
 Cause persistent depolarization of muscle and plates resulting in blockade of
neuromuscular transmission + weakness and paralysis
 Respiratory paralysis (central as well as peripheral)
 Death is generally due to respiratory failure
 Treatment:-
 Maintenance of respiration
 Atropine parenterally in large doses
 Therapy with pralidoxine (choline esterase reactivators)

Cholinergic antagonists (cholinergic blockers or anticholinergic drugs)

  bind to cholinergic receptor but do not trigger the usual receptor mediated intracellular
effects
 These drugs are classified as:Antimuscarinic agents,Ganglionic blockers and
Neuromuscular blocking drugs
A.Anti-muscarinic agents:-
 block the muscarinic synapses of the parasympathetic nerves
 Block muscarinic receptors, they donot block the nicotimic receptors; have no action at
skeletal neuro muscular junctions or autonomic ganglia.
 Classification of antimuscarinic agents:
a) Natural alkaloids: atropine, hyoscine (scopolamine)
b) Semi-synthetic derivatives: homatropine, atropine methonitrate, hyoscine butyl bromide,
ipratropium bromide, tiotropium bromide
c) Synthetic compounds: cyclopentolate tropicamide, propantheline, oxyphenonium,
clindinium, pipenzolate methyl bromide, isopropamide, glycopyrrolate, dicycclomine,
oxybutynin, flevoxate, pirenzepine, telenzepine, benzhexol, procyclidine, biperiden,
benztropine, cycrimine, ethopropazine

 Pharmacological actions of antimuscarinic agnets

1. Atropine as prototype:-
 Can be predicted from the knowledge of parasympathetic responses
 Atropine is an alkaloid found in atropa belladons
 It blocks all subtypes of muscarnic receptors (central & peripheral)
CNS: has an overall CNS stimulant action
Eye:
 result in mydriasis (dilation of pupil)
 Unresponsiveness to light & cycloplegia (inability to focus for near vision)
 In patients with glaucoma, intraocular pressure may rise dangerously
GI: - Antispasmodic, reduce activity of GI tract
Urinary systems:-
 Reduce hypermotility of the urinary bladder
 occasionally used in enuresis (involuntary voiding of bladder) among children
Cardio vascular:-At higher doses increased cardiac rate (tachycardia)
Secretions:-
 Block salivary glands – dry mouth (xerostomia) talking & swallowing become
difficult
 Block sweat glands elevated body temperature
 Block lacrimal gland, and tracheobronchial secretion
 Secretion of acid, pepsin & muscus is decreased
 Intestinal & pancreatic secretions are not significantly decreased
Therapeutic uses:-
 Ophthalmic: for diagnostic purpose
 Antispasmodic agent: to relax GIT and urinary bladder
 As antidote for cholinergic agonists for the treatment of overdoses of
organophosphates (which are found in some insecticides) and some type of
mushroom poisoning
 Antisecretory agent: to block secretion in the upper and lower respiratory tracts prior
to surgery
Pharmacokinetics:-is readily absorbed, partially metabolized by the liver and eliminated
primarily in urine, and it has a half-life of 3-4 hours
Adverse effect: - dry mouth, blurred vision, tachycardia & constipation
Presentation: - atropine sulphate 1mg/ml inj. 1% eye drop & ointment is available.
2. Hyoscine (scopolamine)
 is an alkaloid obtained from hyoscyamys niger
 produces peripheral effects similar to those of atropine
 has greater action on the CNS
 Actions: - the most effective anti-motion sickness drugs available (it degrees the
vestibular apparatus)
 Therapeutic use: - anti motion sickness agent, antispasmodic.
 Phk & adverse effect: similar to atropine
 Presentation: buscopan (hyoscine butyl bromide) 10mg tab, 20 mg/ml amp is available,
syrup 5mg/ml and oral drops 1mg/ml.
3. Propantheline: -
  has been the most popular anticholinergic used for peptic ulcer and gastritis
 reduce gastric secretion
 Action lasts 6-8 hours
 Probanthine 15 mg tab available
4. Clidinium: -
Used in combination with benzodiazepines for nervous dyspesia, gastritis, irritable
colon, petic ulcer etc.
Librax, bralix is available (chidinium bromite + cholorodiazepoxide) (2-5 mg + 5 mg)
B.Drugs Acting on Autonomic Ganglios (Ganglionic Blocker)
 Act on the nicotinic receptor
 block the nicotinic receptors of the sympathetic and parasympathetic ganglia
 Show no selectivity toward the parasympathetic or sympathetic ganglia
 They block the entire output of the autonomic nervous system at the nicotinic receptor.
The response observed are complex & unpredictable, making impossible to have
selective actions
 Rarely used therapeutically today. However they often serve as toods for experimental
pharmacology
 Pharmacological effects:-
 Depends on the quantity and the relative proportion of the total autonomic input
coming from sympathetic or parasympathetic nerve
 Hypotension because of the vasodilation, resulting from the sympathetic ganglia
blockade
 Constipation, tachycardia, blurred vision dry mouth and urine retention, all of which
are because of the parasympathetic ganglia blockade
 These are classified as:-
A) Competitive blockers
I. Quaterinary ammonium compounds
o Hexa methonuim
o Pentolinium
II. Amines (secondary/tertiary)
o Mecamylamine
 o Pempidine
III. Monosulfonium compound
o Trimethaphan
B) Persistent depolarizing blockers
 Nicotine (large dose)
 Anticholinesterases (large dose)
Nicotine: -
 is a natural liquid alkaloid obtained from Nicotina tobacum
 Small doses of nicotine activate the nicotinic cholinergic receptors, while large doses
inhibit the receptor by exerting persistent depolarization
 It’s pharmacological effects result from its action on the adrenal medulla, on the ganglia
(both sympathetic & parasympathetic), on the neuromuscular junction and on the CNS
 In small doses:-
 Rise in blood pressure because of the release of catecholamine from the adrenal
medulla and sympathetic ganglia, leading to increase heart rate and
vasoconstriction
 Increase secretion of glands because of the parasympathetic stimulation
 Contraction of skeletal muscle b/c of its action on the neuromuscular junction
 Excitation because of its action on the CNS
 Higher doses:-
 at higher doses, the blood pressure falls because of gangliomic blockade, and
activity both in Gl tract & bladder musculature ceases
 It’s not used clinically, because no useful purpose can be served by stimulating
both sympathetic and parasympathetic ganglia concurrently
Trimethaphan:-
 Is a short acting, competitive nicotinic ganglionic blocker
 The drug is used for emergency lowering of blood pressure
Neuromuscular blocking drugs
 block the nicotinic receptors at neuromuscular junctions
 Block cholinergic transmission between motor nerve endings and the nicotinic receptors
on the neuromuscular end plate of skeletal muscle
  These are structural analogue of acetyl choline and act either as antagonists (non-
depolarizing type) or agonists (depolarizing type)
 They are useful clinically during surgery to produce complete muscle relaxation
1. Non depolarizing blockers (competitive)
Drug belong to this group includes

D-tubocurarine Pancuronium Atracurium

Doxacurium Rocironium
Gallamine Alcuronium
Vecuronium Mivacurim
2. Depolarizing blockers
Drug belong to this group
o Suxamethonium (succiny/choline)
o Decamothonium
Non-depolanizing (competitive) blockers
 The first drug was curare, which the native hunters of the amazon in south America used
to paralyze animals
 Tubocurarine was ultimately purified and introduce into clinical practice
 Mechanism of action
 Combine with the niotinic receptor and prevent the binding of acetylcholine
 Their action can be overcome by increasing the concentration of acetylcholic in
the sympatic cleft eg administration of cholincsterase inhibitors such as
neostigmine or edrophonium
 Therapeutic uses: - adjuvants drugs in anesthesia during surgery to relax skeletal muscle
Depolarizing agents
 Mechanism of action:-
 attaches to the nicotinic receptor and acts like
 The depolarizing agent persist at high cocentration in the synaptic cleft, remaining
attached to the receptor for a relatively long time of the receptor, which renders
the receptor un capable of transmitting further impulses
 Therapeutic uses: because of rapid onset and short duration, useful when rapid
endotracheal intubation is refured during the induction of a anesthesia
Adrenergic system & drugs
Adrenergic neuron
 Release norepinephrine as the neurotransmitter.
 found in the CNS, and also in the sympathetic nervous system
 The adrenergic receptors are located either presynaptically on the neuron or post-
synaptically on the effector organ.
Adrenergic receptors (adrenoceptors)
 Two families of receptors, “α” and “β” were identified on the basis of their response to
the adrenergic agonist epinephrine, nor epinephrine, & isoproterenol (synthetic agonist)
  α-adrenoceptors
 the rank order = epinephrine> norepinephrine > isoproterenol
 divided into two groups α1 and α2 based on their phenylephrine (agonist); α 1 has
greater affinity than α2
α1 Receptors:
o present on the post synaptic membrane of effector organs
o mediate many of the classic effect, constriction of smooth muscle
α2 receptors:
o located primarily on pre-synaptic nerve endings and on other cells, such as β-cell of the
pancreas
o Stimulation of α2-receptor causes feedback of the ongoing release of nor-epinephrine
when there is high sympathetic activity.
 β-receptors:-
 isoproterenol > epinephrine > nor epinephric
 The β-receptor can subdivide into two major groups.
β1 receptors: have approximately equal affinity for epinephrine and nor-epinephrine
β2 receptors: have higher affinity for epinephrine than nor epinephrine

Distribution of receptors
 Adrenergically innervated organs & tissues tend to have a predominance of one type of
receptors e.g. Vasculature of skeletal muscles have both α1 and β2 receptors, but theβ2
receptor predominate
 Other tissues may have one type of receptors exclusively, with particular no significant
number of others e.g. Heart contains predominantly β1 receptors
Characteristic responses mediated by adrenoceptors
α1
 Vasoconstriction (skin & abdomen)
 Increases peripheral resistance
 Mydriasis (eye)
 Increase closure of internal sphincter of bladder
α2
  Inhibition of nor-epinephrine release
 Inhibition of insulin release (β -cells of pancreases)
β1
 Tachycardia
 Increased lipolysis
 Increases myocardial contraction
β2
 Vasodilation (Skeletal Muscle)
 Increases muscle & liver glycogenolysis
 Increases release of glucagon
 Relax uterine smooth muscle

Characterstics of Adrenergic Agonists

 Chemically classified as
1. Catecholamine
2. Noncatecholamines
 Most of the adrenergic drugs are derivatives of β- phenyl ethylamine
 Substitution on the benzene ring or on the ethylamine side chain produce a great variety
of compounds with varying abilities to differentiate b/n α and β receptors & to penetrate
CNS
1. Catecholamine
 Sympathomimetic amines that contain the 3,4 di hydroxyl benzene group (catechol) such
as epinephrine, nor-epinephrine, isoproterenol & dopamine
 These compounds share the following properties:
 High potency: - in activating α or β receptors show the highest potency
 Rapid inactivation:-metabolized by COMT post synaptically and MAO intra
neuronally and also metabolized in other tissues
E.g. By COMT: in the gut wall and By MAO: in gut wall & liver
 Only have a brief of action when given parentrally, and are ineffective when
administered orally because of inactivation
  Poor penetration into the CNS: -Catecholamine are polar & therefore do not penetrate
into the CNS; nevertheless have some clinical effects that are attributed to the action
of CNS.
2. Noncathecolamines:-
 compounds lacking the catechol hydroxyl groups
 have longer halflives because:
 they are not inactivated by COMT
 they are poor substrate for MOA
 Permits greater access to CNS
 These include phenylephrine,ephedrine & amphetamine
Mechanism of action of adrenergic agonists
1.Direct-acting agonists:-
 act directly on α or β receptors, producing effect similar to adrenaline (epinephrine) or
nor-epinephrine e.g. Epinephrine, nor epinephrine isoproterenol & phenylephrine
A.Epinepherine:-
 Commonly used in therapy
 Interacts with both α and β receptors
 Actions:-
Cardiovascular
 the major action of epinephrine is on CV
 Strenghtens the contractility of the myocardium (positive inotropic: β1action) & increase
rate of contraction (positive chronotropic β1action)
 Cardiac output is increased
 Constricts arterioles in the skin mucous membranes & vicera (α effects) and dilates
vessels going to the liver and skeletal muscle (β2 effects)
Respiratory system
 cause powerful bronchodilation by acting directly on bronchial smooth muscle β2action)
Hyperglycemia
 a significant hyperglycemic effect b/c of increased glycogenolysis in liver( β2 effect)
increased release of glucagons( β2effect) and a decreased release of insulin (α2 effect)
Lipolysis
  Initiates lipolysis through its agonist action on the β -receptors of adipose tissue.
 Biotransformation :- Metabolized by COMT and MAO
 Therapeutic uses
Bronchospasm
 it is the primary drug used in emergency treatment of any condition of
bronchoconstriction
 Therefore used in treatment of acute asthma & anaphylactic shock
 However, selective β2agonists, such as terbutaline, are favoured in chronic treatment of
asthma because of longer duration of action and minimal cardiac stimulatory effect
Glaucoma:
 it reduces the production of aqueous humor by vasoconstriction of the cillary body blood
vessles
Anaphylactic shock: -
 it is the drug of choice from the treatment of type1 hypersensitive reaction in response to
allergens
In anesthetics:-
 it increase the duration of local anesthetics byproducing vasoconstriction at the site of
injection, there by allowing the local anesthetic to persist at the site before being
absorbed in the circulation and metabolized (1:100,000 parts)
 Pharmacokinetics
Rapid onset but short duration
It is given iv, sc or by endothracheal tube, by inhalation, or topically to the eye
Oral administration is ineffective b/c its inactivated by intestinal enzymes
 Adverse effects
 CNS disturbances: anxiety, fear, tension, headache and tremor
 Hemorrhage: may induce cerebral hemorrhage as a result of a marked elevation of
blood pressure
 Cardiac arrhythmias
 Pulmonary edema: epinephrine is contraindicated in hypersensitive, hyperthyroid and
angina patients
 Preventation: adrenaline 1mg/1ml inj.
B. Norepinephrine
 the α -adrenergic receptor is most affected
 Therapeutic uses: is used to treat shock because it increases blood pressure
 never used in asthma
C. Isoproterenol
 is direct acting synthetic catecholamine
 Predominantly stimulates both β1 and β2adrenergic receptor (it is not selective on the β -
receptors)
 It’s action on α -receptor is insignificant
 Actions
Cardiovascular
 Produce intense stimulation of the heart (increase rate & force of contraction) β1effect.
 Dilates the arterioles of skeletal muscle, resulting in decreased peripheral resistance
 It’s useful for the treatment of cardiac arrest
Pulmonary
 A profound and rapid bronchodilation is produced by the drug (β2action)
Other effects:
 increase in blood sugar and increased lipolysis
Therapeutic uses:-
 Rarely used as a bronchodilator in asthma
 Can be employed to stimulate the heart in emergency situation
Pharmacokinetics:
 it is a marginal substrate for COMT and is stable to MAO action
 it can be administered sub-lingually or parenterally
D.Dopamine:-
 Activate α and β adrenergic receptors
 In addition, D1 & D2 dopaminergic occur in the peripheral mesenteric & renal vascular
beds, where bending of dopamine produce vasodilation
 Therapeutic uses:-
Shock:
 dopamine is the drug of choice for shock and is given by continuous infusion
  It raises the blood pressure by stimulating the heart ( β1action) in addition it enhances
perfusion to the kidney and splanchmic areas
 Dopamine is for superior to norepinephrine, which diminishes the blood supply to the
kidney & may cause kidney shut down.
E.Dobutamine
 A synthetic, direct acting catecholamine that is a β1receptor agonist
 Therapeutic uses:- used to increase cardiac out put in congestive heart faiture
F.Phenylephrine
 Synthetic, direct acting adrenergic drug
 binds primarily to α-receptors favors α 1 receptors over α2
 Therapeutic use:- act as nasal decongestant and produces prolonged vasoconstriction
G.Albuterol (Salbutamol)
 Is a selective β2 agonist with properties similar to those of terbutaline.
 The drug widely used as an inhalant to relieve bronchospasm
2. Indirect acting adrenergic agonists
 are taken up into the presynaptic neuron and cause the release of nor-epinephrine from
the cytoplasmic pools or vesicles of the adrenergic neurons e.g. Amphetamine &
tyramine
 Cause nor epinephrine release from presynpatic terminals
Amphetamine
 Marked central stimulatory action is often mistaken by drug abusers as its only action.
 However, the drug can increase blood pressure significantly by α-agonist action on
vasculature as well as β -stimulatory effects on the heart
 Its actions are mediated primary through the cellular release of stored catecholamines
 Effects: euphoria (feeling of happiness), postponement of sleep, suppress apetite,
decrease the feeling of fatigue.
 Uses- Narcolepsy

3. Mixed-action adrenergic agonists:-

 have the capacity both to directly stimulate adrenoceptors and to release nor-epinephrine
from the adrenergic neuron e.g. Ephedrine & metaraminol
  Induce the release of norepinephrine from presynaptic terminals and activate adrenergic
receptors on post synaptic memberane
Ephedrine
 A plant alkaloid, is now made synthetically
 If releases stored norepinephrine from nerve endings and directly stimulate both α and β
receptors
 It is not a catechol and is poor substrate for COMT and MAO; thus, the drug has a long
duration of action but less potent
 Has excellent absorption orally and penetrates in to the CNS
 It raises blood pressure by vasoconstriction and cardiac stimulation
 It produces bronchodilation, but it is less potent than epinephrine or isoproternol &
produce it’s action more slowly
 has been used to treat asthma, as nasal decongestant, and to raise blood pressure
 The clinical use of ephedrine is declining due to availability of better, more potent agents
which cause fewer site effects
Adrenergic Antagonists (blockers):-
 bind to adrenoceptors but do not trigger the usual receptor mediated intracellular effect
 act by either reversibly or irreversibly attaching to the receptor
 classified according to their relative affinity for α or β receptors in the penipheral neurons
systems
α -adrenergic blocking agents
 α -adrenoceptors profoundly affect blood pressure
 They decreased peripheral vascular resistance, which induces a reflex tachycardia
resulting from the lowered blood pressure
A. Phenoxybenzamine
B. Phentolamine
C. Prazosin, terazosin & doxazosin
Therapeutic uses: - used as antihypertensive

β -adrenergic Blocking Agents

 All the clinically available β -blockers are competitive (reversible) antagonists
  Non-selective β -blockers act on both β1 and β2 receptors; where as cardio selective β -
antagonists priarly block β1 -receptors
 The names of all β -blockers end in “olol”

A) Propranolol: a non-selective β-antagonist (blocks both β1 and β2receptors)

Actions
 Cardiovascular:- diminishes cardiac output, having both negative inotropic and
chronotropic effects by blockage of β1 -receptors
 Peripheral vasoconstriction:- prevents β2 -mediated vasolidation
 The reduction in cardiac output leads to decreased blood pressure – triggers a
reflex peripheral vasoconstriction, which is reflected in reduced blood flow to
the periphery.
 Bronchoconstiction:-blocking β2 receptors in the lungs of susceptible patients causes
contraction of the bronchiolar smooth muscles
 Therefore β-blockers are thus contraindicated in patients with asthma
 increased Na+ retention: -reduced blood pressure causes a decrease in renal perfusion,
resulting in an increase in Na+ retention & plasma volume which may elevate blood
pressure therefore β -blockers are often combined with a diuretic to prevent Na+ retension
 Disturbances in glucose metabolism:-
 B-blockade leads to decreased glycogenolysis and decreased glucagons secretion
therefore if an insulin dependent diabetic is to be given propranolol, may leads to
pronounced hypoglycemia may occur after insulin injection

Therapeutic uses
 Hypertension: - lower blood pressure in hypertneison by decreasing cardiac output
 Angina pectoris: -decrease the oxygen requirements of heart muscle
Adverse effects
 Bronchoconstriction:-
 Arrhythmias:-
 Disturbances in metabolism:-leads to decreased glycogenolysis & decreased glucagons
secretion
Drug interactions:-
 Cimetidine, furosemide & chloropromazine inhibit metabolism of propranolol
which may potentiate its anti hypertensive effect
 Barbiturates, phenytoin & rifampcin stumlate metabolism of propranolol can
mitigate its effects.
B) Timolol & nadolol:
 Non selective β -antagonists
 Are more potent than propranolol
 Timolol reduces the production of aqueous humor in the eye and is use topically in the
treatment of chronic glaucoma; and occasionally for system treatment of hypertension
C) Atenolol, acebutolol metoprolo and esmolol:
 Selective β1 antagonists
 Elminate the unwanted bronchoconstrictor effect (β2) of propranolol seen among
asthmatic patients
 Therapeutic use:-
 useful for hypertensive patients with impaired pulmonary function
 useful in diabetic hypertensive patients who are receiving insulin or oral
hypoglycemic agents
Drugs Affecting Neurotransmitter Release or Uptake
 Reserpine
 Guanethidine

Drugs Acting on the Central Nervous System (CNS)

 CNS receives thousands of information from different sensory organs and then integrates
all these information to determine the response to be made by the body
 Basic function of neuron in the CNS or in the ANS involve the release of
neurotransmitters that diffuse across the synaptic space to bind to specific receptor on
post synaptic neuron
 The CNS communicates through the use of more than 10 (perhaps as many as 50)
different neurotransmitters
  Neurons (functional units of the nervous system) that composed of the soma, axon and
dendrites while synapses are junctions between two neurons
 Hundreds and thousands of synaptic nobs lie on the surface of dendrites and soma
 Excitatory synaptic nobs: - Secret a substance that excites the neuron when released
in to the synaptic cleft
 Inhibitory synaptic nobs: - Secret substances that inhibit the neuron when released
in to the synaptic cleft
 Neurotransmitters can be classified as excitatory or inhibitory depending on action they
elicit
 Drugs may either increase or decrease the amount of neurotransmitter at the synapse
These neurotransmitters are:-
 GABA (Gamma amino butyric acid)- inhibitory (primarily in brain & less extent in
spinal cord)
 Glycine- inhibitory (primarly in the spinal cord)
 Aspartate and Glutamate- excitatory
 Acetylcholine –usually excitatory
 Catecholamines- Dopamine,Epinephrine,Norepinephrine-excitatory to some neurons
and inhibitory to others
 5-hydroxy tryptamine (5-HT)
 Histamine

Hypnotics and Sedatives

Sedative drugs
 Drugs which are used to sedate i.e calm anxious and restless patients without making
sleep
 Taken at bed time may however encourage sleep without actually causing it.
Hypnotics
 Are drugs that produce sleep
 In many instances, the sedative drugs in larger doses can be used as hypnotics
A.Benzodiazepines (Diazepam, Chlordiazepoxide, Lorazepam, Nitrazepam)
 Their all effects result from their actions on the CNS
  These effects are sedation, hypnosis, decreased anxiety, muscle relaxation, amnesia and
anticonvulsant activity
 Mechanism of action:
 By interacting with inhibitory neurotransmitters directly activated by GABA.
 Their binding to their receptors enhances the affinity of GABA to GABA
receptors
Diazepam
Pharmacokinetics:
 Well absorbed orally and intravenously
 Maximum plasma concentration reaches with in 1-4 hours
 Has a 99% plasma protein binding
 Metabolized to an active metabolite
Justify: Diazepam has longer duration of action
Uses:
 Sedation and Hypnosis
 Anxiolytic
 Anticonvulsant
 Skeletal muscle relaxant
 In alcohol withdrawal syndrome
Side effects: Light headedness, motor incoordination, confusion, amnesia
Caution: in patients driving vehicles or operating machineries
B.Barbiturates (Phenobarbital, Butabarbital, Pentobarbital)
 Depress the CNS in a dose dependent fashion, progressively producing calming or
drowsiness (sedation),hypnosis,unconsciousness,coma,surgical anesthesia and fatal
depression of respiration and cardiovascular regulation
 Mechanism of action:
 Stimulation of GABA receptors
 Barbiturates are not used commonly for sedation & hypnosis because:
 They have lower therapeutic index than benzodiazepines.
 Produce more frequent tolerance
 Liability for abuse
  Have considerable drug interactions
 For these reasons barbiturates are now widely replaced by benzodiazepines
 Uses: Sedative, hypnotic, anticonvulsant, anesthetic
 Adverse effects: Drowsiness, distortion of mood, impairement of judgement, depress
motor skill, vertigo, nausea, vomiting, diarrhea
 Drug interaction:
 Increased CNS depression with alcohol
 induce the secretion of drug metabolizing enzymes from the liver
 So concurrent administration may decrease the effect of drugs like Theophyline,
oral anticoagulants, ß- blockers, doxycycline, corticosteroids, hormonal
contraceptives (estrogen), metronidazole, etc
C.Miscelaneous agents
 Antihistamines eg. Diphenhydramine, Promethazine produce some degree of sedation but
not commonly used for this purpose.
 Older agents like chloralhydrate have sedative effects but no longer used because of the
availabiloity of drugs with more effect with less adverse effects

Antianxiety drugs
Anxiety
 Is an uncomfortable feeling that occurs in response to the fear of being hurt or losing
something & is a common human emotion.
 The symptoms of severe anxiety are tachycardia, wet armpits, trembling hands &
palpitation
Antianxity drugs
 Are also called anxiolytics, minor tranquilizers, tranquilosedatives or antineurotics
 Classification of antianxiety drugs:
1. Benzodiazepines: Diazepam, Chlordiazepoxide, Clonazepam
2. Barbiturates are now obsolete for anxiolytic effect and replaced by benzodiazepines
5-HT receptor agonists-anxiolytic drugs with little sedation: Buspirone, Ipsapirone
 4. ß-adrenergic receptor blockers-used to reduce physical symptoms of anxiety (tremor,
palpitation etc)
5. Miscellaneous agents: - Chloralhydrate, Meprobamate, Metaqualon

Antiepileptic Drugs
Epilepsy
 is a syndrome characterized by sudden transient alterations in brain function (seizure),
leading to motor, sensory, autonomic or psychic symptoms, often accompanied by
unconsciousness with or with out convulssion.
 All types of epilepsy start with sudden (paroxysmal) discharge of neuron in the brain
(focus) & this discharge may be confined in certain areas of the brain or distributed to
other parts of the brain
 Outcome of treatment in epilepsy depends on right diagnosis & use of right drug
 There are different types of epileptic seizures (Reading assignment)
Classification of antiepleptic drugs

Hydantoins Oxazolidinediones Succinimides Benzodiazepines Miscellaneous

Phenytoin Trimethadiones Ethosuximide Diazepame Valproic acid

(diphenyl paramethadione Phensuximide Clonazepame Carbamazepine
hydantoin) Methsuximide
Mephentoin
A.Barbiturates
1. Phenobarbital
 Availability- 15mg, 30mg, 100mg tablets
 Mechanism of action- Potentiation of GABA receptors.It inhibits the spread of
discharge & increase seizure threshold.
 Use- Generalized tonic-clonic epilepsy, Simple partial seizures
 Adverse effects-,respiratory depression, hangover effects, CNS depression,
confussion, vertigo, dizziness,drowsiness or sedation (the most frequent undesirable
effect apparent to some extent in all patients upon initiation of therapy, but tolerance
develops during chronic medication)
 Drug interactions
 Increased CNS depression with alcohol
 Induces drug metabolizing enzymes so it decreased effects of: Theophyllines,
oral anticoagulants,beta-blockers,doxycycline,corticosteroids,hormonal
contraceptives and estrogens, metronidazole, phenylbutazones, quinidine,
felodipine
2. Phenytoin (diphenyl hydantoin)
 Availability- 50mg, 100mg
 Effective against all types of seizures except abssence seizure
 Excerts antiseizure activity with out causing depression of the CNS activity
 Mechanism of action-Inhibition of Na+ dependent action potential and voltage gated
Ca++ channels.
 PK- extensively bound to plasma protein (90%)
 Uses
 Epilepsy (all types of seizures except abssence seizure)
 Cardiac arrhythmia
 Trigeminal neuralgia
 Side effects-depend on dose and time of expossure; arrhythmia, GI sympthoms,
gingival hyperplesia, megaloblastic anemia, hirsutism (an annoying effect in young
females), osteomalacia
  Interactions-Decreased pharmacologic effects of: Corticosteroids, cyclosporine,
doxycycline, estrogens, furosemide, levodopa, methadone, hormonal contraceptives,
quinidine, carbamazepine, diazoxide
2. Others: mephobarbital, metobarbital, primidone
B. Succinimides
Ethosuccimide
 The drug of choice in petit mal epilepsy.
 Reduces low threshold Ca++ currents in thalamic neurones
Uses- Drug of choice in absence seizure.Not in tonic-clonic seizure
Side effects
GI – Nausea,vomiting,anorexia
CNS-drowsiness,lethargy,euphoria,dizzyness,headache

Carbamazepine
Availability- 100mg, 200mg,400mg
Antiepileptic mechanism-Inhibition of Na+ dependent action potential.
Adverseeffects-GI irritation ,applastic anemia , hepatotoxicity , ataxia , dizziness , diplopia,
vertigo
Uses
 Epilepsy( Generalised tonic clonic and partial seizures)
 Mania
 Trigeminal neuralgia
Interactions
 Carbamazepine is known to induce its own metabolism.
 Increased serum levels and manifestations of toxicity with erythromycin,
cimetidine , isoniazid, verapamil; dosage of carbamazepine may need to be reduced
(reductions of about 50% recommended with erythromycin)
 Decreased anticoagulant effect of warfarin, oral anticoagulants; dosage of warfarin
may need to be increased during concomitant therapy but decreased if
carbamazepine is withdrawn.
Valproic acid
Availability- 200mg, 500mg.
Mechanism of action- Increases the availability of GABA.
Uses
 Epilepsy ( Generalized tonic clonic,Partial seizure,Absence seizure)
 Mania
Adverse effects- GI irritation, hepatotoxicity, weight gain, appetite stimulation.
Interactions
 Increased serum levels and toxicity with salicylates, cimetidine, chlorpromazine,
erythromycin
 Decreased effects with carbamazepine, rifampin,
 Increased sedation with alcohol, other CNS depressants

Benzodiazepins (Diazepam and Clonazepam)

are used as adjunct in status epilepticus and severe recurrent convulsive seizures
(parenteral); adjunct in convulsive disorders (oral). (Refer the pharmachology of
benzodiazepines under sedatives and hypnotics).
5.8 Psychopharmacological Agents

The psychopharmacological agents are those having primary effects on psyche

(mental process) & are used for treatment of psychiatric disorders.
Psychiatric diagnostic catagories are often imprecise. The criteria adopted overlap in
individual patient.Based on predominant manifestation the most common ones are:-

Psychosis
is the most severe mental illness characterized by complete abnormal behavior,
which the patient is not aware of & a serious inability to think correctly, to
understand reality or to gain insight into the abnormality.

Psychiatric disorders include.

 Schizophrenia (split mind) i.e. splitting of perception and integration from reality-
delusions and hallucination especially of voice. The patient usually feels that his
 thoughts sensations and actions are controlled or shard with others.Inability to think
coherentlyWithdrawal from social contact.
 Paranoid state: with marked persecutory or other kinds of fixed delusions and loss
of insight into the abnormality.
 Affective disorders (mood disorders): the primary symptom is change in mood
state; main manifestations are mania and depression.
 Mania: - excessive elated mood to do something, over confidence, increased
activity, thought and speech are rapid to the point of incoherence, impaired
judgment, flight of ideas, the person may act irresponsibly (financially,sexually etc.)
and sometimes is violent.
 Depression:- Characterized by mental sadness, loss of interest in life, retarded
activity, behavior is governed by pessimism, disturbed sleep, appetite and
concentration.
 Manic-Depressive-disorder (bipolar disorder)-Repeated episodes of depression and
mania.

Classification of Psychopharmacological agents (Psychotropic)

Antipsychotic (major tranquillizers)
drugs used in affective disorders (antidepressants)
Antipsychotics: these drugs are also called neuroleptics or major tranquillizers.
Phenothiazines
- chlorpromazine
- thioridazine
- fluphenazine
- trifluperazine
Butyrophenones
- haloperidol
- droperidol
Throxanthencs
- chlorprothixene
- flupanthixol
Indol derivatives
 - reserpine
Miscellanwous
- clozapine
Chlorpromazine
o the first of the phenothiazine neuroleptics
o it revolutionized psychiatric treatment.
Therapeutic use
o acute & chronic psychosis
o for pre and post-operative sedation
o maniac phase of maniac depressive syndrome
o for control of sever nausea & vomiting.
Mechanism of action
o α- receptor antagonist
o serotonine antagonist
o muscarine antagonist
o dopamine antagonist
o histamine antagonist
 Mechanism for tranquillizing effect is due to blockage of central adrenergic
transmission and dopaminergic receptors in the limbic system.
Pharmacological effects
 Impairment of vigilance performance in variety of tasks (decrease alertness)
 Normalization of sleep disturbance in psychotics
 Extra pyramidal effect like Parkinsonism by blocking the dopaminergic activity.
 Skeletal muscle relaxation by acting on CNS
 Decreased seizure threshold
 Antimetic effect by acting on chemoreceptor trigger zone.
 Hypotension & hypothermia(oe-blockage) & failure in ejaculation in male
 Endocrime effect: Increase plasma prolactine secretion
Adverse effects:
- Chloropromazine has various actions those which are not utilized for therapeutic
purpose are considered to be the adverse effects
  Antipsychotic drugs have similar pharmacologic effects and they mainly differ in the
potency and also the degree of adverse effects produced.
 Their effects are summarized in the following table.
Antidepressants
 In depression the level of monoamines such as serotonin and noradrenaline
decreases.
 Treatment is elevating this level by inhibiting monoamine uptake by nerve terminals
or by inhibiting their enzymatic degradation.
Classification of antidepressants
1. Reuptake inhibitors
 Non selective reuptake inhibitors
 Tricyclic antidepressants
- Amitriptyline
- Imipramine
 Selective serotonine reuptake inhibitors
- Fluoxetine
- Paroxietine
2. Monoamine oxidase inhibitors
- Phenelzine
- Isocarboxazide
- Meclobemide
Reuptake inhibitors
o Tricyclic antidepressants have three ring fused nucles.
o The drugs are well absorbed from the GIT hence given orally.
o They all have high first pass effect.
Mechanism of action
o TCAs inhibit the neuronal uptake of norepinephrine and serotonine in to presynaptic
nerve terminals.
o TCAs are potent anticholinergics.
Pharmacological actions
o TCAs elevate mood, improve mental alertness and increase mental activity.
 o Due to their anticholinergic action, cause dry mouth, blurring of vision constipation
and urinary retention.
Therapeutic uses
o TCAs are effective in treating several major depressions.
o Imipramine has been used to control bed wetting in children but not used now for
this purpose because the risk outweighs the benefit.
Adverse effects
o Blurred vision, dryness of mouth, urinary retention, constipation, increased
intraocular pressure, Cardiac arrhythmia.
Precautions
o TCAs have narrow therapeutic index.e.g. 5-6 times the maximum dose of
imipramine can be lethal.So caution is required during prescribing and dispensing of
such drugs.
Selective serotonin reuptake inhibitors/SSRIs/
o Newer drugs that specifically inhibits serotonin reuptake.
o They have some important advantages over TCAs.
o They do not cause anticholinergic effects and cardiac toxicity.
o They have a wider safety index (relative safety in overdose).
Adverse effects: anorexia, weight reduction, insomnia, tremor, disturbance of sexual
function.

2. Monoamine oxidase inhibitors

 MAO is an enzyme found in neuronal and other tissues, such as gut and liver.
 MAO inhibitors are orally effective drugs which act by inhibiting MAO from
destroying monoamines, leading to their accumulation.
 These drugs also inhibit oxidases that catalyse oxidative deamination of drugs and
potentiate toxic substances.e.g. Tyramine
Therapeutic uses
 Indicated for depressed patients who are unresponsive to TCAs.
Adverse effects
 Severe & unpredictable adverse effects limit the wide spread use of MAO inhibitors.
  Tyramine contained in certain foods (cheese, beer and red wines) is inactivated by
MAO in the gut.
 Tyramine + MAOI = hypertension, cardiac arrhythmia & stroke.
 With meclobemide, this hazard is much reduced because it inactivates only MAO A
and does so in a reversible manner.
iii) Antimaniac Drugs
 Lithium salts (Lithium carbonate)
 Are effective in controlling the maniac phase.
 Act by increasing the neuronal reuptake of nor adrenaline and serotonine and by
decreasing the release of noradrenaline.
 The effects are usually seen ten days after the start of treatment.
 Therapeutic index is extreamly low.
Adverse effects: fine tremor, ataxia, seizures, pollyurea & impairement of thyroid function.

 Other drugs used in mania include Carbamazepine, Sodium valproate.

5.9 Opioid Analgesics & Antagonists

 OPOIDS are natural or synthetic compounds that produce morphine like effects.
 They act by binding to specific opioid receptors in the CNS to produce effects that
mimic the action of endogenous opioid peptides (enkephalines. endorphins &
dynorphines).
 Although the opioids have a broad range of effets their primary use is to relive
intense pain.

OPOID RECEPTORS

 The major effects of the opioids are mediated by four families of receptors.
 Mu (µ): Supra spinal analgesia, respiratory deprssion, Euphoria, Physical
dependence, decreased GI motility, pupil constriction.
 Kappa (κ): Spinal analgesia, dysphoria, pupil constriction.
 Sigma (σ): dysphoria, hallucinations, pupil dilation.
  Delta (δ): More important in the periphery but may also contribute to analgesia.

Classification of opoids

- Strong agonists: Fentanyl. Heroin, Meperidine, Methadone, Morphine &

suffentanil.
- Moderate Agonists-codeine, propoxyphene.
- Antagonists: Naloxone, Naltrexone.

Strong Agonists
Morphine
 Is the major analgesic drug contained in crude opium
 It has a high affinity for & low affinity for receptors.
Mechanism of action: opioids exert their major effects by interacting with opioid receptors
in the CNS & GIT.

◊ It inhibits the release of many excitatory transmitters from nerve terminals carrying
painful stimuli.
◊ It also acts on the spinal cord and decrease the release of substance P, which
modulate pain perception in spinal cord.

Actions:
 Analgesia: causes relief of pain.
 Euphoria: produces a powerful sense of wellbeing, over confidence & over
optimism.
 Respiratory depression: by reduction of the sensitivity of respiratory center
neurons to CO2.
 Depression of cough reflex: morphine & codeine have antitussive properties.
 Miosis: pin point pupil.
 Emesis: directly stimulate chemo receptor trigor zone.
 Constipation: by decreasing motility of smooth muscles.
  Histamine release: release histamine from mast cells, which cause broncho
constriction.
 Urinary retention: because or release of the antidiuretic hormone (ADH).
Therapeutic Uses:-
 Analgesic
 Treatment of diarrhea
 Antitusive
Pharmacokinetics
 Absorption: absorption from GIT is slow & erratic, so given by IM, SC or IV
injections.
 Distribution: enters all body tissues including the fetuses of pregnant woman. Only
small % of morphine crosses the B.B.B. (least lipophillic of the common opoids).
 Elimination: metabolized in the liver & excreted in urine.
Tolerance & physical dependence: repeated uses produce tolerance.

B. Heroin (Diacety1 morphine)

 Does not occur naturally but is produced by acetylation of morphine, which leads to
threefold increase in potency.
 Its greater lipid solubility allows it to cross B.B.B, causing a more exaggerated
euphoria.
 It has no accepted medical use.

Codeine
 Much less potent analgesic than morphine but it has a higher oral efficacy.
 Shows good antitussive activity.
 Has a lower abuse potential & rarely produce dependency.
 Produce less euphoria than morphine.
 It's used as antitussive, but now widely replaced by dextrometorphan, a synthetic
cough depressant that has low potential for abuse.
Meperidine (Pethidine)

 Produce pharmacologic effect similar to morphine.

 A predominant receptor agonist.
 Has more effect in the CNS.
 Used as analgesic and not used for the treatment of cough or diarrhea.

Diphenoxylate and Loperamide

 Are derivatives of meperidine devoid of central effects.
 Slow GI motility and used as antidiarrheals.

Tramadol
o A synthetic codein analogue that is a week receptor agonist.
o Part of its analgesic effect is obtained by inhibition of uptake of norepinephrine and
serotonine.
o In the treatment of mild to moderate pain tramadol is as effective as morphine or
meperidine. However it is less effective in severe and cronic pain.
o Respiratory depression is less than morphine and constipation is less than equivalent
doses of morphine.
o Has less abuse potential but should never be used in patients with a history of
addiction.

Antagonists
 Bind with high affinity to opioid receptors but fail to activate the receptor mediated
response.
Naloxone
 Is used to reverse the coma & respiratory deprssion of opioid overdose. (Antidote for
opioid).

Naltrexone
 Actions similar to Naloxone but has longer duration of action.
Parkinson’s disease & drugs used in Parkinson’s disease
Parkinsonism is a progressive neurological disorder of muscle movement characterized by:
 Tremors (hand, ankles) common at rest
 Muscle rigidity
 Postural abnormalities
 Bradykinesia (slowness in initiating & carrying out voluntary movements)
Etiology:
 The disease is correlated with a reduction in the activity of inhibitory dopaminergic
neurons in the corpus striatum part of the brain basal ganglia system that is
responsible for motor control
 Nerve fibers from the cerebral cortex & thalamus secret Ach in the neostraitum
causing excitatory effect that initiate and regulate intentional movement of the body
Symptoms: imbalance b/n the excitatory cholinergic neuron and the greatly diminished
number of inhibitory dopaminergic neurons
Therapy: restore the dopamine in the basal ganglia & antagonizing the excitatory effect of
cholinergic neurons. Thus re-establishing the correct dopamine and Ach balance.
Drugs used in Parkinson’s disease
  Currently available drugs offer temporary relief from the symptoms of the disorder
but do not arrest or reverse the neuronal degeneration caused by the disease.
1. Levodopa (L-dopa) & Carbidopa
 Dopamine can’t cross blood brain barrier (BBB) but its immediate precursor
levodopa is readily transported to the CNS & converted to dopamine in the CNS.
 The effect of L-dopa on the CNS can be greatly enhanced by co administering
carbidopa, a dopa decarboxylase inhibitor that can’t cross the CNS.Thus increase the
availability of L-dopa to the CNS.
 Absorption:
 The drug is rapidly absorbed from the small intestine.
 Ingestion of meals, particularly of high protein contents compete with
absorption from the gut and transport in to the CNS.
 L-dopa should be taken on an empty stomach (45 minutes before meal)
 Adverse effects
 Peripheral effects: anorexia, nausea, vomiting occur because of stimulation
of emetic center, Tachycardia, mydriasis
 CNS effects: visual & auditory hallucination, mood changes, anxiety &
depression
 Interaction
 Pyridoxine (vit.B6) increases the peripheral break down of L-dopa and
diminishes its effectiveness
 Concomitant administration with MAO inhibitors can produce
hypertension crisis caused by enhanced catecholamine production.
2. Bromocriptine
 Is a synthetic dopamine receptor agonist with more prolonged actions with fewer
side effects than dopamine
 used in the management of Parkinsonism together with L-dopa
3. Amantidine
 Is antiviral drug effective in the treatment of influenza & has antiparkinsonism
action
 Decreases inactivation of dopamine by blocking the presynaptic uptake of the
transmitter & is given along with L-dopa
4. Antimuscarinic drugs
 Blockage of cholinergic transmission produces effects similar to augmentation of
dopaminergic transmission
 These drugs are much less efficacious than L-dopa & play only an adjuvant role in
Parkinsonism therapy.These are Benztropine, Trihexphenidyl.
 Adverse effects:-Similar to anti muscarinic agents
 Xerostomia (dryness of mouth)
 interfere with GIT peristalysis
 Sandy eye (dry eye)
General anesthetics
 Drugs which produce reversible loss of all sensations and consciousness
 Their features are:-
 Los of sensation, especially of pain
 Sleep (unconsciousness) & amnesia (loss of memory)
 Immobility & muscle relaxation
 Abolition of reflexes such as muscular movement & cardiovascular stimulation
 No single drug is capable of achieving these effects rapidly and safely.So
combination of drugs should be used to achieve these modalities.
 An ideal anesthetic should:
 Have anxiolytic effect
 Have sedative property
 Have analgesic activity
 Not bring about emesis
 Cause muscle relaxation
 Possess rapid induction and recovery
 Be chemically stable, non-flammable, non-toxic & easy to administer
 Be inexpensive
 No currently available anesthetic agent possesses all ideal anesthetic properties at
tolerable doses; hence, the need for pre-anesthetic medication (use of drugs prior to
administration of an anesthetic) to produce a balanced anesthesia
 Preanesthetic medication purposes:-
  Decrease anxiety; by use minor tranquilizers such as phenothiazines and
benzodiazepins
 Induce sedation by use of sedatives such as Barbiturates & Benzodiazepins
 Relief pre & postoperative pain by use of opioid analgesics
 Decrease postoperative emesis by use of antiemetics
 dry secretions by making use of atropine like drugs
 induce muscle relaxation by use of muscle relaxant drugs

Classification of general anesthetics

1. Inhalational anesthetics
 Exist either in the form of gas or volatile liquids
 Anesthesia is produced when specific concentration of the agent is reached at the
site of action. This depends on the pharmacologic property of the agent.
 There are two main pharmacokinetic properties, which affect the induction &
recovery of an anesthetic agent
1. Minimum alveolar concentration (MAC): is an anesthetic dose expressed in percentage of
the total gases in inspired air which has an effect in 50% of the population. It is an index of
potency; an anesthetic with low MAC is said to be potent.E.g-Nitrous oxide (N 2O), MAC >
100% → poor potency & Cyclopropane, MAC = 9.2 % → potent anesthetic activity
2. Solubility of anesthetic in blood: -
 The most important property determining induction and recovery
 It is expressed as blood –gas partition coefficient (λ) equal to the ratio of an
anesthetic concentration in the blood to in a gas phase when the partial pressure has
reached equilibrium
 Drugs with low blood solubility eg.N2O (λ =0.47), Cyclopropane (λ =0.41) have fast
induction & recovery
2. Volatile liquid anesthetics (Diethyl ether, Enflurane, Halothane, Desflurane, Isoflurane)
 Are liquid at room temperature but get vaporized upon inhalation
 Are more potent anesthetics (MAC < 1.9 %) and more soluble in the blood & tissue
than their gaseous counterparts
 Their high solubility makes induction of anesthesia slow and renders slow excretion
via lungs, leading to slow recovery
  Employed together with adjuvant anesthetics like N2O to make induction faster
1. Halothane
 Is a volatile anesthetic agent with λ of 2.3 (intermediate-reasonable induction &
recovery)
 Is very potent (MAC =0.75%)
 Has very pleasant smell, there fore is accepted by many patients
2. Diethyl Ether (C2H5-O-C2H5)
 Is a volatile liquid with λ of 12 (slow induction & recovery)
 Is potent anesthetic (MAC=1.9%)
3. Intravenous Anesthetics
 Are generally used for induction because of rapidity of onset of action (highly lipid
soluble cross the BBB rapidly)
 Have short duration of action so anesthesia is usually maintained by an inhalational
agent
 The rapid cessation of action is attributed to redistribution to tissues out of the CNS
& effect subsides before the agent leaves the body
 They can also be used as a sole anesthetic for short procedures
 Unlike inhalational agents, most injectable anesthetics (except ketamine) affect
consciousness only and are devoid of analgesic activity
4. Ultra short acting barbiturates
1. Theopental
 Produce sedation, sleepiness or anesthesia
 Has high lipid solubility.On intravenous injection, it causes unconsciousness with in
20 seconds and this lasts for 5-10 minutes
2. Benzodiazepines
 Diazepam, midazolam and lorazepam are useful in anesthesia
 Midazolam has a veryfor short duration of action which permits a prompt return of
psychomotor activity
 Have minimal depressant effect to the CVS and respiratory system than the
barbiturates
 Intravenous administration causes loss of consciousness with out analgesia
 Act less rapidly than thiopental
5. Dissociative anesthesia
Ketamine
 It is lipophylic and enters the brain very quickly
 The patient may appear awake and reactive but does not respond to sensory stimuli
 The patient is not in a full conscious state
 Produces profound analgesia, immobility, amnesia with light sleep
 On regaining consciousness, the patient may experience a disconnection between out
side reality and inner mental state
 Frequently there is memory loss for the duration of the recovery period.
6. Neurolept anesthesia
 Refers to the combined use of a short acting analgesic, an injectable anesthetic,a
short acting muscle relaxant and a slow dose of neuroleptic
Local anesthetics
 Are drugs which upon topical application or local injection cause reversible loss of
sensory perception especially of pain in restricted areas of the body
 block generation & conduction of nerve impulse at all parts of the neurons where
they come in contact by decreasing the entry of Na + in to the nerve through a
membrane pore protein
 Since local anesthetics block Na+ influx not only in sensory nerves but also in other
excitable tissues, too rapid entry in to circulation would lead to:
 Blockade of inhibitory CNS neurons leading to restlessness,seizures,general
paralysis with respiratory arrest
 Blockade of cardiac impulse conduction due to impaired AV conduction
which may result in cardiac arrest
 Are intended to produce their effect at the site of administration and their systemic
distribution will reduce the intensity and duration of anesthetic effects
 They can be classified as

A.Injectables anesthetics:
1. Low potency & short duration: Procain, Chlorprocain
2. Intermidiate potency & duration: Lignocain (Lidocain)
3. High potency and long duration: Tetracain
B.Surface anesthetics:
 Usually applied on mucous membrane & abraded skin
 .E.g. Cocain, Lignocain, Tetracain & Benzocain
Procain
 Is the first synthetic local anesthetic
 Its popularity declines after the introduction of lignocain
 forms poorly soluble salt with benzyl penicilline;PPF(IM acts for 24 hours)
Lignocain (Lidocain, Xylocain)
 Currently the most widely used local anesthetic agent
 Good for surface application and injection
 blocks conduction within 3 minutes
 Anesthesia is more intense and longer lasting
Cocain
 A natural alkaloid from leaves of Erythroxylum coca
 Is good surface anesthetic
 Should never be injected because it causes tissue necrosis
 Blocks uptake of cathecholamines at adrenergic nerve endings
 Produces permanent CNS stimulation with marked effect on mood & behavior
 Induces a sense of wellbeing, delays fatigue and increase power of endurance
 Is abused for its central action

Difference between General & Local anesthetic

GA LA
1. Site of action nerves CNS Peripheral

2. Consciousness Lost Unaltered

3. Area of body involved Whole body Restricted area

4. Preferential use Major surgery Minor surgery

Information Sheet XVI:- Chemotherapy of infectious diseases

INTRODUCTION
 Chemotherapyis the use of chemical agents (either synthetic or natural) to destroy
infective agents (microorganisms i.e. bacteria, fungus and viruses, protozoa, and
helminthes) and to inhibit the growth of malignant or cancerous cells
General principle of chemotherapy
 Antimicrobial therapy takes advantage of the biochemical difference that exist b/n
microorganisms and human beings.
 Antimicrobial drugs are effective in the treatment of infections because of their
selective toxicity, i.e. they have the ability to injure or kill an invading microorganism
without harming the cells of the host.
 Antimicrobials are among the most commonly used and misused of all drugs
 Widespread and irrational use of antimicrobial agents Þ Emergence of antibiotic-
resistance
 Antibiotics have three general uses
 Empirical (initial) therapy
 They should cover all the likely pathogens either by combination therapy or a
single broad-spectrum agent
 Definitive therapy
 Once the infecting microorganism is identified, a narrow-spectrum, low-toxicity
agent is instituted
 Prophylactic or preventive therapy
Factors that affect selection of antibiotics
 Selection of the most appropriate antimicrobial agent requires knowledge of
1) The organism's identity
2) The organism's susceptibility to a particular agent
3) The site of the infection
4) Patient factor
- Age, Pregnancy, Drug allergy, Renal dysfunction, Hepatic dysfunction Poor
perfusion, Lactation
5) The safety of the agent
 6) The cost of therapy
9.1 ANTIBACTERIAL
Classification
 Based on spectrum of activity
1. Narrow-spectrum antibiotics
- Chemotherapeutic agents acting only on a single or a limited group of microorganisms are
said to have a narrow spectrum.
o For example, isoniazid is active only against mycobacterium
2. Extended-spectrum antibiotics
- Extended spectrum is the term applied to antibiotics that are effective against gram-
positive organisms and also against a significant number of gram-negative bacteria. For
example, ampicillin is considered to have an extended spectrum, because it acts against
gram-positive and some gram-negative bacteria

3. Broad-spectrum antibiotics
- Drugs such as tetracycline and chloramphenicol affect a wide variety of microbial species
and are referred to as broad-spectrum antibiotics
- Administration of broad-spectrum antibiotics can drastically alter the nature of the normal
bacterial flora and precipitate a super infection of an organism such as Candida albicans,
the growth of which is normally kept in check by the presence of other microorganisms.
 Based on types of action
a) Bacteriostatic
 Bacteriostatic drugs arrest the growth and replication of bacteria at serum levels
achievable in the patient, thus limiting the spread of infection while the body's immune
system attacks, immobilizes, and eliminates the pathogens.
b) Bactericidal
 Bactericidal drugs kill bacteria at drug serum levels achievable in the patient.
 Because of their more aggressive antimicrobial action, these agents are often the drugs of
choice in seriously ill patients.
 NB: - it is possible for an antibiotic to be bacteriostatic for one organism and bactericidal
for another. For example, chloramphenicol is bacteriostatic against gram-negative rods and
is bactericidal against other organisms, such as S. pneumoniae.
 Based on chemical structure and proposed MOA
1. Cell wall synthesis inhibitors , e.g. b-lactam antibiotics, cycloserine, vancomycin, and
bacitracin
2. Agents that act directly on the cell membrane of the microorganism, e.g.
Polymyxin,nystatin and amphotericin B, daptomycin
 3. Agents that affect ribosomal protein synthesis (e.g., CAF,TTCs, erythromycin,
clindamycin, aminoglycosides)
4. Agents that affect bacterial nucleic acid metabolism,
e.g. the rifamycins and the quinolones
antimetabolites, including trimethoprim&sulfonamides
9.1.1 CELL WALL SYNTHESIS INHIBITORS
A. b-Lactam Antibiotics
 inhibit the synthesis of the bacterial peptidoglycan cell wall
 include penicillins, cephalosporins, b-lactamase inhibitors, carbapenems and monobactam
 the antibacterial effects of all the β-lactam antibiotics are synergistic with the aminoglycosides
1. The Penicillins
 Mechanism of action
 inhibit bacterial growth by interfering with the transpeptidation reaction of bacterial cell wall
synthesis
 They are bactericidal
 Classification
 Currently penicillins are divided in to 4 groups based on the spectra of activity
 Natural penicillins:- Penicillin G, Penicillin V
 Penicillinase-resistant penicillins (antistaphylococcals)
 cloxacillin, Nafcillin, Oxacillin, Methicillin,
 Extended spectrum penicillins (amonopenicillins):- Amoxicillin, Ampicillin
 Antipseudomonal penicillin:- Piperacillin, Ticarcilllin
A. Natural Penicillins
 Are acid labile and b-lactamase sensitive
 Active against most g(+) and g(-) aerobic cocci, some g(+) aerobic and anaerobic bacilli, and
most spirochetes.
 Most streptococci are susceptible
 More than 90% of staphylococcal strains are now resistant
 Penicillin G
 non-suitable for oral administration (IM or IV)
 Depot IM formulations of penicillin G (procaine penicillin and benzathine penicillin)
have decreased solubility, delayed absorption, and a prolonged t½
 potassiumpenicillin G is administered IV and IM
 Therapeutic use
  drug of first choice for infections caused by sensitive gram-positive cocci:- e.g
pneumonia and meningitis caused by Streptococcus pneumoniae
(pneumococcus), pharyngitis caused by Streptococcuspyogenes, and infectious
endocarditis caused by Streptococcus viridans
 preferred agent for infections caused by several gram-positive bacilli,
specifically, gas gangrene (caused by Clostridium perfringens), tetanus (caused
by Clostridium tetani), and anthrax (caused by Bacillus anthracis)
 drug of first choice for meningitis caused by N. meningitidis (meningococcus)
 drug of choice for syphilis, an infection caused by the spirochete T. pallidum
 Penicillin V
 More stable in acidic media and is better absorbed from the GIT
 Have similar antibacterial spectrum as penicillin G.
 Used to treat streptococcal infections when oral therapy is appropriate and desirable.
B. Penicillinase-resistant penicillins (antistaphylococcal penicillins)
 resistant to staphylococcal penicillinase (hence effective against streptococci and most
community-acquiredpenicillinase-producing staphylococci)
 Generally less active against Pen G susceptible organisms than other penicillins
C. Extended spectrum penicillines (Aminopenicillins)
 Semi synthetic penicillins with enhanced activity against g (-) bacteria (including Haemophilus
influenzae, Escherichia coli, Salmonella, and Shigella) compared to natural and penicillinase-
resistant penicillins
 Include-Amoxicillin & ampicillin
 Used orally for the treatment of infections of upper & lower RTI, GIT, skin and skin
structures, genitourinary tract, & otitis media caused by susceptible organisms.
 IM or IV for the treatment of meningitis, endocarditis, or severe RT, GIT, bone and joint or
genitourinary tract infections by susceptible organisms.
 Amoxicillin is absorbed more rapidly and completely from the GIT than is ampicillin (the major
difference between the two drugs)
 Both have essentially identical spectrum of antimicrobial action, except that amoxicillin is less
effective than ampicillin for shigellosis.
D. Antipseudomonal penicillins
 Semi synthetic penicillins with wider spectra of activity than the other penicillins.
 Are active against P. aeruginosa and certain Proteus spp. that are resistant to ampicillin and its
congeners.
 Piperacillin is the most potent of these antibiotics
  Their use is generally limited to treatment of serious infections caused by susceptible g(-)
bacilli or mixed aerobic-anaerobic infections
Untoward effects of penicillins
 Hypersensitivity reactions
 All penicillins are cross-sensitizing and cross-reacting.
 rash, fever, bronchospasm, vasculitis, serum sickness, exfoliative dermatitis, Stevens-
Johnson syndrome, and anaphylaxis
 Other adverse reactions
 Nausea, vomiting, diarrhea
 Pain and sterile inflammatory reactions at the sites of intramuscular injections
2. Cephalosporins
 These drugs are bactericidal, often resistant to beta-lactamases, and active against a broad
spectrum of pathogens
 Classification
 Classified into four based on their spectrum of activity
A. First generation cephalosporins (e.g. Cephalexin ...)
 very active against gram-positive cocci, such as pneumococci, streptococci, and staphylococci
 have only modest activity against gram-negative bacteria and do not reach effective
concentrations in CSF
B. Second generation cephalosporins (e.g. Cefoxitin …)
 Have greater stability against b-lactamase
 Greater activity against three additional gram-negative organisms: H. influenza, Enterobacter
aerogenes, and some Neisseria species, whereas activity against gram-positive organisms is
weaker.
C. Third generation cephalosporins (Ceftazidime, Ceftriaxone)
 Have Higher b-lactamase stability and expanded spectrum of activity against g(-) aerobes
 Have enhanced activity against gram-negative bacilli, including those mentioned above, as
well as most other enteric organisms
 Ceftazidime has activity against P.aeruginosa
 In contrast to first- and second-generation cephalosporins, the third-generation agents reach
clinically effective concentrations in CSF
D. Fourth generation cephalosporins (Cefepime)
 More resistant to inactivation by b-lactamases
 Expanded spectrum of activity against g(-)
  Active against some g(-) including Pseudomonasaeruginosa and certain Enterobacteriaceae,
that are generally resistant to 3rd GC
 Therapeutic Uses
 Skin and soft tissue infections due to S. aureus and S. pyogenes (1st GCs)
 3rd GCs (with or without aminoglycosides)
 third-generation cephalosporins are drugs of choice for meningitis caused by enteric,
gram-negative bacilli
 Drugs of choice for serious infections caused by Klebsiella, Enterobacter, Proteus,
Serratia, and Haemophilus spp.
 Ceftriaxone is the drug of choice for all forms of gonorrhea and for severe forms of
Lyme disease.
 Ceftazidime is of special utility for treating meningitis caused by P. aeruginosa.
 Treatment of community-acquired pneumonia
 Adverse reaction
 Hypersensitivity
 Anaphylaxis, bronchospasm, and urticaria
 Cross-reactivity with penicillin allergy (in 5–10%)
 Diarrhea, disulfiram-like reaction
(Reading assignment 1. Other b-lactam antibiotics (Carbapenems, Monobactams)
2. Other Cell Wall Inhibitors (vancomycin)
b-LACTAMASE INHIBITORS
 B-Lactamase inhibitors, such as clavulanic acid, sulbactam, and tazobactam, contain B-lactam
ring but do not have significant antibacterial activity by themselves
 Instead, they bind to and inactivate B-lactamases, thereby protecting the antibiotics that are
normally substrates for these enzymes.
 The B-lactamase inhibitors are therefore formulated in combination with B-lactamase sensitive
antibiotics
 Amoxicillin + clavulanate (augmentin)
 Ticarcillin + clavulanate (Timentin)
9.1.2 QUINOLONES AND FOLIC ACID ANTAGONISTS
A. FOLIC ACID ANTAGONISTS
i. Sulfonamides
 include sulfamethoxazole, sulfadiazine, sulfadoxine
 Mechanism of action
  Competitively inhibit dihydropteroate synthase (DHPS) and block folic acid synthesis Þ are
bacteriostatic
 antimicrobial spectrum
 active against a broad spectrum of microbes
 Susceptible organisms include gram-positive cocci (including MRSA), gram-negative bacilli,
Listeria monocytogenes, actinomycetes (e.g., Nocardia), chlamydiae (e.g., Chlamydia
trachomatis), some protozoa (e.g., Toxoplasma, plasmodia), and two fungi: Pneumocystis
jiroveci and Paracoccidioides brasiliensis.
 Clinical uses.
- Infrequently used as single agents.
- Largely replaced by trimethoprim-sulfamethoxazole (Cotrimoxazole).
- Can be useful for treatment of urinary tract infections, Nocardiosis
- sulfonamides are alternatives to doxycycline and erythromycin for infections caused by C.
trachomatis (trachoma, inclusion conjunctivitis, urethritis, lymphogranuloma venereum)
- used in conjunction with pyrimethamine to treat two protozoal infections: toxoplasmosis and
malaria caused by chloroquine-resistant Plasmodium falciparum
 Adverse Reactions
 All sulfonamides and their derivatives are cross-allergenic
 Skin rashes, urticaria, photosensitivity, arthritis, conjunctivitis, hematopoietic
disturbances, hepatitis
 Precipitate in urine (at neutral or acid pH) producing crystalluria, hematuria, or even
obstruction
ii. Trimethoprim
 Competitively inhibits dihydrofolate reductase (DHFR)
Trimethoprim in combination with a sulfonamide blocks sequential steps in folate synthesis,
resulting in marked enhancement (synergism) of the activity of both drugs.
 Antibacterial Spectrum & Resistance
- Trimethoprim exhibits broad-spectrum activity
- active against most enteric gram-negative bacilli of clinical importance, including E. coli,
Klebsiella pneumoniae, Proteus mirabilis, Serratia marcescens, Salmonella, and Shigella
 Clinical use
 In acute urinary tract infections (100 mg twice daily)
 Adverse Effects
 produces the predictable adverse effects of an antifolate drug, especially megaloblastic
anemia, leukopenia, and granulocytopenia
 iii. Trimethoprim –Sulfamethoxazole (TMP-SMX)
 The combination shows synergistic effect as the two affect different points in the folic acid
synthetic pathway
 Therapeutic use
 valuable for urinary tract infections, otitis media, bronchitis, shigellosis, and pneumonia
caused by P. jiroveci
 adverse effect
 The most common adverse effects are nausea, vomiting, and rash
 may cause all of the untoward reactions associated with sulfonamides
 the usual adultdosage is 160 mg TMP plus 800 mg SMZ administered every 12 hours for 10 to
14 days
iv. Pyrimethamine
 Acts by inhibiting DHFR
 Used for Malaria and Toxoplasmosis in combination with a sulfonamide
Pyrimethamine and sulfadiazine have been used for treatment of leishmaniasis and
toxoplasmosis.
In falciparum malaria, the combination of pyrimethamine with sulfadoxine (Fansidar) has
been used
B. FLUOROQUINOLONES
 The important quinolones are synthetic fluorinated analogs of nalidixic acid
 ciprofloxacin, norfloxacin, ofloxacin, levofloxacin, etc
 Fluorinated 4-quinolones
 Have broad antimicrobial activity and relatively few side effects.
 Effective after oral administration for the treatment of a wide variety of infectious
diseases
 Microbial resistance does not develop rapidly
 MOA
 Quinolones block bacterial DNA synthesis by inhibiting bacterial topoisomerase II (DNA
gyrase) and topoisomerase IV.
 All the fluoroquinolones are bactericidal.
a) Ciprofloxacin
 active against a broad spectrum of bacteria, including most aerobic gram negative bacteria
and some gram-positive bacteria
 The drug is highly active against most bacteria that cause enteritis (e.g., Salmonella,
Shigella, Campylobacter jejuni, E. coli)
  Active against P.aeruginosa
 Clinical Uses
 UTI by even MDR bacteria, e.g., Pseudomonas
 Also for bacterial diarrhoea caused by shigella, salmonella, E coli, or campylobacter
 Infections of soft tissues, bones, and joints and in intra-abdominal and RTI
 Chlamydial urethritis or cervicitis
 a DOC for prophylaxis and treatment of anthrax
 Occasionally in the treatment of TB
 AdverseEffects
 Most common: nausea, vomiting, and diarrhea
 Occasionally, headache, dizziness, insomnia, skin rash, or abnormal liver function tests
develop.
 Photosensitivity, tendon rupture, usually of the Achilles tendon
 Drug interaction
 interact with multivalent cations, forming chelation complexes resulting in reduced
absorption
 antacids, iron salts, zinc salts, sucralfate, and milk and other dairy products
 increase plasma levels of several drugs, including theophylline, warfarin and
tinidazole
 Contraindication
 They should be avoided during pregnancy in the absence of specific data
documenting their safety
 Dosage
 The dosage for urinary tract infections is 250 or 500 mg 2 times a day, usually for 7
to 14 days.
 For other infections, dosages range from 500 to 750 mg 2 times a day
b) Norfloxacin
 approved for prostatitis caused by E. coli and for UTIs caused by P.aeruginosa
 For uncomplicated UTIs, the usual dosage is 400 mg twice daily for 3 days.
 Prolonged treatment (10 days to 3 weeks) is employed for patients with complicated
infections of the urinary tract
9.1.3 PROTEIN SYNTHESIS INHIBITORS
1. Aminoglycosides
include Gentamicin, Tobramycin, Amikacin, Streptomycin, Neomycin, ...
Have bactericidal activity
Mechanism of action
 All members of this family are believed to inhibit bacterial protein synthesis irreversibly.
 these drugs bind to the 30S ribosomal subunit, and thereby cause (1) inhibition of protein
synthesis, (2) premature termination of protein synthesis, and (3) production of abnormal
proteins (secondary to misreading of the genetic code)
Antibacterial Spectrum
 narrow-spectrum antibiotics, used primarily against aerobic gram-negative bacilli
 Produce synergistic bactericidal effect in vitro (against enterococci, streptococci, and
staphylococci) when combined with a cell wall-active agent
Because they are polycations, the aminoglycosides cross membranes poorly. As a result, very
little (about 1%) of an oral dose is absorbed. Hence, for treatment of systemic infections,
aminoglycosides must be given parenterally (IM or IV)
Therapeutic Use
 Parenteral Therapy (gentamicin, Amikacin, tobramycin)
 treatment of serious infections due to aerobic gram-negative bacilli (Primary target
organisms are Pseudomonas aeruginosa and the Enterobacteriaceae such as E. coli,
Klebsiella, Serratia, Proteus mirabilis)
 Topical Therapy
 Neomycin is available in formulations for application to the eyes, ears, and skin.
 Topical preparations of gentamicin and tobramycin are used to treat conjunctivitis caused
by susceptible gram-negative bacilli
Untoward effects
 ototoxicity and nephrotoxicity
 Neuromuscular Blockade
 Allergic reaction:- contact dermatitis is a common reaction to topically applied neomycin.
Individual drugs
 Gentamicin
 First choice due to low cost and reliable activity against all but the most resistant
gram-negative aerobes.
 Available for parenteral, ophthalmic, and topical
 can be combined with vancomycin, a cephalosporin, or a penicillin to treat serious
infections caused by certain gram positive cocci, namely, Enterococcus species, some
streptococci, and Staphylococcus aureus
 Therapeutic Uses
 Urinary Tract Infections, Pneumonia, Meningitis, Bacterial Endocarditis, Sepsis
  Streptomycin
 generally less active than other members of the class
 Therapeutic Uses
 Bacterial Endocarditis:- Streptomycin and penicillin in combination
 used in combination with other drugs to treat tuberculosis
2. Macrolides
 Include erythromycin, clarithromycin, azithromycin
 Erythromycin is the prototype drug
Erythromycin
 Mechanism of Action
 Inhibit protein synthesis by binding reversibly to 50S ribosomal subunit
 Inhibits the translocation step wherein a newly synthesized peptidyl tRNA molecule moves
from the acceptor site on the ribosome to the peptidyl donor site.
 usually bacteriostatic
 Antibacterial Activity
 Erythromycin is effective against many of the same organisms as penicillin G; therefore, it
is used in patients allergic to the penicillins.
 Pharmacokinetics
 Food interferes with the absorption of erythromycin and azithromycin but can increase that of
Clarithromycin.
 Erythromycin is extensively metabolized and is known to inhibit the oxidation of a number of
drugs through its interaction with the cytochrome p450 system
 Clinical uses
 preferred treatment for pneumonia caused by Legionella pneumophila (legionnaires' disease)
 drug of first choice for individuals infected with Bordetella pertussis, the causative agent of
whooping cough
 treatment of choice for acute diphtheria
 Mycoplasma pneumonia infections (A macrolide or TTC is the drug of choice)
 Chlamydial Infections:- can be treated effectively with any of the macrolides
 as a substitute for penicillin to treat respiratory tract infections caused by Streptococcus
pneumoniae
 Adverse Effects
 The incidence of side effects associated with erythromycin therapy is very low.
 Mild GI upset with nausea, diarrhea, and abdominal pain (more common)
 The usual adult dosage for erythromycin base and erythromycin stearate is 250 to 500 mg every
6 hours
Clarithromycin
 A lower incidence of gastrointestinal intolerance and less frequent dosing
 Used for the prevention of disseminated Mycobacterium avium complex infections in patients
with advanced HIV infection
 used for H. pylori infection
Azithromycin
 Its spectrum of activity and clinical uses are virtually identical to those of clarithromycin
 used for infections caused by Chlamydia trachomatis, for which it is a drug of choice
 its absorption is increased by food
3. Tetracyclines (TTCs)
 Mechanism of Action
 TTCs inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and
preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome
complex
 Antibacterial Spectrum
 bacteriostatic antibiotics active against a wide range of aerobic and anaerobic g(+) & g(-)
bacteria
 Sensitive organisms include Rickettsia, spirochetes, Brucella,Chlamydia, Mycoplasma,
Helicobacter pylori, Borrelia burgdorferi, Bacillus anthracis, andVibrio cholerae
 Pharmacokinetics
 Absorption
 Impaired by Food (all except doxycycline and minocycline)
 TTCs form insoluble chelates with calcium, magnesium, and other metal ions
- simultaneous administration with milk (calcium), magnesium hydroxide, aluminum
hydroxide, or iron will interfere with absorption
 Significant differences in serum half-life allow the grouping of the tetracyclines into
subclasses
 short acting- Serum half-life of 6-8 hours
- tetracycline, …
 intermediate acting- Serum half-life of 12 hours
- demeclocycline
 Long acting- Serum half-life of 16-18 hours
- minocycline and doxycycline
  Elimination
 Doxycycline and minocycline are excreted primarily in the feces.
 TTCs of choice in renal insufficiency.
 The other tetracyclines are eliminated primarily in the urine by glomerular filtration.
 Obviously, these tetracyclines have greater urinary antibacterial activity than those
that are excreted by nonrenal mechanisms.
 Therapeutic Uses
 the drugs of choice for treatment of cholera, rickettsial diseases, relapsing fever, the
chlamydial diseases (trachoma, lymphogranuloma venereum, urethritis, cervicitis),
brucellosis, pneumonia caused by Mycoplasma pneumoniae
 used in combination regimens to treat gastric and duodenal ulcer disease caused by
Helicobacter pylori
 Tetracyclines are clinically effective in acne
 Adverse effects
 Gastrointestinal Adverse Effects:- NVD, epigastric burning, cramps
 Bony Structures and Teeth
 Discoloration of the teeth and brittle bone in children
 Liver Toxicity;- especially during pregnancy
 Kidney Toxicity, Photosensitization, Vestibular Reactions
 Contraindications
 In pregnant women
 Children under the age of 8 years
4. CHLORAMPHENICOL
 Mechanism of Action
 Binds reversibly to the 50S ribosomal subunit and inhibits the peptidyl transferase step of
protein synthesis.
 Antimicrobial Actions
 Broad spectrum antimicrobial activity
 Salmonella typhi, H. influenzae, Neisseria meningitidis, and S. pneumoniae
 active against rickettsia, mycoplasmas, and treponemes
 It is either bactericidal (for strep. Pneumonia) or static (for gram negative rods) depending on
the organism.
 Therapeutic Uses
 Because of its toxicity, its use is restricted to life threatening infections for which no
alternatives exist.
  Used for treatment of typhoid fever
 alternative to tetracycline for rickettsial diseases, especially in children younger than 8 years
 used topically in the treatment of eye infections because of its broad spectrum and its
penetration of ocular tissues and the aqueous humor
 Untoward effects
 gray baby syndrome,
 bone marrow depression
 Drug Interactions
 CAF inhibits hepatic CYP450s and prolongs the t ½ of drugs metabolized by this system
(warfarin, phenytoin, antiretroviral protease inhibitors)

(Reading assignment: - other protein synthesis inhibitors: - clindamycin, spectinomycin,

etc)
ANTIMYCOBACTERIAL DRUGS
1. ANTITUBERCULOSIS DRUGS
 Drugs for Tuberculosis
 First-line drugs are superior in efficacy and possess an acceptable degree of toxicity.
 Include isoniazid, rifamycins, pyrazinamide, ethambutol
 Most patients with tuberculosis can be treated successfully with these drugs.
 Second-line drugs are more toxic and less effective
 Indicated only when the M. tuberculosis organisms are resistant to the first-line
agents.
 Include fluoroquinolones, streptomycin, capreomycin, amikacin, kanamycin,
cycloserine, ethionamide, p-aminosalicylic acid, ...
I. ISONIAZID (isonicotinic acid hydrazide, INH)
 Mechanism of Action
 Isoniazid inhibits synthesis of mycolic acids, which are essential components of
mycobacterial cell walls.
 Antibacterial Activity
 The most active drug for the treatment of tuberculosis caused by susceptible strains
 Isoniazid is bactericidal against actively growing M. tuberculosis and bacteriostatic against
“resting” organisms
 Clinical Uses
 For the treatment of active TB (in combination with at least one drug)
 As a single agent for treatment of latent tuberculosis
 Adverse Reactions
 Hepatitis (greater risk in alcoholics & pregnancy and is a contraindication to further use of the
drug).
 Peripheral neuropathy, CNS toxicity (memory loss, psychosis, and seizures)
 Drug interaction- INH is an enzyme inhibitor and increases serum level of other drugs like
phenytoin.
II. RIFAMYCINS
 The rifamycins include rifampin, rifabutin, rifapentine
Rifampin
 Mechanism of Action
 inhibits bacterial DNA-dependent RNA polymerase, and thereby suppresses RNA synthesis

 Antibacterial Activity
 broad-spectrum antibiotic
 bactericidal to M. tuberculosis and M. leprae
 effective against many gram-positive and gram-negative organisms (e.g. S. aureus, N.
meningitides, H. influenzae)
 well absorbed if taken on an empty stomach
 Clinical Uses
 For the treatment of active TB
 Alternative to INH in the treatment of latent TB infection
 for the treatment of leprosy in combination with antileprosy agent
 Adverse Reactions
 common adverse reactions include nausea, vomiting, fever and rash
 Imparts orange colour to urine, sweat, tears
 hepatitis
 Drug interaction
 It is a strong inducer of most cytochrome P450 isoforms (PIs, NNRTIs, oral contraceptives,
warfarin
III. PYRAZINAMIDE
 bactericidal to actively dividing organisms, but the mechanism of its action is unknown
 Clinical uses
 For the treatment of active TB in combination with rifampin, isoniazid, and ethambutol
 Adverse effects
 Hepatotoxicity, nausea, vomiting, drug fever, and hyperuricemia
 IV. ETHAMBUTOL
 Mechanism of Action
 Inhibits arabinosyl transferases involved in cell wall biosynthesis.
 Antibacterial Activity
 Nearly all strains of M. tuberculosis and M. kansasii as well as a number of strains of MAC
are sensitive
 bacteriostatic
 Clinical Uses
 Commonly included as a 4 th drug, along with INH, pyrazinamide, and rifampin, in patients
infected with MDR strains.
 Adverse Reactions
 The most important adverse effect is optic neuritis, which results in diminished visual acuity
and loss of ability to discriminate between red and green
2. DRUGS USED IN LEPROSY
 Leprosy is divided into two main classes: (1) paucibacillary (PB) leprosy and (2) multibacillary
(MB) leprosy
 The distinction between PB leprosy and MB leprosy is important because treatment differs for
the two forms
 As with TB, the cornerstone of treatment is multidrug therapy. If just one drug is used,
resistance will occur
 For patients with MB leprosy, the World Health Organization (WHO) recommends 12
months of treatment with three drugs: rifampin, dapsone, and clofazimine
 For patients with PB leprosy, theWHO recommends 6 months of treatment with two drugs:
rifampin and dapsone
I. DAPSONE
 MOA
 Like the sulfonamides, it inhibits folate synthesis
 weakly bactericidal to M. leprae
 Dapsone may also be used to prevent and treat Pneumocystis jiroveci pneumonia in AIDS
patients
 Adverse reaction
 Dapsone is usually well tolerated.
 The most common adverse effects are GI disturbances, headache, rash and fever
 dosage
 100 mg daily, self-administered
  always combined with another antileprosy drug
II. RIFAMPIN
 by far our most effective agent for treating leprosy
 A single monthly dose of 600 mg may be beneficial in combination therapy.
III. CLOFAZIMINE
 slowly bactericidal to M. leprae
 always combined with another antileprosy drug (eg, rifampin, dapsone)
 A common dosage is 50 mg/d orally.
 Adverse reaction:-
 Gastrointestinal intolerance occurs occasionally
 imparts a harmless red color to feces, urine, sweat, tears, and saliva
9.2 ANTIFUNGAL DRUGS
 Antifungals are classified into different classes based on their action, and chemistry.
 Based on chemistry
i. Polyene antifungals :- Amphotericin B, nystatin
ii. Azole antifungals
A. Imidazoles:- Ketoconazole, miconazole, clotrimazole
B. Triazoles :- Itraconazole, fluconazole, voriconazole
iii. Miscellaneous :- Griseofulvin, flucytosine, terbinafine, white field
 Based on their actions
i. drugs for systemic mycoses:- Amphotericin B, Fluconazole, Ketoconazole,
itraconazole, voriconazole, Flucytosine, .....
ii. drugs for superficial mycoses:- clotrimazole, miconazole, Griseofulvin, Nystatin,
Ketoconazole, .....
SYSTEMIC ANTIFUNGAL DRUGS FOR SYSTEMIC INFECTIONS
A. AMPHOTERICIN B
 In spite of its toxic potential, amphotericin β is the drug of choice for treatment of life treating
systemic mycoses & it is also useful for the treatment of V. leishimaniasis.
 MOA
 bind to ergosterol, and thereby disrupt the fungal cell membrane
 Amphotericin B remains the antifungal agent with the broadest spectrum of action
 Clinical Use
 a drug of choice for most systemic mycoses (e.g. Blastomycosis, Candidiasis,
Coccidioidomycosis, Cryptococcosis, Histoplasmosis, Mucormycosis,
Paracoccidioidomycosis, Sporotrichosis)
 Adverse Effects
 The toxicity of amphotericin B can be divided into two broad categories: immediate
reactions, related to the infusion of the drug, and those occurring more slowly.
 These infusion-related reactions are nearly universal and consist of fever, chills, muscle
spasms, vomiting, headache, and hypotension.
 Renal damage is the most significant toxic reaction.
B. THE AZOLES
 have broad-spectrum fungistatic activity
 have lower toxicity and can be administered by mouth
 The triazoles tend to have fewer side effects, better absorption, better drug distribution in body
tissues, and fewer drug interactions.
a. Itraconazole
 MOA
 inhibits the synthesis of ergosterol, an essential component of the fungal cytoplasmic
membrane
 Clinical Uses
 a drug of choice for blastomycosis, histoplasmosis, paracoccidioidomycosis, and
sporotrichosis,
 an alternative to amphotericin B for aspergillosis, candidiasis, and coccidioidomycosis
 Adverse Effects
 well tolerated in usual doses
 Gastrointestinal reactions (nausea, vomiting, diarrhea) are most common
 inhibit drug-metabolizing enzymes, and can thereby raise levels of other drugs
 Drugs that decrease gastric acidity can greatly reduce absorption of oral itraconazole.
Accordingly, these agents should be administered at least 1 hour before itraconazole or 2 hours
after
b. Fluconazole
 Clinical Uses
 used for blastomycosis; histoplasmosis; meningitis caused by Cryptococcus neoformans and
Coccidioides immitis; and vaginal, oropharyngeal, esophageal, and disseminated Candida
infections
 Adverse Effects
 Fluconazole is well tolerated.
 Nausea, vomiting, abdominal pain, diarrhea, and skin
 c. Ketoconazole
 active against most fungi that cause systemic mycoses, as well as fungi that cause superficial
infections (dermatophytes and Candida species)
 Pks
 ketoconazole can be administered orally. It requires gastric acid for dissolution and is
absorbed through the gastric mucosa.
 Clinical Uses
 less useful for severe, acute infections than for long-term suppression of chronic
infections
 alternative drug for the treatment of coccidioidomycosis, histoplasmosis,
paracoccidioidomycosis

 Adverse effects
 Generally well tolerated. The most common adverse reactions are nausea and vomiting
 The most serious effect is hepatotoxicity
 Endocrine effects:-gynecomastia, decreased libido, impotence, and menstrual
irregularities,
 Drug interaction
 ketoconazole is an enzyme inhibitor and potentiates the action of other drugs like
cyclosporine, tolbutamide, warfarin etc
 rifampin lower plasma ketoconazole levels
C. FLUCYTOSINE
 MOA
 Disruption Of Fungal DNA And RNA Synthesis
 Antifungal Spectrum And Therapeutic Uses
 has a narrow antifungal spectrum:- active against Candida species and Cryptococcus
neoformans
 indicated only for candidiasis and cryptococcosis
 for treatment of serious infections (e.g., cryptococcal meningitis, systemic candidiasis),
flucytosine should be combined with amphotericin B
 ADR
 hematologic effects (e.g. neutropenia or thrombocytopenia) and hepatotoxicity
 inhibits hepatic drug-metabolizing enzymes
DRUGS FOR SUPERFICIAL MYCOSES
A. AZOLES
 The two azoles most commonly used topically are clotrimazole and miconazole.
I. Clotrimazole
 Clotrimazole is a broad-spectrum fungistatic imidazole drug used in the topical treatment
of oral, skin, and vaginal infections with C. albicans.
 It is also employed in the treatment of infections with cutaneous dermatophytes.
 Although clotrimazole is generally well tolerated, local abdominal cramping, increased
urination, and transient liver enzyme elevations have been reported
II. Miconazole
 Miconazole is a broad-spectrum imidazole antifungal agent used in the topical treatment of
cutaneous dermatophyte infections and mucous membrane Candida infections, such as
vaginitis.
 Local irritation to skin and mucous membranes can occur with topical use; headaches,
urticaria, and abdominal cramping have been reported with treatment for vaginitis.
III. Ketoconazole
 approved for oral and topical therapy of superficial mycoses
 Oral ketoconazole provides effective treatment of dermatophytic infections as well as
candidiasis of the skin, mouth, and vagina
 Topical use includes treatments of seborrheic dermatitis, dandruff, tinea versicolor,
dermatophytic infections and candidiasis of the skin
IV. Fluconazole
 used for oral therapy of vulvovaginal candidiasis, oropharyngeal candidiasis, and
onychomycosis

B. GRISEOFULVIN
 MOA
 Griseofulvin's mechanism of action at the cellular level is unclear, but it is deposited in
newly forming skin where it binds to keratin, protecting the skin from new infection.
 Therapeutic use
 Its only use is in the systemic treatment of dermatophytosis
 not active against Candida species, nor is it useful against systemic mycoses
 Adverse effects
 Transient headache, rash, insomnia, tiredness, and GI effects (nausea, vomiting, diarrhea)
 induces hepatic drug-metabolizing enzymes and can thereby decrease the effects of warfarin
C. NYSTATIN
 Nystatin is active against most candida species and is most commonly used for suppression of
local candidal infections. Some common indications include oropharyngeal thrush, vaginal
candidiasis, and intertriginous candidal infections.
 Oral nystatin occasionally causes GI disturbance (nausea, vomiting, diarrhea). Topical
application may produce local irritation.

9.3 ANTIPROTOZOALS
A. Drugs Used For Amebasis, Gardiasis And Trichomoniasis
i. Metronidazole
 MOA
 disrupts replication and transcription and inhibits DNA repair
 Antimicrobial Spectrum
 active against several protozoal species, including E. histolytica, G. lamblia, and
Trichomonas vaginalis
 It is also bactericidal for obligate anaerobic gram-positive and gram-negative bacteria
 Clinical Uses
 a drug of choice for symptomatic intestinal amebiasis and systemic amebiasis
 a drug of choice for giardiasis, and for trichomoniasis
 Adverse Effects
 The most frequently observed adverse reactions to metronidazole include nausea, vomiting,
cramps, diarrhea, and a metallic taste.
 The urine is often dark or redbrown.
 Drug interaction and contraindication
 has disulfiram-like actions
 Metronidazole interferes with the metabolism of warfarin and may potentiate its
anticoagulant activity.
 The drug is not recommended for use during pregnancy.
ii. Tinidazole
 similar actions, indications, interactions, and adverse effects with metronidazole
 has a longer half-life than metronidazole, and hence dosing is more convenient
iii. Iodoquinol
 a drug of choice for asymptomatic intestinal amebiasis
 employed in conjunction with metronidazole to treat symptomatic intestinal infection and
systemic amebiasis
 Iodoquinol is generally well tolerated.
  Mild reactions include rash, acne, slight thyroid enlargement, and GI effects (nausea,
vomiting, diarrhea, cramps)
iv. Diloxanide furoate
 effective luminal amebicide but is not active against tissue trophozoites
 considered by many the drug of choice for asymptomatic luminal infections
 It is used with a tissue amebicide, usually metronidazole, to treat serious intestinal and
extraintestinal infections
 Diloxanide furoate does not produce serious adverse effects. Flatulence is common, but nausea
and abdominal cramps are infrequent and rashes are rare
 The drug is not recommended in pregnancy
B. Drugs Used For The Treatment Of Trypanosomiasis
i. Pentamidine
 MOA
 Pentamidine binds to DNA and may inhibit kinetoplast DNA replication and function
 It also may act by inhibiting dihydrofolate reductase and interfering with polyamine
metabolism.
 Antimicrobial Spectrum
 Pentamidine is active against T. brucei gambiense, Pneumocystis carinii, and
leishmaniasis
 Clinical Uses
 It is an alternative agent for the treatment of P. jiroveci pneumonia.
 Pentamidine is an alternative drug for visceral leishmaniasis, especially when sodium
stibogluconate has failed or is contraindicated.
 Pentamidine is also a reserve agent for the treatment of trypanosomiasis before the CNS is
invaded.
 Adverse reactions
 Rapid drug infusion may produce tachycardia, vomiting, shortness of breath, headache, and
a fall in blood pressure.
 Changes in blood sugar (hypoglycemia or hyperglycemia) necessitate caution in its use,
particularly in patients with diabetes mellitus.
ii. Suramin
 must be given parenterally (IV)
 Clinical Uses
 a drug of choice for the early phase of East African trypanosomiasis (sleeping sickness)
 adverse reactions
  Side effects can be severe
 An acute reaction in sensitive individuals results in nausea, vomiting, colic, hypotension,
urticaria, and even unconsciousness;
 Rashes, photophobia, paresthesias, and hyperesthesia may occur later; these symptoms
may presage peripheral neuropathy.
iii. Melarsoprol
 a drug of choice for both East African and West African trypanosomiasis (sleeping sickness)
 employed during the late stage of the disease (i.e., after CNS involvement has developed)
C. Drugs Used For The Treatment Of Leishmaniasis
i. Sodium stibogluconate
 administered by intramuscular or slow intravenous injection
 Clinical use
 generally considered first-line agents for cutaneous and visceral leishmaniasis
 Adverse reactions
 Most common are gastrointestinal symptoms, fever, headache, myalgias, arthralgias, and
rash.
ii. Amphotericin
 an alternative therapy for visceral leishmaniasis
D. Drugs Used For The Treatment Of Toxoplasmosis
Pyrimethamine and sulfadiazine
 the treatment of choice for toxoplasmosis
E. Antimalarial Drugs
1. Quinolines And Related Compounds
a. Chloroquine
 MOA
 poison the parasite’s feeding mechanism
 Antimalarial Actions
 When not limited by resistance, chloroquine is a highly effective blood schizonticide
 Highly effective against erythrocytic forms of P. vivax, P. ovale, P. malariae, and chloroquine-
sensitive strains of P. falciparum.
 Therapeutic Uses
 drug of choice for mild to moderate acute attacks caused by sensitive strains
 preferred chemoprophylactic agent in malarious regions without resistant falciparum
malaria
 Amebic liver abscess
 Toxicity and Side Effects
 Chloroquine is usually very well tolerated, even with prolonged use
 Dizziness, headache, itching (especially in dark skinned people), skin rash, vomiting, and
blurring of vision
b. Quinine
 MOA
 It may poison the parasite’s feeding mechanism, and it has been termed a general
protoplasmic poison, since many organisms are affected by it.
 Antimalarial Actions
 Quinine is a rapidly acting, highly effective blood schizonticide against the four species of
human malaria parasites.
 Therapeutic Uses
 Treatment of choice for drug-resistant P. falciparum malaria
 Quinine is commonly used with a second drug (doxycycline, tetracycline or clindamycin)
 Not used for prophylaxis (due to toxicity and short half-life)
 Side Effects
 frequently causes mild cinchonism, a syndrome characterized by tinnitus, headache, visual
disturbances, nausea, and diarrhea
c. Quinidine
 share quinine's antimalarial mechanism and adverse effects
 IV quinidine gluconate is the treatment of choice for severe malaria
 should be accompanied by doxycycline, tetracycline, or clindamycin
d. Mefloquine
 Mechanisms of Action
 Exact mechanism of action of mefloquine is unknown but may be similar to that of
chloroquine
 Antimalarial Actions
 Highly active blood schizonticide
 Therapeutic Uses
 drug of choice for prophylaxis of malaria in regions where chloroquine-resistant P.
falciparum or P. vivax is found
 Reserved for the treatment of malaria caused by drug-resistant P. falciparum.
 Toxicity and Side Effects
 Generally well tolerated
  Mild-to-moderate toxicities (e.g., disturbed sleep, dysphoria, headache, GI disturbances, and
dizziness)
 Vomiting, Nausea, dizziness, and neuropsychiatric effects, severe CNS toxicities (seizures,
confusion, acute psychosis)
 It should not be coadministered with quinine, quinidine, or halofantrine, and caution is required if
quinine or quinidine is used to treat malaria after mefloquine chemoprophylaxis.
e. Primaquine
 Antimalarial Actions
 Destroys primary and latent hepatic stages of P. vivax and P. ovale
 Therapeutic Uses
 drug of choice for the eradication of dormant liver forms of P vivax and P ovale
 can also be used for chemoprophylaxis against all malarial species
 Side Effects
 Mild-to-moderate abdominal distress
 hemolysis and hemolytic anemia in patients with G6PD deficiency
f. Atovaquone/Proguanil
 MOA
 atovaquone - disrupting mitochondrial electron transport
 proguanil - inhibits plasmodial dihydrofolate reductase
 therapeutic use
 highly effective for both the prophylaxis and treatment of malaria caused by chloroquine-
resistant plasmodia
 adverse effect
 the principal adverse effect is rash
 Other reactions include NVD, headache, fever, and insomnia
2. Pyrimethamine/Sulfadoxine
 Antimalarial Actions
 A slow-acting blood schizonticide
 Therapeutic Uses
 Restricted to the treatment of chloroquine-resistant P. falciparum malaria in areas where
resistance to antifolates has not yet fully developed
3. Artemisinin and Its Derivatives
 include artemether, artesunate,....
 Artemisinins are
 Potent and fast-acting antimalarials
  Which generally are regarded to be safe
 Mechanism of Action
 kills plasmodia by releasing free radicals that attack the cell membrane
 Antiparasitic Activity
 very rapidly acting blood schizonticides against all human malaria parasites
 Therapeutic Uses
 Initial treatment of multidrug-resistantP. falciparum infections, not for prophylaxis
 Not used alone because of their incomplete efficacy and to prevent the selection of resistant
parasites
 most widely used as a fixed-dose combination of artemether and lumefantrine
(Coartem)
 Toxicity
 The most commonly reported adverse effects have been nausea, vomiting, and diarrhea.
9.4TREATMENT OF HELMINTHIC INFECTIONS
1. Benzimidazoles
 Includes mebendazole, thiabendazole and albendazole,
A. Mebendazole
 MOA
 Mebendazole inhibits microtubule synthesis in nematodes, and irreversibly impairing
glucose uptake. As a result, intestinal parasites are immobilized or die slowly.
 Clinical Uses:
 drug of choice for most intestinal roundworms
 pinworms, hookworms, whipworms, and giant roundworms
 Hydatid Disease: Mebendazole is the alternative.
 It is an alternative agent for the treatment of trichinosis and hydatid disease
 Adverse Reactions
 Mild nausea, vomiting, diarrhea, and abdominal pain
B. Albendazole
 MOA
 inhibit microtubule-dependent uptake of glucose
 Clinical use
 drug of choice for treatment of hydatid disease and cysticercosis
 also used in the treatment of pinworm and hookworm infections, ascariasis,
strongyloidiasis and trichuriasis
 Adverse reaction
  Mild and transient epigastric distress, diarrhea, headache, nausea, dizziness.
C. Thiabendazole
 Thiabendazole is the drug of choice for the treatment of strongyloidiasis.
 MOA
 The mechanism of action of thiabendazole is probably the same as that of other
benzimidazoles.

 Clinical Uses
 alternative drug for the treatment of strongyloidiasis
 Adverse Reactions
 the most common are dizziness, anorexia, nausea, and vomiting
2. Pyrantel Pamoate
 MOA
 The drug is a neuromuscular blocking agent that causes release of acetylcholine and
inhibition of cholinesterase; this results in paralysis, which is followed by expulsion of
worms.
 Clinical Uses
 alternative to mebendazole or albendazole for infestations with hookworms or pinworms or
ascariasis
 Adverse Reactions
 include nausea, vomiting, diarrhea, abdominal cramps, dizziness, drowsiness, headache,
insomnia, rash, fever, and weakness.
3. Piperazine
 Piperazine causes paralysis of ascaris by blocking acetylcholine at the myoneural junction; unable
to maintain their position in the host, live worms are expelled by normal peristalsis.
 Clinical Uses
 alternative for the treatment of ascariasis
 adverse effects and drug interaction
 Occasional mild -include nausea, vomiting, diarrhea, abdominal pain, dizziness, and
headache.
 Concomitant use of piperazine and chlorpromazine or pyrantel should be avoided.
4. Diethylcarbamazine Citrate
 MOA
 immobilizes microfilariae and alters their surface structure, making them more
susceptible to destruction by host defense mechanisms
 Clinical Use
 drug of choice for certain filarial infections, such as Wuchereria bancrofti, Brugia malayi
and Loa loa
 Adverse Reactions
 Reactions to the drug itself are mild and transient includes: headache, malaise, anorexia,
and weakness are frequent.
5. Ivermectin
 MOA
 disrupts nerve traffic and muscle function in target parasites
 Clinical Uses
 It is the drug of choice in onchocerciasis and strongyloidiasis
 quite useful in the treatment of other forms of filariasis, ascariasis,
 Adverse Reactions
 The Mazotti reaction occurs in patients treated for onchocerciasis. Principal symptoms are
pruritus, rash, fever, lymph node tenderness, and bone and joint pain

6. Praziquantel
 MOA
 Praziquantel appears to increase the permeability of trematode and cestode cell
membranes to calcium, resulting in paralysis, dislodgement, and death.
 Clinical Uses
 the drug of choice for all forms of schistosomiasis
 the drug of choice for tapeworms and other fluke infestations
 Adverse Reactions
 Transient headache and abdominal discomfort are the most frequent reactions
7. Niclosamide
 MOA
 Adult worms (but not ova) are rapidly killed, presumably due to inhibition of oxidative
phosphorylation or stimulation of ATPase activity.
 Clinical Uses
 a second-line drug for the treatment of most tapeworm infections
 can be used as an alternative drug in the treatment of Fasciolopsis buski
 Adverse Reactions, Contraindications, & Cautions
  Infrequent, mild, and transitory adverse events include nausea, vomiting, diarrhea, and
abdominal discomfort.
 The safety of the drug has not been established in pregnancy or for children younger than
2 years of age.
8. Metrifonate (Trichlorfon)
 Metrifonate is a safe, low-cost alternative drug for the treatment of Schistosoma haematobium
infections.
 It is not active against S. mansoni or S. japonicum.
 Adverse Reactions
 mild and transient cholinergic symptoms, including nausea and vomiting, diarrhea,
abdominal pain, bronchospasm, headache, sweating, fatigue, weakness, dizziness, and
vertigo
9.5 ANTIVIRAL AGENTS
Antiherpesvirus Agents
Acyclovir
 active only against members of the herpes virus family
 most effective against HSV-1 and HSV-2, but it has some activity against VZV and CMV
 MOA
 inhibits viral replication by suppressing synthesis of viral DNA
 Clinical use
 Oral acyclovir is effective for treatment of primary infection and recurrences of genital
and labial herpes.
 Intravenous acyclovir is the treatment of choice for herpes simplex encephalitis, neonatal
HSV infection and for severe primary, recurrent HSV genital and labial infections and for
those who cannot ingest oral pills
 Acyclovir ointment is used in the treatment of initial genital herpes but is not effective for
recurrent disease.
 Ophthalmic acyclovir formulations are effective in the treatment of herpes
keratoconjunctivitis

 Adverse effects
 Acyclovir is generally well tolerated. Nausea, diarrhea, and headache have occasionally
been reported.
 IV infusion may be associated with renal insufficiency or neurologic toxicity.
(Read about valacyclovir, famciclovir, drugs for CMV infection such as ganciclovir and
foscarnet, drugs for HBV, HCV, influenza)

Antiretroviral Agents
 The drugs in clinical use are classified as nucleoside reverse transcriptase inhibitors (NRTIs),
nonnucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase
inhibitors (NTRTIs), and protease inhibitors (PI).

 Single agents are seldom used to treat HIV infection. Instead, multidrug therapy is used to
counteract the rapid mutation rate of HIV and to minimize drug toxicity. Highly active
antiretroviral therapy (HAART) uses combinations of reverse transcriptase inhibitors and
protease inhibitors
1) Nucleoside Reverse transcriptase inhibitors
 MOA
 inhibit synthesis of HIV DNA primarily by causing premature termination of the growing
DNA strand
A. Zidovudine(AZT/ ZDV)
 Clinical use
 Zidovudine, in combination with one or more other antiretroviral agents, is approved for the
treatment of HIV infection in adults and children and for post exposure prophylaxis.
 It is used alone or in combination for the prevention of transmission to the baby by HIV-
infected pregnant women.
 Adverse reaction
 headache, nausea, vomiting, and anorexia
  The most common adverse effect is bone marrow suppression, resulting in macrocytic
anemia or neutropenia

 drug interaction
 Zidovudine should be used cautiously with any other agent that causes bone marrow
suppression, such as trimethoprim–sulfamethoxazole, dapsone, foscarnet, ganciclovir
 The coadministration of zidovudine with stavudine is contraindicated.
B. Stavudine(d4T)
 It is approved for the therapy of HIV infection as part of a multidrug regimen and is also used for
post exposure prophylaxis.
 The dosage of stavudine should be reduced in patients with renal insufficiency and low body
weight
 Adverse effects
 Peripheral neuropathy, Lactic acidosis,Hepatic Steatosis, Pancreatitis
 Zidovudine inhibits the phosphorylation of stavudine; thus, this combination should be avoided.
C. Lamivudine (3TC)
 active against HIV-1, HIV-2, and hepatitis B virus
 It is approved as part of a multidrug regimen for the therapy of HIV infection in adults and
children and has been used for HIV post exposure prophylaxis.
 Lamivudine is the best-tolerated NRTI. Its most common adverse effects include headache,
malaise, fatigue, and insomnia.
 Lamivudine should not be used in combination with zalcitabine, because they inhibit each other’s
activation by phosphorylation.
D. Didanosine (ddI)
 Absorption is decreased by food
 It is approved as part of a multidrug regimen for the therapy of HIV infection and is also used as
post exposure HIV prophylaxis
 Adverse effect
 most common adverse àdiarrhea
 Abdominal pain, nausea, vomiting, anorexia, and dose-related peripheral neuropathy may
occur
 The use of zalcitabine with didanosine is not recommended because that combination carries an
additive risk of peripheral neuropathy
 didanosine with stavudine àincreases the risk of pancreatitis, hepatotoxicity, and peripheral
neuropathy
 Stavudine should not be given with didanosine to pregnant women because of the increased risk
of metabolic acidosis
E. Abacavir (ABC)
 It is used as part of a multidrug regimen and is available in a fixed-dose combination with
zidovudine and lamivudine (Trizivir). It is also used for pos exposure HIV infection prophylaxis.
 Abacavir is associated with side effects such as anorexia, nausea, vomiting, malaise, headache,
and insomnia.
 A potentially fatal hypersensitivity reaction develops in approximately 5% of patients, usually
early in the course of treatment. Fever and rash are the most common symptoms of this reaction
 Abacavir undergoes extensive hepatic metabolism; therefore, patients with liver disease should be
monitored closely if this drug is given.

F. Emtricitabine (FTC)
 Like lamivudine, emtricitabine is active against HIV and hepatitis B virus (HBV)
 has a long intracellular half-life, and hence dosing can be done just once a day
 generally well tolerated
 The most common adverse effects are headache, diarrhea, nausea, and rash
G. Zalcitabine (ddc)
 It is used for the treatment of HIV infection in adults as part of a multidrug regimen.
 It may be less effective than the other nucleoside inhibitors and is used less frequently.
 Peripheral neuropathy occurs in up to 50% of patients taking zalcitabine.
 Zalcitabine should not be used in combination with didanosine, lamivudine, or stavudine.
2) Nucleotide Reverse Transcriptase Inhibitors
Tenofovir (TDF)
 the only available agent of its class
 It is converted by cellular enzymes to tenofovir diphosphate, which competes with
deoxyadenosine triphosphate (dATP) for access to reverse transcriptase and causes chain
termination following its incorporation.
 Tenofovir was approved as part of a combination therapy for HIV in adults who failed treatment
with other regimens; it appears to be effective against HIV strains that are resistant to NRTIs.
 Tenofovir is taken once daily and is generally well tolerated, perhaps because it produces less
mitochondrial toxicity than the NRTIs.
 Nausea, vomiting, flatulence, and diarrhea are the common ADR
3) Nonnucleoside Reverse Transcriptase Inhibitors (NNRTI)
 Include- nevirapine, efavirenz, delavirdine
 The NNRTIs bind directly to HIV-1 reverse transcriptase, resulting in blockade of RNA- and
DNA-dependent DNA polymerase.
 Unlike the NRTI agents, NNRTIs neither compete with nucleoside triphosphates nor require
phosphorylation to be active.
 NNRTI agents are all substrates for CYP3A4 and can act as inducers (nevirapine), inhibitors
(delavirdine), or mixed inducers and inhibitors (efavirenz).
A. EFAVIRENZ
 Pharmacokinetics
 the only NNRTI approved for once-daily dosing
 efavirenz should be taken on an empty stomach
 toxicity may increase owing to increased bioavailability after a high-fat meal,
 Efavirenz is approved for the therapy of HIV infection of adults and children and is also used for
post exposure prophylaxis.
 adverse effects
 central nervous systemàdizziness, drowsiness, insomnia, headache, confusion, amnesia,
agitation, delusions, depression, nightmares, euphoria
 these may occur in up to 50% of patients and may be severe.
 However, they tend to resolve after the first month of treatment.
 Rash, although rarely severe, is a common adverse effect of efavirenz.
 Efavirenz should be avoided in pregnant women, particularly in the first trimester.
 Efavirenz is both an inducer and an inhibitor of CYP3A4, thus inducing its own metabolism and
interacting with the metabolism of many other drugs
B. Nevirapine (NVP)
 Clinical use
 Nevirapine is approved for the treatment of HIV infection in adults and children as part of a
combination therapy.
 Adverse effects
 Rash occurs in approximately 17% of patients, most typically in the first 4–6 weeks of
therapy
 When initiating therapy, gradual dose escalation over 14 days is recommended to
decrease the incidence of rash.
 Hepatotoxicity
 Drug interaction
  Nevirapine is a moderate inducer of CYP3A system, resulting in decreased levels of
amprenavir, indinavir, lopinavir, saquinavir, efavirenz, and methadone if administered
concurrently.
5. PROTEASE INHIBITORS
 These drugs inhibit the activity of HIV protease, an enzyme required for the production of a
mature infectious virus
 The protease inhibitors are used in the multidrug therapy of HIV infection.
 All protease inhibitors can produce nausea, vomiting, diarrhea, and paresthesia.
 Protease inhibitors may also cause hypercholesterolemia and hypertriglyceridemia.
 Fat redistribution is common and can manifest as central fat accumulation, peripheral wasting,
buffalo hump at the base of the neck, breast enlargement, and/or lipomas.
 Protease inhibitors may increase the risk of bleeding in hemophiliacs.
 These drugs should be used with caution in patients with diabetes, lipid disorders, and hepatic
disease.
 All of the antiretroviral PIs are substrates and inhibitors of CYP3A4
 Ritonavir is the most potent inhibitor of CYP3A4
A. Lopinavir–Ritonavir
 In thisregimen, a low dose of ritonavir is used to inhibit therapid inactivation of lopinavir by
CYP3A4.
 In addition to improved patient compliance due to reduced pill burden, lopinavir/ritonavir is
generally well tolerated.
 Side effects, which are generally mild, include diarrhea, nausea and headache. Pancreatitis occurs
rarely.
 Increased dosage of lopinavir/ritonavir is recommended when co-administered with efavirenz or
nevirapine, which induce lopinavir metabolism.
 Other PIs
 Amprenavir, Nelfinavir, Atazanavir andFosamprenavir
 indinavir, saquinavir
 Information Sheet XX:- Cancer chemotherapy

Cancers account for 20-25% of deaths in clinical practices.Cancer refers to a malignant neoplasm or
new growth.
Cancer cells manifest ;
 uncontrolled proliferation,
 loss of function due to loss of capacity to differentiate,
 invasiveness, and the ability to metastasize
Cancer arises as a result of genetic changes in the cell, the main genetic changes being;
 inactivation of tumor suppressor genes and
 activation of oncogenes

There are three approaches for the management of cancer:

 Radiotherapy
 Surgery
 Chemotherapy
Chemotherapy is the use of drugs to inhibit or kill proliferating cancer cells, while leaving host cells
unharmed, or at least recoverable.
Tumor cells can be classified as ;
 Proliferating cells and
 Non-proliferating cells.
Most anticancer drugs are antiproliferative, and hence affect rapidly growing dividing normal cells.
Most chemotherapy drugs act by damaging DNA or inhibiting DNA synthesis.
Anticancer drugs are broadly classified into two:
 Cytotoxic drugs and
 Hormones
Cytotoxic drugs are further classified into:
1. Alkylating agents and related compounds;
Alkylating agents act via a reactive alkyl (RCH2- CH2 + -) group that reacts to form covalent bonds
with nucleic acids.
There follows either cross-linking of the two strands of DNA, preventing replication, or DNA
breakage.
All alkylating agents are kill rapidly proliferating cells, also kill non proliferating cells
Examples: Mechlorethamine - the first drug used in the treatment of cancer
Examples: Cyclophosphamide - most widely used in clinical therapy for treatment of cancer at
present.
Others, lomustine, thiotepa, cisplatin

2. . Antimetabolites
Antimetabolites are analogues of normal metabolites and act by competition, replacing the natural
metabolite and then subverting cellular processes.
Examples of antimetabolites include:
 Methotrexate , 5-Fluorouracil, Cytarabine, 6-Mercaptopurine
3. Natural Products
This group is determined by the source of the drug
The major classes of natural products include
 Antibiotics
 Vinca alkaloids
 Enzymes
Antibiotics (e.g. Doxorubucin, bleomycin, dactinomycin).
Vinca (plant) alkaloids
 Vincristine and vinblastine are alkaloids
 derived from the periwinkle plant.
 Both can cause bone marrow suppression and neurotoxicity

Hormones and antagonists

The growth of some cancers is hormone dependent. Growth of such cancers can be inhibited by :
 Surgical removal of hormone glands
 Administration of hormones or
 Antihormones is preferred
Hormones and their antagonists are used in hormone sensitive tumors.

 Glucocorticoids for lymphomas,

 Oestrogens for prostatic cancer,
 Tamoxifen for breast tumors.
Why Don’t We Cure Cancer With Chemotherapy?

 Toxic side effects limit dose

 Cancer cells show drug resistance- innate drug resistance, or acquired resistance during treatment
Toxic Effects of Chemotherapy
 Generic side effects are damage to rapidly dividing normal cells
- bone marrow, gut mucosa, hair follicles
 Nausea due to triggering CNS vomiting centres
 Toxicity increases with dose of drug used
Principles of combination therapies

In order to enhance curative effect, to decrease the toxicity and to reduce the drug resistance,
combination therapies are often used in the treatment.
Advantages of drug combinations:
 They provide maximal cell kill within the range of tolerated toxicity.
 They may slow or prevent the development of resistance.
The principles are:
1. Combinations of antineoplastic drugs with other therapies
Examples: chemotherapy plus operation,
chemotherapy plus radiotherapy
2. Combination of low-toxic drugs with hightoxic ones
3. Use right dose e.t.c.
Information Sheet XXI:-Pregnancy drug category and classification
 The clinical challenge is to provide effective treatment for the mother while avoiding harm to
the fetus or nursing infant.
 Some drugs are used to treat pregnancy-related conditions, such as nausea, constipation, and
preeclampsia.
 Some are used to treat chronic disorders, such as hypertension, diabetes, and epilepsy.
 The prescriber is obliged to balance risks versus benefits,
 The health of the fetus depends on the health of the mother. Hence, conditions that threaten
the mother's health must be addressed—for the sake of the baby as well as the mother.
Physiologic Changes during Pregnancy and Their Impact on Drug Disposition and Dosing
 By the third trimester, renal blood flow is doubled, causing a large increase in glomerular
filtration rate. As a result, there is accelerated clearance of drugs that are eliminated by
glomerular filtration. Elimination of lithium, for example, is increased by 100%. To
compensate for accelerated excretion, dosage must be increased.
 Tone and motility of the bowel decrease in pregnancy, causing intestinal transit time to
increase. Because of prolonged transit, there is more time for drugs to be absorbed. In theory,
this could increase levels of drugs whose absorption is normally poor. Similarly, there is more
time for reabsorption of drugs that undergo enterohepatic recirculation, and hence effects of
these drugs could be prolonged. In both cases, a reduction in dosage might be needed.
Placental Drug Transfer
Essentially all drugs can cross the placenta, although some cross more readily than others. The
factors that determine drug passage across the membranes of the placenta are the same factors
that determine drug passage across all other membranes. Accordingly, drugs that are lipid soluble
cross the placenta easily, whereas drugs that are ionized, highly polar, or protein bound cross with
difficulty. Nonetheless, for practical purposes, the clinician should assume that any drug taken
during pregnancy will reach the fetus.
Adverse Reactions during Pregnancy
 Regular use of dependence-producing drugs (eg, heroin, barbiturates, alcohol) during
pregnancy can result in the birth of a drug-dependent infant.
Drug Therapy during Pregnancy: Teratogenesis
The term Teratogenesis is derived from teras, the Greek word for monster. Translated literally,
Teratogenesis means to produce a monster. Consistent with this derivation, we usually think of birth
defects in terms of gross malformations, such as cleft palate, clubfoot, and hydrocephalus. However,
birth defects are not limited to distortions of gross anatomy; they also include neurobehavioral and
metabolic anomalies.
Teratogenesis and Stage of Development
 Fetal sensitivity to teratogens changes during development, and hence the effect of a
teratogen is highly dependent upon when the drug is given.
 Development occurs in three major stages: the preimplantation/ presomite period
(conception through week 2), the embryonic period (weeks 3 through 8), and the fetal
period (week 9 through term).
 During the preimplantation/ presomite period, teratogens act in an “all-or-nothing”
fashion. That is, if the dose is sufficiently high, the result is death of the conceptus.
Conversely, if the dose is sub lethal, the conceptus is likely to recover fully.
 Gross malformations are produced by exposure to teratogens during the embryonic period
(roughly the first trimester). This is the time when the basic shape of internal organs and
other structures is being established. Hence, it is not surprising that interference at this
stage results in conspicuous anatomic distortions. Because the fetus is especially
vulnerable during the embryonic period, expectant mothers must take special care to avoid
exposure to teratogens during this time.
 Teratogen exposure during the fetal period (i.e., the second and third trimesters) usually
disrupts function rather than gross anatomy. Of the developmental processes that occur in
the fetal period, growth and development of the brain are especially important. Disruption
of brain development can result in learning deficits and behavioral abnormalities.
Pregnancy Risk Categories
 According to this system, drugs can be put into one of five risk categories: A, B, C, D, and X.
 Drugs in Risk Category A are the least dangerous; controlled studies have been done in
pregnant women and have failed to demonstrate a risk of fetal harm.
 In contrast, drugs in Category X are the most dangerous; these drugs are known to cause
human fetal harm, and their risk to the fetus outweighs any possible therapeutic benefit.
 Drugs in Categories B, C, and D are progressively more dangerous than drugs in Category A
and less dangerous than drugs in Category X.
Drug Therapy during Breast-Feeding
 Drugs taken by lactating women can be excreted in breast milk. If drug concentrations in milk
are high enough, a pharmacologic effect can occur in the infant, raising the possibility of
harm.
  Although nearly all drugs can enter breast milk, the extent of entry varies greatly. The factors
that determine entry into breast milk are the same factors that determine passage of drugs
across membranes.
 Drugs that are lipid soluble enter breast milk readily, whereas drugs that are ionized, highly
polar, or protein bound tend to be excluded.
 When drugs must be used, steps should be taken to minimize risk. These include:-
 Dosing immediately after breast-feeding (to minimize drug concentrations in milk at the next
feeding)
 Avoiding drugs that have a long half-life
 Avoiding sustained-release formulations
 Choosing drugs that tend to be excluded from milk
 Choosing drugs that are least likely to affect the infant
 Avoiding drugs that are known to be hazardous
 Using the lowest effective dosage for the shortest possible time
Information Sheet XXII:- Describing fluids and minerals
 Electrolytes are used to correct disturbances in fluid and electrolyte homoeostasis or acid-base
balance and to re-establish osmotic equilibrium of specific ions.
3.1Oral Electrolytes

Ammonium Chloride

 Ammonium chloride may be used as a systemic acidifying agent for the treatment of
metabolic alkalosis or to acidify the urine.
 Ammonium salts are no longer used as diuretics, but are sometimes used to maintain an acid
pH of urine.
 This may be useful as an adjunct in treating urinary tract infections or for increasing urinary
excretion of drugs after an overdose.
 Other conditions that have been treated with ammonium chloride include hypochloremia with
severe metabolic alkalosis, Meniere's disease, and premenstrual syndrome.
 Side effects: ammonium salts are irritant to the gastric mucosa and may produce nausea and
vomiting.

 Dose and Administration:

 The usual dose is one gram three times daily for up to 6 days.
  To maintain an acidic pH of the urine, ammonium chloride 1 to 2 grams is administered
every 4 to 6 hours for no longer than six days.
 For forced acid diuresis to aid in the excretion of basic drugs, such as amphetamines, 4
grams every two hours may be given.
Calcium Gluconate
 Indications: as a source of calcium ion for treating calcium depletion occurring in conditions
such as chronic hypoparathyroidism, pseudo-hypoparathyroidism, osteomalcia, rickets,
chronic renal failure, and hypocalcaemia secondary to the administration of anticonvulsant
medications.It is also used as a dietary supplemental therapy for persons who may not get
enough calcium in their regular diet.
 Drug interactions: calcitonin, calcium channel blocking agents such as verapamil, calcium
or magnesium containing medications, estrogens, milk and milk products phenytoin, oral
tetracyclines, vitamin D.
 Contraindications: Primary or secondary hypercalcemia, hypercalciuria or calcium renal
calculi, sarcoidosis.
 Side effects: acute hypercalcemic syndrome (drowsiness, continuing nausea, and vomiting,
weakness), calcific renal calculi.
Oral Rehydration Salts (ORS)
 Indications: For the prevention and treatment of mild to moderate dehydration, particularly
dehydration from acute diarrhea of any cause, in all age group.
 Treatment of diarrhea: In diarrhoea with moderate dehydration: 75ml of ORS solution per
Kg of body weight in 4—6 hours. Repeat if dehydration persists.

Potassium chloride
 Uses, Dosage, and Preparations.
 Oral potassium chloride may be used for both prevention and treatment of potassium
deficiency. Dosages for prevention range from 16 to 24 mEq/day. Dosages for deficiency
range from 40 to 100 mEq/day.
 Oral potassium chloride is available in solution and in solid formulations: immediaterelease
tablets, sustained-release tablets, effervescent tablets, and powders. The sustainedrelease
tablets (eg, K-Dur, Micro-K) are preferred. Why? Because they are more convenient and
better tolerated than the other formulations, and hence offer the best chance of patient
adherence.
 Adverse Effects.
  Potassium chloride irritates the GI tract, frequently causing abdominal discomfort, nausea,
vomiting, and diarrhea. With the exception of the sustained-release tablets, solid formulations
can produce high local concentrations of potassium, resulting in severe intestinal injury
(ulcerative lesions, bleeding, and perforation). To minimize GI effects, oral potassium
chloride should be taken with meals or a full glass of water. If symptoms of irritation occur,
administration should be discontinued. Rarely, oral potassium chloride produces
hyperkalemia. This dangerous development is much more likely with IV therapy.

 Drug interactions: special hazard if given with drugs liable to raise plasma potassium
concentration such as potassium-sparing diuretics, angiotension converting enzyme inhibitors,
or cyclosporins.
 Contraindications: severe renal impairment, plasma potassium concentrations above 5 m
mol/liter.
Sodium Bicarbonate
 Indications: Management of metabolic acidosis; gastric hyperacidity; as an alkalinization
agent for the urine; treatment of hyperkalemia; management of overdose of certain drugs,
including tricyclic antidepressants and aspirin
 Contraindications: metabolic or respiratory alkalosis, in patients with hypocalcemia in
whom alkalosis may induce tetany, in patients with excessive chloride loss from vomiting or
continuous GI suctioning, and in patients at risk of developing diuretic–induced
hypochloremic alkalosis. The drug should not be used orally as an antidote in the treatment of
acute ingestion of strong mineral acids.
 Side effects: stomach cramps, belching, and flatulence, alkalosis on prolonged use.
Sodium Chloride
 Indications: used for the treatment of extracellular volume depletion and in the prevention or
treatment of deficiencies of sodium and chloride ions and in the prevention of muscle cramps
and heat prostration resulting from excessive perspiration during exposure to high
temperature.
 Contraindications: in patients with conditions in which administration of sodium and
chloride is detrimental.
 Side effects: administration of large doses may give rise to sodium accumulation and
oedema, nausea, vomiting, diarrhoea, abdominal cramps, thirst, reduced salivation and
lachrymation, sweating, fever, tachycardia, hypertension, renal failure.
3.2 Pareteral electrolytes
  Solutions of electrolytes are given intravenously, to meet normal fluid and electrolyte
requirements or to replenish substantial deficits or continuing losses, when the patient is
nauseated or vomiting and is unable to take adequate amounts by mouth.Sodium, potassium,
chloride, magnesium, phosphate, and water depletion can occur singly and in combination
with or without disturbances of acid - base balance.
Calcium Chloride
 Indications: Cardiac resuscitation when epinephrine fails to improve myocardial
contractions, cardiac disturbances of hyperkalemia, hypocalcemia, or calcium channel
blocking agent toxicity; emergent treatment of hypocalcemic tetany, treatment of
hypermagnesemia.
 Contraindications: In ventricular fibrillation during cardiac resuscitation, hypercalcemia,
and in patients with risk of digitalis toxicity, renal or cardiac disease; not recommended in
treatment of asystole and electromechanical dissociation; patients with suspected digoxin
toxicity.
 Drug interactions: Thiazide diuretics, digoxin, calcium channel blockers (eg. verapamil)
 Side effects: Bradycardia, cardiac calcemia, hypercalciuria, hypotension, lethargy, mania,
muscle weakness, syncope, tissue necrosis, vasodilation, ventricular fibrillation.
Calcium gluconate (levulinate)
 Indications: in the treatment of hypocalcaemia in conditions that require a rapid increase in
serum calcium - ion concentration, such as neonatal hypocalcaemia tetany; tetany due to
parathyroid deficiency.
 It is also indicated to decrease or reverse the cardiac depressant effect of hyperkalemia on
electrocardiographic (ECG) function and as an aid in the treatment of CNS depression due to
over dosage of magnesium sulfate.
 Drug interactions: calcitonin, verapamil, calcium and magnesium containing medications,
digitalis glycoside, magnesium sulfate, milk and milk products, phenytoin, oral tetracyclines,
vitamin D.
 Contraindications: digitalis toxicity, primary or secondary hypercalcemia, hypercalciuria,
calcium renal calculi, sarcoidosis.
 Side effects: hypotension (dizziness), flushing and/or sensation of warmth or heat, irregular
heartbeat; nausea or vomiting, skin redness, rash, pain, or burning at injection site, sweating,
tingling sensation.

Dextrose
 Indications: for the treatment of hypoglycemia due to insulin excess or other causes.
  Contraindication: anuria.
 Side effects: rapid administration may cause local pain; hyperglycemia and glycosuria, which
if undetected and untreated can lead to dehydration, coma, and death.
Dextrose in Normal Saline
 Indications: In states of sodium depletion like vomiting and diarrhoea due to gastroenteritis,
Diabetic keto acidosis, Paralytic ileus, salt losing bowel disease, Renal salt wasting diseases.
 Cautions: In volume overload states.
Lactated Ringer's injection (Hartmann's solution)
 Indications: for replacement of electrolytes and water losses in severe dehydration.
 Contraindications: severe liver and renal damage.
Potassium chloride
 Indications: treatment of potassium depletion or hypokalaemia, with or without metabolic
alkalosis, in chronic digitalis intoxication, and in patients with hypokalaemia familiar periodic
paralysis.
 Drug interactions: potassium sparing diuretics, angiotension converting enzyme inhibitors
cyclosporins, digitalis glycoside, parenteral calcium salts, laxatives.
 Contraindications: hyperkalemia.
 Side effects: rapid infusion toxic to heart.
Sodium chloride
 Indications: used for extracellular fluid replacement and in the management of metabolic
alkalosis in the presence of fluid loss and mild sodium depletion.
 Hypertonic (3%, 5%) sodium chloride injection is used in the management of severe
sodium chloride depletion when rapid electrolyte restoration is essential.
 Contraindications: in patients with conditions in which administration of sodium and
chloride is detrimental. Sodium chloride 3% and 5% injections are also contraindicated in the
presence of increased, normal, or only slightly decreased serum electrolyte concentrations.
 Side effects: venous thrombosis or phlebitis, extravasation, hypervolemia, hypernatremia (on
excessive administration).
3.3 Enteral Nutrition
 Enteral nutrition includes feeding by mouth, by nasogastric or nasoenteric tube, or directly
into a gastrostomy or other enterostomy.
 It may be supplemental, if normal food intake is possible but inadequate, or total.
 Individual patients vary in their requirements according to age, size, and metabolic state, but a
diet supplying 2000 to 3000 kcal of energy and 10-15g of nitrogen (as 60 to 90 g of protein)
 in 2 to 3 litres of fluid is fairly typical; because absorption from the gastrointestinal tract is
incomplete requirements are higher than by parenteral route.
 Preparations containing whole protein (often derived from milk or soya) are generally
preferred.
 Although preferred to parenteral nutrition, enteral feeding is not without complications.
Patients may be at risk of oesophagitis, aspiration, and regurgitation as a result of the tube
insertion; other potential problems include diarrhea, nausea and vomiting, gastric retention,
hyperglycaemia, fluid and electrolyte disturbances, and microbial contamination of the feed
regimen.
1. Calcium Caseinate
2. Soya-based non-milk preparations
4. Vitamins
 Vitamins are used for the prevention and treatment of specific deficiency states or when the
diet is known to be inadequate. Large doses of vitamins (megavitamin therapy) have been
proposed for a variety of disorders, but adequate evidence of their value is lacking. Excessive
intakes of most water - soluble vitamins have little effects due to their rapid excretion in
urine, but excessive intakes of fat - soluble vitamins accumulate in the body and are
potentially dangerous.

4.1 Vitamins, single

Ascorbic Acid (Vitamin C)
 Indications: for prophylaxis and treatment of vitamin C (ascorbic acid) deficiency states
which lead to scurvey.
 Cautions: caution should be necessary not to take large amount during pregnancy.Caution is
required in those with sensitivity to ascorbic acid.
 Drug interactions: cellulose sodium phosphate, deferoxamine, disulfiram and vitamin B12
(with large doses of vitamin C).
 Side effect: dizziness or faintness, kidney stones (oxalate)
Calciferol (Ergocalciferol/Vitamin D2)
 Indications: used in the treatment of chronic hypocalcemia, hypophosphatemia, rickets and
osteodystrophy associated with various medical conditions including chronic renal failure,
familial hypophosphatemia, and hypoparathyroidism (post surgical or idiopathic or
 pseudohypoparathyroidism); for prevention and treatment of vitamin D deficiency states; and
to treat anticonvulsant induced rickets & osteomalacia.
 Ergocalciferol may not be the preferred agent in the treatment of familial hypophosphatemia
or hypoparathyroidism because the large doses needed are associated with a risk of overdose
and hypercalcemia, and ergocalciferol not usually preferred in patients with renal failure since
these patients have impaired ability to synthesize calcitriol from colecalciferol and
ergocalciferol.
 Cautions: ergocalciferol should be administered with extreme caution, if at all, to patients
with impaired renal function and with extreme caution in patients with heart disease, renal
stones, or arteriosclerosis; large doses of VitaminD analogs should not be administered to
nursing women; take care to ensure correct dose in infants and pregnant.
 Drug interactions: antacids (magnesium containing), in high doses of calcium containing
preparations and diuretics (thiazide), vitamin D analogs.
 Contraindications: hypercalcemia, hypervitaminosis D, Renal Osteodystrophy with
hyperphosphatemia, metastatic calcification, hypersensitivity to effects of Vitamin D.
 Side effects: symptoms of over dosage include anorexia, lassitude, nausea and vomiting,
diarrhoea, weight loss, polyuria, sweating, headache, thirst, vertigo, and raised concentrations
of calcium and phosphate in plasma and urine.
.

Folic Acid
 Indications: for prevention and treatment of folic acid deficiency states, including
megaloblastic anemia and in anemias of nutritional origin, pregnancy, infancy, or childhood;
folic acid is being used in the diagnosis of folate deficiency.
 Cautions: women receiving antiepileptic therapy need counseling before starting folic acid.
 Drug interactions: cyanocobalamin; agents causing folic acid deficiency with long term use
(phenytoin, oral contraceptives, isoniazid, NSAIDs in high doses and glucocorticosteroids);
antifolate agents (trimethoprim, pyrimethamine and methotrexate)
 Contraindications: should never be given without vitamin B12 in undiagnosed
megalolblastic anaemia or other vitamin B12 deficiency states because risk of precipitating
subacute combined degeneration of the spinal cord; folate-dependent malignant disease, folic
acid injection that contains benzyl alcohol as a preservative should not be used in new born
and immature infants.
  Side effects: allergic reaction, specifically; bronchospasm; erythema; fever; general malaise;
skin rash; or itching.
Nicotinamide
 Indications: nicotinamide and nicotinic acid (niacin) are used to prevent niacin deficiency
and to treat pellagra. Niacin (but not nicotinamide) is also indicated in the treatment of
hyperlipidemia.
 Drug interactions: niacin reportedly potentiates the hypotensive effect of ganglionic
blocking drugs.
 Contraindications: niacin and nicotinamide are contraindicated in patients with, active
peptic ulcer, or hypersensitivity to the drugs. Niacin is also contraindicated in patients with
arterial hemorrhaging or severe hypotension
 Side effects: anaphylactic reaction with injection only, hepatotoxicity or cholestasis with high
doses of extended – release niacin.

Pyridoxine Hydrochloride (Vitamin B6)

 Indications: for prevention and treatment of pyridoxine deficiency states that may occur as a
result of inadequate nutrition or intestinal malabsorption.
 It is also used as antidote in cyclosporin poisoning and to terminate seizures and prevent
neuropathy associated with isoniazid poisoning.
 Drug interactions: levodopa, cycloserine, isoniazid, penicillamines, hydralazine.
 Side effects: sensory neuropathy in prolonged use .
Thiamine Hydrochloride (Vitamin B1)
 Indications: for prevention and treatment of thiamine deficiency states that may occur as a
result of inadequate nutrition or intestinal malabsorption.It is used for temporary metabolic
correction of genetic enzyme deficiency diseases such as subacute nercotizing
encephalomyelopathy (SNE, Leigh’s disease), maple syrup urine disease (branched-chain
aminoacidopathy), and lactic acidosis associated with pyruvate carboxylase deficiency and
hyperalaninemia.
 Side effects: anaphylactic reaction (coughing, difficulty in swallowing; hives; itching of the
skin, swelling of face, lips or eyelids, or wheezing or difficulty in breathing).
Vitamin A
  Indications: for prevention or treatment of vitamin A deficiency states, causing
keratomalacia, xerophthalmia and nyctalopia (night blindness). This may occur as a result of
inadequate nutrition or intestinal malabsorption.
 Drug interactions: calcium supplements, isotretinoin, tetracycline, vitamin E,
cholestyramine, colestipol, mineral oil, oral neomycin.
 Contraindications: hypervitaminosis A
 Side effects: symptoms of acute overdose - bleeding from gums or sore mouth; bulging soft
spot on head-in babies, confusion or unusual excitement; diarrhoea, dizziness, or drowsiness,
double vision, severe headache, severe irritability, peeling of skin, especially on lips and
palms; severe vomiting
Vitamin E (Tocopherol)
 Indications: Dietary supplement
 Interactions: warfarine, tipranavir
 Contraindications: hypersensitivity to Vitamin E or any component of the formulation.
 Side effects: diarrhoea and abdominal pain with doses more than 1 g daily.
4.2 Vitamins, Combinations
Vitamin B complex preparations

 The most important B group vitamins appear to be thiamine (vitamin B1), riboflavin (vitamin
B2), pyridoxine (vitamin B6), Pantothenic acid (vitamin B5), nicotinic acid/nicotinamide
(niacin, vitamin B3, and niacinamide), cyanocobalamin (vitamin B12) and folic acid/folate.
Indications: supplement for use in the wasting syndrome in chronic renal failure, uremia, impaired
metabolic functions of the kidney, dialysis; labeled for OTC use as a dietary supplement.
LO2. Minimize potential risk to the safe administration of medications

Information Sheet I:- Checking expiate date

Expiry date: The date after which the manufacturer will not guarantee the safety and quality of the
medicine, despite optimum storage conditions. The table below gives guidance on the interpretation
of the different expiry date formats used by manufacturers of medicines.

 All Nurses must review the expiry date on all medicines prior to administering them to patients.
 Expired medicines, and opened oral liquid medicines with no date of opening stated, must be
given to the Clinical Director for disposal.
 The opening of a mutli-use vial of local anaesthetic must be dated and disposed of after 3 days

Information Sheet II:- Medication chart

Medication charts help to standardise medication management and can increase medication safety.
The charts are based on the best evidence available at the time of development. Healthcare
professionals are advised to use clinical discretion and consider the circumstances for individual
patients when using the charts for patient medication management in acute care settings.

The national medication charts are used in inpatient settings to record the medicines prescribed and
administered to a patient, along with any allergies and adverse reactions from medicines.
Information Sheet III:- Common contraindications and adverse reactions

Pharmaceutical drug interaction

Eg. Diazepam if added in infusion fluid, there will be a precipitate formation.→ loss of therapeutic effect.
2. Pharmacokinetic drug interaction
 Is an interaction, which occurs during the process of absorbtion, distribution, metabolism
or excretion of drugs.
i. Absorbtion: Tetracycline +Calcium → decreased absorbtion of Tetracycline.
ii. Distribution:Sulphonamides + Salicylates→Sulphonamide toxicity. (Because sulphonamides
will be displaced from their binding site.)
iii. Metabolism:
 Iduction: Warfarine + Barbiturate (enzyme inducer) → decrease anticoagulation.
 Inhibition:Warfarine + metrindazole (enzyme inhibitor) → heamorrhage
iv. Excretion: Penicillin +probencid →increase the duration of action of penicillin (both are
excreted through tubular secretion.)
1. Pharmacodynamic Interaction
i. Additive effect: - combined effect of the two drugs having the same action is equal to the
sum of their individual effects.E.g Ephedrin + Aminophyillin
ii. Potentiation: - the effect of one drug is increased by the other which does not have the same
action.E.gAmoxycillin + Clavulenicacid,Caffiene + Ergotamine
iii. Supra-aditive effect (synergism):- combined effect of two drugs having same action is
greater than the sum of their individual effect. E.g trimethoprim + sulphemethoxazole
Drug toxicity and management of drug poisoning
 The drug that produce useful therapeutic effect may also produce unwanted or toxic effects
An adverse drug reaction is defined or any resposnse to a drug that is noxious and unintended and that occurs at
doses used in man for prohylaxis, diagnosis or therapy.
 Adverse effects may develop promptly or only after prolonged medication or even after stop
of the drug.
 The adverse effects are
Side effects: -
 Are pharmacological effects produced with therapeutic dose of the drug.
 Undesirable,but often inseparable and unavoidable,extension of pharmacological effects of
the drug E.g Dryness of the mouth with Atropine
Untoward effects: -
 Develop with therapeutic dose of a drug.
 They are undesirable and if very severe, may necessitate the cessation of treatment.
E.g Potasium loss (hypo kalemia) with diuretics like Frusomide.
Allergic Reaction-
 Most drugs when administered at therapeutic doses are capable of causing allergic
(hypersensitive) reactions.
 An altered response to a drug resulting from aprevioussentizing exposure & immunological
mechanism
 These reactions may be mild or severe.
Idiosyncratic reactions: -
 Indicate one’s peculiar response to drugs.
 Many idiosyncratic reactions have been found to be genetically determined.
E.g premaquine, Deprosone, Sulfonamides Cause haemolysis in patients with G-6pd enzyme
defficiency
 Teratogenic effect: -
 Some drugs given in the first three months of pregnancy may cause congenital abnormalities
and are said to be teratogenic.
 The most sensitive period of teratogenesis during pregnancy is 3-10 weeks of pregnancy i.e
the time of organogenesis.
 Teratogenesityrecevices a great attention after thalidomide disaster in 1959-61 in West
Germany leading to large number of cases of phocomelia (seal limbs).
 At present, it is mandatory to test the teratogencity of any new drug in animals before
introduction in therapy.
NB. It is advisable not to use any drug during pregnancy unless definitely indicated.

Information Sheet IV:- Checking allergies

An allergy test is an exam performed by a trained allergy specialist to determine whether your body
has an allergic reaction to a known substance. The exam can be in the form of a blood or skin test
(prick/patch).

Your immune system is your body’s natural defense. Allergies occur when your immune system
overreacts to something in your environment. For example, pollen, which is normally harmless, can
cause the immune system to overreact. This overreaction can lead to:

 a runny nose
 sneezing
 blocked sinuses
 itchy, watery eyes
 coughing or wheezing
Types of allergens
Allergens are substances that can cause an allergic reaction. There are three primary types of
allergens:
 Inhaled allergens affect the body when they come in contact with the lungs or membranes of the
nostrils or throat. Pollen is the most common inhaled allergen.
 Ingested allergens are present in certain foods, such as peanuts, soy, and seafood.
 Contact allergens must come in contact with the skin to produce a reaction. An example of a
reaction from a contact allergen is the rash and itching caused by poison ivy.
Allergy tests involve exposing you to a very small amount of a particular allergen and recording the
reaction.

Skin tests
Skin tests are used to identify numerous potential allergens. This includes airborne, food-related, and
contact allergens. The three types of skin tests are scratch, intradermal, and patch tests.
Your doctor will typically try a scratch test first. During this test, an allergen is placed in liquid, then
that liquid is placed on a section of your skin with a special tool that lightly punctures the allergen
into your skin’s surface.
You’ll be closely monitored to see how your skin reacts to the foreign substance. If there’s localized
redness, swelling, elevation, or itchiness of the skin over the test site, you’re allergic to that specific
allergen.
If the scratch test is inconclusive, your doctor may order an intradermal skin test. This test requires
injecting a tiny amount of allergen into the dermis layer of your skin. Again, your doctor will monitor
your reaction.
Another form of skin test is the patch test (T.R.U.E. TESTTrusted Source). This involves using
adhesive patches loaded with suspected allergens and placing these patches on your skin. Patch
testing is performed to evaluate for cases of allergic contact dermatitis.
The patches will remain on your body after you leave your doctor’s office. The patches are then
reviewed at 48 hours after application and again at 72 to 96 hours after application.

Blood tests

If there’s a chance you’ll have a severe allergic reaction to a skin test or cannot perform a skin test,
your doctor may order a blood test.
For this test, a blood sample is tested in a laboratory for the presence of antibodies that fight specific
allergens. Called ImmunoCAP, this test is very successful in detecting IgE antibodies to major
allergens.

LO3. Preparing medications

Information Sheet I:- Common terminology associated with drug, fluid and
electrolytes

1. Prescription:- is a written direction for the preparation and administration

of a drug
2. Pharmacist:- a person licensed to prepare and dispense drug
 3. Clinical pharmacist: - is a specialist who often guides the physician in
prescribing drugs.
4. Pharmacy: - is the art of preparing, compounding and dispensing drugs.
- also refers to the place where drugs are prepared
4. Pharmacy assistant: - is a member of the health feam who administers drugs
to clients.
5. Physician: - is a person legally responsible for prescribing medications.
- He conveys the medications plans to others by an order called
prescriptions.
6. Patient: - is a person who is waiting for or undergoing medical treatment and
care.
7. Client: - is a person who engages the advice or service of another
- The service or advice is provided by a qualified person
8. Consumer: - is an individual, a group of people or a community that uses a
service or commodity
e.g. – If you uses electricity in home is a consumer of electricity.
- If you uses health care products or services are the consumers of health
care systems.
 So, in some instances clients in the preferred term other than pts and
consumers.
9.Pharmacopia:-is a book containing a list of products used in medicine
(medication)
 It is describes the following characteristics
- Source
- Physical & chemical properties
- Chemical tests for determining identity and purity
- Method of storage
- Normal dosage
- Formulas for certain mixtures
 It is revised every five years to contain newly developed and essential
drugs.
Harmful drugs that have better substitutes are omitted in the new edition.
E.g. - united stated pharmacopeia
- British pharmacopeia
 - Canada pharmacopeia
 Drugs contained in pharmacopeia are called official drugs.
10. Formulary: - is a collection of formulas and prescriptions.
e.g. Ethiopia formulary
- Canadan formulary
- United states formulary etc.
11. Nurse: - is a person who performs the following roles
 Care provider  Change agent
 Teacher  Leader
 Communicator/helper  Manager
 Counselor  Researcher
 Client advocate
Abbreviation of NURSE
N= nobel
U= unselfish
R= Reliable
S= Smart
E= Energetic
12. Nurse Generalist
That issues
 General nursing
practices
 Medical – surgical
nursing
 Gernotologic nursing
 Pediatric nursing
 Prenatal nursing
 College health nursing
 Psychiatric nursing
(mental)
 Home health nursing
 Pharmacology nursing
 Some times said to be
RN
13. Nurse clinician:-
 Provides bed side or direct care in a specially area
 They may or may not have advanced educational preparation
14. Nurse practitioner
 Gives the nurses basic care giving role
 The provision of primary care

15. Nurse specialist

 Has advanced knowledge and skills in a particular area of nursing
 An educational prerequisite is a master’s degree in nursing
e.g. medical surgical nursing
- Gernotologic nursing
- Community health nursing
- Psychiatric and mental health nursing
 The nurse specialist practice in
- Hospitals
- Communities
 In the hospitals, the nurse specialist gives
- Direct client care
- Advise other nurses
- Coordinate nursing activities
 So, after the pharmacists prepares the medication, the nurse or OR
administers the medication to the pt.
 The nurses are responsible to control the substance that found hospital by
the means of
- Locked drawer
- Cup board
Medication cart

Information Sheet II:- Medication preparation

Drug preparation
 Drugs are available in many forms (preparations)
 The form in which the drug is prepared may determine the route of
administration
 Some drugs may prepare in only one form to be administered by a certain
route.
Types of drug preparation
1. Aqueous solutions: - one or more drugs dissolved in water.
2. Aqueous suspension:- one or more drugs finely divided in a liquid such
as water
3. Transdermal patch: - a semi permeable membrane shaped in the form
of disk or patch that contains a drug to the absorbed through the skin
over a lengthy period of time.
4. Tincture:- An alcoholic or water and alcohol solutions prepared from
drugs derived from plants
5. Spirit: - a concentrated alcoholic solution of alcohol used as a vehicle for
medicinal agents.
6. Elixir:- a sweetened and aromatic solution of alcohol used as a vehicle for
medicinal agents
7. Extract:- a concentrated form of a drug made from a vegetable or
animals
8. Fluid extract: - an alcoholic solution of a drug from a vegetable source.
- the most concentrated of all fluid preparations
9. Aerosol spray or foam: - a liquid, powder, or foam deposited in a thin
layer on the skin by air pressure
10. Liniment: - an oily liquid used on the skin
11. Lozenges (troche):- a flat, round or oval preparation that dissolves and
releases a drug when held in the mouth
12. Cream: - a non – greasy, semisolid preparation used on the skin
13. Gel or jelly: - a clear or translucent semisolid that liquidities when applied
on the skin
14. Ointment: - a semisolid preparation of one or more drugs used for
application to the skin and mucous membrane
 15. Paste: - a preparation like an ointment, but thicker and stiffer, that
penetrates the skin less than an ointment.
16. Pill: - one or more drugs mixed with a cohesive material in oval, round or
flattened shapes.
17. Powder: - a finely ground drug or drugs
- Some are used internally other externally
18. Suppository: - one or several drugs mixed with a firm base such as gelatin
and shaped for insertion in to the body.
- The base dissolves gradually at body T o, releasing the drugs.
19. Tablet: - a powdered drug compressed in to hard small disk
- Some are readily broken along a scored line ‘
- Others are enteric coated to prevent them from dissolving in the
stomach.
20. Capsule: - a gelatinous container to hold a drug in powder liquid or oil form.
21. Syrup: - an aqueous solution of sugar often used to disguise un pleasant
tasting drugs.
22. Suspension: - is finely divided, un dissolved parties use in a liquid medium
should be shaken before use.

Information Sheet:- Forms of medication

Drugs are classified from different perspectives. They are classified by:-
 Body system
 Clinical indication
The classification of drugs body systems are
 Cardio vascular drugs  Neurological drugs
 Respiratory drugs  Urinary drugs etc
 GIT drugs
The classifications of drugs by clinical indications are
 Analgesic
 Antibiotic
 Antiemetic
 Antihypertensive
 Anti diarrhea
 Anti pyerutic etc.
Information Sheet IV:- Site of injections

An injection is a way of administering a liquid to a person using a needle and syringe. It’s also
sometimes also called a ‘shot’ or ‘jab’. Injections are used to give a wide variety of different
medications, such as insulin, vaccines and Botox (onabotulinumtoxinA), but not all injections are
the same.

The best site on your body to receive an injection depends on factors such as the medication
being given, what you are treating, how quickly or slowly the medication needs to work, and the
type of injection you are receiving. The best type of injection for you may also be influenced by
your weight, age, cost, the frequency of administration and other factors.

Where can intravenous injections be

administered?
n IV injection is usually given by a healthcare professional. A small plastic tube called a catheter
is typically inserted into the vein for an IV injection to be administered through, especially when
more than one injection is required. IV catheters are best placed where they are easy to access
and the blood flow is good.
An IV catheter is most commonly placed into a vein in the:
 Forearm
 Back of the hand
 Antecubital fossa - the depression on the inside of the elbow joint
 Ankle, close to the foot - for small patients such as babies and neonates
When selecting a site to place an IV catheter it’s important to avoid infected areas of skin and
placing a catheter in a flexible joint where it may bend. Injured or sore areas, and stiff or very
thin veins should also be avoided.

Where can intramuscular injections be

administered?
Usually an IM injection, such as a vaccine, will be given by a healthcare professional. IM
injections need to be injected into a muscle. It is recommended that an IM injection is given into
a muscle in your:
 Thigh - vastus lateralis muscle between the hip and knee
 Bottom - Ventrogluteal muscle just below the hip on the side of the body
 Upper arm - deltoid muscle between the top of the shoulder and the arm pit
The best site for your IM injection may vary depending on the drug you are receiving. Some IM
injections need to be administered into a larger muscle than the deltoid for example. When
selecting an injection site for an IM injection it’s important to pick one that is:
 A safe distance from the surrounding nerves, bones and large blood vessels
 Large enough for the amount of medication
 Not the site of an injury, abscess, or dying skin
 Not a muscle that is emaciated or atrophied

Where can subcutaneous injections be

administered?
f you’re prescribed an injection that you have to administer yourself at home then it’s likely it’ll
be a SC injection. This type of injection is used to administer medications like insulin for
diabetes, hormone injections for fertility treatment and blood thinning agents to prevent blood
clots.
SC injections need to be injected into an area on the body with subcutaneous fat. It is
recommended that you inject a SC injection into:
 The lower abdomen (belly or stomach area), except for the 2 inches (5cm) area around the
navel (belly button)
 The front or outer sides of the thighs
 The upper area of the buttock
 The upper outer area of the arms (if being administered by someone else)
When selecting an injection site take care to avoid areas where the skin is sunken or lumpy, or
areas where you might inject into a muscle rather than subcutaneous tissue. Also avoid sites
where the skin is injured or damaged.

Where can intradermal injections be

administered?
ID injections are commonly used for allergy and TB testing. The most common sites for an ID
injection are:
 The inside or ventral aspect of the forearm
 Upper back, under the shoulder blade
When administering an ID injection for allergy testing it is best to avoid areas of the body with
moles, scars, rashes or a lot of hair as they can make it difficult to interpret the results of testing.
Skin lesions should also be avoided except when an ID injection is being administered to help
treat them, such as in the case of steroid injections for psoriasis plaques.
Information Sheet V:- Route of administration

There are many routes of medication administration. Some of these are

1. Oral route: - having patient swallow drug.
i. Enteral route:- administering drug through an enteral or NG
tube
ii. Sublingual administration:- placing drug under tongue
iii. Buccal administration: - placing drug b/n cheek and gum.
2. Parenteral route:-
a. Intravenous injection :- injecting drug into vein
b. Intramuscular injection:- injecting drug into muscle tissue
c. Intra dermal injection: - injecting drug into corium (under
epidermis).
d. Subcutaneous injection:- injecting drug into subcutaneous
tissue
e. Intra arterial injection:- injecting drugs into artery
f. Intra cardiac injection:- injecting drug into heart tissue
g. Intra peritoneal injection:- injecting drugs into peritoneal cavity
h. Intra thecal (Intraspinal) injection:- injecting drug into the spinal
cord
i. Intra osseous injection: - injecting drug into the bone.
3. Topical route
A = Vaginal administrations inserting drug into vagina
B = Rectal administration: - inserting drug into rectum
C = Inunctions: - Rubbing drug into skin
D = Instillation: - placing drug into direct contact with mucous
membrane.
F = Irrigation: - Flushing mucous membrane with drugs in solution
G = skin application: - applying transdermal patch
Pulmonary route: - having patient inhale drug.

Information Sheet VI:- Principles of medication administration

When administering any drug, regardless of the route of administration, the
nurse must do the following
1. Identify the client
 Errors can occur b/c one clients gets a drug intended for another
 In hospitals, most clients wear some sort of identification such
as a wrist band with
Name of the pt. and
Hospital identification number.
 Before giving the clients any drug, check the identification band
with the medication card

2. Administer the drug

 Administer the medication in the prescribed dosage by the route
ordered, at the correct time
3. Providing adjunctive interventions as indicated
 Clients may need help when receiving medication
E.g. position during intramuscular injections

4. Record the drug administered

 The facts recorded in the chart are:-
 Name of the drug
 Dose of the drug
 Methods of administration
 Specific relevant data such as
- Pulse rate and
- Any pertinent information

 The exact time of administration

 The signature of the nurse providing the medication
5. Evaluate the clients response to the drug
 The kinds of behavior that reflect the action
  The clients are change the response, the nurse may be report
the clients response directly to physician

N.B before giving the medication to the clients, check three times for safe
medication administration
First check.
- Read the medication administration record and remove the
medication from the client’s drawer, verify that the client’s name
and room number match the MAP.
- Compare the label of the medication against the MAR
- If the dosage does not much the MAC, determine if you need to do
a match calculation.
- Check the expiration date of the medication.
Second check
- While preparing the medication (if. Pouring, drawing up or placing
un opened package in a medication cup), look at the medication
label and check against the MAR.

Third check
Recheck the label on the container (e.g. Vial, bottle or unused unit dose
medications) before returning to its storage place
Information Sheet VII:- Potential risk related with medication administration
Nurses are primarily involved in the administration of medications across settings. Nurses can
also be involved in both the dispensing and preparation of medications (in a similar role to
pharmacists), such as crushing pills and drawing up a measured amount for injections

The common types of medication errors includes

 wrong dose, wrong choice, wrong drug, known allergy, missed dose, wrong time, wrong
frequency, wrong technique, drug-drug interaction, wrong route, extra dose, failure to act on
test, equipment failure, inadequate monitoring, preparation error, and other
 omission due to late transcription, wrong administration technique, and
infiltration/extravasation.

Information Sheet IIV:- Storing & handling of medication

Every medication has its own recommended storage condition from room temperature, to
refrigerating, to freezing. The majority of medications are recommended to be stored at room
temperature, between 59 to 77 degrees Fahrenheit. As a common rule, medications should be
stored away from heat, air, light, and moisture.

Apart from the storage place, climatic conditions should also be considered when storing. This is
because the potency and the overall effectiveness of your medications depend on appropriate
storage. Inappropriate storage can turn medications harmful if ingested. Now with that being
said, let’s take a look at a guide on storing medications

Medication Storing Temperatures

The main information you need for storing medication is the recommended storing temperature.
This is the first thing that will help you store your medication in an accurate place. Read the
medication cover for storing temperatures or check with your pharmacist about it.
Usually, the packages will specify the storage as to be stored at room temperature, cool
temperature, refrigeration or freezing. If your medication has already frozen and shouldn’t be,
then check our guide on medication that has frozen.
Room temperature specifies the temperature range between 59 to 77 degrees Fahrenheit, cool
temperature between 46 to 59 degrees Fahrenheit, refrigeration temperature between 35.6 to 46
degrees Fahrenheit, and freezing temperature means -13 to 14 degrees Fahrenheit. The table
below is a good quick reference guide.

Medication Storage Places

Medication Storage, Where, How, Temperatures, Types, and Guidelines

Posted October 21, 2019 by Michael Chamberlain - See Editorial Guidelines
Do you ever wonder what the best way to store that vital medication you need is? In this
blog we are going to offer some crucial guidelines to follow in order to ensure proper
medication storage. Prescription drugs come in many forms with different guidelines. We’ll
go over what you need to do to store them effectively.
What is proper medication storage? Every medication has its own recommended storage
condition from room temperature, to refrigerating, to freezing. The majority of
medications are recommended to be stored at room temperature, between 59 to 77 degrees
Fahrenheit. As a common rule, medications should be stored away from heat, air, light,
and moisture.
Apart from the storage place, climatic conditions should also be considered when storing.
This is because the potency and the overall effectiveness of your medications depend on
appropriate storage. Inappropriate storage can turn medications harmful if ingested. Now
with that being said, let’s take a look at a guide on storing medications.
Medication Storing Temperatures
The main information you need for storing medication is the recommended storing
temperature.
This is the first thing that will help you store your medication in an accurate place. Read
the medication cover for storing temperatures or check with your pharmacist about it.
Usually, the packages will specify the storage as to be stored at room temperature, cool
temperature, refrigeration or freezing. If your medication has already frozen and shouldn’t
be, then check our guide on medication that has frozen.
Room temperature specifies the temperature range between 59 to 77 degrees Fahrenheit,
cool temperature between 46 to 59 degrees Fahrenheit, refrigeration temperature between
35.6 to 46 degrees Fahrenheit, and freezing temperature means -13 to 14 degrees
Fahrenheit. The table below is a good quick reference guide.
Medication Package Storing Guidelines Degrees Fahrenheit

Room Temperature 59 to 77

Cool Temperature 46 to 59
Refrigeration 35.6 to 46

Freezing -13 to 14

Medication Storage Places

Depending on the temperature recommended you can use an appropriate place that fits the
temperature range. Like I said the majority of the medications are recommended to be stored at
room temperature. Such medications can be stored in a dresser drawer, a storage box, a closet, or
even a shelf.
Obviously, to chill the temperature you’ll need it to be kept in a cool place, whereas refrigerating
and freezing clearly require a refrigerator.
As a general rule, most of the liquid medications are recommended to be stored in the fridge.
Liquid formulations such as syrups and suspensions can support the growth of micro-organisms.
So, the growth of these micro-organisms is inhibited by refrigerating.
Especially liquid medications without preservatives – they should be refrigerated at all times. But
when refrigerating make sure that meds are stored in an area within the fridge that can maintain a
consistent temperature.
When the meds include preservatives, it’s not recommended to store them in the fridge. This is
because the effectiveness of the preservatives increases with the temperature. So, when
refrigerating these medications, the effectiveness is cut down.
So, unless specified by the manufacturer or the pharmacists, never refrigerate medications that
contain preservatives. One good example is Cetirizine oral solution that contains parabens as
preservatives.
Children’s liquid medications significantly vary in the recommended storage conditions. Some
liquids should be refrigerated like Cephalexin, while some should be stored at room temperature
like Azithromycin and some others may have different expiration dates depending on which
option is chosen – like Amoxicillin.
So, it’s very important to double-check the storage requirements with your pharmacist if you’re
not clear on the packaging guidelines.
Apart from the recommendations discussed above, it’s a good rule, in general, to always read the
label and packaging thoroughly when you need to figure out the best storage for your
medication.

LO4.Performing medication administration

Information sheet I:- Ten rights of medication administration

Ten “Rights” of medication administration
4. Right medication
The medication given was the medication ordered
5. Right dose
o The dose ordered is appropriate for the client.
 o Give special attention if the calculation indicates multiple
pills/tablets or a large quantity of a liquid medication. This can
be a “cue” that the match
Calculation may be incorrect
o Double check calculations that appear questionable
o Known the usual dosage range of the motion
o Question a close old side of the usual dosage range
6. Right Time
o Give medication at the right frequency and at the time ordered
o Medications given within 30 minutes before or after the
scheduled time are considered to meet the right time standard.
7. Right route
o Give the medication by the ordered route
o Make certain that the route is safe and appropriate for the
client
8. Right client
o Medication is given to the intended client
o Check the client is identification band with each administration
of medication.
9. Right client education
o Explain information about the medication to the client eg. Why
receiving what to expect.
10. Right documentation
o Document medication administration after giving it, not before.
11. Right to refuse:
o - Adult clients have the rights to refuse any medication
12. Right assessment
o Some medications requires specific assessments before (prior)
to administration.
Eg. Apical plus, B/P, lab results
o Medication orders may include specific parameters for
administration
 Eg. Do no give if pulse less than 60 or systolic blood pressure less
than 100.
13. Right Evaluation
Conduct appropriate follow up

Information Sheet II:- Administering Oral medication

G Competency: - Administer Range of Medications

G Learning outcome: administer medications to patients
G Skill 1: - Giving of drugs through Enteral route
Equipment’s
Clean Equipment’s
Clean glove Waste Receiver (disposable plastic
Face towel or tissue paper container)
Ordered medication (suspension, Chart (Medical Administration
tablet, capsule or others) record) (MAR)
Screen
Files (crusher) (Mortar or Pestle) if
needed
Spatula (sublingual route)
Glass of water or straw
Medication cup
S.N Steps of procedure Value Remark
Yes No
1. Check the order (MAR) related to ( 10 writes of medication Administration
2. (Explain )Know the reason why the client is receiving the medication (drug
classification, dosage, side effect, contraindications & nursing considerations
3. Assess general status of a patient (Verify the client’s ability to take medication
orally)
4. Perform hand washing & wear clean glove
5. Arrange the medication on medication try out of patient room
Check the medication against MAR
6. Bring all medications to working area
7. Keep patient privacy
8. Adjust working area in suitable position including patient
Sitting if they tolerate
Semi fowlers position
9. Place face towel or tissue paper near to patient neck
10. Double check the MAR again with drugs including Expired date.
11. Prepare medications with correct dose & forms accordingly
Crush (tablet)
Shake (suspension)
Place in cup (capsule)
12. Give a cup of water before medication to facilitate swallowing & absorption
13. Allow a client to hold a medication or cup if they can
14. Administer medication to specific patient through specific route
Oral (direct swallow)
Sublingual (lift the tongue & place under it)
Buccal (open mouth & put to the gum)
15. Instruct a patient
To take water /liquid or straw to swallow a medication in case of oral route
To hold a drug in place for 5-10 minutes in case of buccal & sublingual
16. Remove towel & wipe the mouth area with it
17. Reposition a patient in good position (keep patient safety)
18. Dispose all used equipment’s
19. Follow patients reaction to medications properly (30 minutes)
20. Return equipment’s to their proper place
21. Perform hand hygiene
22. Document all relevant information’s

G Competency: - Administer Range of Medications

G Learning outcome: administer medications to patients
G Skill 2: - Giving of drugs through Eye, Ear & Nose
Equipment’s

Clean Equipment’s
Clean glove Chart (Medical Administration
Tissue paper record) (MAR)
Ordered medication (Drops, Dry sterile absorbent sponges
ointments, nebulizers (spray) or Moisture-resistant towel
others) Sterile absorbent sponges soaked in
Dropper sterile normal saline
Screen Cotton tip applicator
Waste Receiver (disposable plastic Washing basin
container)

S. Steps of procedure Value Remark

N Yes No
1. Check the order (MAR) related to ( 10 writes of medication Administration
2. (Explain )Know the reason why the client is receiving the medication (drug
classification, dosage, side effect, contraindications & nursing considerations
3. Assess general status of a patient can apply him/her/ self or not
4. Perform hand washing & wear clean glove
5. Arrange the medication on medication try out of patient room
 Check the medication against MAR
6. Bring all medications to working area
7. Keep patient privacy
8. Adjust working area in suitable position including patient
Sitting & lean back ward (Semi fowlers position)
Side lying (affected ear facing up)
Slightly inclined to unaffected area to access the ear
An upright position
9. Place face towel or tissue paper near to patient neck
10. Double check the MAR again with drugs including Expired date.
11. Prepare medications with correct dose & forms accordingly
Eye, Ear or Nose drops with dropper if not included with drugs package
Eye ointment
Nebulized or spray drug
12. Prepare a specific site before administration
Wash the eye using sterile saline gauze from inner to outer cantus
Clean the ear using cotton tip applicator
Clean a nose using cotton tip applicator
13. Administer medication to specific patient through specific route
For Eye medication
G Instruct a patient to look up or down (open the lower eye lid using
hands
G Stand on the side of a patient’s eye
G Apply a pressure on the head to stabilize & cheek bone to expose a
conjunctiva with other hand
G Hold a dropper 1-2 CM above eye lid
G Apply proper amount of drug on the eye
G Apply ointment along inside of the eye lid both lower & upper one
For Ear medication
G Straighten the ear canal by pulling the pinna
o Down and back for children less than 3 years of
 o Upward and outward in adults
G Slowly instill the drops into the ear canal
G Holding the dropper at least 1/2 inch above the ear canal
For Nose medication
Ask the client to blow nose and clear nostrils of discharge
Have the client exhale and close one nostril?
Ask the client to inhale while the spray is pumped or sprayed into the
first nostril
Insert nasal dropper only about 3/8 inch into the nostril
For Nebulizer medication
Shake the prepackaged nebulizer
Have client place mouthpiece in mouth
Have the client press down on the prepackaged dispenser as the client
simultaneously inhales
14. Instruct a patient
To close the eye lid & move eyes & Briefly place fingers on either side of the
client’s nose to close the tear ducts and prevent the medication from draining
out of the eye using dry gauze (Eye medication administration)
Ask the client to maintain the position for 2 to 5 minutes & Place a cotton ball
on the outermost part of the canal (Ear medication administration)
Ask the client to blot excess drainage from the nostril; stay in the appropriate
position for 5 minutes & Ask the client to breathe through the nose after the
decongestion administration (Nasal medication administration)
Instruct the patient to Inhale when we pressed down the prepacked metric dose
inhaler as properly (Metric dose inhaler medication administration)
15. Remove towel or tissue paper & wipe the eye with it
16. Reposition a patient in good position (keep patient safety)
17. Dispose all used equipment’s
18. Follow patients reaction to medications properly (30 minutes)
19. Return equipment’s to their proper place
20. Perform hand hygiene
21. Document all relevant information’s

G Competency: - Administer Range of Medications

G Learning outcome: administer medications to patients
G Skill 3: - Giving of drugs on skin surface (Topical route)
Clean Equipment’s

Clean glove
Ordered medication (powder, ointments, lotion, paste, cream, patches or spray)
Screen
Waste Receiver (disposable plastic container)
Chart (Medical Administration record) (MAR)
Gauze pads
Transparent semipermeable dressing
Adhesive plaster
Sterile tongue blade
Irrigation solution
S. Steps of procedure Value Remark
N Yes No
1. Check the order (MAR) related to ( 10 writes of medication Administration
2. Explain the procedure to a patient
3. Assess general status of a patient can apply him/her/ self or not
4. Perform hand washing & wear clean glove
5. Arrange the medication on medication try out of patient room
Check the medication against MAR
6. Bring all medications to working area
7. Keep patient privacy with covering close
8. Adjust working area in suitable position including patient
Suitable position to a patient
9. Double check the MAR against with drugs including Expired date.
10. Prepare medications with correct dose & forms accordingly
 Powder, Ointments, Lotion, Paste, Cream, Patches Or Spray
11. Prepare a specific site before administration
If previously dressed, remove the dressing
Assess skin condition
Wash the skin appropriately
Dry thoroughly before apply drug
12. Administer medication to specific patient through specific route
G If lotion & ointment apply with thin layer on skin
G If aerosol spray, shake & spray on it
G If powders are used, dust it lightly
G If gels or pastes are used, use applicator to distribute on skin in hair
direction & apply clean dressing
G If transdermal patch is used, directly apply patch on skin surface
13. Instruct a patient
To avoid using any external skin moisturizing substances on skin
14. Reposition a patient in good position (keep patient safety)
15. Follow patients reaction to medications properly (30 minutes)
16. Dispose & Return equipment’s to their proper place
17. Perform hand hygiene
18. Document all relevant information’s

G Competency: - Administer Range of Medications

G Learning outcome: administer medications to patients
G Skill 4: - Giving of drugs through rectal wall (rectal route) rectal suppository
Clean Equipment’s

Clean glove
Tissue paper
Ordered medication (suppository, laxatives or enema)
Screen
Waste Receiver (disposable plastic container)
 Chart (Medical Administration record) (MAR)
Lubricant
Bed pan
Towel /pad/

S. Steps of procedure Value Remark

N Yes No
1. Check the order (MAR) related to ( 10 writes of medication Administration
2. Assess general status of a patient
3. Explain the procedure to a patient
4. Perform hand washing & wear clean glove
5. Arrange the medication on medication try out of patient room
Check the medication against MAR
6. Bring all medications to working area
7. Keep patient privacy
8. Adjust working area in suitable position including patient
Side-lying Sims’ position, preferably the left side with upper leg drawn up
toward chest.
9. Place towel or pad under the bed
10. Double check the MAR against with drugs including Expired date.
11. Prepare medications with correct dose & forms accordingly
Suppository
Enema
12. Prepare a specific site before administration
Externally assess the client’s external anus
Remove a drug from a wrapper
13. Administer medication to specific patient through specific route
Rubricate a tip along with inserting finger
Retract the anus with non-dominant hand & insert gently & slowly with
dominant hand
14. Instruct a patient
 To hold any passing of stool until 10 minutes
Pinch the anus for at least 3-5
Wipe the area with towel or tissue paper
To maintain the position for 10 to 15 minutes
If any sensation of defecate, provide bedpan
15. Remove towel or tissue paper & wipe the eye with it
16. Reposition a patient in good position (maintain patient comfort)
17. Follow patients reaction to medications properly (30 minutes)
18. Dispose & Return equipment’s to their proper place
19. Perform hand hygiene
20. Document all relevant information’s

G Competency: - Administer Range of Medications

G Learning outcome: administer medications to patients
G Skill 5: - Giving of drugs through vaginal wall (vaginal pessary) vaginal suppository
Clean Equipment’s

Clean glove (latex free)

Tissue paper /
Ordered medication (Cream, Foam, Jelly, or Suppository)
Screen
Waste Receiver (disposable plastic container)
Chart (Medical Administration record) (MAR)
Wash cloth with basin
Water-soluble lubricating jelly (for suppository)
Warm water (optional)
Applicator if needed
Light
Perineal pad
Pad towel
S. Steps of procedure Value Remark
N Yes No
1. Check the order (MAR) related to ( 10 writes of medication Administration
2. Explain the procedure to a patient
3. Assess general status of a patient can apply her/ self or not
4. Perform hand washing & wear clean glove
5. Arrange the medication on medication try out of patient room
Check the medication against MAR
6. Bring all medications to working area
7. Keep patient privacy with screen
8. Adjust working area in suitable position including patient
Assist the client to void urine
Dorsal recumbent or sims position
9. Double check the MAR again with drugs including Expired date.
10. Prepare medications with correct dose & forms accordingly
Cream, Foam, Jelly, or Suppository
11. Prepare a specific site before administration
Give simple perineal care
Clean from farthest to the nearest with front to back principle. Then central part
Use clean water or saline solution
Drape client’s abdomen and lower extremities appropriately.
Provide towel or protective pad on bed.
Position lighting to illuminate vaginal orifice.
12. Administer medication to specific patient through specific route
Assess perineum for sign of inflammation, discharge or others
Fill applicator if used or clean gloved finger
Apply water soluble lubricant on applicator or finger
Open labia with non-dominant hand & insert gently until 3 inch (5-7 cm)
Wipe the perineal area well
Apply perineal pad if avail
13. Instruct a patient
To keep a position 20-30 minutes
Changed in to supine position & extend the leg
14. Remove towel or tissue paper & wipe with it
15. Reposition a patient in good position (patient comfort)
16. Follow patients reaction to medications properly (30 minutes)
17. Dispose & Return equipment’s to their proper place
18. Perform hand hygiene
19. Document all relevant information’s

G Competency: - Administer Range of Medications

G Learning outcome: administer medications to patients
G Skill 6: - Intradermal injection
Clean Equipment’s

Clean glove (latex free) Safety box

Ordered medication (Vial or Chart (Medical Administration
Ampule) record) (MAR)
Distilled water Alcohol swap
Screen Light
Waste Receiver (disposable plastic Pen/marker
container) Syringe with needle (1-3ml)
S. Steps of procedure Value Remark
N Yes No
1. Check the order (MAR) related to ( 10 writes of medication Administration
2. Explain the procedure to a patient
3. Assess general status of a patient
4. Perform hand washing & wear clean glove
5. Arrange the medication on medication try out of patient room
Check the medication against MAR
6. Bring all medications to working area
7. Keep patient privacy with screen
8. Adjust working area in suitable position including patient
Sitting/Sleeping position
Relax the arm with elbow and forearm extended on a flat surface
9. Double check the MAR against with drugs including Expired date.
10. Prepare medications with correct dose & forms accordingly
 From vial or Ampule (0.1 ml)
11. Select appropriate site of intradermal injection
Anterior part of forearm, upper chest & inferior scapular
12. Prepare a specific site before administration
Assess a site free from any inflammation
Use antiseptic swab in a circular motion to clean the site
13. Administer medication to specific patient through specific route
Tighten the skin to make it firm to prevent skin movement
Insert a needle 15 degree to skin with direction of needle bevel up
Recognize the needle is inside of skin
Slowly inject a drug until you got resistance
Evidence small bleb & raised swell under the skin
Remove a needle after putting pressure with dry cotton
Put marks using marker/indian ink/pen to identify reactions
14. Instruct a patient
Don’t apply any pressure on injection site
To avoid massage
Wait for 10/15 minutes for correct diagnosis
15. Reposition a patient in good position (patient comfort)
16. Follow patients reaction to medications properly (15 minutes)
17. Dispose & Return equipment’s to their proper place
18. Perform hand hygiene
19. Document all relevant information’s

G Competency: - Administer Range of Medications

G Learning outcome: administer medications to patients
G Skill 7: - Subcutaneous injection
Clean Equipment’s
 Clean glove (latex free) Safety box
Ordered medication (Vial or Chart (Medical Administration
Ampule) record) (MAR)
Distilled water Alcohol swap
Screen Light
Waste Receiver (disposable plastic Syringe with needle
container)
S. Steps of procedure Value Remark
N Yes No
1. Check the order (MAR) related to ( 10 writes of medication Administration
2. Explain the procedure to a patient
3. Assess general status of a patient can he/ she inject her/him self
4. Perform hand washing & wear clean glove
5. Arrange the medication on medication try out of patient room
Check the medication against MAR
6. Bring all medications to working area
7. Keep patient privacy with screen
8. Adjust working area in suitable position including patient
Sitting/Sleeping position/standing position
Relax the upper arm, leg or abdomen
9. Double check the MAR against with drugs including Expired date.
10. Prepare medications with correct dose & forms accordingly
From vial or Ampule (1ml)
11. Select appropriate site of intradermal injection
Anterior part of upper arm, abdomen or scapular
Distract client by talking about an interesting subject
12. Prepare a specific site before administration
Assess a site free from any inflammation
Use antiseptic swab to clean the site
13. Administer medication to specific patient through specific route
Pinch the skin with non-dominant hand
Insert a needle 45-90 degree to skin
Check three times for coming of blood or not
 If no blood, slowly inject a drug in to the site
Remove a needle after putting pressure with dry cotton
Gently massage the area to distribute a drug
14. Instruct a patient
To apply pressure on injection site if it bleeds
Encourage to massage the area
15. Reposition a patient in good position (Patient comfort)
16. Follow patients reaction to medications properly (30 minutes)
17. Dispose & Return equipment’s to their proper place
18. Perform hand hygiene
19. Document all relevant information’s

G Competency: - Administer Range of Medications

G Learning outcome: administer medications to patients
G Skill 8: - Intramuscular injection
Clean Equipment’s

Clean glove (latex free) Safety box

Ordered medication (Vial or Chart (Medical Administration
Ampule) record) (MAR)
Distilled water Alcohol swap
Screen Light
Waste Receiver (disposable plastic Syringe with needle
container)
S. Steps of procedure Value Remark
N Yes No
1. Check the order (MAR) related to ( 10 writes of medication Administration
2. Explain the procedure to a patient
3. Assess general status of a patient
4. Perform hand washing & wear clean glove
5. Arrange the medication on medication try out of patient room
Check the medication against MAR
6. Bring all medications to working area
7. Keep patient privacy with screen
8. Adjust working area in suitable position including patient
For vastus lateralis, lying flat or supine with knee slightly flexed.
For ventrogluteal, lying on side or back with knee and hip slightly flexed.
For deltoid, standing with arm relaxed at side, sitting with lower arm relaxed
on lap, or lying flat with lower arm relaxed across abdomen.
9. Double check the MAR against with drugs including Expired date.
10. Prepare medications with correct dose & forms accordingly
From vial or Ampule (5-10 ml)
11. Select appropriate site of intradermal injection
Deltoid, Ventrogluteal, Vastus lateralis
Distract client by talking about an interesting subject
12. Prepare a specific site before administration
Assess a site free from any inflammation
Use antiseptic swab to clean the site
13. Locate proper landmarks
Deltoid from acromion process, 4 fingers beneath & select the triangle muscle
shape
Ventrogluteal, using greater trochanter, form 4 quadrants with imaginary line
& select the outer part
Vastus lateralis, use lateral condyle of knee & mark the middle one & select
outer part
14. Administer medication to specific patient through specific route
Pinch/Spread the skin with non-dominant hand
Insert a needle 90 degree to skin
Check three times for coming of blood or not
If no blood, slowly inject a drug in to the site
Remove a needle after putting pressure with dry cotton
Gently massage the area to distribute a drug
15. Instruct a patient
To apply pressure on injection site if it bleeds
 Encourage to massage the area for fast distribution
Instruct a client to move his hand or leg
16. Reposition a patient in good position (Patient comfort)
17. Follow patients reaction to medications properly (30 minutes)
18. Dispose & Return equipment’s to their proper place
19. Perform hand hygiene
20. Document all relevant information’s

G Competency: - Administer Range of Medications

G Learning outcome: administer medications to patients
G Skill 9: - Intravenous cannulation or injection
Clean Equipment’s

Clean glove (latex free) Syringe with needle

Surgical glove
Sterile towel
Fenestrated towel
IV fluids
IV stand
IV set
Plaster
Forceps
Tourniquet
IV cannula
If Ordered medication (Vial or
Ampule)
Distilled water
Screen
Waste Receiver (disposable plastic
container)
Safety box
Chart (Medical Administration
record) (MAR)
Alcohol swap
Light
S. Steps of procedure Value Rem
N Yes No
1. Check the order MAR ( 10 writes of medication Administration) & Cannulation
2. Explain the procedure to a patient
3. Assess general status of a patient
4. Perform hand washing & wear clean glove
5. Arrange the medication on medication try out of patient room
Create sterile field & assemble necessary equipment’s
If any drug is ordered check the medication against MAR
6. Bring all medications to working area
7. Keep patient privacy
Close door or window
Screen or use personal close

8. Adjust working area in suitable position including patient

Sitting or sleeping position
Relax the upper arm, leg
9. Double check the MAR against with drugs including Expired date.
10. Prepare medications with correct dose & forms accordingly
From vial or Ampule (1ml)
Put a bag on IV stand & remove air
11. Select appropriate site of intradermal injection
Hand or Leg area
Distract client by talking about an interesting subject
12. Prepare a specific site before administration
Assess a site free from any inflammation
Apply tourniquet
Instruct a patient to close & open the fist, and hang the hand below the heart
Done sterile glove
Clean the area using forceps
Apply fenestrated towel
13. Administer medication to specific patient through specific route
Apply firm pressure on the hand
Insert cannula 25-30 degree straight to vein
If blood is come, indicator of you are in vein
Remove a needle back & push the cannula in to vein
Remove a needle after putting pressure on tip of cannula
Remove fenestrated towel
Connect IV set or close with cup of a cannula
Apply plaster in better fly shape
Place patients hand in comfortable position
Calculate drop rate & label on the bag
If there any drug need, add on the bag or give by IV push

14. Instruct a patient

Not to flex the hand
Don’t stand without turn off IV set clamper
15. Reposition a patient in good position (Patient comfort)
16. Follow patients reaction to medications properly (30 minutes)
17. Dispose & Return equipment’s to their proper place
18. Perform hand hygiene
19. Document all relevant information’s