Assessment of the course

● Midterm exam…………………….30 marks

❑ Final exam-………………….………..60marks

● PSW-------------------------------------10marks
● TOTAL------------------------------100 marks

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 Pharmacology

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 Pharmacology

Pharmakon : drug
Logos: Science

Is the science that deals with interaction

of exogenously
administered chemical molecules(drugs)
with living system.

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 Pharmacology

Drug
Drug = Drogue = a dry herb

It is any chemical substance that modify

physiological system or pathological state and can
be used for diagnosis, prevention or treatment of
disease.

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Name of drugs

1.chemical name
2.general name
3.trade name
Pharmacology is divided into two parts:
Pharmacology

⮚Pharmacokinetics

What the body does to the drug?

⮚Pharmacodynamics
What the drug does to the body?

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PharmacokineticsPharmacology
Are studies of the absorption,distribution,
metabolism &
excretion of drugs.

Pharmacodynamics
Are studies of
✔Mechanisms of drug action.
✔Pharmacological effects.

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 Pharmacology

Pharmacodynamics
deals with the action of drugs on
living cells and mechanisms by
which such effects are produced.
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Drug sources
1. Drugs are derived from many sources plants, animals, and minerals .
2. Drugs are synthetic chemical compounds manufactured in
laboratories.
3. Semisynthetic drugs that are chemically altered (e.g. , levorphanol) .
4. Genetically altered this group of drugs is growing in importance as a
source of drugs today

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 route of administration (ROA

The route of administration (ROA) that is

chosen may have a profound effect upon
the speed and efficiency with which the
drug acts

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III. ROUTES OF
DRUG
ADMINISTRATIO
N
 ROUTES OF DRUG
ADMINISTRATION

LOCAL ROUTES SYSTEMIC ROUTES

❖These routes can only be

used for localized lesions at ❖The drug administered
accessible sites and for drugs through systemic routes is
whose systemic absorption
from these sites is minimal, intended to be absorbed into
slow or absent. Thus, high bloodstream and distributed
concentrations are attained
at the desired site without all over, including the site of
exposing the rest of the body. action, through circulation

❖ Systemic side effects or

toxicity are consequently
absent or minimal.
LOCAL ROUTES .1
1. Topical
● This refers to external application of the drug to the surface for
localized action.
● It is often more convenient and efficient mode of delivering the
drug to skin, or opharyngeal/nasal mucosa, eyes, ear canal, anal
canal, vagina, etc.

2. Deeper tissues
● Certain deep areas can be approached by using a syringe and
needle, but the drug should be such that systemic absorption is
slow,
● e.g. Intrathecal injection (lidocaine, amphotericin B), intraarticular
injection (hydrocortisone acetate), retrobulbar injection
(hydrocortisone acetate).

3. Arterial supply
● Close intra-arterial injection is used for contrast media in
angiography; anticancer drugs can be infused in femoral or brachial
artery to localize the effect for limb malignancies.
SYSTEMIC ROUTES .2
 Oral

Advantages
• Convenient (Easily self-
administered)
• Low risk of systemic infections that
could complicate treatment.
• Toxicities and overdose may be
overcome with antidotes, such as
activated charcoal.
• Economic: no need for special
instruments or personnel
• Both solid& liquid dosage forms can
be used.
2. Sublingual (s.l.) or buccal

● Closely related to the oral route; however, the

dosage form is not swallowed.
● The tablet is to be dissolved under the tongue
(sublingual) or in the pouch of the cheek (buccal).
● Only lipid-soluble and non-irritating drugs can be so
administered
● Absorption is relatively rapid—action can be
produced in minutes.
● The chief advantage is that liver is bypassed and
drugs with high first pass metabolism can be
absorbed directly into systemic circulation.
3. Rectal

Advantages:
● Suitable for irritant and unpleasant drugs can be put into
rectum as suppositories or retention enema for systemic effect.
● This route can also be used when the patient is having
recurrent vomiting.
● Drug absorbed into external haemorrhoidal veins (about 50%)
bypasses liver, but not that absorbed into internal
haemorrhoidal veins.

Disadvantages:
● inconvenient and embarrassing; absorption is slower, irregular
and often unpredictable.
● Rectal inflammation can result from irritant drugs.
 5. Inhalation

● Volatile liquids and gases are given by inhalation for

systemic action, e.g. general anaesthetics.

● Absorption takes place from the vast surface of alveoli—

action is very rapid as i.v. injection .

● When administration is discontinued, the drug diffuses

back and is rapidly eliminated in expired air. Thus,
controlled administration is possible with moment-to
moment adjustment.

● Irritant vapors (ether) cause inflammation of respiratory

tract and increase secretion.
6. Nasal

● Through the nose

● The mucous membrane
of the nose can readily
absorb many drugs;
digestive juices and liver
are bypassed
e.g. Desmopressin
 7. Parentral
(Par—beyond, enteral—intestinal)

Advantages Disadvantages

1. Drug action is faster and surer 1. The preparation has to be

(valuable in emergencies). sterilized and is costlier.
2. Gastric irritation and vomiting are 2. The technique is invasive and
not provoked. painful, assistance of another
3. Parenteral route can be employed person is mostly needed (though
in unconscious, uncooperative or self- injection is possible, e.g.
vomiting patient. insulin by diabetics).
4. There are no chances of 3. There are chances of local tissue
interference by food or digestive injury and in general it is more
juices. risky.
5. Liver is bypassed . 4. Correction of an error in dosing
may be impossible (i.v)
 (i) SC / subcutaneous

● The drug is deposited in the loose subcutaneous tissue

which is richly supplied by nerves (irritant drugs cannot be
injected) but is less vascular (absorption is slower).

● Self-injection is possible because deep penetration is not

needed.

● This route should be avoided in shock patients who are

vasoconstricted— absorption will be delayed.

● Repository (depot) preparations—oily solutions or aqueous

suspensions can be injected for prolonged action.
 (ii) Intramuscular (i.m.)

● The drug is injected in one of the large skeletal

muscles.

● Muscle is less richly supplied with sensory nerves

(mild irritants can be injected) and is more vascular
(absorption is faster).

● It is less painful, but self injection is often

impracticable— deep penetration is needed.

● Depot preparations can be injected by this route.

 (iii) Intravenous (i.v.)

● The drug is injected as a bolus or infused slowly over

hours in one of the superficial veins.

● The drug directly reaches into the bloodstream and effects

are produced immediately (great value in emergency).

● Bioavailability is 100%

● The intima of veins is insensitive and drug gets diluted

with blood, therefore, even highly irritant drugs can be
injected i.v., but hazards are— thrombophlebitis of the
injected vein and necrosis of adjoining tissues if
Intravenous (i.v.) )iii(

● These complications can be minimized by diluting

the drug or injecting it into a running i.v. line.

● Only aqueous solutions (not suspensions) can be

injected i.v. and there are no depot preparations for
this route.

● The dose of the drug required is smallest

(bioavailability is 100%) and even large volumes can
be infused.
 (iv) Intradermal injection

● are made into the skin between the dermis and epidermis.
Small volumes |(0.1-0.2 ml) are injected mainly for
diagnosis of allergy and immunity.

● The drug is injected into the skin raising a bleb (e.g. BCG
vaccine, sensitivity testing) or scarring/multiple puncture of
the epidermis through a drop of the drug is done.

● This route is employed for specific purposes only.

 r t an t
Im p o
Very fo!
In

No single method of drug

administration is ideal for all
drugs in all circumstances

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First pass effect

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 ADME

Absorption
Distribution
Metabolism
Excretion

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II - Absorption of drugs:
Absorption is the transfer of a drug from its
site of administration to the bloodstream.
.

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The rate and efficiency of absorption depend on the route of
administration. For IV delivery, absorption is complete; that is,
the total dose of drug reaches the systemic circulation.
Drug delivery by other routes may result in only partial
absorption and, thus, lower bioavailability. For example, the
oral route requires that a drug dissolve in the gastrointestinal
fluid and then penetrate the epithelial cells of the intestinal
mucosa; some abnormalities and diseases of the GI tract or the
presence of food may affect this process

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A- Transport of a drug from the GI tract:

Depending on their chemical properties, drugs

may be absorbed from the GI tract by either
passive diffusion or active transport.

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1- Passive Diffusion:
The driving force for passive absorption of a drug is the
concentration gradient across a membrane separating two body
compartments; that is, the drug moves from a region of high
concentration to one of lower concentration.
Passive diffusion does not involve a carrier, and is not saturable.
The vast majority of drugs gain access to the body by this
mechanism.
Lipid-soluble drugs move across the biological membrane itself,
whereas water-soluble drug penetrate the cell membrane through
aqueous channels.
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2- Active Transport:

This mode of drug entry involves specific carrier proteins that

span the membrane.
Active transport is energy-dependent. It is capable of moving
drugs against a concentration gradient, that is, from a region of
low drug concentration to one with a higher drug
concentration.
This process can be saturated.

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B- Physical factors influencing absorption:
1- Effect of pH on drug absorption:
Most drugs are either weak acids or weak bases,
which makes their absorption related to the pH
and the pka.

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2- Blood flow to the absorption site:
Blood flow to the intestine is much greater than the flow
to the stomach; thus, absorption from the intestine is
favored over that from the stomach.
Another example is the subcutaneous administration: for
example, shock severely reduces blood flow to cutaneous
tissues, thus minimizing the absorption from subcutaneous
administration. By contrast, heat increases blood flow to
cutaneous tissues, thus increasing the absorption.
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3- Total surface area available:
Because the intestine has a surface rich in microvilli, it has
a surface area about 1000 fold that of the stomach; thus,
absorption of the drug across the intestine is more efficient.

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4- Contact time at the absorption rate:
If a drug moves through the GI tract very
quickly, as in severe diarrhea, it is not well
absorbed.

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III - Bioavailability
Bioavailability is the fraction of administered drug that
reaches the systemic circulation.
Bioavailability is expressed as the fraction of
administered drug that gains access to the systemic
circulation in a chemically unchanged form.
For example, if 100 mg of a drug are administered orally
and 70 mg of this drug are absorbed unchanged, the
bioavailability
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is 70%. 41
A- Determination of Bioavailability:
Bioavailability is determined by comparing plasma levels of a
drug after a particular route of administration (for example,
oral administration), with plasma drug levels achieved by IV
injection, in which all of the agent enters the circulation.
When the drug is given orally, only part of the administered
dose appears in the plasma.
Bioavailability of a drug administered orally is the ratio of the
concentration achieved in oral administration compared with
the concentration achieved in IV injection.

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B- Factors that influence bioavailability:
1- First-pass hepatic metabolism:
When a drug is absorbed across the GI tract, it enters the
portal circulation before entering the systemic
circulation.
If the drug is rapidly metabolized by the liver, the
amount of unchanged drug that gains access to the
systemic circulation is decreased.
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2- Solubility of the drug:
For a drug to be readily absorbed, it must be
largely lipophilic (lipid-soluble), yet has some
solubility in aqueous solutions (some water
solubility).

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3- Chemical instability:
Some drugs are unstable in pH of the gastric
contents or destroyed in the GI tract by
degradative enzymes, which makes their
bioavailability less.

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 Nature of the drug formulation

To be absorbed, a drug must dissolve in the

fluid of the GI tract. Several factors influence
the ease of dissolution of the drug in the fluid,
therefore, alter the bioavailability: particle
size, salt form and the presence of excipients.

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 Drug Distribution
IV -
Drug distribution is the process by which a drug
reversibly leaves the bloodstream and enters the
extracellular fluid or the cells of the tissues.
Blood distribution depends on blood flow, capillary
permeability,
the degree of binding of the drug to plasma and
tissue proteins, and the volume of distribution

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A:
– Blood Flow
The rate of blood alters the drug distribution.
The higher blood flow to an organ, the faster the drug
achieves to this organ.

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 B- Capillary Permeability
:
The capillary permeability varies from an organ to
another. Some membranes are easier to be penetrated than
others.
The Blood-brain barrier is the barrier that protects the
brain. To enter the brain, the drugs must pass through it. It
is the hardest membrane to be penetrated.
Only lipid-soluble drugs, in small particles, can penetrate
the BBB.
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 C- Binding of drugs to proteins
:
In the plasma and in some tissues, proteins are able to
bind drugs on their surfaces. Plasma-albumin is the major
drug-binding protein.
Bound drugs are pharmacologically inactive, only the
free, unbound drug can act on target sites in the tissues,
give a biological response and also be available to
elimination.
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 Volume of Distribution
D- :
The volume of distribution, also known as apparent
volume of distribution, is a term used to quantify the
distribution of a medication throughout the body after
an oral or parenteral dosing. It is defined as the volume
in which the amount of drug will need to be uniformly
distributed in to produce the observed blood
concentration.
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V- Drug Metabolism
Drugs are most often eliminated by biotransformation
and/or excretion into the urine or bile.
The liver is the major site for drug metabolism, but specific
drugs may undergo biotransformation in other tissues.
Some agents are initially administered as inactive
compounds (pro-drugs); they must be metabolized to their
active forms.

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A- Reactions in drug metabolism:

The drug metabolism is divided into 2 phases: Phase I and

Phase II.
1- Phase I:
The reactions of Phase I are oxidation, reduction and/or
hydrolysis.
Following Phase I, the drug may be activated (if it is a pro-
drug), unchanged, or most often, inactivated.

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2- Phase II:
This phase consists of conjugation reactions.
Following this phase, the metabolite will be
more water-soluble, thus, easier to be excreted
in the urine.

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Note:

Not all drugs undergo Phase I and Phase II reactions in that

order.
For example,
- Some drugs directly enter Phase II metabolism.
- Other drugs, following Phase I, will be sufficiently water-
soluble and will be directly excreted in the urine without
undergoing Phase II.
- Some drugs enter first a Phase II reaction, followed by a
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Phase I reaction.
C- Bioequivalence:
Two related drugs (same active agent in two different
preparations) are bioequivalent if they show comparable
bioavailability and similar times to achieve peak blood
concentration.

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B- Factors affecting drug metabolism

The phase I and Phase II reactions depend on

enzymes.
If enzymes levels or activity go down, the rate of drug
metabolism will decrease.
If enzymes levels or activity increases, the drug metabolism
increases.
Generally, the changes in drug metabolism are quantitative,
not qualitative.
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1- Inducers:
A drug A is able to increase the synthesis of an enzyme
responsible of the metabolism of a drug B.
The rate of metabolism of Drug B will be increases, Drug B
will be more metabolized and inactivated, which leads to a
less activity for Drug B.
In this case, Drug A is called an inducer.

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2- Inhibitor:
The most common form of inhibition is through competition
for the same enzyme. For example, drug C competes with
drug D on the same enzyme for metabolism. If they are
taken together, drug D will be less metabolized because drug
C is already fixed on the enzyme responsible of the
metabolism. The rate of metabolism of drug D is decreased
and its activity in the body is increased.
In this case, drug C is called an inhibitor.

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 3- Other Factors:
- Age;
- Disease;
- Pregnancy;
- Drug dose;
- Diet;
- Heredity.

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VI- Excretion of Drugs

Drugs are eliminated from the body either unchanged by the process of excretion or
converted to metabolites then excreted.
Lipid-soluble drugs are not readily eliminated until they are metabolized to water-soluble
compounds. However, water-soluble drugs can be directly eliminated without
undergoing metabolism.
The kidney is the most important organ for excreting drugs and their metabolites. A
patient with renal failure may undergo dialysis, which will remove small molecules, such
as drugs.

Other routes include the bile, intestine, lung, or milk in nursing mothers:

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- Substances excreted in the feces are principally unabsorbed
orally ingested drugs or drugs metabolites excreted either in
the bile or secreted directly into the intestinal tract and not
reabsorbed.
- Excretion of drugs in breast milk is important not because of
the amounts eliminated, but because the excreted drugs are
potential sources of unwanted pharmacological effects in the
nursing infant.
- Excretion from the lung is important mainly for the
elimination of anesthetic gases.
- Excretion of drugs into sweat, saliva, and tears is
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quantitatively not important.
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∙Pharmacodynamics
A- Mechanism of Drug Action:
A drug may produce its effects through various
mechanisms:
1- Physical action:
⮚ Osmosis:
Drug retains water by osmosis as osmotic diuretics
(Mannitol) and osmotic purgatives (Lactulose).
⮚ Adsorption:
Drug adsorbs diverse substances including
toxins and fluid on its
surface thereby inactivating them (activated
charcoal).
2- Chemical action:
⮚ - Antacids neutralize gastric acidity (e.g.
NaHCO3)
⮚ - Chelating agents form biologically inactive
complex with other substances
3- Regulatory Proteins (Body Control systems):
- Enzymes:
Drugs may inhibit or activate certain enzymes.
-Carrier Molecules:
Drugs may increase their synthesis or block their recognition
site.
-Ion Channels:
Drugs may open ion channels by acting on specific receptor
which forms the channel or drugs may physically close the
channel.
-Receptors:
Responses to drug-receptor interaction can be as
Agonist (substance binds and activates the
receptor) or Antagonist (substance blocks the
receptor, thereby blocking the action of agonists).
 B- Dose response relationship:
Potency
✔Absolute amount of drug required to
produce an effect
✔More potent drug is the one that
requires lower dose to cause same effect
✔depends on its affinity for its receptor and on
its efficacy
✔ it is measured as the inverse of the EC50 for
that drug
 Dose response relationship

Drug Efficacy :
is the magnitude of response obtained from
optimal receptor site occupancy by a drug with the
same affinity .
measures the maximum strength of the effect
itself, at saturating drug concentrations, regardless
of dose.
Drug Affinity:
is its ability to bind to its biological target
(receptor, enzyme, transport system, etc.)

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Figure 1: Potency and efficacy of a drug. The potency is defined as
1/EC50, whereas the efficacy the effect observed at saturating conc.

Drug A is more potent than B

Drug A is less effective than B
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 Dose Response Relationships
Threshold (minimal) dose
Least amount needed to produce desired
effects
Maximum effect
Greatest response produced regardless of
dose used

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 Dose Response Relationships
o Loading dose
Bolus of drug given initially to rapidly reach
therapeutic levels
• Maintenance dose
Lower dose of drug given continuously or at
regular intervals to maintain therapeutic
levels

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 Factors Altering Drug Responses
⮚Age
Pediatric or geriatric
Immature or decreased hepatic,
renal function
⮚Weight
Big patients “spread” drug over larger
volume
⮚Gender
Difference in sizes
Difference in fat/water distribution
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 Factors Altering Drug Responses
❑Environment
oHeat or cold
❑ Fever
❑ Shock

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 Factors Altering Drug Responses
Pathology
✔Drug may aggravate underlying
pathology
✔Hepatic disease may slow drug
metabolism
✔Renal disease may slow drug
elimination
✔Acid/base abnormalities may
change drug absorption or
elimination
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 Influencing factors

❑Genetic effects
▪Lack of specific enzymes
▪Lower metabolic rate
❑Psychological factors
▪Placebo effect

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 Pediatric patient

❑Higher proportion of water

❑Lower plasma protein levels
✔More available drug
❑Immature liver/kidneys
✔Liver often metabolizes more slowly
✔Kidneys may excrete more slowly

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 Geriatric Patients

oChronic disease oDietary deficiencies

oDecreased oUse of multiple
plasma protein medications
binding oLack of compliance
oSlower
metabolism
oSlower excretion

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1- Agonist:
If a drug binds to a receptor and produces a biologic
response that mimics the response to the endogenous ligand,
it is known as an agonist.
2- Antagonist:
Antagonists are drugs that decrease the actions of another
drug or endogenous ligand.
Antagonists have no intrinsic activity and, therefore, produce
no effect by themselves.
If both the antagonist and the agonist bind to the same site on
the receptor, they are said to be competitive.
If the antagonist binds to a site other then where the agonist
binds, the interaction is non-competitive.
 Pharmacodynamics

Affinity:
Ability of a drug to combine with the receptor.
Efficacy:
Capacity of a drug to activate receptor and produce
action.
Agonist
is a drug that combines with receptor and produce a
response ( has affinity and efficacy).
 Pharmacodynamics

Antagonist
is a drug that combines with a receptor
without producing responses. It blocks the
action of the agonist ( Has affinity but no or
zero efficacy). It has structural similarity to
agonist. without producing responses.
Types of agonists
❖Full agonist.
❖Partial agonist.
❖Inverse agonist.
1) Full Agonist :
A drug that combines with its specific receptor to produce
maximal effect .
It Has both high affinity & full efficacy.
 Pharmacodynamics

Types of agonists
2) Partial agonist :
A drug that combines with its specific receptor to produce
submaximal effect regardless of concentration (Full
receptor occupancy).
It has high affinity & partial efficacy.
3) Inverse Agonist
combines with its receptor & produce response opposite to
those of the agonist.
It has high affinity & negative efficacy.
Pharmacodynamics
Median effective dose(ED50 ).
❖is a dose of the drug that gives a response
equals to 50% of the maximal response.
❖is a measure of the potency

Write on ur book
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88
EFFICACY

Efficacy is the maximal effect produced by a drug . This is important toknow ●

when deciding between two drugs that have similar action. For example, two
antibiotics may effectively kill the same organism, but one may take more
.doses than another, making the other more effective

Depends on the number of drug receptors ●

.formed
.Efficacy is more important than potency ●

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90
Adverse effect

LD50

Drug(log conc) 91
 Therapeutic index(TI)
● Therapeutic index = LD50 / ED50
● ED50 is a measure of safety
● Large value a wide margin of safety.
Penicillin
● Small value a narrow margin of safety
warfarin
● If (TI) is equal to or less than one, the drug is Toxic

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 t
ec
eff

c t
ffe
ti c

e
u
pe

rse
era

ve
Ad
Th
Minimal Maximal acceptable
therapeutic effect adverse effect
Effect

ED50 LD50
🡨Therapeutic rang🡪

Drug(log conc) 93
94
95
 Risk-benefit ratio
• This term is used in the judgment of any drug . it
estimated on the estimated harm (adverse effect) versus
expected advantages (relief of symptoms, cure).
• The drug should be prescribed only when the benefits
outweigh the risks.
• Risk-benefit ratio can hardly ever be accurately
measured for each instant of drug use. The physician
have to rely on data from use of drug from large
population ,and his own experience of the drug and the
patient.
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 Combined effect of drugs
When two or more drugs are given simultaneously
or directly after each other, they may be either
indifferent to each other or exhibit synergism or
antagonism

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 Antagonism
When one drug decreases or abolishes the action of
another.
Effect of drug A+ B < Effect of drug A+ Effect of drug
B
Types :
⮚ Physical antagonism
⮚ Chemical antagonist.
⮚ Physiological antagonist.
⮚ Pharmacological antagonist. 98
Drug Antagonism

1) Physical Antagonism
● Based on physical property.
● No receptor.
Examples
● Charcoal adsorbs alkaloids and can prevent their
absorption used in alkaloid poisoning.

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Drug Antagonism
2) Chemical Antagonism
● Simple chemical reaction.
● No receptor.
Examples
● Antacid & tetracycline.
● Heparin & penicillin
● Tannins & alkaloids.

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Drug Antagonism
3) Physiological Antagonism
● Physiological effect is antagonized.
● Drugs acting on different receptors:
● Noradrenaline → Vasoconstriction → ↑ BP.
● Histamine → Relax vascular smooth → ↓BP.
● Noradrenaline is used in anaphylactic shock to
raise BP.
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Drug Antagonism
4) Pharmacological Antagonism
● Two drugs compete for the same receptor.
● The antagonist partially or completely prevents the
pharmacological agonist effect.
● Pharmacological antagonist
⮚ Competitive
■ Reversible
⮚ Non-competitive
■ Irreversible
102
● Competitive Antagonist
● The antagonist dissociates rapidly from the
receptor.
● The antagonist effect can be overcome by
increasing the agonist concentration.
● The dose-response curve is shifted to right.
● Dose-Response curve is parallel.
● Emax is maintained.
e.g. acetylcholine and atropine.
Write on ur book 103
● Noncompetitive Antagonist

● The antagonist dissociates very slowly or not

at all from the receptor .
● The action of antagonist cannot be overcome
by increasing the agonist concentration .
● The dose -response curve is shifted to right.
● The two curves are not parallel.
● Emax is not maintained. 104
105
Variation in drug response
● Drug resistance
● Tolerance

106
Drug resistance
● The loss of the effectiveness of antimicrobial
drugs .
● Due to tolerance of microorganisms to
inhibitory action of antimicrobials.
● eg. streptococci to penicillin

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Tolerance
● A gradual decrease in response to repeated
administration of a drug.
● Slow in onset (takes days or weeks to
develop).
● Original effect can be produced by increasing
the dose.
● e.g. alcohols, morphine, barbiturates.

108
 Unit II
Drugs acting on
Autonomic Nervous
System
I- Physiological functions of autonomic
nervous system
The Autonomic Nervous System has two
branches, the Sympathetic and the
Parasympathetic, which regulate the involuntary
processes of the body, the viscera, and sense
organs, glands and blood vessels. Its anatomical
circuitry is broadly dispersed, creating a general
response, quite unlike the highly specific
pathways and response of the CNS. This
generalized; widely distributed structure enables it
to mediate overall changes in state of the body.
 Nervous System

Peripheral Central

Somatic
Autonomic System
System

Parasympatheti Sympatheti
Skeletal c c
Muscle
111
112
A- Function of the sympathetic
nervous system:
Although situations, continually active
to some degree, the sympathetic
division has the property of adjusting
in response to stressful situations,
such as trauma, fear, hypoglycemia,
cold, or exercise.
1- Effects of stimulation of the sympathetic division:
The effect of sympathetic output is to increase heart rate and
blood pressure, to mobilize energy stores of the body, and to
increase blood flow to skeletal muscles and the heart while
diverting flow from the skin and internal organs.
Sympathetic stimulation results in dilatation of the pupils and
the bronchioles. It also affects gastrointestinal motility (it
decrease), and the function of the bladder and sexual organs.
Functions of the parasympathetic nervous system:
The parasympathetic division maintains essential bodily
functions, such as digestive processes and elimination of
wastes, and is required for life. It usually acts to oppose or
balance the actions of the sympathetic division and is
generally dominant over the sympathetic system in "rest and
digest" situations. The parasympathetic system is not an entity
as such, and never discharges as a complete system. Instead,
discrete parasympathetic fibers are activated separately, and
the system functions to affect specific organs, such as the
stomach or eye.
 Cholinergic Receptors

Muscarinic Receptors Nicotinic Receptors

M1 M2 NN
(Nerve Cells) (Heart & SM) NM Autonomic ganglia,
(Neuromuscular) Adrenal medulla &
CNS
M3 M4
(SM &
(Heart & SM)
Glands)

116
 Adrenergic Receptors

α-adrenergic receptors ß-adrenergic receptors

(Epinephrine > Isoproterenol) (Isoproterenol>Epinephrine)

α1-adrenergic α2-adrenergic ß 3-
ß 1-adrenergic
receptors receptors adrenergic
receptors
(Phenylephri (Clonidine > receptors
(EPI = NE)
ne Phenylephrine (NE > EPI)
> Clonidine) )
ß2-adrenergic
receptors
(EPI > NE)

117
II- Neurotransmitters - Receptors
All neurons are distinct anatomic units, and no structural continuity exists
between most neurons. Communication between nerve cells and between
nerve cells and effector organs, occurs through the release of specific
chemical signals, called neurotransmitters, from the nerve terminals. This
release is triggered by the arrival of the action potential at the nerve ending,
leading to depolarization. Uptake of Ca²+ ensues to initiate docking of the
synaptic vesicles and release of their contents.
The neurotransmitters rapidly diffuse across the synaptic gap (synapse) and
combine with specific receptors on the postsynaptic cell (target cell).
A- Types of neurotransmitters:
Acetylcholine and norepinephrine (noradrenaline)
are the primary chemical signals in the autonomic
nervous system.
1- Acetylcholine:
The autonomic nerve fibers can be divided into two
groups based on the chemical nature of the
neurotransmitter released. If transmission is mediated
by acetylcholine, the neuron is termed cholinergic.
Acetylcholine mediates the transmission of nerve
impulses in both the sympathetic and parasympathetic
nervous systems.
1- Adrenergic receptors:
The adrenergic receptors are of two
types: alpha (α) and beta (β).
-α receptors:
They are associated mainly with
increased contractibility of
vascular smooth muscle and
intestinal relaxation.
α 1: contracts smooth muscle of
peripheral blood vessels:
α 2: relaxes the intestinal tract
-β receptors:
They are associated with vasodilatation and
relaxation of non-intestinal smooth muscle and
cardiac stimulation.
β 1: causes cardiac stimulation and lipolysis
β 2: causes bronchodilatation. Relaxation of blood
vessels (usually skeletal muscle) and muscle
glycogenolysis.
2- Cholinergic receptors:
The cholinergic receptors are of two types: muscarinic
and nicotinic.

-Muscarinic receptors:
Those receptors are found on ganglia of the peripheral
nervous system and on autonomic effector organs,
such as the heart, smooth muscle, brain and exocrine
glands.
-Nicotinic receptors:
Nicotinic receptors are located in the
central nervous system, adrenal
medulla, autonomic ganglia, and the
neuromuscular junction.
III- Sympathomimetic agents
(Adrenergic Agonists)

The adrenergic drugs affect receptors that are

stimulated by noradrenaline or adrenaline
(norepinephrine or epinephrine). Some
adrenergic drugs act directly on the adrenergic
receptor by activating it, and are said to be
Sympathomimetic.
These drugs may either directly or indirectly
stimulate the adrenergic receptors.
B-Classification of
Sympathomimetics:
Sympathomimetic agents can be
classified by two different ways:
1- According to Structure:
∙ Catecholamines:e.g.adrenaline,
noradrenaline, isoprenaline, dopamine and
dobutamine.
∙ Non-Catecholamines.
2- According to relative receptor selectivity:
∙ Mixed agonists:
- Epinephrine (α1, α2, β1,
β2)
- Dopamine (β1 > α1)
∙ Mainly α agonists:
- Norepinephrine (α1, α2, β1)
- Nasal decongestant non-catecholamines:
Phenylephrine, naphazoline.
C- Main adrenergic agonists:
Adverse effects:
∙ It can cause anxiety, headache, hypertension,
and tachycardia.
∙ It should be used cautiously in-patients who
have hyperthyroidism, ischemic heart
disease, and arrhythmia.
 2- Norepinephrine (Noradrenaline)
Therapeutic uses:
∙ Hypotension and shock: to restore
normal blood pressure by its
vasoconstriction effect;
∙ Prolongs the action of local
anesthetics;
Adverse effects:
(same of epinephrine
3- Isoprenaline (Isoproterenol):
Therapeutic uses:
∙ Acute bronchial asthma;
∙ Cardiac stimulant in instances of heart block;
Adverse effects:
∙ Tachycardia;
∙ Arrhythmia.
4- Dopamine:
Therapeutic uses:
∙ Treatment of shock, including cardiogenic, trauma
or hypovolemic shock;
∙ Resistant heart failure;
Adverse effects:
∙ Large doses have similar adverse effects of
epinephrine.
- Dobutamine:
Therapeutic uses:
∙ Treatment of shock;
∙ Acute heart failure.
- Albuterol, Pirbuterol, and Terbutaline:
These drugs are short-acting β2
agonists used primarily as
bronchodilators.
These drugs produce
Bronchodilatation with less cardiac
stimulation.
7- Salmeterol and Formoterol:
Salmeterol and Formoterol are β2 adrenergic
selective, long-acting bronchodilators. A
single dose provides sustained
Bronchodilatation over 12 hours compared
with less than 3 hours for Albuterol.
IV-Adrenergic Antagonists
The adrenergic antagonists (also called blockers
or sympatholytic agents) bind to adrenoceptors
but do not trigger the usual receptor-mediated
intracellular effects. These drugs act by either
reversibly or irreversibly attaching to the
receptor, thus preventing its activation by
endogenous catecholamine's.
A- α-adrenergic blocking agents:
∙ Prazosin
∙ Terazosin
∙ Doxazosin
∙ Tamsulosin
1- Anti-hypertensive:
Prazosin, terazosin and Doxazosin are indicated in
the treatment of hypertension.
The first dose of these drugs produces an
exaggerated hypotensive response that can result in
syncope (fainting). This action, termed as first-dose
effect may be minimized by reducing the first doses
and giving the drug at bedtime.
- Treatment of Benign Prostatic Hypertrophy:
Tamsulosin is indicated for the treatment
of benign prostatic hypertrophy.
Tamsulosin has little effect on the blood
pressure.
3- Adverse effects:
α-blockers may cause dizziness, a lack of
energy, nasal congestion, headache, drowsiness,
and orthostatic hypotension.
B- β-adrenergic blocking agents:
All the clinically available β-blockers are
competitive antagonists. Nonselective β-
blockers act at both β1 and β2 receptors,
whereas cardioselective β antagonists
primarily block β1 receptors.
Β-antagonists are mainly indicated in
1- Propranolol
Propranolol is the prototype β-adrenergic antagonist
and blocks both β1 and β2 receptors.
Therapeutic uses:
∙ Hypertension
∙ Glaucoma
∙ Migraine (prophylaxis)
∙ Angina perctoris
∙ Myocardial infarction
Adverse effects:
∙ Bronchoconstriction
∙ Arrhythmia
∙ Sexual impairment
∙ Disturbances in glucose metabolism
2- Other Nonselective β antagonists
∙ Timolol
∙ Nadolol
3- Selective β1 antagonists
∙ Acebutolol
∙ Atenolol
∙ Metoprolol
∙ Esmolol
These drugs preferentially block the β1 receptors without the
unwanted bronchoconstriction effect of propranolol seen in
asthmatic patients.
4- Antagonists with partial agonist activity:
∙Pindolol
∙Acebutolol

Acebutolol and Pindolol are not pure antagonists; instead, they have the ability to
weakly stimulate both β1 and β2 receptors, and are said to have intrinsic
sympathomimetic activity (ISA). These partial agonists stimulate the β-receptor to
which they are bound, yet they inhibit stimulation. The result is a diminished effect
on cardiac rate and cardiac output compared to that of β-blockers without ISA.
β-blockers with ISA are effective in hypertensive patients with moderate
bradycardia, because a further decrease in heart rate is less pronounced with these
drugs.
5- Antagonists of both α and ß adrenoreceptors:
∙Labetalol
∙Carvedilol

Labetalol and Carvedilol are reversible ß-blockers with

concurrent α1-blocking actions that produce peripheral
vasodilatation, thereby reducing blood pressure. They contrast
with the other ß-blockers that produce peripheral
vasoconstriction, and are therefore useful in treating
hypertensive patients for whom increased peripheral vascular
resistance is undesirable.
V-Cholinergic agonists
A- Direct-acting cholinergic agonists
1- Acetylcholine:
Acetylcholine is rapidly inactivated by the
cholinesterase, which makes it with no therapeutic
importance.
It decreases the heart rate and the cardiac output, and
decreases the blood pressure.
In the gastrointestinal tract, it increases salivary
secretion and stimulates intestinal secretions and
motility.
Bronchiolar secretions are also increased.
2- Bethanecol:
It is used in urologic treatment to stimulate the atonic bladder, particularly
in postpartum postoperative no obstructive urinary bladder.

3- Carbachol:
Carbachol is used as miotic agent in glaucoma

4- Pilocarpine:
Pilocarpine is the drug of choice in the emergency lowering of intraocular
pressure.
B- Indirect-acting cholinergic agonists:
1- Anticholinesterases (reversible):
∙ Physostigmine, Neostigmine
∙ Tacrine, Donepezil

Physostigmine and neostigmine are mainly used in

glaucoma.
Tacrine and donepezil are used to prevent the progression
of Alzheimer disease.
2- Anticholinesterases (irreversible)
These drugs are extremely toxic. They are mainly
used to treat glaucoma.
VI-Cholinergic antagonists
A- Atropine
Therapeutic uses:
∙ Treat spastic disorders of the gastrointestinal and
lower urinary tract
∙ In ophthalmology, to produce Mydriasis
∙ To treat poisoing from irreversible
anticholiesterases
∙ To suppress respiratory secretions prior to surgery
B- Scopolamine
Therapeutic uses:
∙ To prevent motion sickness
∙ Anti-spasmodic
C- Ipratropium
Therapeutic use:
∙ Treatment of asthma
Pharmacology I
Level 5

Lecture 7
Local Anesthetics

By
Dr. Asmaa Malash
Contents:
I. Overview

II. Classification

III. Chemistry

IV. Onset and Duration of Action

V. Actions

VI. Allergic Reactions

VII. Systemic Local Anesthetic Toxicity

I. Overview
 Local anesthetics
(LAs)
● Local anesthetics (LAs) are drugs
which upon topical application or
local injection cause reversible loss of
sensory perception, especially of
pain, in a restricted area of the body.
● The most widely used of the local anesthetic
compounds are bupivacaine, lidocaine, mepivacaine,
procaine, ropivacaine, and Tetracaine.

● Lidocaine is probably the most commonly used.

● Bupivacaine is noted for its cardiotoxicity.
● Mepivacaine should not be used in obstetric
anesthesia due to its increased toxicity to the
neonate.
 II.
Classification
 Classification

1. Topical (surface) application: Cocaine,

Benzocaine
2. Local injection: Procaine, Bupivacaine,
Mepivacaine
3. Both topical and local injection: lidocaine.
 Classification
Surface
Injectable
Anaesthetic

1) Low potency, short 1) Soluble

duration ▪ Cocaine
▪ Procaine ▪ Lidocaine
2) Intermediate potency ▪ Tetracaine
and duration ▪ Benoxinate
▪ Lidocaine (Lignocaine) 2) Insoluble
3) High potency, long ▪ Benzocaine
duration ▪ Butylaminobenzoate
▪ Tetracaine (Butamben)
▪ Bupivacaine
III. Chemistry
● The clinically useful LAs are weak bases with amphiphilic
property.
● A hydrophilic secondary or tertiary amine on one side and a
lipophilic aromatic residue on the other are joined by an
alkyl chain through an ester or amide linkage.
⮚ Ester linked LAs: Cocaine, procaine, chloroprocaine,
tetracaine, benzocaine.
⮚ Amide linked LAs: Lidocaine, bupivacaine,
prilocaine, ropivacaine.
● Ester linked LAs have short duration, less intense analgesia
and higher risk of hypersensitivity, so the ester linked LAs
are rarely used for infiltration or nerve block, but are still
used topically on mucous membranes.
IV. Onset and
Duration of
Action
● Onset and duration of action of local anesthetics are
influenced by several factors. These include tissue pH, pKa
of the drug, nerve morphology, concentration, and lipid
solubility of the drug. Of these, the most important are pH
of the tissue and pKa of the drug.
● At physiologic pH, these compounds are charged. The
ionized form interacts with the protein receptor of the
sodium channel to inhibit its function and, thereby, achieve
local anesthesia.
● The pH may drop in sites of infection, which causes
onset to be delayed or even prevented.
● Within limits, higher concentration and greater lipid
solubility improve onset to some degree.
● Duration of action depends on the length of time the
drug can stay in the nerve to block sodium channels.
V. Actions
1. Local anesthetics cause vasodilation, which leads
to rapid diffusion away from the site of action
and results in a short duration of action when
these drugs are administered alone.
2. By adding the vasoconstrictor (epinephrine) to the
local anesthetic, the rate of local anesthetic diffusion
and absorption is decreased. This both minimizes
systemic toxicity and increases the duration of
action.
3. Hepatic function does not affect the duration of action
of local anesthesia, which is determined by
redistribution and not biotransformation.
4. Lidocaine has antiarrhythmic effect when
administered intravenously.
VI. Allergic
Reactions
● Patient reports of allergic reactions to local anesthetics are fairly
common, but investigation shows that most of these are of
psychogenic origin.
● Psychogenic reactions are often misdiagnosed as allergic
reactions and may also mimic them, with signs such as urticaria,
edema, and bronchospam.
● True allergy to an amide is exceedingly rare, whereas the ester
procaine is somewhat more allergenic.
● An allergy to one ester rules out use of another ester, because
the allergenic component is the breakdown product para-
aminobenzoic acid, and metabolism of all esters yields this
compound.
● In contrast, an allergy to one amide does not rule out use of
another amide.
N.B.
● A patient may be allergic to other compounds in the local
anesthetic, such as preservatives in multidose vials.
VII. Systemic
Local
Anesthetic
Toxicity
● Toxic blood levels of the drug may be due to
repeated injections or could result from a single
inadvertent (unintentional) IV injection.

● Aspiration before every injection is paramount to safety.

● The most important step in treating local anesthetic

toxicity is to consider the diagnosis in any patient
with altered mental status or cardiovascular instability
following injection of local anesthetic.

● CNS symptoms (either excitation or depression of the

CNS) may be apparent but may also be subtle,
nonspecific, or absent.
● Treatment for systemic local anesthetic
toxicity includes:
1. Airway management
2. Support of breathing and circulation
3. Seizure suppression
4. Cardiopulmonary resuscitation if needed.
5. Administering a 20 % lipid emulsion infusion
(lipid rescue therapy) is a promising asset in
treating local anesthetic toxicity.
Dental pharmacology
I
Level 5

Lecture 8
Pharmacology of
Vasoconstrictors
 :Contents

I. Overview
II. Adrenergic Drugs
III. Vasoconstrictors in Dentistry
IV. Clinically Used Vasoconstrictors
in Dentistry
V. Contraindications to Using
Vasoconstrictor
I. Overview
The general outlay of autonomic nervous system.
N = Nicotinic, M = Muscarinic, α = α-adrenergic, β = β-adrenergic
Functions of the sympathetic nervous system
The sympathetic division has the property of adjusting in response to
stressful situations, such as trauma, fear, or exercise.
Effects of stimulation of the sympathetic division:
The effect of sympathetic output referred to as Fight or flight response
these reactions are triggered by direct sympathetic activation to release
epinephrine is:
● Increase heart rate (tachycardia) .
● Increase blood pressure.
● Mobilize energy stores of the body.
● Increase blood flow to skeletal muscles and the heart.
● Dilation of the pupils (Mydriasis) and dilation of the bronchioles
(Bronchodilatation).
● Decrease gastrointestinal motility .
● Constriction of the sphincter of bladder.
●
Functions of the parasympathetic nervous system

The parasympathetic division maintains essential

bodily functions, such as digestive processes and
elimination of wastes. It usually acts to oppose or
balance the actions of the sympathetic division.
● Decrease or slow heart rate (Bradycardia)
● No effect on blood pressure.
● Miosis of the pupils and constriction of the
bronchioles.
● Increase gastrointestinal motility.
● Relaxation of the sphincter of bladder.
● Increase secretions of glands except sweat glands
and adrenal gland.
 II. ADRENERGIC
DRUGS
(Sympathomimetic
s)
 Drugs affecting the sympathetic nervous system

● Drugs that act directly on the adrenergic receptor (adrenoceptor) and activate
them are said to be sympathomimetics.
● Blockers of adrenoceptors are called sympatholytics
● These are drugs which affect presynaptic adrenergic function.

4/10/2016 197
Classification
 1. Mode of Action
● These are drugs with actions similar to that of Adr or of
sympathetic stimulation.

1. Direct acting sympathomimetics

● They act directly as agonists on α and/or β-adrenoceptors

2. Indirect acting sympathomimetics

● They act on adrenergic neuron to release NA which then
acts on the adrenoceptors.

3. Mixed action sympathomimetics

● They act directly as well as indirectly
 2. Chemical
Structure
▪ Classification by chemical structure is related to the
presence or absence of a catechol nucleus.

1. Catecholamines:
Adrenaline- Noradrenaline- Isoproterenol- Dopamine-
Dobutamine.

2. Noncatecholamine:
Ephedrine- Pseudoephedrine- Amphetamine- Terbutaline-
Albuterol.
 HO CH2 CH NH2 TYROSINE
COOH

tyrosine hydroxylase
Synthesis of HO

catecholamines HO CH2 CH NH2 DOPA

COOH

aromatic L-amino acid decarboxylase

HO

HO CH2 CH2 NH2 DOPAMINE

dopamine β-hydroxylase
HO

HO CH CH2 NH2 NOREPINEPHRINE

OH

phenylethanola mine-
HO N-methyltransferase

HO CH CH2 NH EPINEPHRINE
OH CH3 4/10/2016 202
3. According to Relative
Receptor Selectivity
1. Mixed agonists:
● Epinephrine (α1, α2, β1, β2)
● Dopamine (β1 > α1)

2. Mainly α agonists:
● Norepinephrine (α1, α2, β1)
● Nasal decongestant non-catecholamines: Phenylephrine,
Naphazoline.

3. Mainly β agonists:
● Non selective β stimulants: Isoprenaline.
● Selective β1 stimulants: Dobutamine and Prenalterol.
● Selective β2 stimulants: Salbutamol and Terbutaline

(Bronchodilator)
Adrenergic Receptors
● The adrenergic receptors are of two types: alpha (α) and
beta (β).
α receptors:
● They are associated mainly with increased contractility of
vascular smooth muscle and intestinal relaxation.
1. α 1: contracts smooth muscle of peripheral blood
vessels:
2. α 2: relaxes the intestinal tract
β receptors:
● They are associated with vasodilatation and relaxation of
non-intestinal smooth muscle and cardiac stimulation.
1. β 1: causes cardiac stimulation and lipolysis
2. β 2: causes bronchodilatation. Relaxation of blood
vessels (usually skeletal muscle) and muscle
glycogenolysis.
Major effects mediated by α and β adrenoceptors
III. Vasoconstrictors
in Dentistry
● What happens if you don’t use a
vasoconstrictor?
Plain local anesthetics are vasodilators by nature
1) Blood vessels in the area dilate.
2) Increase absorption of the local anesthetic into the
cardiovascular system.
3) Higher plasma levels 🡪 increased risk of systemic
toxicity.
4) Decreased depth and duration of anesthesia 🡪
diffusion from site.
5) Increased bleeding due to increased blood
perfusion to the area.
▪Why You Need Vasoconstrictors?
Vasoconstrictors resemble adrenergic drugs and are called
sympathomimetic, or adrenergic drugs.

1. Constrict blood vessels 🡪 decrease blood flow to the surgical site

2. Cardiovascular absorption is slowed 🡪 lower anesthetic blood

levels

3. Local anesthetic blood levels are lowered 🡪 lower risk of

systemic toxicity

4. Local anesthetic remains around the nerve for longer periods 🡪

increased duration of anesthesia.
IV. Clinically Used
Vasoconstrictors in
Dentistry
 1. Epinephrine
Therapeutic uses:
1. Acute bronchial asthma: to relieve
bronchospasm.
2. Cardiac arrest: to restore cardiac rhythm.
3. Anaphylactic shock: it is the drug of choice to
overcome the physiological effects of histamine
(substance which causes the Anaphylactoid
reaction)
4. Prolongs the action of local anesthetics: by
vasoconstriction, it increases the time the local
anesthetic is in contact with the affected
tissue.
 1. Epinephrine
(Cont.)
Adverse effects:
1. It can cause anxiety, headache,
hypertension, and tachycardia.
2. It should be used cautiously in patients who
have hyperthyroidism, ischemic heart
disease, and arrhythmia.
Dental pharmacology
I
Level 5

Lecture 9
 Antiseptics&
Disinfectants

By
Dr. Asmaa Malash
 :Contents

I. Overview
II. Properties of an Ideal
Antiseptic/Disinfectant
III. Spectrum of Activity
IV. Mechanisms of Action
V. Factors which Modify the
Activity of Germicides
VI. Classification
VII. Antiseptics and Disinfectants
in Dentistry
I. Overview
● The terms antiseptic and disinfectant indicate an agent
which inhibits or kills microbes on contact.

● Antiseptic: agents used on living surfaces (patient’s

mouth, dentist’s hands, etc.)
● Disinfectant: those used for inanimate objects
(instruments, working surfaces, water supply, etc.).
● Germicide covers both category of drugs.
● Sterilization means complete killing of all forms of
microorganisms.
● Disinfection refers to reduction in the number of viable
pathogenic microbes to a level that they do not pose a
risk to individuals with normal host defense.
● Sanitization and Decontamination also have similar
implication. Thus, in ordinary usage, disinfectants
do not eliminate all microbes.

● Many instruments are sterilized by autoclaving, but

certain instruments, working surfaces and
operating light handles, etc. cannot be autoclaved;
have to be sanitized by disinfectants.
II. Properties of an Ideal
Antiseptic/Disinfectant
A good antiseptic/disinfectant should be:
1. Chemically stable.
2. Cheap.
3. Non-staining with agreeable color and odor.
4. Cidal and not merely static, destroying spores as
well.
5. Active against all pathogens—bacteria, fungi,
viruses, protozoa.
6. Active even in the presence of blood, pus,
exudates and excreta.
7. Require brief time of exposure.
8. A disinfectant in addition should not corrode or
rust instruments and be easily washable
10. Antiseptic in addition should be:
⮚ Rapid in action and afford sustained protection.
⮚ Non-irritating to tissues, should not delay
healing.
⮚ Non-absorbable, produce minimum toxicity if
absorbed.
⮚ Non-sensitizing (no allergy).
⮚ Compatible with soaps and other detergents.
III. Spectrum of
Activity
● Spectrum of activity of majority of antiseptic-
disinfectants is wide, reflecting non-selectivity of
action. However, some are rather selective, e.g.
● Hexachlorophene, chlorhexidine, quaternary
ammonium antiseptics, gentian violet and acriflavin
are more active on gram-positive than on gram-
negative bacteria.
● Silver nitrate is highly active against gonococci.
● Benzoyl peroxide against P. acnes.
IV. Mechanisms of
Action
● Mechanisms of action of germicides are varied, but
can be grouped into:
1. Oxidation of bacterial protoplasm.
2. Denaturation of bacterial proteins including
enzymes.
3. Detergent like action increasing permeability of
bacterial membrane.
V. Factors which Modify
the Activity of
Germicides
Factors which modify the activity of germicides
are:
1. Temperature and pH.
2. Period of contact with the microorganism.
3. Nature of microbe involved.
4. Size of innoculum.
5. Presence of blood, pus or other organic matter
VI. Classification
1. Phenol derivatives: Phenol, Cresol, Hexylresorcinol,
Chloroxylenol, Hexachlorophene, Triclosan.
2. Oxidizing agents: Pot. Permangnate (KMNO4), Hydrogen
peroxide, Benzoyl peroxide.
3. Halogens: Iodine, Iodophores, Chlorine, Chlorophores.
4. Biguanide: Chlorhexidine.
5. Quaternary ammonium (Cationic): Cetrimide,
Cetylpyridinium chloride, Benzalkonium chloride.
6. Soaps: of Sod. and Pot.
7. Alcohols: Ethanol, Isopropanol.
8. Aldehydes: Formaldehyde, Glutaraldehyde.
9. Acids: Boric acid, Acetic acid.
10. Metallic salts: Silver nitrate, Mild silver protein, Zinc
sulfate, Calamine, Zinc oxide.
11. Dyes: Gentian violet, Acriflavine, Proflavine.
VII. Antiseptics
and
Disinfectants in
Dentistry
Dental pharmacology
I
Level 5

Lecture 10
Drugs and Aids with
Specific Application
in Dental Disorders
By
Dr. Asmaa Malash
:Contents

I. ANTIPLAQUE AND
ANTIGINGIVITIS AGENTS
II. ANTICARIES DRUGS
III. DESENSITIZING AGENTS
IV. OBTUNDANTS
V. MUMMIFYING AGENTS
VI. BLEACHNG AGENTS
VII. DISCLOSING AGENTS
VIII. DENTIFRICES
I. ANTIPLAQUE
AND
ANTIGINGIVITIS
AGENTS
● Plaque is a tenaciously adherent soft deposit on the
tooth surface, composed mainly of bacterial
aggregates embedded in a matrix of polysaccharides
and glycoproteins, that resists removal by ordinary
brushing and rinsing.

● Plaque is the primary causative factor in both dental

caries and periodontal diseases.

● The salivary glycoproteins get adsorbed on the tooth

surface and form a thin membrane-like pellicle over it
within minutes after brushing. With time, the
glycoprotein molecules cross-link and form an
insoluble coating over the tooth. The resident oral
bacteria anchor on this coating and gradually develop
● As the plaque grows and ages, gram negative and
anaerobic bacteria predominate.

● Bacterial products like lactic acid, ammonia, hydrogen

sulfide and other toxic metabolites generated in the
plaque irritate gingival margins and produce
inflammation (gingivitis).

● Enzymes like hyaluronidase and collagenase

produced by the pathogens damage the connective
tissue support to the teeth; gums become spongy and
periodontal disease develops.
● Periodontal disease can be prevented as well as
treated by inhibiting plaque formation and removing it
mechanically before it produces inflammatory
changes.

● The two most important properties of an

antiplaque agent are:
1) Antimicrobial spectrum covering the relevant
microbes.
II. ANTICARIES DRUGS
The drugs are:
1) Fluoride: makes tooth more resistant to caries
and has weak antibacterial action.
2) Antiplaque agents (mainly chlorhexidine and
triclosan): reduce the population of cariogenic
bacteria.

Other preventive measures for caries are:

3) Restriction of sugar containing food
4) Frequent brushing of teeth
5) Prevention of xerostomia by good hydration
and other measures, since dryness of mouth
promotes caries.
III. DESENSITIZING
AGENTS
● Desensitizing agents are those which applied to the
teeth diminish dentine sensitivity (also called
dentine hypersensitivity), i.e. shooting pain triggered
from sensitive tooth by thermal (hot and cold),
mechanical (touch, chewing) or chemical (sour and
sweet food) stimuli.

● Dentine may get exposed to external stimuli due to

enamel damage caused by chewing hard
substances, age related tooth attrition, erosion by
acidic food at the crown.
● The desensitizing agents aim to interrupt this pain-
inducing process by either creating a plug in the
dentinal tubules, or by modulating the generation
of painful nerve impulses.

● The commonly used desensitizing agents are:

1. Potassium nitrate
2. Strontium chloride
3. Potassium oxalate
4. Fluoride
5. Formaldehyde
6. Dentine bonding agents
IV. OBTUNDANTS
● Obtundants are almost obsolete drugs which when
applied to the teeth and gums produce a kind of
numbness that could dampen toothache due to
cavity formation and other causes, as well as pain
of excavation.

● They penetrate poorly and do not relieve deep

seated or sharp pain.
V. MUMMIFYING
AGENTS
● Mummification connotes hardening of dead
tissue and rendering it resistant to microbial
attack and degradation.

● Mummifying agents used earlier in dentistry

are protoplasmic poisons having astringent
and preservative properties.

● .
Commonly used mummifying agents were:

1. Formaldehyde or Paraformaldehyde (Paraform)

mixed with zinc oxide or zinc sulfate + creosote and
made into a paste for filling in the root canal.

2. Iodoform + Phenol made into a paste with glycerine

● To improve the smell of the paste, eugenol and
cinnamon oil were generally added.
● The liberated iodine as well as phenol kept the
pulp uninfected.

3. Tannic acid
VI. BLEACHNG
AGENTS
● These are agents used to remove stains from teeth or to
improve their whiteness.
● Most of the bleaching agents act by oxidizing the
stain/yellowish coating on the enamel, but few reducing
agents also have stain removing action.
1. Oxygen releasing agents:
● They release oxygen which reacts with the organic
pigment to decolorize it and loosen it from tooth surface. It
is then washed off to expose the white enamel.
● e.g. Hydrogen peroxide, Carbamide peroxide, Sodium
peroxide

2. Chlorine releasing agent:

● Bleaching powder (chlorinated lime) slowly releases
chlorine which acts as an oxidizing agent and decolorizes
many dyes.
3. Reducing agent:
● Sodium thiosulfate is a reducing agent which is used
for removing certain stains, e.g. iodine stain.
● Sequential application of an oxidizing agent followed
by a reducing agent may be needed for silver stain.

4. Silica:
● It is a nonabrasive adsorbent which has been included
in some whitening toothpastes and tooth powders.

● Use of LASER for whitening the teeth is increasing.

VII. DISCLOSING
AGENTS
● Are dyes used to facilitate clear visualization of dental
plaque.

● By staining the bacterial plaque deeply, they increase the

contrast between plaque and the gums.
● Dyes selected for the purpose are those which:
⮚ have higher affinity for the bacterial plaque than for

oral mucosa/teeth
⮚ are not bad tasting, irritating or toxic.
⮚ diffuse uniformly and stain all supragingival plaque.
⮚ are easily washed off by rinsing after plaque removal.

● Dyes used as disclosing agent are:

1) Erythrosine
2) Fluorescein
3) Two-tone dye
VIII.
DENTIFRICES
● These are powders or pastes used as hygiene aids
for routine dental care during brushing.
● Dentifrices facilitate cleaning of teeth and gums,
improve their appearance and control bad breath.
● They may be medicated to impart specific preventive
and therapeutic properties.