LECTURE ON PHARMACOLOGY

DRUG ACTION
A. Drug taken by mouth goes through 3 phases
I. Pharmaceutic Phase – 1ST Phase
 When a tablet or capsule is taken by mouth, it must become a solution, so
that it can cross the biological membrane.
Pharmaceutic Process
A. Disintegration – small particles
B. Dissolution – liquid form
Excipients
 fillers and inert substances used in drug preparation to allow drug. to take on a
particular size and shape to enhance dissolution
Na and K
 Drug additives that increase the absorbability of a drug.
Rate Limiting
 the time it takes the drug to disintegrate and dissolve to become available in the
body to absorb
*** drugs in liquid forms – more rapidly absorb in thee G.I than are solids
*** drugs are both disintegrated and absorbed faster in acidic fluids with pH of 1 or 2
rather than in alkaline fluids.

II. Pharmacokinetic Phase – 2nd Phase

 process of drug movement to achieve drug action
Composed of 4 Processes
1. Absorption
 movement of the drug practices from the G.I tract to body fluids by passive
absorption – active absorption or pinocytosis.
Remember:
 Most oral drugs are absorbed in the surface of the small intestine through action
of extensive mucosal villi

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  Absorption is reduced if the villi are decreased in number because of the
diseases
 drug effect, or removal of the small intestine.
 Protein based drugs such as insulin and growth hormone are destroyed in the
small intestine by digestive enzymes
A) Passive Absorption
 occurs mostly by diffusion (movement from higher concentration to lower
concentration) with diffusion the drug does not require an energy to move across
the membrane
B) Active Absorption
 requires a carrier such as an enzyme or protein to move the drugs against
concentration gradient.
C) Pinocytosis
 process by which can carry drug across their membrane by engulfing the drug
particles.
Remember:
 G.I membrane is composed mostly of lipid (fat protein) so that drugs that are lipid
soluble pass rapidly thorough the G.I membrane.
 water soluble needs a carrier either enzyme or protein to pass through the
membrane.
 Drugs administer by many routes do not pass through the G.I tract or liver –
parenteral drugs, eye drops, nasal sprays, respiratory inhalants, transdermal
drugs and sublingual drugs.

Absorption:
Several GI change my aging that may influence drug absorption.
- decrease in small bowel surface - swallowing difficulties
- slowed gastric emptying - poor nutrient
- reduced gastric blood flow - dependence on feeding tubes
- 5-10 to decrease in gastric
acid production

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Factors that affect drug absorption
- blood flow
- pain
- stress
- hunger
- fasting
- food
- pH
- vasoconstrictor drugs
- disease
- pro circulation as a result of shock

 Foods that are solid, HOT and Fatty – can slow gastric emptying – lime – so the
drugs remain longer in the stomach.
 some drugs do not go directly into the systemic circulation following oral
absorption but pass from the intestinal lumen to the liver via the portal vein. In the
liver some drugs. maybe metabolize to an active from – EXCRETED –
REDUCING the amount of actual drug.
 First pass effect of hepatic first pass – process where some oral drug passes first
to the liver.
 Ex. – MORPHINE/COUMADON

Bioavailability – sub category of absorption

 the percentage of administered drug dose that reaches systemic circulation
 Grab routes of drugs -bioavailability occurs after absorption and hepatic drug
metabolism
 % of bioavailability for the oral routes – loss than 100%
 IV – 100%
 To obtain the desired effect – oral dose could be 3-5 times larger than drug dose
for IV use.

Factors that alter bioavailability include

1. drug form – ex tablet, capsule, sustained release, transdermal patch,
rectal suppository, inhalation
2. route of administration
3. G.I mucosal and motility
4. food and other drugs

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Distribution
 the process by in which the drug becomes available to the body fluids and body
tissues influenced by
1. protein binding
2. blood flow
3. body tissue affinity
As drugs are distributed in the plasma many are bound to varying depress by protein.
1. highly protein bound – 89% ex. furosemide/diazepam
2. moderately highly protein bound – 61 – 89
3. moderately protein bound – 30 – 60 %
4. low protein bound – 30% gentamycin, metformin
 Free drugs are active drugs that are not bound to protect and can cause a
pharmacologic response.

Metabolism or Biotransformation
 drugs that can be both metabolized in the G.I.T. or in the liver
 half life of a drug – the time it takes for ½ of the drug concentration to be
eliminated
Metabolism/Elimination
 affect the half-life of a drug

Remember:
 in liver or kidney, dysfunction the half-life of the drug is prolonged and has drug in
metabolized and eliminated.
 short half-life – 4 – 8
 long half-life - 24 hou rs or longer

Factors that affect the half of a drug

 the amount of administered
 the amount of drug
 metabolism
 elimination

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Excretion or Elimination
 kidney – main route
- liver metabolism
- bile
- feces
- lungs
- saliva
- sweat
- breast milk

III. Pharmacodynamic Phase

 study of drug concentration and its effect on the body drug response can cause
primary or secondary physiologic effect.
the primary effect – desirable
secondary effect – maybe desirable or undesirable

Dose Response
 relation between the minimal versus the amount of drug dose needed to produce
the desired drug response.
 some client responds to a longer drug dose/some need a higher dose to elicit
desired effect.

Maximal Efficacy
 maximum drug effect

Peak Action
 drug reaches its highest bound or plasma concentration
 Ex. IV drug = 3 – 10 mins for peak time

Onset Action

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  the time it takes to reach the (mic) minimum effective concentration after a drug
is administered

Duration of Action
 length of time the drug has a pharmacologic effect
 some drugs produce effects in minute but others may take hours/day

Time Response Curve Evaluates 3 Parameters of Drug Action

a. Onset of Drug Action
b. Peak Action
c. Duration of Action

Agonist
 a drug that produces a response
 Ex. ISOPROTERENOL (ISUPREL)
 stimulates the beta receptor

Antagonist
 a drug that blocks a response
 Ex. CIMITIDINE (TAGAMET)
 blocks the histamine receptors(H2) preventing excessive gastric acid secretions

Non-Specific
 drugs that affect various body sites or multiple receptors sites
 Ex. BETANECHOL
 maybe prescribed for post-operative urinary retention to increase bladder
contraction.
This drug stimulates the cholinergic receptor located in the bladder and urination occurs
by strengthening bladder contraction.
Because cholinergic are affected other cholinergic sites are also affected. The heart rate
decrease BP gastric acid secretion bronchioles constrict and the EYES (PUPIL)
constrict.

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Non-Selective Drugs
 drugs that affect various receptors
 Ex. EPINEPHRINE
 which is used for the treatment of anaphylaxis or severe asthma exacerbation
acts on the alpha, beta and beta receptors affecting multiple body system

8 Categories of Drug Action- Mechanism

1. Stimulation
 a drug that stimulates enhances intrinsic activity
 Ex. ADRENERGIC DRUGS
 increase heart rate, sweating and respiratory rate during fight or flight response.
2. Depression
 depressant drugs decrease neural activity and bodily functions.
 Ex. BARBITURATES/OPIATES
3. Irritation
 act by mechanism of irritation
 Ex. LAXATIVES
 irritate the inner wall of the colon, thus increasing peristalsis- defecation
4. Replacement
 replaces essential body compounds
 Ex. INSULIN
 for DIABETES MELLITUS

5. Inhibition/ Antimicrobial Action

 interfere with bacterial cell growth of micro organism
 Ex. PENICILLIN
6. Cytotoxic Action
 drugs that enhance or depress the immune system

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  Ex. INTERFERON/METHOTREXATE

Therapeutic Index
 estimates margin of safety of a drug through the use of a ration that measures
the effective dose and the lethal dose.
o The closer the ratio is to the greater the danger pf toxicity
o Drugs with a low therapeutic index may have a narrow margin of safety
o Drugs with a high therapeutic index have a wide margin of safety and less
danger of producing toxic effect

Therapeutic Range-Therapeutic Window

 should be between the minimum effective concentration in the plasma for
obtaining desired drug action and the minimum toxic concentration.

Peak Drug Level

 highest plasma concentration of a drug at a specific time which indicate rate of
absorption.
Remember:
 If the drug is given orally- Peak Time might be 1-3 hrs.
 If the drug is given IV – Peak Time in 10 mins

Trough Drug Level

 lowest plasma concentration of a drug and it measures the rate at which the

Peak and Trough Levels

 are requested for drugs that have a narrow therapeutic index and pre considered
toxic.
*** If better the Peak and Trough Level is too high-toxicity
The Peak is too low- No Therapeutic Effect is achieved.

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Loading Dose
 when immediate drug response is desired initial dose is given to achieve a rapid
minimum effective concentration in plasma

Digitalization Process
 concentration level for Digoxin is achieved in the plasma within a short time.

Side Effects
 Physiologic effects not related to desired effects
 All drugs have side effect- Desirable or Undesirable

Adverse Reactions
 more severe than side-effects

Toxic Effect
 dangerous and maybe considered lethal

Pharmacogenetics
 study of genetic factors that influence an individual response to a specific drug

*** NURSES ROLE

 Must integrate knowledge of Pharmacogenetic
 To identify patients at increased risk for adverse drug reactions
 Must monitor patients for therapeutic drug responses
 Prevent complications to drug therapy

Tolerance
 refers to a decreased responsiveness to a drug over the course of therapy
 *** An individual with drug tolerance requires a higher dosage of drug to achieve
the same therapeutic response

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TACHYPHYLAXIS
 An acute rapid decrease in response to drug
 It may occur after the first dose or after several doses
 Ex. NITROGLYCERINE/RANITIDINE

Placebo Effect
 Psychologic Benefit from a compound that may not have the same chemical
structure of a drug effect.
 Response can be positive/negative
 May be influenced by beliefs, attitudes and expectations of a patient.

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