Chapter 2

General Principles of Drug Action

General Factors that Characterize the action of all Drugs and that Determine the effective level of any

Therapeutic agent at its site of action

Route of administration Passage across body membrane Absorption Transport and distribution Molecular mechanism of drug action Drug metabolism excretion

A. Route of administration

General Routes of Drug Administration

I. Enteral- (Oral and Rectal)

Oral Dosage forms: tablet, capsule, suspension,

solution, pills etc.

Area of Absorption: gastric and intestinal mucosa

oral

Advantages - Safest

- Most convenient

- Cheapest

Disadvantages- Irritation of the gastric

mucosa- Destruction of some

drugs by the gastric acid

- Variable rate of absorption

- Slow rate of absorption

II. Parenteral ( IV, IM, SC ID)

Intravenous

Advantages- Most rapid and uniform

response- More predictable

response- Useful for

administering drugs that poorly absorbed by other routes

Disadvantages- Produces more side

effects- Drugs can not be

withdrawn once injected

Sublingual routes

Area of absorption : oral mucous membrane Drug is placed under the tongue By- Passed effect Example of drug: Nitroglycerine

B. Passage Across Body Membrane

Types of Body MembraneCell membraneIntracellular membraneBlood capillaries

Composition Phospholipid (40%)Protein (50-60%

Physiochemical propertiesLipid solubilityMolecular size and shapeDegree of ionization

pHPka

Types of Passage ( Transport)

I. Passive transport Simple diffusion filtration

II Specialized transport Active transport Facilitated diffusion Pinocytocis

C. Absorption

movement of molecules from the site of administration to the blood stream

Factors Affecting Absorption

Physiochemical factors that affect passage Dosage form (bioavailability) Drug solubility Area of absorbing surface Drug concentration Blood flow

D. Distribution

Movement of molecules from the blood stream to the different tissues of the body

Factors Contributing to the unequal rate of Distribution

Plasma protein binding Cellular binding Storage in body fats Blood-Brain Barrier

E. Molecular Mechanism of Drug action

Receptors

Affinity

Agonist

Antagonist

Factors affecting Drug activity

1. Antagonism

a. pharmacologic

e.g. histamine + antihistamine

b. physiologic

e.g. diuretics + sympathomimetic amide

c. chemical

e.g. heparin + protamine

2. Additve effect

3. Potentiation

4. Cummulation

5. Tolerance /tachyphylaxis

6. Variation in drug response

Drug Termination

Redistribution Excretion (kidney)

Amount of drug excreted by the kidney depends on the following process

1. passive tubular diffusion ( reabsorption)

2. active tubular secretion

3. filtration

*Metabolism

Chapter 3 Adverse Drug Reactions

Classification1. Toxic

a. exaggerated effect on target organ

b. effects on non target organ (side effect)c. effects on fetal development ( terratogenic)d. local reactione. drug interactions

2. Allergic reactions3. Idiosyncrasy4. Interference in natural defense mechanism