introduction

Introduction to Pharmacology

At the end of this lecture, the students will be able to:

1. Define bioavailability.

2. State factors affecting drug bioavailability.
3. Define volume of distribution (Vd) of drugs.
4. Enumerate factors that affect Vd.
5. Define metabolism.
6. Define elimination.
Objectives:

Bioavailability of a drug means the amount of drug reach the blood in an active form, available to produce its effect.

Bioavailability is100% for IV drugs

bioavailability is less than 100% for oral drugs


Bioavailability

Pharmaceutical factors

Biological factors

First pass metabolism

Factors influencing bioavailability:

It is the volume of fluid which contains the total amount of the drug at a concentration which is equal to plasma concentration.

Volume of distribution (Vd):

Factors affect Vd are related to:

Characteristic of drug:

Lipid solubility
Degree of protein and tissue binding

patient's characteristics:
a)body size b) plasma protein concentration
c)body water d)fat content


Clinically, drug displacement from albumin is one of the most significant sources of drug interactions.

Tolbutamide (hypoglycemic agent)

&
Sulfonamide (antibiotic)
Competition for binding between drugs:

Metabolism is defined as the enzymatic alteration of drug structure.

Most drug metabolism takes place in the liver.

Metabolism in the liver is performed by hepatic microsomal enzyme system, also known as the CytochromeP450(CYP450) system.

Metabolism (Biotransformation)

Accelerated renal excretion of drugs

Drug inactivation

Increased therapeutic action


Activation of prodrugs

Increased or decreased toxicity of the drugs

Therapeutic consequences of drug metabolism:

Some drugs can increase the activity of the metabolizing enzymes in the liver by increasing their synthesis.

Enzyme inducers can increase the metabolism of other drugs which are administered concomitantly, leading to decrease their serum concentrations and their effects.

Examples: Phenobarbitone, phenytoin,carbamazepine and rifampicin.

Enzyme induction

Some drugs can decrease the activity of the metabolizing enzymes in the liver.

Enzyme inhibitors can decrease the metabolism of other drugs which are administered concomitantly, leading to increase their serum concentrations and their effects.

Examples: Ciprofloxacin, chloramphenicol, erythromycin, cimetidine

Enzyme inhibitors


Drug excretion is defined as the removal of drugs from the body.

Drugs and their metabolites (after being converted to water soluble compound) can exit the body in urine, bile, sweat, saliva, breast milk and expired air.

Excretion (Elimination):