INTRODUCTION to Pharmacology

What is pharmacology? It is the study of the actions, mechanisms, uses, and adverse effects of drugs A Drug is any natural or synthetic substance that alter the physiologic state of a living organism

Drugs are divided into: Medicinal drugs: These are used in the prevention, treatment and diagnosis of disease Non-medicinal drugs or social drugs: These are used for purposes other than treatment e.g. illegal mood- altering substances such as cannabis, heroin and cocaine

Drugs name and classification Factors that are used to classify drugs: Pharmacotherapeutic action Pharmacologic action Molecular action Chemical nature

Definitions Pharmacodynamics: It is what the drug do to the body i.e. drug actions on the receptor, tissue, organ or system. Pharmacokinetics: It is what the body to the drug i.e. absorption, distribution, metabolism and elimination

Pharmacodynamics

Targets of drugs Receptors Enzymes Ion channels Carrier molecules Physical or Chemical

Drug receptors Highly specific, highly sensitive binding site Found on the surface of the cell membrane, enzyme molecules on nuclear membranes.

Receptor Specificity There are a number of specific ligands and a number of associate receptors Affinity The extent to which the ligand is capable of binding and remains bound to a receptor High affinity: The ligand bind well and remains bound for long enough to activate the receptor Low Affinity: The ligand binds less well and may not remain bound long enough to activate the receptor

The receptor intrinsic activity The extent to which the ligand activates the receptor High intrinsic activity: the ligand produces a large effect on the post synaptic cell Low intrinsic activity: the ligand produces a small or inconsistent effect on the post synaptic cell

Classes of Ligands Agonists High affinity High intrinsic activity Antagonist Low intrinsic activity

Agonists An agonist is a drug that binds to a receptor and activates it to give a response There are 2 types of agonists: Full agonist: is a drug when bound to a receptor produces 100% of the maximum possible biologic response Partial agonist: a drug that produce less than 100% of the maximum possible biologic response no matter how high their concentration

Antagonist An antagonist is a drug that bind to a receptor and produce no response. Type of drug antagonism: Receptor antagonists Competitive: the antagonists competes with the agonist at the same receptor site of an agonist and binds to it reversibly. By increasing the concentration of drug agonist the antagonism is abolished. E.g. antihistamine competes with histamine at its receptor site

Non competitive: the antagonist binds irreversibly to a different site on the enzyme e.g. than the agonist, noncompetitive agonists can not overcome by increasing the concentration of the drug agonist. E.g. succinylcholine is irreversible neuromuscular blocker.

AGONIST R R+ RESPONSE Resting state Activated state -ve -ve ANTAGONIST

Continue … Physiological antagonism: e.g. glucagon and insulin. Histamine and epinephrine Chemical antagonist: is the type of a drug that acts by binding chemically to the compounds and inactivates it. E.g. chelating agents, charcoal (poisoning with iron) Pharmacokinetic antagonist: by increasing the metabolism and excretion of a drug, e.g. enzyme induction to speed metabolism

Dose- response curve The response to increasing doses of an agonist or antagonist are plotted graphically. It can measure the following: Efficacy: is the maximum effect (Emax) which can be obtained from a large dose of the drug. Potency: is the amount (dose) of drug or concentration in the plasma that can produce a similar effect by a dose of another drug

EC50 (Effective concentration): is the concentration that produce 50% of the maximum effect. ED50 (Effective dose): is the dose that produces the response of 50% of subjects LD50 (Lethal dose): is the dose that cause death in 50% of subjects

Non competitive antagonist will bind irreversibly with the receptor leading to decrease in number of receptors available for binding with the agonist This will cause the maximum effect of the agonist to be less than when it is used alone or with competitive antagonist

Therapeutic index Is the ratio between the average maximum tolerated dose LD50 and the average minimal effective dose ED50 TI= LD50/ ED50 It indicates the margin of safety in use of a drug The higher the TI the safer the drug