VPT 311: General and Systemic Veterinary Pharmacology (2+1)

DRUG INTERACTIONS

• A veterinarian is often posed with the necessity of treating a patient with more than one drug simultaneously. It is highly probable that one drug might affect the action of the other, the result of which may be beneficial or harmful to the patient. A clinician should possess adequate knowledge about such interactions to avoid any adverse effects.
• Drugs exhibit synergism or antagonism
• Synergism: It is the cooperation between two drugs where the presence of one drug facilitates or increases the action of the other. It can be of two types:
• Synergism – additive (1+1 = 2) the net effect is only the sum of the individual effects. eg. Aspirin + paracetamol ( analgesic + antipyretic), ephedrine + theophylline (bronchodilator)
• Supraadditive or potentiation (1+1 = 3) net effect is more than the sum of the individual effects
• Sulfonamide + trimethoprim ( bacteriostatic becomes bactericidal), Ach + physostigmine --- (inhibition of breakdown)
• Antagonism: Refers to a decrease or reversal of the pharmacologic response of one drug by another drug. The drug which antagonizes the action of one drug is called an antagonist. Antagonism is of the following types:
• Antagonism – (1+1 = 0 or < 1)
• Can be
• physical – based on physical property – adsorption of alkaloids by charcoal
• chemical – based on chemical property – antacids like NaHCO, chelating agents BAL, EDTA for heavy metals
• Physiological or functional
• histamine and adrenaline – on bronchial muscle
• Insulin and glucagons – on blood sugar
• Receptor antagonism – antagonist binds with the receptor and inhibits generation of response may be competitive or non competitive

Competitive and Non-competitive

• Competitive antagonism: The antagonist is chemically similar to the agonistand compete for the same binding site. The antagonist blocks the effect of the agonist and the antagonistic effect can be overcome by increasing the concentration of the agonist. It is also called surmountable antagonism. Eg: acetylcholine and its antagonist atropine.
• Noncompetitive antagonist: The antagonist is not chemically related to the agonist but modifies the binding of the agonist to the receptor by binding to another site. The antagonistic effect cannot be overcome by increasing the concentration of the agonist. It is also called unsurmountable antagonism. Eg: Acetylchloline and decamethonium.
• Pharmacokinetic antagonism: where one drug alters the action of the other drug by preventing or reducing any one of the pharmacokinetic processes such as absorption, distribution, biotransformation and excretion.
• Eg: Antacids prevent the absorption of other drugs (absorption)
• Aspirin displaces warfarin from its plasma protein binding site (distribution)
• Microsomal inducers and inhibitors modulate the metabolism of other drugs (biotransformation)
• Probenecid antagonizes penicillin excretion by competing for the binding site (excretion)