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

ENZYME MEDIATED DRUG ACTION

• Enzymes are ubiquitous biological catalysts – main targets of drug actions Drugs either increase or decrease enzyme mediated reactions Stimulation is done by endogenous sub. (cofactors) vitamins and minerals

Rate of reaction increases

• Enzyme induction – microsomal induction by drugs – increased synthesis of proteins
• Enzyme inhibition – a most common mode of drug action
• Non specific – metal salts, acids, alkalis inhibit nonspecifically
• Specific - particular enzyme affected – either competitive or noncompetitive
• Competitive – competition with normal substrate

Equilibrating type

• Increasing the concentration of normal substrate reverses drug action
• Eg. sulfonamides and PABA for folate synthetase neostigmine and Ach for cholinesterase

Non-equilibrating type

• React with the same site as that of substrate but form strong covalent bonds or have very high affinity than the normal substrate eg.. organophosphates form covalent bond with cholineesterase methotrexate - 50,000 times more affinity for the enzyme DHFR than DHFAcid
• Non-competitive - reacts with some other site and not on the catalytic site but alters the enzyme loss of catalytic property eg.. aspirin – Cyclooxygenase disulfiram – aldehyde dehydrogenase digoxin - Na⁺ K⁺ ATPase