DRUG MECHANISM

MECHANISMS OF DRUG ACTION (pharmacodynamics) • Pharmacodynamics is study of the effects of drugs on biological processes. • Not all drugs work via receptors but most therapeutic drugs exert their effects by combining w ...

MECHANISMS OF DRUG ACTION (pharmacodynamics) • Pharmacodynamics is study of the effects of drugs on biological processes. • Not all drugs work via receptors but most therapeutic drugs exert their effects by combining with enzymes or transport protein and interfering with its function. • The site of action of drug whether a receptor or macromolecule, binding is usually high specific, with precise steric recognition between small molecular ligand and binding site on its macromolecular target. • Most drugs produce graded concentration effects which can be plotted as a dose-response curve. Receptors and signal transduction • Drugs produce effects at low concentration and specific • Receptors were classified by references to the relative potencies of agonists and preparation containing different receptors. • Receptors fall into four categories, each linked to distinct types of signal transduction mechanism. Three of them are located in the cell membrane, and one is intracellular. • They comprises of: 1. Fast neurotransmitters (e.g. nicotinic receptors), linked directly to a transmembrane ion channel. 2. Slow neurotransmitters and hormones (e.g. muscarinic receptors) linked to an intracellular G-protein. 3. Receptors linked to an enzyme on the inner membrane (e.g. insulin receptors). 4. Intranuclear receptors (e.g. gonadal receptors), ligand bind to their receptor in cytoplasm and the complex then migrate to nucleus and bind to specific DNA site. AGONISTS • Agonists active receptors for endogenous mediators e.g. salbutamol, has effect like increased heart rate and relaxation of airway smooth muscle. • Agonists at nicotinic acetylcholine receptors e.g. suxamethonium exert inhibitory effects by causing long lasting depolarization and the neuromuscular junction thus inactivation of voltage dependent sodium channels that initiate the action potential. ANTAGONISM • Competitive antagonists combine with same receptors as an endogenous agonist but fail to activate it. • When they combine with receptors, they prevent access of the endogenous mediator. • Antagonists that do not combine with the same receptor , reduce the slope of the log dose-response curve and depress its maximum. PARTIAL AGONISTS