3.pharmacodynamics

pharmacodynamics

1. Pharmacodynamics

2. Pharmacodynamics What drug does to the body? The study of physiological and biochemical effects of drugs and their mechanism of action at organ system/subcellular/ macromolecular levels

3. It includes Mechanism of drug action Other pharmacological actions Dose-effect relationship Combined effect of drugs

4. Targets of drug action Receptors Physical/chemical property T ransporters I on channels Enzymes Non receptor

5. Enzymes Drug Enzyme Stimulation Enzyme Inhibition Stimulation - Pyridoxine stimulates decarboxylase Inhibition - Allopurinol inhibits xanthine oxidase

6. Ion channels Drugs can directly bind to ion channels Can affect ion movement through it E.g. – Local anesthetic obstruct voltage sensitive Na + channels - N ifedipine blocks L-type Ca 2+ channels

7. Act by virtue of their physical/chemical property e.g. 1. Activated charcoal – adsorptive 2 . D imercaprol – chelating Physical/chemical property

8. Receptors Macrolecules present either on the cell surface, cytoplasm, or in the nucleus where the drug binds and interact to produce cellular changes.

9. Receptors G-protein coupled Enzyme-linked receptors Receptors with intrinsic ion channels Nuclear receptors

10. Affinity – The ability of the drug to bind with the receptor Intrinsic activity – the ability of the drug to produce pharmacological action after binding to the receptor

11. A gonist – A drug capable of producing pharmacological action after binding to the receptor. Has both affinity & maximal intrinsic activity E.g. adrenaline, histamine Competitive antagonist – Drug that binds to the receptor but cannot produce any action. Has affinity and no intrinsic activity E.g. Propranolol, atropine

12. Non-competitive antagonist – Drug binds to the different site on same receptor and alters receptor in such a way that agonist can no longer bind to it. e.g. bicuculline Drug efficacy – It is maximum effect of the drug. Drug potency – the quantity of a drug required to produce a desired response is potency.

13. Synergism When the action of one drug is facilitated or increased by the other they are said to be synergistic 1 . Acetylcholine + physostigmine 2 . Levodopa + carbidopa

14. Factors modifying drug action 1. Age : Neonates Hepatic and renal functions are not fully developed- less metabolism & less excretion of drug - toxicity e.g. Chloramphenicol – gray baby syndrome in infants

15. Elderly – Hepatic and renal functions decline - less metabolism & less excretion of drug - toxicity e.g Aminoglycoside can cause more nephrotoxicity & ototoxicity hence dose is reduced

16. 2. Genetics : These factors influence drug metaboism , action Succinylcholine causes - succinylcholine apnoea in patients with atypical pseudocholinesterase Sulfonamides causes – hemolysis in G6PD deficiency

17. 3. Psychological states : Belief, expectation, personality of patient and attitude, personality of the doctor – influence drug effect Anxious cases – requires more anesthetic dose N eurotics require larger dose of diazepam

18. Some patients respond to placebo Placebo is a inert substance or dummy medicine having no pharmacological action Effect of placebo depends on Patient Drug Physician

19. 4. Pathological states : GI disorders Malabsorption syndrome – absorption of some drugs reduced Liver disease – Chronic liver disease - decreased metabolism e.g propranolol

20. Renal failure – Decreased excretion – toxicity e.g Aminoglycosides

21. 5. Presence of other drugs : Modification of one drug response by another, when administered together or in quick succession Drug interactions Antacids + iron – forms complex, unabsorbed Penicillin + probenecid – Probenecid inhibits excretion of penicillin

22. 6.Tolerance Repeated administration of certain drugs can results in decrease in their pharmacological effect. Higher doses of such drugs are required to produce a given response. e.g. Ephedrine – bronchial asthma Nitrates – angina pectoris