Pharmacodynamics

pharmacodynamics

1. Pharmacodynamics Yousaf khan IPMS- KMU

2. Pharmacodynamics Gr. Pharmacon : drug; dynamis : power Cover all the aspect relating to what the drug does the to body Mechanism of action, pharmacological action and adverse effect

3. Types of drug action Stimulation : act like increasing the activity of specialized cell e,g adrenaline – heart – increase heart rate and force of contraction. Depression : act like decreasing the activity of specialized cell e.g alcohol, general anaesthtics depress CNS Irritation : certain agents on topical application can cause irritation of the skin and adjacent tissue e.g methyl salicylate useful in joint pain Replacement : deficiency of endogenous substances can be replace by drug e.g insulin in diabetes mellitus Cytotoxic : Drug are selective toxic for the infecting organism/cancel cell e.g antibiotics, anticancer

4. Mechanism of Drug action Receptor mediated Non-Receptor mediated

5. Non-receptor mediated mechanism of action of drugs B y physical action: O smosis : act as exerting an osmotic effect e.g 20% mannitol in cerebral oedema Adsorption : activated charcoal adsorbs toxin hence it is used in the treatment of drug poisoning. Demulcent : Cough syrup produce a soothing effect in pharyngitis by coating the inflamed mucosa Radioactivity : Radioactive isotopes emit rays and destroy the tissue

6. Non-receptor mediated mechanism of action of drugs 2. By chemical action: Antacids are weak bases – neutralise gastric acid – useful in peptic ulcer e.g antacid, ENO, Trisil etc Metal like iron, copper, mercury etc are eliminated from the body with the help of chelating agent. Trap metal – water soluble complex – excreted e.g dimercaprol in arsenic poisoning

7. Non-receptor mediated mechanism of action of drugs 3. Through Enzyme : drug act by inhibiting the enzyme activity e.g ACE inhibitor such captopril, enalapril 4. Through ion channels: drug directly bind to ion channels and alter the flow of ion e.g local anaesthetic block sodium channels in neuronal membrane to produce local anaesthesia . 5. Through antibody production: vaccine produce their effect by stimulating the formation of antibodies e.g vaccine against tuberculosis 6. T ransporters: Some drugs produce their effect by binding to transporters e.g SSRIs – bind to 5-HT transporter – block 5-HT reuptake into neuron – antidepressant effect 7. Others: Anticancer drugs e.g cyclophosphamide – binding to nucleic acids

8. Receptor- Mediated Mechanisms Receptor: Macromolecules present on the cell surface, cytoplasm or in the nucleus – drug bind and interacts to produce cellular changes e.g adrenergic receptor ( alpha and beta) etc Affinity : ability of the drug to get bound to the receptor Intrinsic Activity : ability of the drug to produce pharmacological action after combing with the receptor Agonist : drug that have capable of producing pharmacological action after binding to receptor Agonist has high affinity + high intrinsic activity e.g morhine etc

9. Receptor- Mediated Mechanisms Antagonist : drug that prevents binding of agonist to its receptor or block its effect its does not produce any effect itself. Competitive antagonist : : drug has high affinity with out intrinsic activity Partial agonist : a drug that bind to the receptor but produce an effect less than that of an agonist, it block effect of agonist Inverse agonist: it has full affinity towards the receptor but produce effect opposite to that of an agonist

10. Receptor Families Ligand-gated ion channels (inotropic receptors) G-Protein coupled receptors (Metabotropic receptor) Enzymatic receptors Receptor regulating gene expression or the nuclear receptor

11. Ligand-gated ion channels (inotropic receptors) Location: membrane Effector: ion channels Coupling: direct Time required for response: milliseconds Example: nicotonic , GABA receptor Binding of agonist to iontropic receptor – open the ion channels ( Na, K, Ca , Cl ) – Flow of ions through channels – hyperpolarization/ depolarization – tissue response.

12. G-Protein coupled receptors (Metabotropic receptor) Location: membrane Effector: channels or enzyme Coupling: G proteins ( Gs , Gi , Gq , etc ) Time required for response: Second G protein membrane protein and have three subunits ( α , β and γ ) G protein coupled receptor control cell function via adenylyl cyclase , phospholipase C and Ion channels

13. Binding of agonist to receptors – coupling of G protein to the receptor – GDP bound to α subunit exchange with GTP -- Subunit of Gs protein dissociates and activates adenylyl cyclase -- When hormone is no longer present, the receptor reverts to its resting state. GTP on the subunit is hydrolyzed to GDP, and adenylyl cyclase is deactivated.

14. Enzymatic receptor Location: membrane Effector: enzyme Coupling: direct Time required for response: hours Example: insulin, growth factor, cytokine recptore Binding of agonist to extracellular domain of enzyme linked receptor – dimerization of the receptor – stimulates intrinsic/ cytosolic kinase activity – activate intracellular signaling pathways – gene transcription – tissue response

15. Nuclear receptor Location: intracellular Effector: Gene Transcription Coupling: Via DNA Time required for response: Hours Example: Steroid, thyroid hormone receptor

16. Regulation of receptors Regulate by various mechanism resulting in either their up regulation or down regulation Receptor down regulation: Prolonged use of agonist – ↓↓ receptor number and sensitivity -- ↓↓ drug effect Receptor up regulation: Prolong use of antagonist -- ↑↑ receptor number and sensitivity on sudden stoppage of antagonist -- ↑↑ response to agonist

17. Thank you Dear Students