Pharmacodynamics for BPH

suggestions are welcomed

1. Pharmacodynamics For BPH 1 st Year Dr. Pravin Prasad 2 nd Year Resident, MD Clinical Pharmacology Maharajgunj Medical Campus, Institute of Medicine 22 nd December, 2016 ( Poush 7, 2073), Thursday

2. Introduction “Pharmacodynamics is the study of the biochemical and physiological effects of drugs and their mechanisms of action” - Bluementhal DK, Garrison JC. Pharmacodynamics: Molecular Mechanisms of Drug Action. In: Bruton LL, Chabner BA, Knollmann BC, editors. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. China: Mc Graw Hill Education; 2011. p 41-72 Pharmacodynamics is the study of drug effects What & How

3. Introduction Modification of action of one drug by another drug

4. Principles of Drug Action Stimulation: Selective enhancement of the level of activity of specialized cells Replacement: Use of natural metabolites, hormones, or their congeners in deficiency states Irritation: Non-selective, often noxious effect on less specialized cells Depression: Selective diminution of the level of activity of specialized cells Cytotoxic Action: Selective cytotoxic action on invading microbes or cancer cells

5. Physical interaction Chemical interaction Binding to proteins Binding to Nucleic acids Drug Targets R eceptors I on channels C arriers (transporters) E nzymes Mechanism of Drug Action RICE

6. Drug Target- Enzymes Enzyme stimulation Pyridoxine  decarboxylase Enzyme inhibition Competitive (equilibrium type) Competitive (non-equilibrium type) Non-competitive Non-competitive

7. Drug Target- Enzymes Enzyme Endogenous substrate Inhibitor Type Bacterial folate synthase Para-amino benzoic acid Sulfadiazine Competitive (equilibrium) Cholinesterase Acetylcholine Physostigmine Malathion, OPs Competitive (non-equilibrium) Dihydrofolate reductase DHF Methotrexate

8. Drug Target- Enzymes Enzyme Endogenous substrate Inhibitor Type Carbonic anhydrase H 2 O and CO 2 Acetazolamide Non-competitive H + -K + ATPase H + and K + Omeprazole Cyclooxygenase Arachidonic acid Aspirin

9. Drug Targets- Ion Channels Types: Ligand gated Nicotinic receptors G-protein regulated channels β1 adrenergic receptor activated Ca ++ channels Voltage operated Local anaesthetics, phenytoin, Nifedipine Stretch sensitive

10. Drug Targets- Ion Channels

11. Drug Targets- Transporters (Carriers)

12. Drug Targets- Transporters (Carriers) Carrier Transports Blockers Norepinephrine transporters Noradrenaline (Norepinephrine) Desipramine , Cocaine Gamma butyric acid transporter (GAT1) GABA Tiagabine Na + - K + - 2Cl - co-transporter Na + , K + , Cl - Furosemide Serotonin Transporter Serotonin Fluoxetine

13. Pharmacodynamics For BPH 1 st Year Dr. Pravin Prasad 2 nd Year Resident, MD Clinical Pharmacology Maharajgunj Medical Campus, Institute of Medicine 9 th February, 2017 (Magh 27, 2073), Thursday

14. Drug Targets- Receptors Are the macromolecule or binding site located on the surface or inside the effector cell that serves to recognise the signal molecule/drug and initiate a response to it, but itself has no other function -Tripathi KD. Pharmacodynamics: Mechanism of Drug Action; Receptor Pharmacology. In: Essential of Medical Pharmacology. 7th ed. India: Jaypee Brothers Medical Publishers (P) Ltd; 2014. p 40. Receptors Recognise Response Drug Action Drug Effect

15. Drug Targets- Receptors Receptor Type Examples G-protein coupled receptors Muscarinic receptors, adrenergic receptors Ion channels receptors Nicotinic cholinergic, GABA A , glycine Enzyme-linked Insulin, Epidermal Growth factor, Nerve Growth Factor Transmembrane JAK-STAT binding receptors Cytokines, growth hormone, prolactin, interferons Receptors regulating gene expression Steroids, Vitamin A/D

16. Drug-Receptor Interaction Agonist: Agent which activates a receptor to produce an effect similar to that of the physiological signal molecule Partial agonist: Agent which activates a receptor to produce submaximal effect Inverse agonist: Agent which activates a receptor to produce an effect in the opposite direction to that of the agonist

17. Drug-Receptor Interaction Antagonist: Agent which prevents the action of an agonist on a receptor or the subsequent response, but does not have any effect on its own

18. Dose Response Curve

19. Dose Response Curve: Drug Potency Amount of drug needed to produce a certain response Position of DRC on the dose axis Dictates dose of drug

20. Drug Response Curve: Drug Efficacy Maximal response that can be elicited by the drug Upper limit of DRC Dictates choice of drug

21. Therapeutic Efficacy/Clinical Effectiveness Drug Potency Drug Efficacy Pharmacokinetic variables Pathophysiological variables Therapeutic Efficacy / Clinical Effectiveness

22. Therapeutic Efficacy/Clinical Effectiveness Expressed in terms of: Degree of benefit/relief afforded by the drug (in the recommended dose range) OR Success rate in achieving a defined therapeutic end point

23. Therapeutic window

24. Combined Effect of Drugs Synergism Additive Metformin + Glibenclamide Supra-additive Sulfamethoxazole + trimethoprim Antagonism Physical antagonism Charcoal + alkaloids Chemical antagonism KMnO 4 + alkaloids Physiological antagonism Glucagon & insulin on blood sugar level Receptor antagonism

25. Combined Effects of Drugs- Receptor Antagonism Competitive equilibrium: Acetylcholine & Atropine Competitive non-equilibrium: Phenoxybenzamine + adrenaline ( α receptors) Diazepam & Bicuculline

26. Thank you…