Pharmacodynamics

BSc MLT theory class

1. Pharmacodynamics Dr. Pravin Prasad MBBS, MD Clinical Pharmacology Assistant Professor, Department of Clinical Pharmacology Maharajgunj Medical Campus, TU 14 February 2020 (2 Falgun 2076), Friday

2. By the end of this class, BSc MLT IInd year students will be able to: Explain the term pharmacodynamics and its components List the common drug targets involved in drug action with examples Appraise the different types of: Drug enzyme interaction Drug receptor interaction

3. Introduction

4. Introduction Pharmacodynamics is the study of the biochemical cellular and physiological effects of drugs and their mechanisms of action Pharmacodynamics: What drugs do? Effects How drugs do it? Mechanism

5. Principles of Drug action Stimulation Increased secretion of saliva due to acetylcholine Depression Relaxation of uterine muscle by salbutamol Irritation Local injection of alcohol in refractory neuralgia Replacement Insulin in diabetes milletus Cytotoxic action Antimicrobials

6. Mechanism of Drug action By virtue of physical property Sunscreen By virtue of chemical property Antacids By interacting with protein molecules Colchicine By interacting with nucleic acids Sulfonamides

7. By interacting with macromolecular functional proteins: Ion channels Transporters (Carriers) Enzymes Receptors Drug targets Cellular macromolecule or macromolecular complex with which the drug interacts to elicit a cellular or systemic response. Mechanism of Action of Drugs RICE

8. Drug Targets- Ion channels

9. Drug Targets- Ion channels Ion channels- Modify the intracellular ionic composition of cells Drugs can be used to modify their conductance Drug Ion channel Use Quinidine Myocardial Na + channels Arrhythmia Amiodarone Myocardial K + channels Arrhythmia Ethosuximide T type Ca 2+ channels Epilepsy

10. Drug Targets- Transporters (Carriers)

11. Drug Targets- Transporters 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

12. Drug Targets- Enzymes Enzymes: Optimises the rate of chemical reaction in our body Can be stimulated or inhibited using drugs Increase in activity can also occur by enzyme induction Enzyme stimulation: Thiamine, Pyridoxine: increase decarboxylase activity Metabolism of formaldehyde, formic acid enhanced Enzyme inhibition: Nonselective inhibition: Heavy metal salts, strong acids and alkalis Selective inhibition Competitive (equilibrium, non-equilibrium type) Non-competitive

13. Drug Targets- Receptors 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 Has two sites Ligand binding domain Recognition of physiological molecules/ drugs Effector domain Undergoes functional conformational changes

14. Drug Targets- Receptors Site 1 Site 2

15. Drug Targets- Receptors Types (Based on intracellular signalling molecules) G-protein Coupled receptors α, β receptors, muscarinic receptors Ion channel receptors nicotinic ACh receptors, GABAA receptors Transmembrane-enzyme linked receptors insulin, epidermal growth factors, transforming growth factors Transmembrane JAK-STAT binding receptors cytokines, growth factors, prolactin Intracellular receptors (cytoplasmic/nuclear) glucocorticoids, androgens, thyroxine, vitamin D

16. Drug Targets- Receptors β G α G γ cAMP Phospholipase C Ca 2+ channels K + , Ca 2+ channels

17. Drug Targets- Receptors Agonist binding Site α Na + , K + , Ca 2+ , Cl -

18. Drug Targets- Receptors Agonist binding site Intracellular subunit having enzymatic activity t

19. Drug Targets- Receptors Ligand binding domain Effector domain

20. Conclusion Pharmacodynamics: What drug does, How it does and modification of drug action by another drug Five principles of drug action Drug Targets: mainly proteins (RICE) Other drug targets do exists