Pharmacodynamics.pptx

Pharmacodynamics, Receptors and their types, G protein coupled receptors, Ion channels, Enzyme linked receptors, Intracellular receptors

1. PHARMACODYNAMICS By Dr. Faraza Javaid

2. Pharmacon = Drug , Dynamics = Action/Power “What a drug does to the body ” Pharmacodynamics describes the actions of a drug on the body.

3. Action How and Where the effect is produced is called as Action. Effect The type of response producing by drug.

4. Site of Drug Action Extra cellular Intracellular

5. Types of Drug Action EFFECT (Type of responses): 1.Stimulation 2.Inhibition/Depression 3.Replacement 4.Irritation 5 .Cytotoxic

6. Mechanism of Action of Drugs Drug act either by receptor or by non receptor or by targeting specific genetic changes. Majority of drugs acts by ( HOW) Receptor mediated Non receptor mediated

7. Receptor Mediated A ction Drug produce their effect through interacting with some chemical compartment of living organism c/s Receptor. Receptors are macromolecules Most are proteins Present either on the cell surface , cytoplasm or in the nucleus

8. Receptors Receptor is  a macromolecule in the membrane or inside the cell that specifically (chemically) bind a ligand (drug) .  Unoccupied receptors does not influence intracellular processes. D rug + R e c ep tor D ru g r e c ep tor c o m p l e x R e s pon se

9. Signal Transduction Signal transduction (also known as cell signaling) is  the transmission of molecular signals from a cell's exterior to its interior . Signals received by cells must be transmitted effectively into the cell to ensure an appropriate response.  Drugs act as signals , and receptors act as signal detectors . “ Second messenger ” or effector molecules are part of the cascade of events that translates agonist binding into a cellular response.

10. Receptor Functions 1. Recognization of specific ligand molecule (Ligand binding domain) 2. Transduction of signal into response (Effector domain) Ligand binding domain Transduction of signal into response

11. Drug R eceptor I nteraction Selectivity :- Degree of complimentary co relation between drug and receptor. Ex:- Adrenaline Selectivity for α, ß Receptor Affinity:- Ability of drug to get bound to the receptor. Intrinsic activity (IA) or Efficacy :- Ability of drug to produce a pharmacological response after making the drug receptor complex.

12. Drug C lassification (on the basis of affinity & efficacy)

13. Response No response

14. Receptor F amilies Four types of receptors families : 1 . Ligand-gated ion channels 2 . G-prot ei n coupled receptor 3 . Enzym e Linked receptors 4 . Intracellular/ Receptor regulating gene expression (transcription factors/ Steroid )

15. Ligand-Gated Ion Channels Ion channels are pore-forming membrane proteins whose function is establishing a resting membrane potential , shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across membranes , and regulating cell volume . Functions : N eurotransmission M uscle contraction

16. G-Protein Coupled Receptor G proteins, also known as  guanine nucleotide-binding proteins , involved in transmitting signals and function as molecular switches. Produce effects by: Adenylyl Cyclase Phospholipase C

17. There are many kinds of G proteins (for example, Gs, Gi, and Gq ), but all types are composed of three protein subunits. The α subunit binds guanosine triphosphate (GTP), and the β and γ subunits anchor the G protein in the cell membrane.

18. GTP GDP  GDP GTP  ATP cAMP Cell response AT Protein kinase ADP P Inactive protein Active protein hormone Adenylate cyclase Signaling System AC R S Inhibitor R i  

19. Varieties of G-protein G-protein Receptor for Signaling pathway/ Effector Gs ß adrene r gic, 5H T , AC— cAMP Gi α 2 adrenergic, Ach, AC— cAMP, Open K + Gq Ach Phospholipase-C, IP 3 Go Neu r ot r a n smi t te r s in brain Not yet clear

20. Enzyme Linked R eceptors A group of transmembrane proteins that contain either intrinsic enzyme activity on their intracellular domain or associate directly with an intracellular enzyme. Receptor tyrosine kinases Tyrosine-kinase-associated receptors Receptor serine/threonine kinases Histidine-kinase-associated receptors Receptor tyrosine phosphatases Receptor guanylyl cyclase

21. Basic Receptor S tructure 1. Ligand -binding domain Extracellular to allow easy access for ligands . B ind to same receptor to produce particular cellular responses. 2. Transmembrane domain Contains a series of hydrophobic amino acids.

22. 3. Cytosolic "active" enzyme domain The intracellular domain of receptor itself is an enzyme or interacts directly with an enzyme.

23. Intracellular/ Receptor The fourth family of receptors differs considerably from the other three in that the receptor is entirely intracellular , and, therefore, the ligand (for example, steroid hormones ) must have sufficient lipid solubility to diffuse into the cell to interact with the receptor. The primary targets of activated intracellular receptors are transcription factors in the cell nucleus that regulate gene expression . The activation or inactivation of transcription factors alters the transcription of DNA into RNA and subsequently translation of RNA into proteins. Other targets of intracellular ligands are structural proteins, enzymes, RNA, and ribosomes.

24. Characteristics of R eceptor F amilies Ligand gated G -protein coupled Enzymatic Nuclear Location Membrane Membrane Membrane Intracellular Effector Ion channel Ion Channel or enzyme Enzyme Gene coupling Direct G-protein Direct Via DNA Example Nicotinic Muscarinic Insulin Steroid , hormone

25. Characteristics of S ignal T ransduction Signal transduction has two important features: T he ability to amplify small signals and Mechanisms to protect the cell from excessive stimulation Desensitization or down regulation of receptor Tachy phylaxis

26. THANK YOU