2 receptor ph 2021 xx theory sss pharmacy.pptx

2 receptor ph

1. Receptor Theory Pharmacology I 2022-2023 Dr. Samira Abdulla M Assis. Sara waheed Alkashamy Tripathi 8 th ed Page: 45- 57/ 66-69 1-Generalities about drug actions 2-Receptors , definition, functions 3-Classification of receptors 4-Transducer mechanism 5-Agonists, Antagonists 6-Types of antagonism 7-Receptor theory L. 4

2. 1-Generalities about drug actions (Where , How?) Drug site of drug action cellular site of drug action Functional unit On cell membrane Receptors, ion channels , enzymes most drugs digoxin 2 . Within the cell Carrier protein, DNA, enzymes probenecid &penicillin …. 3. Outside the cell Chemical: antacids , Fe + Desferroxamine Mesna - Scavenging of vasicotoxic reactive metabolites of cyclophosphamide physical: mannitol, Mg SO4, charcoal Main principles of drug action Modification Replacement Cytotoxic action

3. Types of drug actions (modification): Stimulation : adrenaline stimulates heart ( β 1) pilocarpine stimulates salivary glands (m) excessive stimulation is often followed by desensitization ( loss of function) ex. In CNS picrotoxin induce depression Depression : barbiturates depress CNS quinidine depresses heart, omeprazole depresses gastric acid secretion. Acetylcholine : stimulates intestinal smooth muscle but depresses SA node in heart (m 2 ) Irritation : non-selective noxious effect - applied to less specialized cells (epithelium, connective tissue). ...strong irritation results in inflammation/ corrosion/ necrosis and morphological damage. This may result in diminution or loss of function

4. Receptors - Macro-molecular structures that bind ligand and t ranslate this binding into biological responses - Most of them are proteins, others have nucleic acid structures They are located on the cell membrane ( physiological receptors ) - within the cell ( like steroid receptors) - Outside the cell ( Carrier/transporter proteins, especially for reuptake ) 2-Receptors & their Functions

5. HOW DO DRUGS WORK BYACTING ON CELL SURFACE RECEPTORS? Cell Membrane Unbound Endogenous Activator (Agonist) of Receptor Inactive Cell Surface Receptor Extracellular Compartment Intracellular Compartment Epinephrine, Norepinephrine, Ach, Histamine,

6. HOW DO DRUGS WORK BY ACTING ON CELL SURFACE RECEPTORS? Cell Membrane Bound Endogenous Activator (Agonist) of Receptor Active Cell Surface Receptor Extracellular Compartment Intracellular Compartment Cellular Response Ligand Biological response change according to circumstances tachyphylaxis i.e., loss of efficacy with frequently repeated doses

7. 3-Classification of Receptors

8. Physiological Receptors Adrenergic receptors α 1 α 2 β 1 β 2 β 3 Cholinergic receptors m N m N G Dopaminergic receptors D1 D2 Histaminic receptors H1 H2 5-Hyroxytryptamine receptors 5 HT1 5HT2 Aminoacid receptors GABA Glycine GABA a GABA b Asbartate, Glutamate Peptide receptors µ κ δ e nkephalins endorphins Drug receptors o pioid receptors µ κ δ Benzodiazepine receptors Receptors subtypes

9. Examples of receptors of functional families 1. Ligand-gated ion channel nicotinic receptors , GABA a, Glutamate Glycine, Aspartate 2. G-protein coupled receptors muscarinic and adrenergic receptors dopamine, histamine, serotonin, GABA b 3 . Ligang-regulated enzyme peptide hormones, insulin, growth hormones (Catalytic receptors) and certain lymphokines 4. Protein synthesis-regulating receptors Steroid hormones, thyroid hormones, (intracellular receptors) vitamin D

10. Ligand-gated ion channel

11. G-protein coupled receptors

12. Receptor type α1 α2 β 1 β 2 Β 3 Target site Vascular smooth muscle Eye ( Radial muscle, iris) Nerve terminal Pancreas (dominant) Vascular smooth muscle Heart Kidney Central neurons Liver Bronchial smooth muscle Uterus,blood vessels (coronary) Adipose tissue Response Constriction Mydriasis ↓Discharge of Ndr ↓Insulin release Constriction ↑Heart rate, ↑ CC ↑Conduction ↑ Renin release ↑ Noradrenaline discharge Glycogenolysis (↑G, ↑ LA) Relaxation Relaxation Lipolysis (TG) Receptor- Target Site- Response

13. Agonist A drug has affinity and maximal efficacy (IA=1) Partial agonist A drug has affinity and sub-maximal efficacy (IA less than1) Buprenorphine , a partial agonist of opioid, is a generally safer analgesic drug than morphine because it produces less respiratory depression in overdose Antagonist A drug has affinity but no efficacy (IA=0) Invert agonist A drug has affinity with opposite efficacy 4-Transducer mechanism 5- Agonists , Antagonists

14. Back

15. Major functional pathways of G-protein coupled receptors transduction

16. Regulation of receptors p=60+62 Drug synergism p=66+67

17. 6-Types of antagonism Physical antagonism charcoal -morphine Chemical antagonism protamine - heparin Physiological or functional antagonism Pharmacological antagonism competitive non-competitive Antagonism can be useful in some clinical circumstances

18. activated charcoal Back Mesna—Scavenging of vasicotoxic reactive metabolites of cyclophosphamide

19. Competitive inhibition

20. Noncompetitive inhibition

21. Receptor theory: drug-receptor interaction and response generated Occupation Theory of Drug Action : The extent to which a tissue responds depends on the proportion of its receptor population which has become occupied by a drug and the maximal response is reached when the total number of receptors are occupied. Occupation all receptors……..maximal response Partial agonist occupied all receptors…. No max .Res b/c its efficacy is too low to allow a maximal response A drug of high efficacy elicits a maximal response after occupying only a small proportion of receptors

22. 2. Rate Theory of Drug Action : The act of making a drug and receptor associate which donates a unit of stimulus to the cells The greater the number of associations made per unit time the greater is the stimulus provided. For a response to be maintained ,the complex has to break and be re-made . The more rapidly the complex dissociates, the more rapidly can new associations take place Thus for an agonist it is the rate of dissociation which determines potency and this is constant for each drug (dissociation constant-K d

23. Prolonged exposure Desensitization : Following prolonged exposure to agonist , receptors can shift to a state in which they are no longer activated by the agonist. Down-regulation: Loss of response to agonist due to removal or degradation of receptors. Up-regulation: Prolonged exposure to antagonist can lead to increased expression of receptors, resulting in an elevated response (super-sensitivity) to agonist.

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