Cell Signaling 4 2020 PDF

Cell Signaling 4 Stuart Cruickshank So why is any of this relevant to me?  Pharmacology The study of the manner in which the function of living systems is affected by chemical substances How do drugs produce their biological response? Site of action...

Cell Signaling 4 Stuart Cruickshank So why is any of this relevant to me?  Pharmacology The study of the manner in which the function of living systems is affected by chemical substances How do drugs produce their biological response? Site of action Mechanism of action  How is Pharmacology Studied? In vitro studies: Tissue is isolated from the body Drug is added to the tissue and some biological parameter is assayed In vivo studies: Drug is applied to the whole body Complicated by many factors (distribution, metabolism, and the interaction between different systems)  Measurements in Pharmacology Need to provide objective data on the effects of drugs Foundation of pharmaceutical industry and clinical pharmacology research Measure drug binding to receptors or physiological response of cells or organisms  Drug-Receptor Interaction D + R DR DR* Cell’s Response Agonist - a chemical substance which binds to a receptor and activates it, thereby producing a cell’s response.  In vitro Pharmacology Acetylcholine Force Transducer Air Pen Recorder 1g 32oC 0.03 0.1 0.3 1μM ACh Waste Chemical Transmission between Nerve and Muscle CH3 O + 1 H3C N CH2 CH2 O C CH3 CH3 Acetylcholine Stimulator Force Transducer Air Pen Recorder 1g Waste  Types of Agonist Effect Full Agonist: Ability to elicit a maximum response Partial Agonist: Never elicit maximum response even if all receptors occupied Inverse Agonist: ??  H3C CH3 O CH3 N + H2 C OH H H O C H2 N + H3C O OH H3C H Tubocurarine Antagonist - a drug which binds to a receptor, thereby preventing the binding of agonist and blocking its biological response Stimulator Force Transducer Air Pen Recorder 1g Waste  DRUG ANTAGONISM Competitive –Reversible -Irreversible Non-competitive Chemical Pharmacokinetic Physiological  DRUG ANTAGONISM Competitive antagonism: Both agonist and antagonist compete for binding to the same A g o nis t receptor. A g o nis t + A nt a g o nis t Re s p o ns e Reversible Binding: A g o nis t + Mo r e Increasing [agonist] A nt a g o nis t reverses antagonist effect. Log [ A gonis t ]  DRUG ANTAGONISM Competitive antagonism: Both agonist and antagonist compete for binding to the same A g o nis t receptor. Re s po ns e A g o nis t + Irreversible Binding: A nt a g o nis t Increasing [agonist] does not reverse antagonist A g o nis t + Mo r e effect. A nt a g o nis t Lo g [ A g o nis t ]  DRUG ANTAGONISM Non-competitive antagonism: Antagonist block response by inhibiting at some point other than the agonist receptor. e.g. Effect of tetrodotoxin inhibiting acetylcholine response. Chemical antagonism: Not common. Chemical reaction inactivating the agonist. e.g. Dimercaprol reversing the enzyme inhibition of mercury  DRUG ANTAGONISM Pharmacokinetic: Affects the pharmacokinetics of the agonist by reducing absorption, increasing excretion or degradation of the agonist. e.g. The effect of phenobarbitone on warfarin Physiological: Has opposite effect by affecting different system/receptor. e.g. Histamine and Salbutomol.  Summary Drugs produce their biological response via specific sites and mechanisms of action. Drugs may be classified as agonists or antagonists depending on the biological response. Drug development relies on understanding this pharmacological effect.