Pharmacodynamics 2023 PDF

‫فارماکولوژی‪،‬‬ ‫داروشناسی نیست!‬ HOW DRUGS ACT? The Pharmacological Basis of Therapeutics Translation into Clinical Practice Ahmad R. Dehpour  Pharmacology (terminology)  Pharmacology can be defined as the study of the effects of drugs on the function of living systems ...

‫فارماکولوژی‪،‬‬ ‫داروشناسی نیست!‬ HOW DRUGS ACT? The Pharmacological Basis of Therapeutics Translation into Clinical Practice Ahmad R. Dehpour  Pharmacology (terminology)  Pharmacology can be defined as the study of the effects of drugs on the function of living systems  Pharmacodynamics (terminology)  Pharmacodynamics is the study of the biochemical, cellular, and physiological effects of drugs and the mechanisms of action. Physiology-Homeostasis (Order) Biochemistry- Metabolism Phathophysiology- Disorders Pharmacology- Receptors The Four Processes of Drug Therapy  The Pharmaceutical Process  The Pharmacokinetic Process  The Pharmacodynamic Process  The Therapeutic Process  Asthma a) Pathophysiology of asthma (Inflammation, Airway Hyperreactivity, Remodeling) b) Differential diagnosis c) Treatment (Goals of Asthma Therapy: Controller or Reliever) Pharmacological-based Therapy Clinical-based Therapy  Drug  A drug can be defined as a chemical substance of known structure other than a nutrient of an essential dietary ingredient, which could administered to a living organism, produces a biological effect.  Medicine  A medicine is a chemical preparation, which usually, but not necessarily contains one of more drugs, administered with the intention of producing therapeutic effect.  Medicine usually contains other substances (excipients, preservatives, solvents, etc.) besides the active drug, to make them more convenient to use. ‘…...We may, I think, without much rashness, assume that there is some substance or substances in the nerve endings or gland cells which both atropine and pilocarpine are capable or forming compounds. On this assumption then the atropine or pilocarpin compounds are formed according to some law of which their relative mass and chemical affinity for the substances are factors’. G.N. Langley 1878  Corpora Non Agunt Nisi Fixata. (Substances do not act unless bound). Paul Ehrlich (1913) The Binding of Drugs Molecules to Cells We should gratefully acknowledge Paul Erlich for insisting that drug action be explicable in terms of conventional chemical interactions between drugs and tissues, and for dispelling the idea that the remarkable potency and specificity of action of some drugs put them somehow out of reach of chemistry and physics and required the intervention of magical “vital forces”. If a Receptor & its Distribution known Pharmacological profile could be expected e.g. Opioid Receptors: μ, δ and κ  e.g. Morphine known acute effects: Analgesia, sedation, respiratory depression, euphoria, agitation, itching, nausea /vomiting, constipation, hypotension, bradycardia, broncoconstriction,…. physical  Chronic uses: Tolerance and dependence psychological Drugs Action in Relation to the Level of Biological Organization  Molecular level of drug action  Drug action on subcellular structures.  Drug action on cells  Drug action on tissues and organs.  Drug action in the intact organism.  Drug action and the interaction between organisms. Proteins Targets for Drug Binding Four kinds of regulatory proteins are commonly involved as primary drug targets, namely:  Enzymes  Carrier molecules  Ion channels  Receptors  A few other types of protein (tubulin).  Drug-Receptor Interactions 1. Drugs may inhibit enzymes. 2. Drugs may stimulate enzymes. 3. Drugs may alter the permeability of cell membranes. 4. Drugs may interact with DNA.  Biologic Drugs  A large percentage of the new drugs approved in recent years are therapeutic biologics, including genetically engineered enzymes and monoclonal antibodies.  The new agents will have pharmacological properties that are distinctly different from traditional small-molecule drugs.  e.g. Live oncolytic herpes virus for treating melanoma  Drugs Effects Which Do Not Involve a Receptor 1.Interaction with the function of an organ: a. Osmotic diuretics. b. Osmotic cathartics. 2. Interaction with cell membrane: a. Nonspecific destruction of cell membrane. b. Nonspecific alteration of the structure of neuronal membrane. 3. Interaction of drugs with small molecule or ion. Agonists (Primary, Allostric, Inverse, Partial) Antagonists(Competitive, Non-Competitive) Pharmacological Physiological Chemical Allostric Type of Ligand-Receptor Binding  Ionic Bonds, Protein-NH+3 Protein-coo-  Dipole-Dipole  Hydrogen Bonds  Covalent Bonds  VAN DER WAAL’s Bonds Quantitative Aspects of Drugs Action Dose-response curve (Graded, Quantal) ED50 Potency, Efficacy Affinity, Intrinsic Activity  Pharmacodynamics (terminology)  Hyperreactive (Hypersensitivity)  Supersensitive  Hyporeactive (Tolerance, Tachyphylaxis)  Idiosyncrasy  Allergy  Receptor Related Diseases  Myasthenia gravis  In some forms of insulin-resistance diabetes  Testicular feminization (androgen insensitivity)  Familial hypercholesterolemia, and a number of endocrine diseases  Properties of Receptors  Sensitivity  Selectivity  Specificity  Receptor Regulation Desensitization, Tachyphylaxis Down-regulation Up-regulation  Desensitization and Tachyphylaxis  Desensitization and tachyphylaxis  Tolerance, Refractoriness  Drug resistance Many Different Mechanisms Can Give Rise to This Type of Phenomenon They include:  Change in receptors  Loss of receptors  Exhaustion of mediators  Increased metabolic degradation  Physiological adaptation  Active extrusion of drug from cells  Receptor Classification  Pharmacological analysis  Ligand binding  Molecular cloning  Analysis of the biochemical pathways Chirality and Drug Action  dimerization autophosphorilation SH2 proteins Ras activation Raf, MEK activation MAPK dual phosphorilation Gene transcription