Lecture 1 Pharmacodynamics


Published on


  • Sorry 'Agonist are the drugs that block the response' I don't quite understand this doesn't an agonist elicit the same response that the receptor would otherwise have done? For example Pilocarpine stimulates muscarinic receptors
    Are you sure you want to  Yes  No
    Your message goes here
  • is it possible to share
    Are you sure you want to  Yes  No
    Your message goes here
No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

Lecture 1 Pharmacodynamics

  1. 1. Pharmacodynamics Dr Rizwan Ashraf
  2. 2. Lecture Objectives <ul><li>To understand the basic concepts regarding </li></ul><ul><li>pharmacodynamics </li></ul><ul><li>To define agonist and antagonists and other </li></ul><ul><li>terms in relation to pharmacodynamics </li></ul><ul><li>To explain the mechanism of drug receptor </li></ul><ul><li>interaction </li></ul><ul><li>Define spare receptors </li></ul><ul><li>To differentitate between different tyes of </li></ul><ul><li>antagonism </li></ul>
  4. 5. <ul><li>Action of a drug on the body </li></ul><ul><li>receptor interactions, </li></ul><ul><li>mechanisms of therapeutic </li></ul><ul><li>dose-response phenomena, </li></ul><ul><li>toxic action . </li></ul>
  6. 7. <ul><li>A drug will not work unless it is bound </li></ul><ul><li>AGREED or NOT AGREED </li></ul>
  7. 8. <ul><li>BOUND WITH WHAT ? </li></ul>
  8. 9. <ul><li>PARTICULAR CONSTITUENTS OF </li></ul><ul><li>CELLS & TISSUES IN ORDER TO </li></ul><ul><li>PRODUCE AN EFFECT </li></ul><ul><li>PROTEINS </li></ul><ul><li>LIPIDS </li></ul><ul><li>DNA </li></ul><ul><li>RECEPTORS ? </li></ul>
  9. 10. ARE THERE DRUGS THAT ACT WITHOUT BEING BOUND TO ANY OF THE TISSUE CONSTITUENTS <ul><li>YES </li></ul><ul><li>OR </li></ul><ul><li>NO </li></ul>
  10. 11. YES <ul><li>OSMOTIC DIURETICS </li></ul><ul><li>OSMOTIC PURGATIVES </li></ul><ul><li>ANTACIDS </li></ul><ul><li>HEAVY METALS CHELATING AGENTS </li></ul>
  11. 12. BUT <ul><li>PRINCPLES REMAIN TRUE FOR GREAT MAJORITY </li></ul><ul><li>THAT IS _____________________ </li></ul><ul><li>______________________________. </li></ul>
  12. 13. Most drugs act through Receptors
  13. 14. Receptors
  14. 15. Drug Receptor <ul><li>A macromolecular component of a cell with which a drug interacts to produce a response </li></ul><ul><li>Usually a protein </li></ul>
  15. 16. <ul><li>Receptors must be biologically important molecules </li></ul><ul><li>Receptors must have structural features that permit drug specificity </li></ul><ul><li>Receptors must have a drug-binding site and a biologically active site </li></ul>
  16. 17. Characteristics of Receptors       a. specificity       b. selectivity of response       c. sensitivity
  17. 18. Molecules capable of serving as Receptors
  18. 19. <ul><li>Enzymes </li></ul><ul><li>Membrane proteins </li></ul><ul><li>glycoproteins, lipoproteins) </li></ul><ul><li>Nucleic acids </li></ul><ul><li>Complex polysaccharides </li></ul>
  19. 20. <ul><li>Many drugs inhibit enzymes </li></ul><ul><ul><li>in the patient (ACE inhibitors) </li></ul></ul><ul><ul><li>in microbes (sulfas, Penicillins) </li></ul></ul><ul><ul><li>in cancer cells (5-FU, 6-MP) </li></ul></ul>
  20. 21. Types of Protein Receptors <ul><li>Regulatory – mediate the action of endogenous chemicals e.g. hormones, NT,autocoids </li></ul><ul><li>Enzymes – may be inhibited or activated e.g. dihydrofolate reductase receptor for methotrexate </li></ul><ul><li>Transport – e.g. Na + /K + ATP’ase for digitalis glycosides </li></ul><ul><li>Structural – e.g. tubulin,receptor for colchicine </li></ul>
  21. 22. <ul><li>some drugs bind to: </li></ul><ul><ul><li>the genome (cyclophosphamide) </li></ul></ul><ul><ul><li>microtubules (vincristine) </li></ul></ul>
  22. 23. <ul><li>Non-receptor Mediated Effects </li></ul><ul><li>Interaction with small molecules (e.g. binding of heavy metals) </li></ul><ul><li>Interaction with enzymes (e.g. sulfonamides, digitalis) </li></ul><ul><li>Incorporation into a macromolecule (e.g. some anticancer agents - purine and pyrimidine analogues) </li></ul><ul><li>Nonspecific effects (e.g. membrane perturbation by general anesthetics) </li></ul>
  23. 24. <ul><li>Receptor-independent drug actions </li></ul><ul><li>Chemically reactive agents </li></ul><ul><ul><li>Disinfectants </li></ul></ul><ul><ul><li>Alkylating anticancer drugs </li></ul></ul><ul><li>Physically active agents </li></ul><ul><ul><li>Mannitol </li></ul></ul><ul><ul><li>Hydrogen peroxide </li></ul></ul><ul><li>Counterfeit biochemical constituents </li></ul><ul><ul><li>5-bromouracil </li></ul></ul>
  24. 25. Antagonists tend to up regulate receptors   Receptor regulation    1.   Homeostasis    2. Up and down regulation    3. Desensitization    4. Tolerance <ul><li>agonists desensitize receptors </li></ul><ul><li>homologous </li></ul><ul><li>(decreased receptor number) </li></ul><ul><li>heterologous </li></ul><ul><li>(decreased signal transduction </li></ul>
  25. 26. Pharmacodynamics Drug receptor interaction
  26. 27. <ul><li>D + R DR Complex </li></ul>Drug - Receptor Binding Affinity
  27. 28. Drug Receptor Interaction DR Complex Effect
  28. 29. Theories of the  relationship between  binding and response
  29. 30.      a. Occupation theory       D + R  DR  RESPONSE :response is proportional to the fraction of occupied  receptors :maximal response occurs when all the receptors are occupied
  30. 31. <ul><li>  Ariens </li></ul><ul><li>response is proportional to the fraction of  </li></ul><ul><li>occupied receptors  AND  the   intrinsic activity  </li></ul><ul><li>Stephenson </li></ul><ul><li>response is a  FUNCTION  of occupancy </li></ul><ul><li>maximum response can be produced  </li></ul><ul><li>WITHOUT 100% occupation,  </li></ul><ul><li>i.e. tissues have   spare receptors </li></ul>
  31. 32. BIOLOGICAL STIMULUS PERCENT RECEPTOR OCCUPANCY 0% 100% BIOLOGICAL RESPONSE RECEPTOR RESERVE TRETHOLD 0% 100% Max Effect Threshold Effect Schematic representation of the relationship between threshold, receptor reserve, receptor occupancy, biological stimulus and biological response
  32. 33. Receptors are said to be spare for a given pharmacological response when the maximal response can be elicited by an agonist at a concentration that does not result in occupancy of the full complement of available receptors
  33. 34. <ul><li>Spare receptors </li></ul><ul><li>More receptors available than needed </li></ul><ul><li>to elicit maximum response </li></ul><ul><li>allow maximal response without total receptor occupancy – increase sensitivity of the system </li></ul><ul><li>Agonist has to bind only a portion of </li></ul><ul><li>receptors for full effect </li></ul>
  34. 36. Some terminologies regarding drug receptor interaction <ul><li>Affinity </li></ul><ul><li>Efficacy </li></ul><ul><li>Potency </li></ul><ul><li>Ligand </li></ul>
  35. 37. Affinity: measure of propensity of a drug to bind receptor; the attractiveness of drug and receptor Efficacy: Potential maximum therapeutic response that a drug can produce. Potency: A mount of drug needed to produce an effect.
  36. 38. <ul><li>POTENCY </li></ul><ul><li>OR </li></ul><ul><li>EFFICACY </li></ul>Which one is important while selecting a drug for therapy ?
  37. 39. <ul><li>Ligand: </li></ul><ul><li>Molecules that binds to a receptor </li></ul>
  38. 40. Classification of Ligands a.   agonist b.  partial agonist c.  antagonist pharmacological vs. physiological vs. chemical        pharmacological antagonists        -  competitive             surmountable           -  noncompetitive
  39. 41. <ul><li>AGONIST </li></ul>
  40. 42. Agonists <ul><li>Drugs that cause a response </li></ul><ul><li>Drugs that interact with and activate receptors; </li></ul><ul><li>They possess both affinity and efficacy </li></ul><ul><li>Types </li></ul><ul><li>Full agonists </li></ul><ul><li>An agonist with maximal efficacy (response) </li></ul><ul><li>has affinity plus intrinsic activity </li></ul><ul><li>Partial agonists </li></ul><ul><li>An agonist with less then maximal efficacy </li></ul><ul><li>has affinity and less intrinsic activity </li></ul>
  41. 43. Agonists differing in potency and maximum efficacy
  42. 44. Response Dose Full agonist Partial agonist Agonist Dose Response Curves
  43. 45. [D] (concentration units) % Maximal Effect 0.01 0.10 1.00 10.00 100.00 1000.00 0.0 0.2 0.4 0.6 0.8 1.0 Partial agonist Full Agonist Partial agonist PARTIAL AGONISTS - EFFICACY Even though drugs may occupy the same # of receptors, the magnitude of their effects may differ.
  44. 46. Antagonists <ul><li>Interact with the receptor but do </li></ul><ul><li>NOT change the receptor </li></ul><ul><li>Have affinity but NO efficacy </li></ul><ul><li>Block the action of other drugs </li></ul><ul><li>Effect only observed in presence of </li></ul><ul><li>agonist </li></ul>
  45. 47. Types of Antagonists <ul><li>Competitive </li></ul><ul><li>(Surmountable) </li></ul><ul><li>decrease apparent </li></ul><ul><li>Potency </li></ul><ul><li>Noncompetitive </li></ul><ul><li>decrease </li></ul><ul><li>apparent maximum </li></ul><ul><li>efficacy </li></ul>
  46. 48. Competitive Antagonist <ul><li>competes with ________for receptor </li></ul><ul><li>surmountable with increasing agonist </li></ul><ul><li>concentration </li></ul><ul><li>displaces agonist dose response curve to </li></ul><ul><li>the ___________(dextral shift) </li></ul><ul><li>reduces the apparent affinity of the </li></ul><ul><li>__________. </li></ul>
  47. 49. Noncompetitive Antagonist <ul><li>drug binds to receptor and stays bound </li></ul><ul><li>irreversible – does not let go of receptor </li></ul><ul><li>produces slight dextral shift in the agonist DR curve in the low concentration range </li></ul><ul><li>but, as more and more receptors are bound (and essentially destroyed), </li></ul><ul><li>the agonist drug becomes incapable of eliciting a maximal effect </li></ul>
  49. 52. What happen when you increase agonist concentration even higher
  50. 53. How do non competitive antagonist affect receptor function
  51. 55. <ul><li>Summary </li></ul><ul><li> (T or F) </li></ul><ul><li>Pharmacodynamics is the study of absorption, distribution, </li></ul><ul><li>metabolism and elimination of drug. </li></ul><ul><li>Some drugs can act without binding to a receptor </li></ul><ul><li>spare receptors allow maximum response without </li></ul><ul><li>full receptor occupancy </li></ul><ul><li>Efficacy is the amount of drug needed to produce an </li></ul><ul><li>effect. </li></ul><ul><li>Affinity is the attractiveness between 2 drug molecules. </li></ul><ul><li>Agonist are the drugs that block the response. </li></ul><ul><li>Partial agonist has affinity and maximum efficacy. </li></ul><ul><li>Antagonist has efficacy but no affinity. </li></ul><ul><li>Competitive antagonist decreases potency </li></ul><ul><li>Non competitive antagonist decreases efficacy </li></ul>