Drug-Receptor Concepts 3 (2023-24).pdf

WEEK 12 Slide 44 of 76 Drug-Drug Interactions MPharm PHA112 Drug Receptor Concepts WEEK Drug-Drug Interactions 12 Drug Antagonism Summation / Additivity Synergism / Potentiation Slide 45 of 76 MPharm PHA112 Drug Receptor Concepts Drug-Drug Interactions WEEK 12 Drug Antagonism ‘in...

WEEK 12 Slide 44 of 76 Drug-Drug Interactions MPharm PHA112 Drug Receptor Concepts WEEK Drug-Drug Interactions 12 Drug Antagonism Summation / Additivity Synergism / Potentiation Slide 45 of 76 MPharm PHA112 Drug Receptor Concepts Drug-Drug Interactions WEEK 12 Drug Antagonism ‘interaction between two drugs such that the effect of one is diminished or completely abolished in the presence of the other’ Types of drug antagonism Competitive antagonism (pharmacological / receptor) Non-competitive antagonism Chemical antagonism Pharmacokinetic antagonism Physiological or Functional antagonism Slide 46 of 76 MPharm PHA112 Drug Receptor Concepts WEEK Drug Antagonism 12 Competitive Antagonism the agonist & antagonist drugs compete for same receptor binding site antagonist drug binding reduces chances of agonist binding   agonist effect 2 subtypes, depending on nature of antagonistreceptor interaction Reversible or surmountable Irreversible or insurmountable Slide 47 of 76 MPharm PHA112 Drug Receptor Concepts Competitive Antagonism WEEK 12 Reversible Competitive Antagonism both the agonist & antagonist drugs bind reversibly to the receptor the fraction of receptors occupied depends on 2 drugs’ relative receptor affinities & concentrations antagonism can be overcome by increasing concentration of agonist drug this leads to two effects on the agonist log D-R curve (in the presence of an effective dose of the antagonist drug) a parallel shift to the right no reduction in the maximal response Slide 48 of 76 MPharm PHA112 Drug Receptor Concepts WEEK Competitive Antagonism 12 100 E Emax 50 0 Agonist Concentration Slide 49 of 76 MPharm PHA112 Drug Receptor Concepts WEEK Competitive Antagonism 12 Irreversible Competitive Antagonism the antagonist drug binds irreversibly to the receptor (due to high affinity or covalent bonding) a fraction of receptors rendered permanently unavailable for agonist drug binding the antagonism cannot be overcome by increasing concentration of agonist drug this leads to two effects on the agonist log D-R curve (in the presence of an effective dose of the antagonist drug) a reduction in the slope of the curve a reduction in the maximal response Slide 50 of 76 MPharm PHA112 Drug Receptor Concepts WEEK 12 Irreversible Competitive Antagonism System Without Spare Receptors 100 E Emax 50 0 Log Agonist Concentration Slide 51 of 76 MPharm PHA112 Drug Receptor Concepts WEEK 12 Irreversible Competitive Antagonism System with Spare Receptors 100 Irreversible Antagonist Log Agonist Concentration Slide 52 of 76 MPharm PHA112 Drug Receptor Concepts WEEK Drug Antagonism 12 Non-competitive Antagonism the antagonist drug does not compete with agonist drug for same receptor binding site the antagonist drug may bind to a different site on the receptor or interfere with response coupling the antagonism cannot be overcome by increasing concentration of agonist drug this leads to two effects on the agonist log D-R curve (in the presence of an effective dose of the antagonist drug) a reduction in the slope of the curve a reduction in maximal response Slide 53 of 76 MPharm PHA112 Drug Receptor Concepts WEEK Non-competitive Antagonism 12 100 E Emax 50 0 Log Agonist Concentration Slide 54 of 76 MPharm PHA112 Drug Receptor Concepts WEEK Drug Antagonism 12 Chemical Antagonism results from direct interaction between the antagonist & agonist drugs the ‘antagonist’ drug binds to / combines with the active drug (‘agonist’) in solution the active drug is rendered inactive or unavailable to interact with its target receptors typical examples protamine vs heparin dimercaprol vs heavy metals (Cd, Pb) Slide 55 of 76 MPharm PHA112 Drug Receptor Concepts Drug Antagonism WEEK 12 Pharmacokinetic Antagonism the ‘antagonist’ drug acts to reduce the effective concentration of the active drug (‘agonist’) at its site of action possible mechanisms reduced absorption from the GIT ferrous salts vs tetracycline antibiotics increased metabolic degradation phenobarbital vs warfarin increased renal excretion NaHCO3 vs aspirin Slide 56 of 76 MPharm PHA112 Drug Receptor Concepts Drug Antagonism WEEK 12 Physiological / Functional Antagonism interaction of two opposing agonist effects in a single biological system  cancelling out of each other’s effect the two drugs elicit opposing responses by acting on different receptors typical examples acetylcholine vs noradrenaline (heart rate) glucocorticoids vs insulin (blood sugar levels) Slide 57 of 76 MPharm PHA112 Drug Receptor Concepts WEEK Summation / Additivity 12 Summation When the combined effect of two drugs which elicit the same overt response, regardless of their mechanism of action, is equal to the algebraic sum of their individual effects Additivity When the combined effect of two drugs, which act by the same mechanism, is equal to that expected by simple addition of their individual effects Slide 58 of 76 MPharm PHA112 Drug Receptor Concepts WEEK Synergism / Potentiation 12 Synergism or Potentiation When the conjoint effect of two drugs is greater than the algebraic sum of their individual effects the synergist may act to increase the concentration of the other drug at its receptor sites tyramine & MAO inhibitors increase the responsiveness of the other drug’s receptor-effector protein benzodiazepines & GABA (GABAA receptor) Slide 59 of 76 MPharm PHA112 Drug Receptor Concepts WEEK 12 Synergism / Potentiation GABAA Receptor Ion channel Slide 60 of 76 MPharm PHA112 Drug Receptor Concepts WEEK 12 Synergism / Potentiation Potentiation By Benzodiazepines Slide 61 of 76 MPharm PHA112 Drug Receptor Concepts