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Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Agonists and dose-response curves - a recap,An agonist is a,ligand,(drug, hormone or transmitter) that combines with receptors to elicit a cellular response,Two types of dose response relationship,GRADED,QUANTAL,The higher the potency, the lower the EC,50,(,cf,relationship between affinity and,K,d,),Full agonists have high efficacy,Partial agonists have lower efficacy,The results shown below were obtained in a comparison of positive,inotropic,agents (drugs used in heart failure to increase cardiac contractility). Which statement is correct?,Drug A is most effective,Drug B is least potent,Drug C is most potent,Drug B is more potent than Drug C and more effective than Drug A,Drug A is more potent than Drug B and more effective than Drug C.,Drug Receptor Antagonists and the Dose-Response Curve,Learning Outcome,Determine whether an antagonist is competitive or irreversible on the basis of its effects on the graded agonist dose-response curve,Use a,quantal,dose-response curve to establish therapeutic index,An antagonist is a drug which blocks the response to an agonist. Pure antagonists do not by themselves cause any action by binding to the receptor.,e.g.,terfenadine,at the H,1,receptor,Antagonist,Efficacy and Antagonists,An antagonist is a drug which blocks the response to an agonist. Pure antagonists do not by themselves cause any action by binding to the receptor,What effect does this have on efficacy?,A + R,AR,AR*,Affinity dependent,Efficacy dependent,Full agonist (high efficacy) -,AR* very likely,Partial agonist (low efficacy) -,AR* less likely,Antagonist (no efficacy) AR* does not exist,The Competitive Antagonist,AGONIST (A) + RECEPTOR (R), AR COMPLEX, ACTION,ANTAGONIST (D) + RECEPTOR (R), DR COMPLEX,In the presence of the competitive antagonist,Agonist curves have the same form,Agonist curves are displaced to the right,Agonist curves have the same maximal response,The linear portion of the curves are parallel,This is because the competitive antagonist,binds reversibly with the receptor,gives rise to antagonism which,can,be overcome by an increased concentration of agonist,The Irreversible Antagonist,AGONIST (A) + RECEPTOR (R), AR COMPLEX, ACTION,ANTAGONIST (D) + RECEPTOR (R) ,DR COMPLEX,In the presence of the irreversible antagonist,Agonist curves do not have the same form,Agonist curves have a reduced maximal response,This is because the irreversible antagonist,binds irreversibly with the receptor,gives rise to antagonism which,cannot,be overcome by an increased concentration of agonist,Competitive versus Irreversible Antagonists,Competitive,common type of antagonism,examples include,cimetidine,at the H,2,receptor,tamoxifen,at the oestrogen receptor,Irreversible,much less common type of antagonism,examples include,phenoxybenzamine,at the,a,1,adrenoceptor,DOSE-RESPONSE RELATIONSHIPS,GRADED,Response of a particular system (isolated tissue, animal or patient) measured against agonist concentration,QUANTAL (cumulative),drug (agonist or antagonist) dose required to produce a specified response determined in each member of a population,plot fraction of population that responds at each dose against log of dose to produce a,quantal,dose-response curve,Therapeutic Window/Index,
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