An antagonist receptor binds to a ligand/receptor, this does not induce a biological response, but it blocks or dampens agonist activity. An antagonist drug has affinity but NO efficacy.
When agonist and antagonist act at two different receptor sites, these can induce independent but opposite biological effects.
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Give example of physiological antagonism.
Histamine binds to H1 receptor, it decreases arterial pressure through vasodilation, however adrenaline increases arterial pressure through vasoconstriction, by binding to β-adrenergic receptor site.
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Describe competive antagonism.
Antagonist reversibly binds to receptor at the same binding site, as the ligand/agonist, but without activating the receptor – blocks agonist binding.
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Draw the D-R curve for competitive antagonism.
(see notes)
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What are the characteristics of the D-R curve for competitive antagonism?
•D-R curve to an antagonist is parallel to original curve. •D-R curve is shifted to the right. •Maximum response is obtained by D-R curve.
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How can competitive antagonism effects be overcome?
By increasing the concentration of the agonist.
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What effects the extent of the rightward shift in competitive antagonism?
•Concentration of the agonist, •Affinity of antagonist for a particular receptor
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Give concentration ratio equation.
concentration ratio = EC50 D2/ EC50 D1
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Give Schild equation.
(Conc.ratio-1)=(Antagonist conc.)/KB
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Draw Schild Plot, and give intercept.
(see notes)
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Define KB.
dissociation equilibrium constant for competitive antagonist, where the concentration would occupy 50% or receptors at equilibrium. 1/ KB = affinity constant.
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Define pKB.
Is a measure of potency of a competitive antagonist. It is –log(molar conc. Of antagonist) at which equilibrium is 50%
, indicates non-specific binding (to glassware) or lack of antagonist equilibrium. Calculated pA2 underestimates pKB –antagonist less potent than expected.
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If Schild slope < 1 ...
, indicates removal of antagonist by saturable uptake process, or antagonist acting at other receptor site. Calculated pA2 overestimates pKB – antagonist more potent than expected.
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Give example of competitive antagonism.
Tubocuraine on responses to acetylcholine at motor end plates in skeletal muscle compared to Atropine.
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Describe non-competive antagonism.
•Antagonist can bind to agonist, inhibiting binding to receptor. •Antagonist can bind to part of receptor, altering the conformation of binding site to agonist. •Antagonist can bind to receptor, blocking agonist.
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Draw the D-R curve for non-competitive antagonism.
(see notes)
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What are the characteristics of the D-R curve for non-competitive antagonism?
• No rightward shift of antagonist Drug-Response curve • Reduction of slope of D-R curve. • Reduction in MAX response of D-R curve.
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How can non-competitive antagonism be overcome?
No amount of agonist can overcome antagonist response
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Give example of non-competitive antagonism.
: Ca2+ of binding to contractile protein thus cell cannot respond to an agonist.
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