Agonists, Antagonists Lecture Flashcards
Define agonists
Mimics the physiological ligand
Binds to the receptor at the primary site and activates the receptor producing an effect
Define antagonists
Binds to some part of the receptor and alters or prevents binding and /or action of the ligand or agonist drug
Alters dose-response curve
Competitive, noncompetitive, or irreversible
Define pharmacological antagonist
Within the same system
Define physiological antagonist
Against another system
Parasympathetic vs sympathetic systems
How do agonists differ from each other?
Affinity
Efficacy
Potency
Define partial agonists
Produce a submaximal response when compared to a prototype or optimal agent
- Possesses affinity for a given receptor but will elicit only some fraction of pharmacological response
Define competitive antagonists
Binds at drug receptor sites in a reversible, competitive manner but dos not produce an effect
What are the two main properties observed by competitive antagonists?
Log dose shift right
Inhibition can be completely overcome by raising the agonist concentration
What are some examples of competitive antagonists?
NSAIDs
Alzheimer agents (donepezil)
Antidepressants
Antihypertensives
Define surmountable antagonism
Competitive inhibition reduces the receptor’s sensitivity to the agonist but does not diminish the maximum effect that can be attained at very high agonist concentration
What is a clinical point with competitive antagonists?
Overdose with a competitive antagonist can be overcome with a drug that mimics the endogenous ligand for the affect receptor
What is a Schild Plot
Plot for competitive antagonist
Slope of 1 = competitive inhibitor
Define dose ratio
Ratio of agonist concentration that elicits equal response in the presence and absence of antagonist
Define noncompetitive antagonists
Bind at a site different than the active site or primary site
Block action of the receptor and efficacy of agonists will fall
Does not modify affinity (KD stays the same)
Define irreversible antagonists
Primary binding is covalent and so “permanent”
But is an irreversible antagonists really irreversible?
No, while the primary action may be permanent, usually a secondary actions can occur to reverse the inhibition
Define biased agonist
Agonist acting through the same receptor system as a conventional agonist agent but appears to utilize only a subset of the normal signal transduction amplification systems associated with that receptor system
Define constitutive activity
a baseline of activity or tone produced by spontaneous change of some receptors from the resting state to the active state in apparent absence of an agonists
- Moving from inactive to active without an agonists
Define inverse agonist
Inhibits the spontaneous activity (negative efficacy)
Brings down tone (unlike antagonists) by binding to resting state
Left shift
If EC50 is to the left of KD, then?
There is a receptor reserve (usually)
- Could also be, unrecognized ligand or an antagonist
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GO OVER GRAPHS IN LECTURE
