Agonists, Antagonists Lecture

Question 1

Define agonists

Answer 1

Mimics the physiological ligand

Binds to the receptor at the primary site and activates the receptor producing an effect

Question 2

Define antagonists

Answer 2

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

Question 3

Define pharmacological antagonist

Answer 3

Within the same system

Question 4

Define physiological antagonist

Answer 4

Against another system

Parasympathetic vs sympathetic systems

Question 5

How do agonists differ from each other?

Answer 5

Affinity
Efficacy
Potency

Question 6

Define partial agonists

Answer 6

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

Question 7

Define competitive antagonists

Answer 7

Binds at drug receptor sites in a reversible, competitive manner but dos not produce an effect

Question 8

What are the two main properties observed by competitive antagonists?

Answer 8

Log dose shift right

Inhibition can be completely overcome by raising the agonist concentration

Question 9

What are some examples of competitive antagonists?

Answer 9

NSAIDs
Alzheimer agents (donepezil)
Antidepressants
Antihypertensives

Question 10

Define surmountable antagonism

Answer 10

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

Question 11

What is a clinical point with competitive antagonists?

Answer 11

Overdose with a competitive antagonist can be overcome with a drug that mimics the endogenous ligand for the affect receptor

Question 12

What is a Schild Plot

Answer 12

Plot for competitive antagonist

Slope of 1 = competitive inhibitor

Question 13

Define dose ratio

Answer 13

Ratio of agonist concentration that elicits equal response in the presence and absence of antagonist

Question 14

Define noncompetitive antagonists

Answer 14

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)

Question 15

Define irreversible antagonists

Answer 15

Primary binding is covalent and so “permanent”

Question 16

But is an irreversible antagonists really irreversible?

Answer 16

No, while the primary action may be permanent, usually a secondary actions can occur to reverse the inhibition

Question 17

Define biased agonist

Answer 17

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

Question 18

Define constitutive activity

Answer 18

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

Question 19

Define inverse agonist

Answer 19

Inhibits the spontaneous activity (negative efficacy)
Brings down tone (unlike antagonists) by binding to resting state
Left shift

Question 20

If EC50 is to the left of KD, then?

Answer 20

There is a receptor reserve (usually)

- Could also be, unrecognized ligand or an antagonist

Question 21

GO OVER GRAPHS IN LECTURE

Answer 21

GO OVER GRAPHS IN LECTURE