Responses to Antagonists

Question 1

Define Pharmacodynamic Antagonism

Answer 1

Pharmacodynamic Antagonism

- Where a drug binds to a receptor and does not activate it

Question 2

Define Competitive Antagonists

Answer 2

Competitive Agonists

• Bind to the same site as the agonist on a receptor
• Bind reversibly to receptor binding site
• Adding sets up a second equilibrium reaction which competes with the equilibrium for -agonist-receptor binding

Question 3

Define Insurmountable Irriversible Antagonism

Answer 3

Insurmountable Irreversible Antagonism

• Antagonist binds irreversibly (covalently) or with very slow dissociation (very high affinity)
• Effect cannot be reversed by increasing the agonist dose

Question 4

Define Insurmountable Allosteric Antagonism

Answer 4

Insurmountable Allosteric Antagonism

• Antagonist binds to a different site from the agonist and reduces receptor activation (intrinsic efficacy) as well as agonist binding (affinity)
• Effect cannot be reversed by increasing agonist dose of agonist

Question 5

Define Allosteric Antagonism

Answer 5

Allosteric Antagonism
- Antagonist binds to a different site from agonist and reduces agonist binding (affinity) WITHOUT AFFECTING receptor activation (intrinsic efficacy)

Question 6

Define Physiological (Functional) Antagonism

Answer 6

Physiological (Functional) Antagonism

• Agonists with opposing physiological effects on the same tissue
• E.g. acetylcholine will contract bronchial smooth muscle while salbutamol will relax it

Question 7

Define Partial Antagonism

Answer 7

Partial Antagonism

• Properties of both agonists and antagonists
• Cannot produce 100% response in the tissue even when occupying 100% of receptors

Question 8

Define Chemical Antagonism

Answer 8

Chemical Antagonism

• When 2 substances combine to form an inactive compound
• E.g. heavy metals with dimercaprol

Question 9

Explain why and how antagonist affinity and potency can be measured by the antagonist’s effect on agonist response.

Answer 9

Antagonist affinity alters the dose-response curve of an agonist, we can measure this and calculate the agonist concentration needed to recover the EC50 in the presence of an agonist.

Question 10

Explain how the Schild plot is generated and the parameters it yields.

Answer 10

Each agonist curve at one antagonist concentration gives one point of the Schild Plot.

If the slope is 1 = competitive antagonism.

Question 11

Describe the cardinal characteristics of the agonist dose-response curve in the presence of a competitive antagonist and explain these characteristics.

Answer 11

In the presence of a competitive antagonist, the agonist dose-response curve is;

• Parallel
• Shifted to the right
• Attains the same maximum response
• Can be overcome by more agonist