Learning Objective

Understand the effects of antagonists and potentiators on graded dose-response curves, including how they influence potency and efficacy, and recognize parallels with enzyme kinetics.

Antagonists:

Drugs that interfere with receptor activation by agonists.

Potentiators:

Drugs that enhance the effect of agonists.

Types of Antagonism

Pharmacologic antagonism (same receptor)

Competitive antagonists:

• Compete with an agonist for the same receptor.
• Cause parallel rightward shift of the D-R curve.
• Decrease potency, but Emax remains the same.
• It can be overcome by increasing the agonist dose.
• Analogy: Competitive enzyme inhibitors (↑Km, Vmax unchanged).

Noncompetitive antagonists:

• Bind irreversibly or at an allosteric site.
• Cause nonparallel shift of D-R curve.
• Decreased efficacy of the agonist.
• Only partially reversible by increasing the agonist dose.
• Analogy: Noncompetitive enzyme inhibitors (↓Vmax, Km unchanged).

Physiologic antagonism (different receptor)

• Two agonists act at different receptors to produce opposing effects.
• Example: vasoconstrictor vs. vasodilator.

Chemical antagonism

• Direct chemical interaction neutralizes the drug.
• Example: protamine binds heparin to reverse anticoagulation.

Potentiation

• Enhances the effect of an agonist.
• Causes a parallel leftward shift of the D-R curve.
• Appears to increase the potency of the agonist without changing Emax.

Summary Table