Core26: Pharmacodynamic interactions - antagonism

⛔ High-yield / 要点：Pharmacodynamic antagonism reduces agonist effects. Competitive antagonists shift the curve right; non-competitive/irreversible antagonists reduce maximal effect.

Definition / 定義

• Antagonists reduce the effects of agonists, including drugs or endogenous mediators.
• Receptor antagonists bind receptors but do not activate them.

Main types / 主な分類

Type	Mechanism	Curve effect	Example
Competitive reversible	Competes with agonist at same binding site	Right shift; effect can be overcome by more agonist	Naloxone at opioid receptors
Non-competitive	Modifies receptor activity, often via allosteric site	Reduced maximal effect	Ketamine at NMDA receptor
Irreversible	Binds irreversibly/nearly irreversibly, sometimes covalently	Cannot be overcome by more agonist	Phenoxybenzamine at α-adrenoceptors

Competitive antagonism / 競合的拮抗

• Increasing antagonist concentration progressively inhibits agonist response.
• High antagonist concentration can almost completely prevent response.
• More agonist is required for the same effect → curve shifts right.
• Example: naloxone is a competitive antagonist at opioid receptors.

Non-competitive and irreversible / 非競合・不可逆的拮抗

• Non-competitive:
  • Antagonist can bind an allosteric site rather than the orthosteric agonist site.
  • Agonist binding may still occur, but receptor effect is reduced.
• Irreversible:
  • Once receptor is bound, agonist cannot overcome inhibition.
  • Duration depends on receptor turnover.

Remember / 覚え方

• Competitive = same site, right shift
• Non-competitive = different site, lower Emax
• Irreversible = long effect until new receptors