Core10: Tolerance, tachyphylaxis, dependence

🔁 High-yield / 要点：Tolerance develops gradually with repeated use; tachyphylaxis is rapid acute tolerance; dependence causes craving/withdrawal after adaptation.

Definitions / 定義

Concept	Meaning	Time course
Tolerance	Reduced biological response to the same dose after repeated administration	Gradual / chronic
Tachyphylaxis	Sudden rapid decrease in response after administration	Acute / rapid
Dependence	Adaptive bio-psychological state causing need for re-use and withdrawal on cessation	Develops with repeated psychoactive use

Tolerance / 耐性

• Mechanisms:
  • Receptor downregulation after prolonged agonist exposure.
  • Mediator depletion.
  • Enzyme induction → faster drug degradation.
  • Neutralizing antibodies, especially against chimeric biologics.
• Examples:
  • Opioids: fentanyl, oxycodone.
  • Barbiturates.
  • Alcohol.
  • Benzodiazepines: diazepam, oxazepam.
  • Nitrates.

Tachyphylaxis / タキフィラキシー

• Acute form of tolerance; develops quickly, sometimes with initial doses.
• Mechanisms:
  • Depletion of endogenous mediator stores.
  • Receptor desensitization.
• Unlike gradual tolerance, tachyphylaxis may not be overcome simply by increasing dose.
• Examples:
  • Dobutamine.
  • Phenylephrine.
  • Ephedrine.

Dependence / 依存

• Dependence often occurs with drugs that modify neurotransmission and stimulate:
  • CNS reward system.
  • Euphoria.
  • Analgesia.
• Leads to reinforcement of craving behavior.
• Common examples:
  • Alcohol.
  • Opioids.
  • Tobacco.
  • Amphetamines.
  • Cocaine.
  • Cannabis.

Remember / 覚え方

• Tolerance = chronic dose-response loss
• Tachyphylaxis = fast tolerance
• Dependence = withdrawal/craving after stopping