Drug Tolerance

Definition of Drug Tolerance:

• Tolerances is a reduced response to a drug following repeated use, requiring higher doses to achieve the same effect.

Types of Tolerance:

1. Pharmacokinetic (Metabolic) Tolerance

   • Increased drug metabolism reduces drug levels
   • Example: Chronic alcohol use induces CYP2E1, increasing alcohol metabolism

2. Pharmacodynamic (Cellular) Tolerance

   • Downregulation or desensitization of receptors
   • Example: Decreased μ-opioid receptor sensitivity after repeated opioid exposure

3. Behavioral (Learned) Tolerance

   • Adaptation in behavior to compensate for drug effects
   • Example: Alcoholics may appear sober despite high blood alcohol levels

4. Cross-Tolerance

   • Tolerance to one drug leads to tolerance to another with similar mechanism
   • Example: Tolerance to morphine → tolerance to fentanyl (both μ-agonists)

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