Which type of tolerance arises when the liver adapts to the presence of a drug and may produce more of the enzyme needed to break down the drug?

• A. Pharmacodynamic tolerance
• B. Metabolic tolerance
• C. Tolerance
• D. Cross-tolerance

Answer: (B)

Metabolic tolerance occurs when the liver adjusts by increasing the production of drug‑metabolizing enzymes, speeding up how quickly the drug is broken down. With repeated use, enzyme induction—often involving liver enzymes like certain cytochrome P450s—leads to a larger capacity to metabolize the drug, so the same dose produces a smaller effect. This is a pharmacokinetic form of tolerance, tied to how the body processes the drug rather than how its targets respond. It helps explain why someone may need higher or more frequent doses over time to achieve the same effect.

This differs from pharmacodynamic tolerance, where the body’s response at the drug’s target site diminishes, and from cross-tolerance, where tolerance to one drug extends to other drugs with similar effects. An example is chronic alcohol exposure inducing liver enzymes, which can alter the metabolism of other medications.