The most severe adverse reaction to pyrazinamide is which of the following?

• A. Ototoxicity
• B. Hepatotoxicity
• C. Nephrotoxicity
• D. Hypothyroidism

Answer: (B)

The main concept being tested is the safety concern profile of pyrazinamide, specifically its risk of liver injury. Pyrazinamide is well known to cause hepatotoxicity, and this potential for significant liver damage is the most important adverse effect to monitor. Because liver injury can range from mild enzyme elevations to acute hepatitis and even liver failure, it drives the need for routine liver function tests before starting therapy and during treatment. If liver enzymes rise markedly or symptoms of liver injury appear (like jaundice, dark urine, or persistent fatigue), pyrazinamide should be stopped and re-evaluated.

Ototoxicity, nephrotoxicity, and hypothyroidism are not the primary severe concerns with pyrazinamide. Ototoxicity is more characteristic of other drugs such as certain aminoglycosides; nephrotoxicity is not the main issue with pyrazinamide; and hypothyroidism is not a typical or prominent adverse effect associated with this drug.