**Question:** Antitubercular drug that can cause hyperuricemia is:

A. Isoniazid
B. Ethambutol
C. Rifampicin
D. Pyrazinamide

**Core Concept:** Hyperuricemia is a condition characterized by elevated levels of uric acid in the blood. Uric acid is a byproduct of purine nucleotide breakdown in the body, primarily regulated by the liver and kidneys. Antitubercular drugs can affect these organs and enzymes involved in uric acid clearance, leading to hyperuricemia.

**Why the Correct Answer is Right:**

Drug A - Pyrazinamide: Pyrazinamide is a prodrug that gets converted into pyrazinoic acid in the liver, where it inhibits dihydropyrimidine dehydrogenase, an enzyme involved in uric acid clearance. Consequently, pyrazinamide can cause hyperuricemia due to impaired clearance of uric acid.

**Why Each Wrong Option is Incorrect:**

A. Isoniazid: Isoniazid is an inhibitor of pyruvate dehydrogenase complex in the liver, which is involved in the first step of the citric acid cycle. However, it doesn't directly affect uric acid clearance, and therefore doesn't cause hyperuricemia.

B. Ethambutol: Ethambutol is a mycobacteriostatic agent that doesn't significantly impact uric acid clearance or enzyme systems responsible for its regulation. As a result, it is less likely to cause hyperuricemia compared to pyrazinamide.

C. Rifampicin: Rifampicin is an inhibitor of bacterial RNA polymerase, which is crucial for bacterial synthesis. It doesn't directly affect uric acid clearance or enzymes involved in its regulation, so it isn't the primary cause of hyperuricemia among the given options.

**Clinical Pearl:** Hyperuricemia is a potential side effect of antitubercular therapy. Monitoring serum uric acid levels in patients on pyrazinamide-containing regimens can help identify those susceptible to hyperuricemia and allow for appropriate intervention, such as dose adjustments or adding allopurinol or colchicine to reduce uric acid production.

**Correct Answer: D. Pyrazinamide**

Pyrazinamide is the only antitubercular drug among the options that inhibits dihydropyrimidine dehydrogenase, an enzyme involved in the clearance of uric acid from the blood. This leads to impaired uric acid clearance and can result in hyperuricemia.