In a patient with newly diagnosed pulmonary tuberculosis, which anti-tuberculous drug is most likely to cause hyperuricemia and acute gouty arthritis, particularly in patients with pre-existing gout?

Explanation

## Pyrazinamide-Induced Hyperuricemia **Key Point:** Pyrazinamide (PZA) is the anti-TB drug most strongly associated with hyperuricemia and acute gouty arthritis due to competitive inhibition of renal uric acid excretion. ### Mechanism of Hyperuricemia Pyrazinamide and its metabolite pyrazinoic acid compete with uric acid for tubular secretion in the proximal renal tubule. This leads to: 1. **Decreased urinary uric acid excretion** (uricosuric effect reversal) 2. **Elevated serum uric acid levels** (often 6–10 mg/dL within weeks) 3. **Acute gout flares** in susceptible patients, particularly those with: - Pre-existing hyperuricemia - History of gout - Renal impairment - Dehydration ### Clinical Management **High-Yield:** Patients on PZA should have: - **Baseline serum uric acid** measured before treatment - **Adequate hydration** maintained throughout therapy - **Prophylactic allopurinol or febuxostat** considered if baseline uric acid >7 mg/dL or prior gout history - **NSAIDs or colchicine** available for acute gout episodes during treatment **Warning:** Do NOT discontinue PZA in newly diagnosed TB solely due to hyperuricemia—it is a critical first-line drug. Instead, manage the hyperuricemia pharmacologically while continuing PZA. ### Comparison of First-Line Drug Side Effects | Drug | Metabolic/Toxic Effect | Organ Target | | --- | --- | --- | | **Pyrazinamide** | Hyperuricemia, gout | Kidney (tubular reabsorption) | | **Rifampicin** | Hepatotoxicity, drug interactions | Liver (CYP3A4 inducer) | | **Isoniazid** | Peripheral neuropathy, hepatotoxicity | Nerve, liver | | **Ethambutol** | Optic neuritis, color blindness | Optic nerve | | **Streptomycin** | Ototoxicity, nephrotoxicity | 8th cranial nerve, kidney | **Clinical Pearl:** Pyrazinamide-induced gout typically occurs within the first 2–4 weeks of TB treatment. Educate patients to report sudden joint pain, swelling, or redness immediately, as acute gout can be mistaken for TB arthritis or other complications.