## Pyrazinamide-Induced Hyperuricemia **Key Point:** Pyrazinamide (PZA) causes hyperuricemia by inhibiting renal tubular secretion of uric acid, increasing serum urate levels and precipitating acute gout in susceptible patients. ### Mechanism of Hyperuricemia 1. PZA metabolite (pyrazinoic acid) competes with uric acid for secretion in the proximal renal tubule 2. Inhibits urate transporter 1 (URAT1), reducing uric acid excretion 3. Results in **hyperuricemia** (elevated serum uric acid) 4. Can precipitate acute gouty arthritis, especially in patients with pre-existing gout or hyperuricemia ### Clinical Management - **Contraindicated** in patients with: - Active gout - History of gout - Severe hyperuricemia - Monitor serum uric acid levels during PZA therapy - Consider allopurinol prophylaxis if PZA must be used in high-risk patients - Adequate hydration and alkalinization of urine may help reduce uric acid precipitation **High-Yield:** PZA is an essential first-line antitubercular drug, but hyperuricemia is its most clinically significant adverse effect requiring patient counseling and monitoring. **Mnemonic:** **PZA = Purine-related uric Acid elevation** — helps recall the hyperuricemia association. **Warning:** Do not confuse with ethambutol (causes hyperuricemia via different mechanism — less clinically significant) or other first-line agents.
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