Correct Answer: A. Allopurinol
Allopurinol is a xanthine oxidase inhibitor that directly reduces uric acid synthesis by blocking the final two steps of purine metabolism—conversion of hypoxanthine to xanthine and xanthine to uric acid. This mechanism makes it the gold-standard urate-lowering therapy (ULT) for chronic gout management in India, particularly in patients with recurrent attacks, tophaceous gout, or uric acid nephrolithiasis. Unlike acute anti-inflammatory agents, allopurinol addresses the underlying hyperuricemia, preventing future attacks. The drug is initiated at 50–100 mg daily (lower in renal impairment per Indian guidelines) and titrated to achieve serum uric acid <6 mg/dL. Allopurinol is preferred over febuxostat in resource-limited settings and is the first-line ULT per RNTCP and Indian rheumatology practice. Importantly, it must NOT be started during an acute attack—NSAIDs or colchicine are used acutely, then ULT is added after inflammation resolves to avoid paradoxical flare.
Why the other options are wrong
B. Colchicine — Colchicine is an acute anti-inflammatory agent that inhibits neutrophil migration and IL-1β release; it does NOT reduce uric acid synthesis or serum urate levels. It is used to abort acute gout attacks or as prophylaxis during ULT initiation, not for long-term symptom reduction in recurrent gout. The question specifies 'therapy that inhibits uric acid synthesis'—colchicine fails this criterion entirely. C. Probenecid — Probenecid is a uricosuric agent that increases renal uric acid excretion by inhibiting tubular reabsorption; it does NOT inhibit uric acid synthesis. While it lowers serum urate, it is contraindicated in patients with uric acid stones or severe renal impairment (common in Indian gout patients) and is rarely used in India. The stem explicitly asks for a drug that 'inhibits uric acid synthesis'—probenecid works via a different mechanism. D. Diclofenac — Diclofenac is an NSAID used for acute pain and inflammation in gout attacks, not for chronic urate-lowering therapy. It has no effect on uric acid synthesis or serum urate levels. While commonly used in Indian emergency departments for acute gout, it does not prevent recurrent attacks and cannot serve as long-term management for recurrent gout.
High-Yield Facts
- Allopurinol is a xanthine oxidase inhibitor that blocks hypoxanthine → xanthine → uric acid conversion, reducing uric acid synthesis by ~80%.
- Serum uric acid target in gout is <6 mg/dL; allopurinol is titrated from 50–100 mg daily to achieve this (lower doses in renal impairment per Indian guidelines).
- Acute gout flare paradox: allopurinol must NOT be started during an acute attack; NSAIDs/colchicine are used acutely, then ULT added after inflammation resolves.
- Allopurinol-induced SJS/TEN is rare but severe; HLA-B*5801 screening is recommended in high-risk populations (Asian ancestry, renal impairment).
- Uricosuric agents (probenecid) and xanthine oxidase inhibitors (allopurinol) are the two main classes of ULT; allopurinol is first-line in India due to cost and efficacy.
Mnemonics
GOUT ULT: A-P-F Allopurinol (xanthine oxidase inhibitor), Probenecid (uricosuric), Febuxostat (newer xanthine oxidase inhibitor). Allopurinol is first-line in India. Acute vs. Chronic Gout Acute: NSAIDs/Colchicine (anti-inflammatory). Chronic: Allopurinol/Febuxostat (urate-lowering). Never start ULT during flare—wait 2–4 weeks post-attack.
NBE Trap
NBE pairs colchicine with gout to lure students who conflate acute anti-inflammatory management with chronic urate-lowering therapy. The stem's emphasis on "recurrent attacks" and "inhibits uric acid synthesis" is designed to eliminate colchicine and probenecid, which do not reduce synthesis.
Clinical Pearl
In Indian outpatient practice, allopurinol 100 mg daily is the default starting dose for recurrent gout; renal function and HLA-B*5801 status guide dose adjustment. Many patients default on ULT because they feel "cured" after the first attack resolves—counseling on lifelong therapy is critical to prevent tophaceous gout and renal damage.
_Reference: KD Tripathi Ch. 12 (Autacoids & Related Drugs); Harrison Ch. 384 (Gout & Related Disorders)_