A patient with recurrent gout is started on febuxostat. The mechanism of action of febuxostat differs from allopurinol because:
- A Febuxostat is a purine analogue inhibitor of xanthine oxidase; allopurinol is a non-purine inhibitor
- B Febuxostat inhibits uricase; allopurinol inhibits xanthine oxidase
- C Febuxostat blocks renal tubular urate reabsorption; allopurinol inhibits urate synthesis
- D Febuxostat is a non-purine selective inhibitor of both oxidised and reduced forms of xanthine oxidase; allopurinol (via oxypurinol) inhibits only the oxidised form ✓
Explanation
Allopurinol is a purine analogue that is metabolised to oxypurinol, which inhibits xanthine oxidase only in its oxidised (molybdenum-hydroxo) form. Febuxostat is a non-purine compound that inhibits both the oxidised and reduced forms of xanthine oxidase with high selectivity, making it more potent and not requiring metabolic activation. Unlike allopurinol, febuxostat does not affect other purine-metabolising enzymes and is metabolised hepatically, making it usable in mild-moderate renal impairment. Uricase (rasburicase/pegloticase) degrades urate to allantoin—a different drug.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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