Which of the following is the mechanism of action of allopurinol?
Allopurinol (hypoxanthine analog) and recently approved drug, febuxostat (a non-purine drug) decrease the production of uric acid by inhibiting the enzyme xanthine oxidase. Allopurinol is metabolized by the same enzyme to alloxanthine which is a long acting inhibitor of xanthine oxidase. These are indicated as drug of choice for chronic gout in the inter-critical period (between two acute attacks) and also with anticancer drugs (to decrease secondary hyperuricemia). 6-Mercaptopurine and azathioprine are metabolized by xanthine oxidase; therefore dose of these drugs should be decreased when given with allopurinol. Allopurinol is also used as an adjuvant to sodium stibogluconate in the treatment of kala azar. It is contra-indicated in acute gout because uric acid has inhibitory effect on release of cytokines and allopurinol may aggravate the inflammation by reducing uric acid. Most frequent adverse effect with xanthine oxidase inhibitors is precipitation of acute attack of gout. There is strong association between HLA-B*5801 and allopurinol hypersensitivity Combined use of allopurinol and ampicillin causes a drug rash in 20% of patients. * Allopurinol requires dose adjustment in renal failure whereas febuxostat can be administered without dose adjustment. Febuxostat can result in abnormal liver function tests
Inhibits the synthesis of uric acid
Inhibits tubular reabsorption of uric acid
Anti-inflammatory action
Increases phagocytosis of urate crystals
NSAIDs, Gout and Rheumatoid Ahritis