Overview Snapshot A 50-year-old man presents 4 months after an acute gout flare to his primary care physician. Since then, he has had 2 more episodes of minor flares that resolved on its own. He reports wanting better control of this disease. His physician describes several options for chronic gout and suggests allopurinol as a good first-line option. Introduction Chronic gout drugs mechanism of action prevents the build up of uric acid drugs allopurinol febuxostat pegloticase probenecid Acute gout drugs mechanism of action reduces inflammation drugs nonsteroidal anti-inflammatory drugs (NSAIDs) glucocorticoids (oral, intra-articular, and parenteral) colchicine Drugs to avoid low-dose salicylates decreases uric acid excretion, which may precipitate gout Allopurinol Mechanism of action competitive inhibition of xanthine oxidase, which decreases production of urate Clinical use chronic gout prevention of urate nephropathy from tumor lysis syndrome in lymphoma and leukemia Toxicity ↑ accumulation of azathioprine and 6-mercaptopurine (MP) both are metabolized by xanthine oxidase drug rash Febuxostat Mechanism of action inhibition of xanthine oxidase Clinical use chronic gout Toxicity ↑ accumulation of azathioprine and 6-MP some hepatotoxicity Pegloticase Mechanism of action pegloticase is a recombinant uricase catalyzes metabolism of uric acid to allantoin, which is more water-soluble Clinical use chronic gout Toxicity risk of new gout flare infusion reactions Probenecid Mechanism of action inhibition of proximal convoluted tubule resorption of uric acid Clinical use chronic gout Toxicity uric acid calculi this should only be used in uric acid underexcreters and should be avoided in patients who are uric acid overproducers a history of prior uric acid stones is a contraindication for initiating this agent prolonged penicillin serum levels inhibition of proximal convoluted tubule secretion of penicillin Colchicine Mechanism of action inhibition of microtubule polymerization by binding to tubulin, which impairs neutrophil chemotaxis and degranulation and decreases inflammation Clinical use acute and chronic gout Toxicity gastrointestinal irritation