Gout Drugs

Overview

image 2022 09 17T131258.550

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