Gout Flashcards
Allopurinol
MOA: uricostatic effect:
prodrug of oxipurinol (formed by aldehyd dehydrogenase): competitive inhibition of xanthine oxidase → less formation of uric acid
1. decreased [urate] serum
2. higher concentration of hypoxanthine & xanthine
→ feedback inhibition of phosphoribosyl transferase → lower synthesis of purines
IND: - symptomatic hyperuricaemia
- dissolution of (renal) urate crystals
CI: acute gout flare
ADR:
1. often: many harmless ADRs
2. seldom: bone marrow depression
3. very rare: fatal (!) immunological skin reactions:
- Stevens-Johnson syndrome (SJS)
- toxic epidermal necrolysis (TEN)
→ those are associated with a specific HLA type
Benzbromarone
MOA:
uricosuric effect: inhibition of tubular urate re-absorption via URAT1 → enhanced urate excretion (to avoid renal crystalisation of re-absorbed urate, drink at least 2 L/day!
IND: - symptomatic hyperuricaemia
- dissolution of (renal) urate crystals
CI: renal or hepatic insufficiency
ADR: 1. often: many harmless ADRs
2. very rare: fatal (!) hepatic failure
urate-lowering effects of allopurinol & benzbromarone are similar, different fatal ADRs
Colchizine
IND: treatment of an acute gout attack
MOA: inhibition of microtubule polymerisation by binding tubulin
→ inhibition of migration of neutrophils to the sites of inflammation
→ indirect antiinflammatory effect
- no antidote!
Canakinumab
MOA:
human monoclonal antibody targeted at interleukin-1β
→ antiinflammatory effect
IND: - acute gout attack (one-time use only)
- different very rare autoinflammatory diseases
ADRs: many
- costs 12.000 € per injection (still 3rd line therapy :D)
Treatment of an acute attack (gout flare)
- NSAIDs (ibuprofen, diclofenac)
- Glucocorticoids (prednisolone, triamcinolone)
- Colchizine
Reihenfolge:
1. NSAID or Colchizine
then 2. glucocorticoids
3. Canakinumab
Urate lowering Therapy (ULT)
1st line: Allupurinol
2nd line: Benzbromarone
