DRUGS USED IN GOUT
DRUGS USED IN GOUT
Gout is a familial metabolic disease characterized by recurrent episodes of acute arthritis due to deposits of monosodium urate in joints & cartilage.
Formation of uric acid calculi in kidneys may also occur.
Gout is usually associated with high serum levels of uric acid, a poorly soluble substance that is the major end product of purine metabolism.
The treatment of gout is aimed at relieving acute gouty attack & preventing recurrent gouty episodes & urate lithiasis
alkaloid from autumn crocus, Colchicum autumnale.
relieves pain & inflammation of gout in 12-24 hours;
anti-inflammatory effects are due to binding to tubulin → prevent its polymerization into microtubules → inhibition of leukocyte migration & phagocytosis.
NSAIDs are often employed because of diarrhea associated with colchicine therapy.
Colchicine is preferred for prophylaxis of recurrent gouty arthritis,
is effective in preventing attacks of acute Mediterranean fever,
may have effect in sarcoid arthritis & in hepatic cirrhosis.
occasionally N&V, abdominal pain.
rarely hair loss, bone marrow depression, peripheral neuritis & myopathy.
NSAIDS IN GOUT
In addition to inhibiting prostaglandin synthase, also inhibit urate crystal phagocytosis.
Indomethacin is the agent most often used today to treat acute gout.
All other NSAIDs except aspirin, salicylates and tolmetin are used
Probenecid & sulfinpyrazone
are organic acids & act at anionic transport sites of the renal tubule.
uric acid is both reabsorbed & secreted in middle segment of proximal tubule. Uricosuric drugs & large doses of aspirin affect these active transport sites → ↓net reabsorption of uric acid in the proximal tubule is decreased.
secretion of other weak acids, eg, penicillin, is also ↓by uricosuric agents.
used to ↓body pool of urate in patients with tophaceous gout or in those with frequent gouty attacks.
should be avoided in patients who excrete large amount of uric acid (may precipitate formation of uric acid calculi).
→urine volume should be maintained at high level & urine pH kept above 6.0 by the administration of alkali.
Therapy should not be started until 2-3 weeks after acute attack.
allergic dermatitis (probenecid)
nephrotic syndrome (probenecid)
rarely aplastic anemia.
Like uric acid, allopurinol is metabolized by xanthine oxidase→ alloxanthine (also inhibits xanthine oxidase) Pharmacodynamics Important amounts of purine are formed from amino acids in body.
purine ribonucleotides not incorporated into nucleic acids & those derived from degradation of nucleic acids are converted to xanthine or hypoxanthine → oxidized to uric acid
(1) chronic tophaceous gout,
(2) when probenecid or sulfinpyrazone cannot be used
(3) recurrent renal stones;
(4) in patients with renal functional impairment
(5) when serum urate levels are grossly elevated.
(6) to prevent the massive uricosuria following therapy of blood dyscrasias that could otherwise lead to renal calculi
Acute attacks of gout early in treatment when urate crystals are being withdrawn from tissues & plasma levels are below normal → colchicine should be given during initial therapy unless allopurinol is being used in combination with probenecid or sulfinpyrazone.
GI intolerance (N&V, diarrhea)
Peripheral neuritis & necrotizing vasculitis,
Depression of bone marrow, rarely, aplastic anemia
Hepatic toxicity & interstitial nephritis.
Pruritic maculopapular lesions
Interactions & Cautions
When mercaptopurines are given concomitantly, their dose must be ↓ by ~ 75%.
↑increase effect of cyclophosphamide.
(-) metabolism of probenecid & oral anticoagulants
↑ hepatic iron concentration.