Gout

Causes: Increased production or decreased excretion of uric acid.

Pathophysiology: Acid pH promotes precipitation of urate. Leukocytes are damaged by urate, bursting and emptying contents (PGIs, lysosomes, IL-1) into joint tissue. This results in inflammation and propagation of a vicious cycle.

Risk factors: Thiazide diuretics, aspirin, blood diseases, obesity, heavy alcohol intake.

Treatment of acute attack is different than treatment of hyperuricemia.

Colchicine – only effective in gouty arthritis; not analgesic; rapid relief of acute attacks; also effective for prophylaxis; reserved for those who cannot tolerate NSAIDs.

MOA: Binds to tubulin causing depolymerization and disappearance of microtubules in motile granulocytes. Breaks inflammatory cycle by inhibiting leukocyte migration.

Toxicity: Since inhibitory to mitosis, toxic in rapidly proliferating cells such as intestinal epithelium. Long-term therapy may cause marrow depression, myopathy, neuropathy.

NSAIDs (indomethacin, naproxen, sulindac, ibuprofen, fenoprofen) – Preferred treatment for acute attacks. Can also be used for prophylaxis.

Allopurinol – Used to treat hyperuricemia

MOA: Inhibits conversion of hypoxanthine and xanthine to uric acid, thereby reducing production of uric acid. Competitive inhibitor at low concentrations and non-competitive at high concentrations. Converted to alloxanthine, which also is a noncompetitive inhibitor of xanthine oxidase.

Therapeutic place: Stops formation of uric acid stones. The incidence of acute gouty attacks frequently increases during the first months of tx, probably due to mobilization of urate from stores.

Pharmacokinetics: Alkalinization of the urine and increased fluid intake can aid in excretion.

Toxicity: Hypersensitivity is most common. Caution in patients with poor kidney function.

Drug interactions: Enhances effect of probenecid and mercaptopurine toxicity. May interfere with metabolism of oral anticoagulants.

Urosuric agents: Probenecid & Sulfinpyrazone – Both inhibit reabsorption while not affecting excretion of urate. Levels must be high enough, otherwise opposite becomes true. Aspirin inhibits action of both drugs.

Other drugs: Glucocorticoids, strong analgesics

Therapeutic indications

• Acute attack: NSAID (indomethacin/ibuprofen), colchicine for refractory episodes, steroids, analgesics.

• Long-term treatment and prevention: Prophylaxis with low-dose colchicine or indomethacin; urosuric agent; allopurinol; adequate fluid intake; weight reduction, diet modification (no shellfish, sardines, liver), reduce alcohol.

Category: Medicine Notes