Colchicine used in acute gout: (DNB Dec 2010)
|A||Inhibits prostaglandin synthesis|
|B||Decreases excretion of uric acid|
|C||Inhibits accumulation of leucocytes and release of mediators|
|D||Inhibits xanthine oxidase|
a. Colchicine is an alkaloid obtained from Colchicum autumnale, which was used in gout since 1763. Colchicine is neither analgesic nor anti-inflammatory, but specifically suppresses gouty inflammation.
b. It does not inhibit the synthesis or promote the excretion of uric acid and has no effect on blood uric acid levels. An acute attack of gout starts by precipitation of urate crystals in the synovial fluid.
c. This starts an inflammatory response producing chemotactic factors. Granulocytes migrate into the joint and phagocytose the urate crystals and release a glycoprotein, which aggravates the inflammation by increasing lactic acid production by the inflammatory cells.
d. This reduces the local pH and more urate crystals are precipitated in the affected joint. This glycoprotein also releases lysosomal enzyme causing joint destruction.
e. Colchicine does not affect phagocytosis of urate crystals but inhibits release of the glycoprotein and subsequent events.
f. It also inhibits granulocyte migration into the inflamed joint interrupting the vicious cycle. It also causes metaphase arrest by binding to microtubules of mitotic spindle and increases gut motility through neural mechanisms.