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What is Colchicine is: and explain in detail?
Ans. D. None of the above. (Ref. KDT 6th/pg. 206)"Colchicine is neither analgesic nor anti-inflammatory, but it especifically suppresses gouty inflammation. It does not inhibit the synthesis or promote the excretion of uric acid."Rx of Gout:Drugs used in acute gout:Q- NSAIDS; - Colchicine; - CorticosteroidsDrugs for Rx of chronic gout (Hyperuricaemia):Uricosurics: Probenecid, Sulfinpyrazone Synthesis inhibitors: Allopurinol.Colchicine:# is an alkaloid from Colchicum autumnale which is used in gout since 1763.# Colchicine is neither analgesic nor anti-inflammatory. but it especially suppresses gouty inflammation.# It does not inhibit the synthesis or promote the excretion of uric acid.# Thus, it has no effect on blood uric acid levels.# An acute attack of gout is started by precipitation of urate crystals in the synovial fluid, which start an inflammatory response, chemotactic factors are produced k granulocyte migrate in joint; they phagocytose urate crystals and release a glycoprotein which aggregates the inflammation by: Increasing lactic acid production from inflammatory cells k local pH reduced k more crystals precipitate in affected joint. Releasing lysosomal enzymes which can cause joint destruction. Colchicine does not inhibit release of the glycoprotein and the subsequent events.# MOA:- By binding to fibrillary protein tubulin, it inhibits granulocyte migration into the inflammed joint and thus interrupts the vicious cycle.- Other actions of Colchicine are:* Antimitotic: Causes metaphase arrest b\ binding to microtubules of mitotic spindle. It was tried for cancer chemotherapy but abandoned due to toxicity. It is used to produce polyploidy in plants.* It increases gut motility through neural mechanism.# Pharmacokinetics:- Rapidly absorbed orally. Partly metabolized in liver and excreted in bile - undergoes enterohepatic circulation. Ultimate disposal occurs in urine and faeces over many days.# Toxicity:- N&V, watery diarrhea and abdominal cramps occur as dose limiting adverse effects.- Anagen effluvium.- In overdose, produces renal damage, CNS depression, intestinal bleeding and death is due to muscular paralysis and respiratory failure.# Uses:- Rx of acute gout:* Colchicine is fastest acting drug to control an acute attack of gout: 1 mg orally followed by 0.25 mg 1 - 3 hrly till control of the attack (which occurs in 4-12 hrs), or till total dose 6 mg is reached or diarrhea is started.* The response is dramatic, so much so that it may be considered diagnostic.* However, because of higher toxicity, most physicians prefer using a NSAID.* Maintainance doses (0.5-lmg/day) may be given for 4-8 weeks in which time control of hyperuricaemia is achieved with other drugs.- Prophylaxis:* Colchicine 0.5-lmg/day can prevent further attacks of gout, but NSAIDS usually preferred.