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colchicine

colchicine

Historical:

*used by ancient Greeks, so along with the opiates, is probably the earliest recorded medication still in current use

  • 6th C AD, Alexander of Tralles proposed use of colchicine for joint pain
  • 1763, specifically described in the Dx & Rx of gout
  • 1820: 1st isolated
  • recent uses include: familial Mediterranean fever, primary biliary cirrhosis & Behcet's syndrome

Pharmacodynamics:

  • alkaloid f. Colchicum autumnale (autumn crocus or meadow saffron) used for arthritis since 6thC. isol.1820;
  • A unique anti-inflammatory effective only in gout ? acting mainly as an anti-mitotic agent & thus also used in research on cell division & function;
  • binds to the intracellular protein tubulin, preventing its alpha & beta forms polymerising to form microtubules, thereby disrupting the microtubular network causing:
    • impaired protein assembly in the Golgi apparatus
    • decreased endocytosis & exocytosis
    • altered cell shape
    • depressed cellular motility
    • arrest of mitosis - usually in metaphase

Pharmacokinetics:

  • lipid soluble alkaloid
  • well absorbed orally
  • extensive 1st pass metabolism ⇒ oral bioavailability 40%
  • peak plasma levels 30-120min
  • short plasma half-life of 20-90min due to intracellular tissue binding (Vd = 2.1L/kg)
  • elimination:
    • renal 30-40%
    • hepatic with eneterohepatic recycling

Clinical use:

Acute Rx gout:

  • 0.5-1.2mg 1-2hrly
  • NB. used to be given until no pain or GIT effects (4-10mg) BUT 7-8mg may be lethal !

Proph. Rx gout:

  • 0.5mg 2-4x/wk → 1.8mg/d depending on frequency attacks;

Common Adverse Effects:

  • In moderate doses well tolerated;
  • Most common are GIT effects due to effect on rapidly prolif. epith. cells, esp. in jejunum → N/V/D/abdo. pain which are the earliest effects of OD;
  • Thus, give 1-2hrly doses & stop if GIT effects, but these may worsen as lag effect of several hrs b/n dose & GIT effect!

Chronic use:

  • risk of : agranulocytosis; aplastic anaemia, myopathy, alopecia, azospermia;

Specific Precautions:

  • elderly, cardiac/hepatic/renal/GIT disease; PH poor tolerance to it;
  • potentially fatal colchicine toxicity from hepatic/renal disease or drug interactions with CYP3A4 inhibitors such as:
    • clarithromycin (eg. used as part of triple therapy for Helicobacter eradication in peptic ulcer Mx)
colchicine.txt · Last modified: 2011/08/25 21:23 (external edit)