Table of Contents
*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
- the large-scale COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low Dose Colchicine Trial 2) showed a 32% reduction in major adverse cardiovascular events or need for urgent revascularization making it likely it will be added to the secondary prevention guidelines for heart disease
- 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
- reduces CRP levels
- 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)
- renal 30-40%
- hepatic with eneterohepatic recycling
Acute Rx gout:
- While colchicine is effective for treating acute gout it has a slow onset of action, with limited effectiveness if treatment is delayed and a narrow therapeutic index 1)
- Colchicine should not be used unless non-steroidal anti-inflammatories are contraindicated, or have been used and found to lack analgesic efficacy or to have unacceptable side effects in the individual
- The elderly may be more susceptible to cumulative toxicity with colchicine, and due to age-related renal function impairment, other treatments such as corticosteroids should be considered.
- If colchicine is used in the elderly lower doses should be given and a maximum cumulative dose of 3mg over four days should be observed
- Reduce dose in those with moderate renal impairment - do NOT use in those with severe renal impairment.
- Maximum dose in healthy adults in the first 24 hours is 2.5mg and the total dose given in an acute attack should not exceed 6mg over four days.
- regime 1 for otherwise healthy adults over 50kg:
- 1mg initially, then 0.5mg every six hours until pain relief is obtained.
- regime 2 for otherwise healthy adults over 50kg:
- 0.5mg bd for 3 days.
- NB. used to be given until no pain or GIT effects (4-10mg) BUT 7-8mg may be lethal !
Prophylactic Rx of 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!
- risk of :
- aplastic anaemia
- in the COLCOT study, 0.9% risk of pneumonia vs 0.4% in placebo group
- severe renal impairment
- severe hepatic impairment
- hypersensivity reaction
- 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: 2022/07/12 08:10 by gary1