Introduction:
Colchicine is an alkaloid isolated from the autumn
crocus, Colchicum autumnale. It is actually present in the corm of the plant,
the underground swollen part of the stem.
Pharmacokinetics:
Colchicine is absorbed readily when taken in orally. It
reaches peak plasma levels within 2 hours.
It has a serum half-life of 9 hours.
Colchicine is partially deacetylated in the liver and the unchanged drug and
its metabolites are excreted in the bile and undergo intestinal reabsorption.
Colchicine is found in high concentrations in leucocytes, kidneys, the liver and
spleen. Most of the drug is excreted in the feces but 10 to 20% is excreted in
the urine and this proportion rises in patients with liver disorders. For
patients with creatinine clearance of < 50 mL/min, colchicine must be
avoided or used at a lower dose. Colchicine is also distributed into breast
milk.
Pharmacodynamics:
Colchicine relieves the pain and inflammation of gouty
arthritis in 12-24 hours. It does not alter the metabolism or excretion of
urates. It also does not have other analgesic effects.
It is an anti-inflammatory agent.
The mechanism of action
is that it binds to the intracellular protein tubulin, thereby preventing its
polymerization into microtubules. This causes the inhibition of leukocyte
migration and phagocytosis. It also inhibits the formation of leukotriene B4. Colchicine
also blocks cell division by binding to mitotic spindles and arrests the cell
division at metaphase. Several of colchicine's adverse effects are produced by
its inhibition of tubulin polymerization and cell mitosis.
Indications:
NSAIDs have replaced colchicine in the treatment of acute
gout because of the troublesome diarrhea associated with colchicine therapy and
because of its low therapeutic index. Previously it was used to treat an acute
attack. It relieved the pain in more than 95% of cases and also provided a diagnostic
confirmation because it is more or less specific for relief of pain due to acute
gout. Non-gouty arthritis are unaffected.
1) Colchicine is now used for the prophylaxis of
recurrent episodes of gouty arthritis. Its effectiveness is up to 80%.
2) It is also effective in reducing frequency of attacks in acute
Mediterranean fever. It also prevents amyloidosis and reverses proteinuria
3) It may have a mild beneficial effect in sarcoid
arthritis and in hepatic cirrhosis.
Although it can be given intravenously, this route should
be used cautiously because of increased bone marrow toxicity.
Adverse Effects:
Colchicine often causes diarrhea and may occasionally
cause nausea, vomiting and abdominal pain. The GIT is most commonly affected
because it is the route of intake and of major excretion. Rarely chronic use of
colchicine may cause hair loss and bone marrow depression (aplastic anemia,
neutropenia) as well as peripheral neuritis and myopathy.
Acute intoxication after overdoses is characterized by
burning throat pain, bloody diarrhea, shock, hematuria and oliguria. Fatal
ascending central nervous system depression has been reported. Treatment is
supportive. The fatal dose is as low as 7 mg.
Dosage:
1) The prophylactic dose of colchicine is 0.5-0.6 mg 1-3 times daily.
2) If used to terminate an attack of gout, the
traditional initial dose of colchicine is usually 0.6 or 1.2 mg, followed by
0.6 mg every 2 hours until pain is relieved or nausea and diarrhea appear. A
lower dose regimen of 1.2 mg initially, followed by 0.6 mg oral is as effective
as the high dose regimen.
Normally we should not exceed 6 mg per acute attack and
the dose should not be repeated within 7 days.
3) For Mediterranean fever, 1-1.5 mg 3 times/day is the
prophylactic dose.
N.B:
1) IV use of colchicine is not recommended.
2) Colchicine use is contraindicated in pregnancy.
3) 0.6 mg/day for a creatinine clearance of 35-50 mL/min,
0.6 mg every 2 to 3 days for creatinine clearances of 10-35 mL/min and
avoidance in those with creatinine clearance of less than 10 mL/min or with
combined hepatic and renal disease.
4) Use of colchicine with clarithromycin, erythromycin or
tolbutamide may cause colchicine toxicity. Thiazide diuretics may increase
serum uric acid and interfere with the activity of colchicine.
5) Colchicine may impair the absorption of vitamin B12.
6) Acute myopathy has been reported in patients with
chronic renal impairment given colchicine with Simvastatin. This is so because
both drugs are metabolized by the cytochrome P450 isoenzyme CYP3A4.
7) Tetraparesis developed in a patient who took
colchicine with verapamil. This was considered to be due to a pharmacokinetic
interaction which increased serum and CSF concentrations of colchicine.
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