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ACUTE EXPOSURE INFORMATION
- USES: Colchicine is a natural alkaloid found in plants such as the autumn crocus (Colchicum Autumnale) and glory lily (Gloriosa superba). As a medication, it functions as an antimitotic and anti-inflammatory agent used to treat gout, familial Mediterranean fever, secondary amyloidosis, and scleroderma. Exposure occurs by oral and IV routes.
- PHARMACOLOGY: Colchicine binds to tubulin, a main component of microtubules, and causes cytoskeletal changes. Its anti-inflammatory properties are due to inhibiting the migration of leukocytes and proinflammatory cytokines into affected tissues. Finally, it inhibits uric acid crystal deposition in gout.
- TOXICOLOGY: Colchicine inhibits mitosis of dividing cells and functions as a microtubule or spindle poison. In overdose, it preferentially affects rapidly dividing cells. In high concentrations it is a general cellular poison.
- EPIDEMIOLOGY: Poisoning is very uncommon but causes significant morbidity and mortality.
- WITH THERAPEUTIC USE
- ADVERSE EFFECTS: COMMON: At therapeutic doses, gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain) are commonly seen. LESS COMMON: Alopecia and anorexia may occur less frequently. RARE: Agranulocytosis, aplastic anemia, dysrhythmias, bone marrow suppression, hepatotoxicity, myopathy, peripheral neuritis, and rash may rarely be observed.
- DRUG INTERACTIONS: Substances that inhibit CYP 3A4 (eg; atazanavir, erythromycin, clarithromycin, ketoconazole, nefazodone, and grapefruit juice) and substances that inhibit P-glycoprotein (eg; cyclosporine, ranolazine) increase colchicine plasma concentrations, and cause toxicity at lower doses.
- WITH POISONING/EXPOSURE
- MILD TO MODERATE POISONING: Mild overdose causes mainly nausea, vomiting, diarrhea, and abdominal pain.
- SEVERE POISONING: Severe overdose causes clinical findings in 3 phases but may be delayed initially a few hours:
- PHASE I (0 TO 24 HOURS) – GASTROINTESTINAL: Nausea, vomiting, diarrhea (bloody), abdominal pain, dehydration, leukocytosis, volume depletion, and hypotension.
- PHASE II (1 TO 7 DAYS) – MULTIORGAN SYSTEM FAILURE: Possible risk of sudden cardiac death, dysrhythmias; confusion, coma, seizures; pancytopenia, renal failure, hepatic failure, sepsis, acute lung injury, electrolyte imbalances, rhabdomyolysis. Patients with severe overdose may die during this phase.
- PHASE III (OVER 7 DAYS) – RECOVERY OR DEATH: Alopecia; myopathy, neuropathy, myoneuropathy, or rebound leukocytosis; death usually is caused by respiratory failure, intractable shock, dysrhythmias, and cardiovascular collapse.
- FACTORS ASSOCIATED WITH POOR PROGNOSIS POST-INGESTION: A large dose; increased INR; WBC greater than 18K within 24 hours of ingestion; cardiogenic shock within 72 hours.
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