Colchicine toxicity: Difference between revisions

Revision as of 18:04, 10 August 2018

Background

Derived from C. autumnale (wild saffron, meadow saffron, autum crocus, naked lady) and G. superba (glory lily)
- C. autumnale resembles wild garlic
- G. superba may be confused for sweet potatoes
First published in the first century in Pedanius Dioscorides De Materia Medica

Uses

Gout
Familial Mediterranean fever
Pericarditis

Toxicokinetics

Inhibitor of microtubule formation and function
Rapidly absorbed in the jenjunum and ileum
Bioavaiability of 25-50%
Lipid soluble
Volume of distribution from 2.2-12L/kg, may increase to 21L/kg in overdose
50% bound to plasma proteins
Peak serum concentration in 1-3 hours
Metabolized by liver via CYP3A4
- Undergoes enterohepatic recirculation
Serum half-life 9-108 minutes
Toxicity usually occurs at levels >3ng/ml

Clinical Features

Triphasic

Phase I
- Onset 12-24 hours post ingestion
- GI manifestations
Phase II
- 24 hours- several days
- Wide spread organ dysfunction
Phase III
- Recovery or death
- Lasts approximately 1 week

GI

Vomiting and diarrhea
Abdominal pain

Hematopoietic

Peripheral leukocytosis followed by profound leukopenia
Pancytopenia within 48-72 hours
Recovery of all cell lines occurs if patient survives

Cardiovascular

Dysrhythmias
Cardiac arrest
- Occurs within 24-36 hours

Pulmonology

Acute respiratory distress syndrome

Neurologic

Myopathy
Neuropathy
Myoneuropathy
Seizures

Musculoskeletal

Rhabdomyolysis

Differential Diagnosis

Heavy metal toxicity

Evaluation

Colchicine levels do not return in a timely manner
- No correlation with severity of illness
- >3.0ng/ml generally associated with toxicity
BMP
- Including calcium, magnesium, and phosphorus
LFTs
CBC
Coagulation factors
CPK
UA
EKG
CXR
Depending on clinical situation
- Troponin
- ABG
- Lactate
- Fibrinogen

Management

Supportive care
GI Decontamination
- Orogastric lavage in patients who present within 1-2 hours without vomiting
- Activated charcoal and consider MDAC
Antidotal therapy
- Colchine-specific Fab fragments
  - Not commercially available
- Granulocyte-colony stimulating factor (G-CSF)
  - useful in treating patients who develop leukopenia and thrombocytopenia
Extracorporeal elimination
- No benefit

Disposition

All symptomatic patients require admission to ICU
Patients who do not develop GI symptoms within 8-12 hours after ingestion likely have not developed significant poisoning
Consult Toxicology or Poison Control Center

References

Schier, J. Colchicine, Podophyllin and the Vinca Alkaloids. In: Goldfrank's Toxicologic Emergencies. 9th Ed. New York: McGraw-Hill; 2011: 537-547

Authors:

@@ Line 1: / Line 1: @@
 ==Background==
 *Derived from C. autumnale (wild saffron, meadow saffron, autum crocus, naked lady) and G. superba (glory lily)
-**C. autumnale resembles wild garlic [[File:https://upload.wikimedia.org/wikipedia/commons/5/53/Colchicum_autumnale_002.JPG|thumbnail]]
+**C. autumnale resembles wild garlic
 **G. superba may be confused for sweet potatoes
 *First published in the first century in ''Pedanius Dioscorides De Materia Medica''
 ===Uses===
+*Gout
+*Familial Mediterranean fever
+*Pericarditis
 ===Toxicokinetics===
+*Inhibitor of microtubule formation and function
+*Rapidly absorbed in the jenjunum and ileum
+*Bioavaiability of 25-50%
+*Lipid soluble
+*Volume of distribution from 2.2-12L/kg, may increase to 21L/kg in overdose
+*50% bound to plasma proteins
+*Peak serum concentration in 1-3 hours
+*Metabolized by liver via CYP3A4
+**Undergoes enterohepatic recirculation
+*Serum half-life 9-108 minutes
+*Toxicity usually occurs at levels >3ng/ml
 ==Clinical Features==
-===Acute===
+===Triphasic===
+*Phase I
+**Onset 12-24 hours post ingestion
+**GI manifestations
+*Phase II
+**24 hours- several days
+**Wide spread organ dysfunction
+*Phase III
+**Recovery or death
+**Lasts approximately 1 week
+===GI===
+*Vomiting and diarrhea
+*Abdominal pain
+===Hematopoietic===
+*Peripheral leukocytosis followed by profound leukopenia
+*Pancytopenia within 48-72 hours
+*Recovery of all cell lines occurs if patient survives
+===Cardiovascular===
+*Dysrhythmias
+*Cardiac arrest
+**Occurs within 24-36 hours
+===Pulmonology===
+*[[Acute respiratory distress syndrome]]
+===Neurologic===
+*Myopathy
+*Neuropathy
+*Myoneuropathy
+*Seizures
+===Musculoskeletal===
+*Rhabdomyolysis
 ==Differential Diagnosis==
 ===[[Heavy metal]] toxicity===
@@ Line 39: / Line 77: @@
 *[[Zinc toxicity]]
 ==Evaluation==
+*Colchicine levels do not return in a timely manner
+**No correlation with severity of illness
+**>3.0ng/ml generally associated with toxicity
 *BMP
+**Including calcium, magnesium, and phosphorus
 *LFTs
 *CBC
+*Coagulation factors
 *CPK
+*UA
 *EKG
+*CXR
+*Depending on clinical situation
+**Troponin
+**ABG
+**Lactate
+**Fibrinogen
 ==Management==
+*Supportive care
+*GI Decontamination
+**[[Orogastric lavage]] in patients who present within 1-2 hours without vomiting
+**[[Activated charcoal]] and consider [[MDAC]]
+*Antidotal therapy
+**Colchine-specific Fab fragments
+***Not commercially available
+**Granulocyte-colony stimulating factor (G-CSF)
+***useful in treating patients who develop leukopenia and thrombocytopenia
+*Extracorporeal elimination
+**No benefit
 ==Disposition==
+*All symptomatic patients require admission to ICU
+*Patients who do not develop GI symptoms within 8-12 hours after ingestion likely have not developed significant poisoning
 *Consult Toxicology or Poison Control Center