Toxicology Brief: Successful treatment of baclofen overdose with intravenous lipid emulsion - Veterinary Medicine
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Toxicology Brief: Successful treatment of baclofen overdose with intravenous lipid emulsion


VETERINARY MEDICINE


DISCUSSION

Baclofen is a centrally acting skeletal muscle relaxant. Prescribed in people to alleviate muscle spasticity associated with multiple sclerosis and spinal disorders, it has been recently used in treating the side effects of alcohol withdrawal and is also becoming a common drug of abuse.2

Its administration in dogs has been intermittent, specifically for the relief of urinary retention secondary to urethral muscle spasticity. Dosages for this purpose are reported to be 1 to 2 mg/kg orally three times a day, though even at therapeutic doses, adverse drug effects such as ataxia or weakness are frequently noted. Baclofen administration in cats is not recommended.3

Toxicokinetics

Baclofen acts as a mimic of gamma-aminobutyric acid at the spinal end of upper motor neurons, functionally inhibiting monosynaptic and polysynaptic reflexes at the spinal level. The inhibition results in a flaccid paralysis of skeletal muscles. Poor penetration of the blood-brain barrier limits central nervous system (CNS) signs at therapeutic doses, but in overdose situations, CNS signs can be significant.4

The dose of baclofen an animal ingests appears to affect the pharmacokinetic profile. At or near therapeutic doses, absorption is rapid and complete, with peak plasma concentrations occurring roughly three hours after ingestion. With higher doses, the absorption is more incomplete and has been shown to be prolonged.2 The presence of food in the gastrointestinal tract does not appear to affect bioavailability.5 In people, the half-life shows similar dose variations, with half-life increasing from 2.5 hours to six hours for therapeutic doses. In cases of significant overdose, the half-life has been noted to increase to more than 34 hours.2

Baclofen is primarily eliminated unchanged by the kidneys, though fluid diuresis alone has not been shown to enhance excretion. Small amounts are metabolized through deamination in the liver and excreted in the bile.2

Toxicity

Baclofen toxicosis is potentially lethal because of respiratory arrest from the paralytic effect on intercostal and diaphragm muscles. No LD50 has been established in dogs. However, according to preliminary information retrieved from the toxicology database at the ASPCA Animal Poison Control Center (APCC), fatal events have been noted with baclofen doses as low as 4 mg/kg and more consistently with doses > 10 mg/kg.1

Independent of dose, clinical signs have generally been noted within two hours of exposure, with a few cases showing signs in as little as 15 minutes and as late as seven hours. Once they develop, clinical signs can persist for several hours; clinical signs from larger doses potentially last several days because of slow clearance from the CNS.4

Exposure to baclofen can result in a constellation of clinical signs. In the cases reported to the ASPCA APCC, the most common clinical signs were ataxia, vomiting, and vocalizing. Vocalization was noted frequently in cases that were otherwise nonresponsive. Other frequently reported clinical signs were dyspnea, seizures, depression, tachypnea, hypothermia, and hypotension.1,4 Hypokalemia and hypoglycemia are frequent findings in human exposures but were not consistently reported in animal cases.2

Differential diagnoses

When diagnosing baclofen toxicosis, it is important to rule out other possible causes of the clinical signs, including:

  • An overdose of other skeletal muscle relaxants (e.g. cyclobenzaprine), amphetamines, avermectins, barbiturates, benzodiazepines, 5-hydroxytryptophan, opioids, propofol, tricyclic antidepressants, selective serotonin reuptake inhibitors, zaleplon, zolpidem, zopiclone, and botulinum toxin
  • Ionophore toxicosis
  • Coonhound paralysis
  • Tick paralysis
  • CNS trauma.


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Source: VETERINARY MEDICINE,
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