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Chapter: Modern Medical Toxicology: Neurotoxic Poisons: Anticonvulsants and Antiparkinsonian Drugs

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Gabapentin - Anticonvulsant (Anti-Epileptic) Drug

Gabapentin is an amino acid structurally related to gamma-aminobutyric acid (GABA), the major endogenous inhibitory neurotransmiter in the brain, and is used in the treatment of partial seizures by combining with other anticonvulsants.

Gabapentin

Gabapentin is an amino acid structurally related to gamma-aminobutyric acid (GABA), the major endogenous inhibitory neurotransmiter in the brain, and is used in the treatment of partial seizures by combining with other anticonvulsants. It acts by enhancing the promoted release of GABA, though the exact mechanism is unclear. It does not interact with GABA recep-tors and it is not an inhibitor of GABA uptake or degradation.

Gabapentin is used as an add-on anticonvulsant agent in the treatment of refractory partial seizures. It also appears effective in generalised seizures.

Gabapentin is well-absorbed after oral administration and is not metabolised at all. It is excreted unchanged in the urine.

Common adverse effects include drowsiness, vertigo, ataxia, nystagmus, hypertension, and fatigue. Hypertension has been reported following therapeutic doses, as also alopecia. Serious leukopenia has been reported rarely. Impotence has occurred following therapeutic doses. Weight gain and painful gynaecomastia have also been reported. Abrupt cessation of gabapentin after prolonged use can cause withdrawal (seizures or catatonia).

Therapeutic serum levels have not been established. Some investigators report a reference range for therapeutic gabapentin serum level of 2 to 15 mcg/ml.

Overdose results in slurred speech, diplopia, ataxia,dizziness, somnolence, and sedation. Other effects have included gastrointestinal effects, especially diarrhoea. Symptoms usually resolve in 18 to 24 hours without specific therapy. Overdoses as high as 108 grams have been reported with full recovery following symptomatic therapy.

Gastric lavage may be done if the patient is seen within 3 hours. Monitor vital signs regularly. For mild/moderate asymp-tomatic hypertension, pharmacologic intervention is generally not necessary. Sedative agents such as benzodiazepines may be helpful in treating hypertension and tachycardia in agitated patients, especially if a sympathomimetic agent is involved in the poisoning. For hypertensive emergencies (severe hyperten-sion with evidence of end organ injury (CNS, cardiac, renal), or emergent need to lower mean arterial pressure within one hour, nitroprusside is preferred.

Gabapentin can be removed by haemodialysis; however, since toxicity after acute overdose is generally mild it is unlikely to be necessary. Haemodialysis may be indicated by the patient’s clinical status or in patients with significant renal impairment.


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