Faculty Bibliography

OBJECTIVE: Amiodarone, a class III antidysrhythmic agent, blocks Na+, Ca2+, and K+ channels as well as the beta-adrenergic receptor. Despite increased use of amiodarone for wide-complex tachycardia, its efficacy in the treatment of dysrhythmias induced by tricyclic antidepressants has not been tested. We investigated the effect of amiodarone and amitriptyline in a mouse lethality model. METHODS: The LD50 of amitriptyline obtained from reference sources was confirmed by giving 100 mg/kg to 40 mice by intraperitoneal (IP) injection. The safety of the treatment dose of amiodarone was confirmed by giving 50 mg/kg by IP injection to 10 mice. One hundred and nine mice were randomized to receive pretreatment with 50 mg/kg amiodarone (n=55) or an equal volume of saline or water as a volume control (n=54). Thirty minutes after pretreatment or control injection, the mice received amitriptyline, 100 mg/kg. Outcome was defined as death or survival 3 h after amitriptyline injection. RESULTS: In our confirmation of the LD50 of amitriptyline, 25/40 mice died (62.5%). None of the 10 mice that received only amiodarone died. In the control + amitriptyline arm, 36/54 (66.7%) died, compared with 39/55 (70.9%) in the amiodarone+amitriptyline arm (X2, p=0.663). Power analysis demonstrated a 90% chance of finding a 28% difference. CONCLUSIONS: Pretreatment with amiodarone does not appear to significantly alter the lethality of amitriptyline poisoning in mice. Given the inability to monitor cardiac activity in this model, further investigation in a larger animal is required

Tiagabine is an antiepileptic drug used as adjunctive therapy for partial seizures that is believed to selectively inhibit the presynaptic reuptake of gamma aminobutyric acid (GABA). We describe a case of a tiagabine overdose that resulted in status epilepticus (SE) in a patient with no seizure history. A 14-year-old girl with a history of asthma presented with convulsive SE after ingestion of an unknown amount of her sister's tiagabine in a suicide attempt. Attempted anticonvulsant therapy included a total of diazepam 10 mg IV, lorazepam 6 mg IV, pyridoxine 5 g IV, and fosphenytoin 20 mg PE/kg. All were without effect. A computed tomography and electrocardiogram were normal. Continuous bedside EEG monitoring showed suppression of seizure activity following intravenous midazolam. A tiagabine level obtained on ED arrival was 420 ng/mL (therapeutic 20-103 ng/mL). The patient was discharged to psychiatry within 1 week with no neurologic sequelae