Faculty Bibliography

The pharmacokinetics and adverse effects of an oral loading dose of carbamazepine administered in tablet or suspension form were studied. Patients on a hospital epilepsy unit who were to receive carbamazepine as a discharge medication were randomly assigned to receive either an oral 8-mg/kg loading dose of the tablet formulation or the same dose of the suspension on an empty stomach. Blood samples were drawn before and at intervals up to 12 hours after the loading dose. Adverse effects were evaluated subjectively and objectively. Total and free serum carbamazepine and carbamazepine-10, 11-epoxide (CBZE) concentrations were determined by high-performance liquid chromatography. Six adult patients were enrolled in and completed the study. All the patients achieved therapeutic total carbamazepine levels; the suspension group did so within two hours and the tablet group within five hours. Maximum serum carbamazepine concentrations ranged from 7.10 to 9.92 mg/L, area under the concentration-versus-time curve from 54.85 to 82.23 micrograms.hr/L, and terminal elimination half-life from 14.05 to 15.71 hours. Adverse effects were mild, few, and short-lived; none of the patients developed gastrointestinal toxicity. Adverse effects were not associated with total or free carbamazepine and CBZE concentrations or with total or free CBZE:carbamazepine ratios. An oral loading dose of carbamazepine 8 mg/kg achieved therapeutic levels within two hours when given as a suspension and within five hours when given as tablets and was well tolerated in all patients

Although newer antidepressants have been introduced over the past several years, the tricyclic antidepressants (TCAs) continue to be a leading cause of morbidity from drug overdose in the United States. Overdose features depend on the particular cyclic antidepressant ingested and its pharmacological properties, and can include CNS depression, cardiac dysrhythmias, hypotension, seizures, and anticholinergic symptoms. Life- threatening events almost always begin within two hours, and certainly within six hours, after arrival to the emergency department. Plasma TCA levels are unreliable predictors of TeA toxicity and are therefore not recommended. An ECG with a prolonged QRS complex more than 100 msec seems to be the best indicator of serious sequelae with TCA overdose. Management consists of stabilization of vital signs, gastrointestinal decontamination, intravenous sodium bicarbonate, and supportive care. Agents once thought to be useful for the treatment of cardiac dysrhythmias and seizures such as phenytoin and physostigmine should be avoided. The future of TCA antibody fragments in the treatment of TCA overdose seems promising. Amoxapine, bupropion, and maprotiline seems to be as toxic as the TCAs. Overdose data is limited for venlafaxine, and mirtazapine, and preclude firm conclusions. A significant interaction between cyclic antidepressants and monoamine-oxidase inhibitors exists. Management includes supportive care and basic poison management. Prevention of poisoning seems to be the most logical and effective method of maintaining patient safety. TCAs should be avoided in children younger than 6 years old. All adults with suicidal ideations should receive no more than a one-week supply (less than 1 g) of drug. Newer and, to some degree, safer antidepressants in overdose have recently been introduced, and they include fluoxetine, sertraline, paroxetine, trazodone, and nefazodone. Finally, consideration should be given to using one of these newer, safer antidepressants in all patients with suicidal ideations