Multiple-dose activated charcoal compared to urinary alkalinization for the enhancement of phenobarbital elimination.

BACKGROUND: Urinary alkalinization and multiple-dose activated charcoal are modalities advocated for the enhancement of phenobarbital elimination in poisoned patients. However, no studies exist comparing the efficacy of these two means of elimination enhancement. We compared their effects on the pharmacokinetic disposition of intravenously administered phenobarbital. METHODS: Ten healthy volunteers participated in each of three randomly ordered study phases. During each phase, 5 mg of intravenous phenobarbital per kilogram of body weight was administered. During phase I, no interventions were made in attempt to enhance phenobarbital elimination. In phase II, participants underwent 24 hours of urinary alkalinization. Throughout phase III, volunteers received six doses of activated charcoal and two doses of sorbitol over 24 hours. RESULTS: The phenobarbital elimination half-life was 148 hours, 47 hours and 19 hours during the control, alkalinization and charcoal phases, respectively. Statistically significant differences in the elimination of phenobarbital were detected when each of the following phases were compared: I vs II, I vs III and II vs III. CONCLUSIONS: Both urinary alkalinization and multiple doses of activated charcoal are effective for the enhancement of phenobarbital elimination but multiple-dose charcoal was superior to urinary alkalinization in our study population.

Methanol inhalation toxicity.

Significant toxicity can result from intentional methanol inhalation. We report seven cases, involving four patients, of intentional inhalation of CARB-MEDIC carburetor cleaner containing toluene (43.8%), methanol (23.2%), methylene chloride (20.5%), and propane (12.5%). Patients arrived at the emergency department with central nervous system depression, nausea, vomiting, shortness of breath, photophobia, and/or decreased visual acuity. Treatment included correction of acidosis, leucovorin and/or folic acid, ethanol infusions, and supportive care. Hemodialysis was necessary in three cases. Measured blood methanol levels ranged from 50.4 to 128.6 mg/dL. Blood formic acid levels were 120, 193, and 480 micrograms/mL, respectively, in three patients. Ophthalmic examinations revealed hyperemic discs and decreased visual acuity in one patient. One individual was found pulseless with several CARB-MEDIC cans nearby. Attempts at revival were unsuccessful. Clinicians should be aware that significant blood methanol and formic acid levels may occur after inhalation of methanol.

Theophylline toxicity from an over-the-counter preparation.

The clinical presentation of theophylline poisoned patients has been well described in the literature. These individuals may develop severe and potentially fatal cardiac, neurologic, and gastrointestinal manifestations. While patients may present following an intentional over-dose, a significant percentage become toxic accidentally or iatrogenically, as a result of theophylline's narrow therapeutic index. Another factor, not well known or described in the literature, is the availability of theophylline in a variety of over-the-counter formulations. We present a case of theophylline toxicity from a nonprescription combination product containing theophylline, ephedrine, and phenobarbital. Clinicians should be aware of the potential for serious toxicity from over-the-counter medications, particularly those commonly thought of as "prescription only."

Methotrexate and nonsteroidal antiinflammatory drug interactions.

OBJECTIVE: To determine if the coadministration of methotrexate (MTX) and nonsteroidal antiinflammatory drugs (NSAIDs) results in a clinically significant drug interaction. DATA SOURCES: A case report of hematologic toxicity following the administration of MTX and flurbiprofen at our institution is presented. Six previously published case reports and five pharmacokinetic studies regarding MTX and NSAID interactions are available to assist in the evaluation of this potential interaction. DATA SYNTHESIS: Cases of various clinical manifestations during concomitant MTX and NSAID administration, including acute renal failure and pancytopenia, have been reported. The exact mechanism of the interaction has not been fully elucidated. Suggested theories to explain the mechanism of MTX toxicity include reduction in MTX clearance secondary to renal capillary constriction induced by NSAIDs, displacement of MTX or its metabolite from plasma proteins, competition between MTX and NSAIDs for renal tubular excretion, or impairment of hepatic metabolism of MTX by NSAIDs. Studies comparing MTX pharmacokinetics with or without concurrent NSAID therapy have not shown statistical differences in the parameters evaluated. However, one study did demonstrate differences in the pharmacokinetics of 7-hydroxy-methotrexate, the active metabolite of MTX, when MTX was administered with aspirin. CONCLUSIONS: Although a clinically significant interaction does not occur in all patients, numerous case reports are available that demonstrate possible problems following the coadministration of MTX and NSAIDs. To date, the specific circumstances during which the reaction may occur have not been well defined.

Features and treatment of rabies.

The epidemiology, virology, transmission, pathology, clinical manifestations, diagnosis, and treatment of rabies infection are described. The incidence of rabies is increasing. The virus is usually transmitted through the bite of an infected animal; however, corneal transplantation from an infected donor and viral inhalation may also result in infection. The clinical course of rabies occurs in five stages. Stage I is the incubation period, stage II is the prodromal period, stage III is the neurological period, stage IV is coma, and stage V, which occurs infrequently, is recovery. Early in the disease, constitutional symptoms and signs of local wound healing may be present. During the later stages, a wide array of clinical manifestations may occur, including hydrophobia and aerophobia, which are pathognomonic for rabies. Once inoculation with the rabies virus is suspected, prompt therapy, including appropriate wound care and rabies vaccination, is imperative, even in previously immunized individuals. Human diploid-cell vaccine and rabies vaccine adsorbed, which stimulate the production of antibodies, and human rabies immune globulin, which provides protective antibodies, are nearly 100% effective in preventing progression from stage I disease. If left untreated, rabies is usually fatal. However, treatment with human diploid-cell vaccine or rabies vaccine adsorbed and with human rabies immune globulin is nearly always curative if initiated early in the incubation period.