Phenytoin as a possible cause of acetaminophen hepatotoxicity: case report and review of the literature.

A 55-year-old woman was hospitalized for treatment of community-acquired pneumonia. Unexplained, moderate elevations in hepatic transaminase and enzyme levels prompted review of her drug regimen. She had taken acetaminophen 1,300-6,200 mg/day during the hospitalization. She also received phenytoin for posttraumatic seizures. Acetaminophen was discontinued, and the patient's liver chemistries returned to normal within 2 weeks of discharge. Acetaminophen is metabolized in part by cytochrome P450 (CYP) 2E1, and inducers of CYP2E1 are known to predispose patients to acetaminophen-related hepatotoxicity. Phenytoin induces CYP2C and CYP3A4 isoforms, but not CYP2E1. The literature suggests, however, that CYP3A4 may participate in acetaminophen metabolism to a greater extent than previously realized, and induction of this isoform may predispose patients to acetaminophen-induced hepatotoxicity.

Defining and achieving optimum therapeutic goals in critically ill patients.

Patients who are critically ill with sepsis, shock, respiratory failure, trauma, or major surgical procedures may have reduced morbidity and mortality when hemodynamic and oxygen transport variables are augmented to values higher than those traditionally considered normal. Lactate production and suboptimum oxygen transport values are associated with anaerobic metabolism and insufficient tissue oxygenation. Since lactate can be a marker of inadequate tissue oxygenation, serial lactate measurements may be useful in individualizing therapy to reverse tissue hypoxia. Optimum hemodynamic and oxygen transport values are highly individual, and no accepted method has been established for guiding therapy. These values, together with plasma lactate concentrations, may assist in individualizing therapy in critically ill patients. No consensus can be reached at this time as to which specific therapeutic end points are optimal, how to achieve these end points, and which subset of patients will benefit from this therapy.

Use of transdermal nicotine systems in a possible suicide attempt.

BACKGROUND: Transdermal drug delivery systems, a relatively recent development, are well accepted by physicians and patients because of reliability and ease of administration. The patch reservoirs, however, contain large quantities of drug, and the potential for considerable toxicity exists if they are used incorrectly. A case is presented of an apparent suicide attempt that involved the use of nicotine transdermal patches. METHODS: This case report involved a patient seen in the emergency department by one of the authors. Data were obtained from the patient's medical record while maintaining confidentiality. RESULTS: The drug overdose was a potentially serious one. The patient recovered fully after an uneventful hospital course. CONCLUSIONS: Transdermal drug delivery systems now deliver many drugs, several of which are quite potent. Intentional or unintentional misuse of the systems can result in toxicity. The physician and pharmacist should carefully instruct each patient in the appropriate use and handling of transdermal drug delivery systems.