A 62-year-old woman is hospitalized for cellulitis and prescribed antibiotic pharmacotherapy. On the morning following admission, the patient becomes diaphoretic, tremulous, anxious, and tachycardic. A few hours later, she has a generalized tonic-clonic seizure. Medical history is significant for depression, chronic hepatitis C virus infection, multiple substance use disorders, hypertension, and hyperlipidemia. The patient is minimally adherent to medication. Temperature is 37 C (98.6 F), blood pressure is 139/87 mm Hg, pulse is 103/min, and respirations are 16/min. Examination is significant for persistent anxiety, tremulousness, and diaphoresis. Laboratory results are as follows: Which of the following is the most appropriate pharmacotherapy for this patient's condition?

Question

A 62-year-old woman is hospitalized for cellulitis and prescribed antibiotic pharmacotherapy.  On the morning following admission, the patient becomes diaphoretic, tremulous, anxious, and tachycardic.  A few hours later, she has a generalized tonic-clonic seizure.  Medical history is significant for depression, chronic hepatitis C virus infection, multiple substance use disorders, hypertension, and hyperlipidemia.  The patient is minimally adherent to medication.  Temperature is 37 C (98.6 F), blood pressure is 139/87 mm Hg, pulse is 103/min, and respirations are 16/min.  Examination is significant for persistent anxiety, tremulousness, and diaphoresis.  Laboratory results are as follows:  Which of the following is the most appropriate pharmacotherapy for this patient's condition?

Quizplus · Accepted Answer

11ec25c8_d78f_437f_bc81_17425a31fe74_MD0003_00 This patient's tremulousness, diaphoresis, tachycardia, anxiety, and seizures in the setting of a 2:1 ratio of aspartate aminotransferase to alanine aminotransferase are consistent with alcohol withdrawal. The cornerstone of treatment for alcohol withdrawal is benzodiazepines. The choice of benzodiazepine depends on the preferred route of administration as well as pharmacokinetic and metabolic considerations. In patients with liver disease (eg, chronic hepatitis C, elevated INR, low platelets), the preferred benzodiazepines are those that lack active metabolites and undergo hepatic metabolism via phase II glucuronidation instead of phase I cytochrome P450 reaction. The benzodiazepines lorazepam, oxazepam, and temazepam fulfill these criteria. Among the benzodiazepines listed, lorazepam is the most appropriate in this patient with evidence of active liver disease. The most commonly used benzodiazepines for alcohol withdrawal are chlordiazepoxide, diazepam, and lorazepam. Lorazepam and diazepam are available in intravenous formulations, unlike chlordiazepoxide. Both chlordiazepoxide and diazepam have long half-lives and active metabolites that risk buildup and toxicity in patients with liver dysfunction (Choices A and B). (Choices C, E, and F) Levetiracetam, topiramate, and valproate are antiseizure medications used in the treatment of epilepsy. This patient's seizure is due to alcohol withdrawal; therefore, it should be treated with a benzodiazepine. Educational objective: In patients with liver disease, the benzodiazepines lorazepam, oxazepam, and temazepam are preferred due to their shorter half-life and lack of active metabolites. Benzodiazepines with longer half-lives and active metabolites, such as chlordiazepoxide and diazepam, place patients with hepatic dysfunction at risk for toxic drug buildup. References: Alcohol withdrawal syndrome: benzodiazepines and beyond. (http://www.ncbi.nlm.nih.gov/pubmed/26500991) A way of conceptualizing benzodiazepines to guide clinical use. (http://www.ncbi.nlm.nih.gov/pubmed/26554326)

A 62-Year-Old Woman Is Hospitalized for Cellulitis and Prescribed Antibiotic