A 44-year-old man hospitalized for acute cholecystitis is being evaluated for anxiety and agitation. He underwent an open cholecystectomy without having any operative complications. Two days after admission, the patient experiences anxiety and tremulousness, and he becomes irritable, severely agitated, and verbally abusive to the nursing staff. He has no other medical problems. The patient does not use tobacco or illicit drugs but admits to drinking 6-8 beers daily for the last several years. He has no known drug allergies, and family history is insignificant. Blood pressure is 160/90 mm Hg and pulse is 110/min. Examination shows hand tremors bilaterally. Which of the following is the most appropriate pharmacotherapy for this patient?
This patient's acute onset of tremulousness, agitation, and elevated pulse and blood pressure within 48 hours of admission is suggestive of alcohol withdrawal. Alcohol is a CNS depressant that binds to the GABAA receptor complex, enhancing the inhibitory action of GABA (the major inhibitory neurotransmitter in the brain). Abrupt cessation of alcohol decreases inhibitory tone and results in CNS excitation. Alcohol withdrawal symptoms typically start within 8-12 hours after the last drink and include insomnia, tremulousness, anxiety, and autonomic hyperactivity (variable blood pressure, diaphoresis, and tachycardia). Alcohol withdrawal seizures can occur within 12-48 hours, and delirium tremens (disorientation, severe agitation, fever) typically begins within 48-96 hours.
Alcohol, barbiturates, and benzodiazepines have similar effects on GABA receptors and act by enhancing GABA inhibitory action. Benzodiazepines (eg, lorazepam, diazepam, chlordiazepoxide) are used as first-line therapy for psychomotor agitation associated with alcohol withdrawal and to prevent progression to seizures and delirium. Longer-acting benzodiazepines and those with active metabolites are preferred in the majority of patients due to self-tapering effects, resulting in a smoother course of withdrawal.
(Choice A) Baclofen is an agonist of GABA B receptors and is used to treat spastic conditions. It is less effective than benzodiazepines for treating alcohol withdrawal.
(Choice B) Carbamazepine may have a role in outpatient management of mild alcohol withdrawal, but there is insufficient evidence for its use in moderate to severe alcohol withdrawal.
(Choices C and D) Chlorpromazine and haloperidol are antipsychotic medications that lower the seizure threshold. They should not be used to treat alcohol withdrawal as these patients are already at significant risk for seizure.
(Choice F) Phenobarbital is a barbiturate anticonvulsant that enhances GABA activity. It is no longer used as first-line treatment for alcohol withdrawal because it has a worse safety profile than benzodiazepines.
(Choice G) The beta blocker propranolol can treat tremor, tachycardia, and hypertension, but it has not been shown to prevent development of seizures or delirium tremens. Treatment with benzodiazepines is the most crucial step in the management of alcohol withdrawal.
Educational objective:
Alcohol withdrawal should be considered in hospitalized patients who develop tremulousness, agitation, and elevated pulse and blood pressure within 48 hours following admission. Benzodiazepines act as a substitute for the effects of alcohol on GABA receptors, preventing alcohol withdrawal from occuring.