Case #6: Drunk at a bar?
Author: Theresa Kim, MD
Peer Reviewer: Michele Zell Kanter, PharmD, DABAT
A 21 year old female with a past medical history of depression and anxiety is brought in by ambulance for altered mental status. Her friends called EMS because she became increasingly difficult to arouse at a bar. Initially, they thought she was just drunk, but then they tell you she only had two shots the whole night. Her friend asks you if the new anxiety pills she took right before she drank may have caused her symptoms.
Vitals: Temp: 98.8, HR: 80, BP: 100/82, RR: 12, O2 Sat: 99% on RA
On exam, the patient smells of alcohol, is lethargic but arousable, and her speech is slurred. The rest of the exam is non-focal.
While you are examining the patient, a bottle of lorazepam tablets rolls out of her purse.
What other drugs could have caused a similar presentation?
-Antidepressants (SSRIs, SNRIs)
-Antihistamines
-Antipsychotic medications
-Barbiturates
-Chloral hydrate
-Ethanol
-Gamma hydroxy butyrate (GHB)
-Opioids
-Skeletal muscle relaxants
-TCAs
What is the classic presentation of someone who has overdosed on benzodiazepines (BZDs)?
The classic presentation of CNS depression with normal vital signs is often referred to as the ‘sedative-hypnotic toxidrome’. Unlike barbiturates, respiratory depression is less common in isolated ingestion of oral benzodiazepines. When combined with other sedative-hypnotic agents like ethanol, however, the risk of prolonged sedation and respiratory depression increases significantly. Drugs that inhibit the CYP3A4 enzyme (including macrolide antibiotics, diltiazem, and HIV protease inhibitors) have also been shown to interfere with the metabolism of BZDs, and subsequently increase the risk of adverse side effects.
Is there a BZD antidote and how does it work?
Yes, flumazenil. It acts as a non-specific BZD competitive antagonist. Use this agent cautiously, as it can precipitate withdrawal or seizures. Patients with suspected TCA overdose, patients who may require BZDs for the treatment of life threatening conditions (such as increased ICP or status epilepticus), chronic BZD users, and patients with hypersensitivity to flumazenil should not receive this antidote. Of note, while flumazenil consistently reverses the sedative effects of benzodiazepines, studies have shown that it does not always reverse the respiratory depression seen in overdose.
What complication should you look out for if this antidote is given?
Signs and symptoms of withdrawal can be precipitated when flumazenil is initiated (especially in chronic benzodiazepine users). The physician should watch for tremors, anxiety, hallucinations, dysphoria, and seizures. Longer half-life benzodiazepines such as diazepam and chlordiazepoxide have a lower risk for withdrawal than shorter half life BZDs (e.g. midazolam) as these remain in the blood stream for longer periods of time.
References:
Marriott S, Tyrer P. Benzodiazepine dependence. Avoidance and withdrawal. Drug Saf. 1993 Aug;9(2):93-103.
Seger DL. Flumazenil–treatment or toxin. J Toxicol Clin Toxicol. 2004;42(2):209-16.
Shalansky SJ, Naumann TL, Englander FA. Effect of flumazenil on benzodiazepine-induced respiratory depression. Clin Pharm. 1993 Jul;12(7):483-7.
Weinbroum AA, Flaishon R, Sorkine P, et al. A risk-benefit assessment of flumazenil in the management of benzodiazepine overdose. Drug Saf. 1997 Sep;17(3):181-96.
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