Benzodiazepines

Snapshot

A 56-year-old man is brought to the emergency department after being found in the park in a lethargic state. The patient has a history of multiple hospital visits for pain management of acute pancreatitis. Medical history is significant for alcohol use disorder. On physical exam, the patient has slurred speech, nystagmus, and unsteady gait. Laboratory testing is significant for an elevated blood alcohol level. Urine and serum toxicology is negative for illicit drugs. He is started on intravenous thiamine and glucose. Approximately 6 hours after admission the patient becomes nauseous, anxious, tremulous, and develops palpitations. He is subsequently started on intravenous lorazepam. (Alcohol withdrawal)

Introduction

Medications
- short-acting benzodiazepines
  - alprazolam
  - triazolam
  - oxazepam
  - midazolam
- longer-acting benzodiazepines
  - flurazepam
  - chlordiazepoxide
  - lorazepam
  - diazepam
Mechanism of action
- ↑ the frequency of Cl^– channel opening and thus facilitating GABAA action
  - via its binding to the α and γ subunit of the GABAA receptor
    - this in turn ↓ neuron firing
Metabolism
- oxazepam, temazepam, and lorazepam
  - is not dependent on liver metabolism
Adverse reaction
- dependence
- can have an additive CNS depressive effect with other CNS depressants (e.g., alcohol and barbiturates)
- the antidote to benzodiazepine overdose is
  - flumazenil
    - a competitive benzodiazepine receptor antagonist
    - can provoke seizures in chronic benzodiazepine users
Clinical use
- anxiety and panic disorder
- status epilepticus
- alcohol withdrawal
- anesthesia premedication
- sleep walking and other parasomnias
- skeletal muscle relaxation
- insomnia