Regarding Benzodiazepine Toxicity ..

A 24-year-old woman is brought to the emergency department with confusion, blurred vision, dizziness, and somnolence. Her friend states that the woman is generally healthy but is taking medication for occasional episodes of intense fear, sweating, nausea, and abdominal and chest pain. Physical examination reveals a respiratory rate of 8/min.

What is the most likely diagnosis?
Benzodiazepine toxicity, as characterized by respiratory depression, confusion, and other symptoms of central nervous system depression.

What class of drugs might be responsible for this patient’s symptoms?
Her friend’s description is consistent with a diagnosis of panic disorder. Benzodiazepines (such as
clonazepam, lorazepam, and alprazolam) are commonly used in the short-term treatment of panic disorder.

What treatment was likely administered to this patient in the emergency department?
Flumazenil, a competitive antagonist at the γ-aminobutyric acid (GABA) receptor, is effective in reversing symptoms of benzodiazepine overdose.


How does the mechanism of action of benzodiazepines differ from that of barbiturates?
Normally, GABAA receptors respond to GABA binding by opening chloride channels, which raises the membrane potential of the neuron and inhibits neuronal firing. Benzodiazepines and barbiturates enhance the affinity of GABA for GABAA receptors. Benzodiazepines increase the frequency of chloride channel openings. Barbiturates increase the duration of chloride channel openings.

What are the advantages of treatment with benzodiazepines over barbiturates?
Benzodiazepines have a lower risk of dependence, P450 system involvement, respiratory depression,
coma, and loss of rapid eye movement sleep. They are considered to be much safer than barbiturates in cases of overdose (specifically, barbiturates have a lower therapeutic index).

What drugs, when taken with benzodiazepines, increase the risk of toxicity?
• Acetaminophen
• Alcohol
• Cimetidine
• Disulfiram
• Isoniazid
• Valproic acid