Toxicity, Benzodiazepine ?>

Toxicity, Benzodiazepine

Toxicity, Benzodiazepine
Introduction


Background

Since initial development in the 1950s, benzodiazepine has become popular in the treatment of various medical disorders and as a drug of abuse.1, 2 Benzodiazepine overdoses (usually combined with alcohol) are commonly observed in emergency departments (EDs) and intensive care units (ICUs).
Pathophysiology

Ingested benzodiazepines are rapidly absorbed. In the serum, more than 70% of the drug is protein bound and thus unavailable to produce a clinical affect. The unbound fraction crosses the blood-brain barrier and interacts with neuronal benzodiazepine receptors in the CNS.

In the CNS, benzodiazepines exert their clinical effect by enhancing the activity of the inhibitory neurotransmitter GABA. GABA receptors, located on postsynaptic neurons, cause an influx of negatively charged chloride ions into the neuron when stimulated by GABA. This influx of negative charge causes a hyperpolarization of the cell membrane and therefore inhibits depolarization. The binding of a benzodiazepine molecule to a site on the GABA receptor complex potentiates the inhibitory effect of GABA by increasing the frequency of chloride channel opening.

Duration of the clinical effect is proportional to the drug concentration in the CNS. Benzodiazepines that quickly diffuse from the CNS (more lipophilic) have a relatively short duration of action yet may have a long half-life. The clinical effects of GABA release and binding of the GABA receptor include sleep induction and excitement inhibition.
Frequency
United States

In 1998, 40,004 benzodiazepine overdoses and 53 deaths were reported.
Mortality/Morbidity

Benzodiazepine overdose in itself is remarkably safe. Numerous studies have demonstrated that most patients with benzodiazepine overdose can be managed in the ED and released home after appropriate care. When combined with other sedatives (most frequently alcohol), patients with benzodiazepine overdose can present with profoundly depressed levels of consciousness.
Clinical
History

History should include the time, dose, intent of the overdose, and if possible, the type of benzodiazepine, as some may be more toxic than others. Determine the presence of co-ingestants and the duration of benzodiazepine use. Benzodiazepine’s main effect is CNS depression, thus patients’ complaints center on decreased neurologic function. Complaints may include blurred vision, dizziness, confusion, drowsiness, anxiety, agitation, and unresponsiveness or coma.

A recent study found a strong association between anterograde amnesia with benzodiazepines in patients who take benzodiazepines in an overdose. Sedation does not predict the degree of anterograde amnesia.

Physical

Physical examination should focus on vital signs and cardiorespiratory and neurologic function.
Vital signs
Decreased respiratory rate
Hypotension
Decreased oxygen saturation level
Central nervous system
General
Hallucinations
Slurred speech
Ataxia
Altered mental status
Coma
Impairment of cognition
Examination
Nystagmus
Hypotonia
Weakness
Respiratory depression
Cardiovascular system (CVS) – Hypotension

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