A 35-year-old man is brought to the emergency department in a drowsy, ataxic state. His friend reports he took an unknown sedative 2 hours ago. On examination, he has slurred speech and anterograde amnesia. An EEG is performed and shows the pattern marked **B** in the diagram — excessive frontal beta activity with amplitude >25 microvolts occupying >50% of the recording. Which of the following best explains the mechanism by which this EEG finding occurs in benzodiazepine intoxication?
A. Benzodiazepines inhibit the reuptake of GABA at the synaptic cleft, prolonging GABAergic transmission
B. Benzodiazepines block glutamate receptors, reducing excitatory tone and unmasking underlying beta rhythms
C. Benzodiazepines directly open GABA-A chloride channels independent of GABA binding
D. Benzodiazepines act as positive allosteric modulators at the GABA-A receptor, increasing the frequency of chloride channel opening when GABA binds
Explanation
Why "Benzodiazepines act as positive allosteric modulators at the GABA-A receptor, increasing the frequency of chloride channel opening when GABA binds" is right
The excessive frontal beta activity marked B is the characteristic EEG signature of benzodiazepine intoxication. This pattern arises because benzodiazepines bind to the benzodiazepine binding site on the GABA-A receptor (a pentameric chloride channel) and function as positive allosteric modulators. They increase the FREQUENCY of chloride channel opening when GABA binds, enhancing inhibitory GABAergic tone. This enhanced neuronal inhibition manifests as the pathological fast beta rhythm (>13 Hz, often 20–25 Hz) with amplitude >25 microvolts predominantly over frontal and frontocentral regions. The mechanism is distinct from direct channel opening and is the mechanistic basis for the EEG finding in this patient (Goodman & Gilman 14e, Hypnotics and Sedatives).
Why each distractor is wrong
Benzodiazepines directly open GABA-A chloride channels independent of GABA binding: This describes the mechanism of barbiturates, which increase channel OPENING DURATION and can open channels without GABA present. Benzodiazepines require GABA binding to exert their effect and are allosteric modulators, not direct agonists.
Benzodiazepines inhibit the reuptake of GABA at the synaptic cleft, prolonging GABAergic transmission: This is the mechanism of action of some antidepressants (e.g., SSRIs inhibit monoamine reuptake), not benzodiazepines. Benzodiazepines do not act on GABA transporters.
Benzodiazepines block glutamate receptors, reducing excitatory tone and unmasking underlying beta rhythms: Benzodiazepines do not primarily block glutamate receptors. While reducing excitatory tone might contribute to sedation, this is not the mechanism that produces the characteristic excessive frontal beta activity on EEG.
High-YieldNEET PG
Benzodiazepine-induced excessive frontal beta activity (>25 μV, >50% of recording) is a key EEG sign of intoxication; the mechanism is positive allosteric modulation of GABA-A, increasing chloride channel opening frequency — distinct from barbiturates, which increase opening duration.
Goodman & Gilman 14e — Hypnotics and Sedatives
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