A 32-year-old woman with generalized anxiety disorder presents to the emergency department after becoming unresponsive at a social event. She has taken alprazolam 2 mg daily for 8 months and consumed approximately 240 mL of alcohol (three standard drinks) over 90 minutes. Witnesses report progressive drowsiness, ataxia, and anterograde amnesia. On examination: BP 102/68 mmHg, HR 58 bpm, RR 10 breaths/min, oriented to person only, slurred speech, horizontal nystagmus, and generalized hypotonia. Serum ethanol level is 95 mg/dL. Laboratory studies show normal liver function tests and normal benzodiazepine levels for her stated dose. Which of the following mechanisms best explains her severe CNS depression and altered mental status?
- A)Competitive inhibition at cytochrome P450 3A4 preventing benzodiazepine metabolism
- B)Inhibition of GABA-A receptor chloride channel opening by both substances acting synergistically
- C)Additive allosteric enhancement of GABA-A receptor sensitivity at multiple binding sitesGABARITO
- D)Alcohol-induced hepatic enzyme induction increasing benzodiazepine clearance
- E)Acetaldehyde accumulation impairing NMDA receptor function and benzodiazepine clearance
Explicação
Both benzodiazepines and alcohol are allosteric modulators of GABA-A receptors. They enhance the frequency and duration of chloride channel opening at distinct allosteric sites on the GABA-A receptor complex. This produces a synergistic (supraadditive) CNS dep... Ver explicação completa e trilha adaptativa →