Pathophysiology
Clinical meaning
The sedative-hypnotic toxidrome results from excessive CNS depression caused by agents that enhance GABA-A receptor activity (benzodiazepines, barbiturates, ethanol, GHB, zolpidem) or suppress excitatory neurotransmission. Benzodiazepines bind to the GABA-A receptor and increase the FREQUENCY of chloride channel opening (ceiling effect — rarely fatal in isolation). Barbiturates bind to a different site and increase the DURATION of chloride channel opening; at high doses, they can directly activate the channel WITHOUT GABA (no ceiling effect — respiratory arrest and death possible). The toxidrome presents with: CNS depression (drowsiness → coma), respiratory depression, hypotension, hypothermia, hyporeflexia, and midpoint/variable pupils. Key distinction: benzodiazepine overdose rarely causes death alone but is lethal with opioids or ethanol; barbiturate overdose can directly cause cardiovascular collapse. The NP must differentiate this from opioid toxidrome (miosis, responds to naloxone) and assess for co-ingestion, which greatly increases mortality.