Pharmacology, Toxicology and Addiction MedicineTier 1Disease (DEADMAN)

Toxidromes - sedative-hypnotic

Description

CNS depression: dec GCS, slurred speech, ataxia, nystagmus
Pupils and vitals usually normal unless severe or co-ingestant present
Causes: benzodiazepines, Z-drugs (zolpidem, zopiclone), barbiturates, GHB/GBL

Epidemiology

Common in deliberate self-poisoning, often co-ingested with alcohol or opioids
GHB - recreational and facilitated-sexual-assault context; unpredictable dose-response, narrow margin between recreational dose and coma

Aetiopathogenesis

Benzodiazepines/Z-drugs: GABA-A receptor potentiation -> inc chloride influx -> hyperpolarisation
- Requires endogenous GABA - ceiling effect -> alone, rarely fatal
Barbiturates: directly open the chloride channel at high dose - no ceiling effect, more dangerous
GHB: acts at GABA-B and GHB receptors -> profound but short-lived coma, rapid unpredictable emergence

Diagnosis

Clinical - depressed conscious state, preserved brainstem reflexes at moderate dose
GHB: classic rapid-onset deep coma -> rapid awakening within hours, +/- combativeness on waking
Consider co-ingestion (opioids, alcohol, TCAs) whenever resp depression or haemodynamic instability present

Management

Supportive care, airway protection, positioning
Flumazenil generally avoided - risk of seizures in chronic benzodiazepine users or mixed TCA overdose; reserve for pure iatrogenic overdose in a benzodiazepine-naive patient, given in small titrated doses under close observation
GHB - supportive only, ventilate if needed; recovery typically within hours despite depth of coma

Associations

Co-ingestion with opioids/alcohol -> synergistic resp depression - leading cause of polydrug deaths
GHB - facilitated sexual assault
Chronic benzodiazepine/Z-drug use -> falls, cognitive impairment, dependence

Natural history & complications

Benzodiazepine/Z-drug overdose alone - usually full recovery with supportive care
Barbiturate overdose - can be fatal (resp depression, no ceiling)
GHB - resolves within several hours; risk lies in unwitnessed apnoea, not prolonged toxicity

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