Toxidromes - withdrawal

Description

General withdrawal toxidrome = unmasked excitatory neurotransmission after cessation/dec of a chronically used substance
Two opposite patterns
- CNS depressant withdrawal (alcohol, benzodiazepines, GHB, barbiturates, opioids) -> autonomic hyperarousal: tachycardia, HTN, diaphoresis, tremor, agitation, +/- seizures, +/- hallucinations
- Stimulant withdrawal (amphetamines, cocaine) -> opposite "crash": fatigue, hypersomnia, dysphoria, inc appetite
Onset/severity track the drug's half-life - shorter half-life = earlier, more intense

Detox/relapse settings, unrecognised dependence in hospital inpatients, postoperative patients
Under-recognised - screen with a substance history on every admission

Chronic depressant exposure -> downregulated inhibitory (GABA) / upregulated excitatory (glutamate/NMDA) tone - neuroadaptation
Abrupt cessation -> unopposed excitatory signalling -> autonomic storm
Opioid withdrawal: locus coeruleus noradrenergic rebound (mu receptor no longer suppressing NA release)
Stimulant withdrawal: dopamine depletion -> anhedonia, fatigue

Key discriminators

	Alcohol / sedative-hypnotic	Opioid	Stimulant
Pupils	normal	dilated	dilated
Vitals	HTN, tachycardia, fever, seizure risk	mild tachycardia/HTN	bradycardia/normal, low mood
Distinctive	tremor, tactile/visual hallucinations, delirium tremens day 2-4	piloerection, lacrimation, yawning, cramps, diarrhoea - miserable, not usually dangerous	hypersomnia, hyperphagia, dysphoria, +/- suicidality
Danger	can kill (seizures, DTs)	rarely fatal directly	rarely physically dangerous

Objective scoring: CIWA-Ar (alcohol), COWS (opioid) - guide symptom-triggered dosing

Benzodiazepine substitution/taper - alcohol and sedative-hypnotic withdrawal; the only class proven to prevent seizures and delirium tremens
- Thiamine before glucose - avoid precipitating Wernicke encephalopathy
Alpha-2 agonist (clonidine) or opioid substitution (buprenorphine/methadone) - opioid withdrawal; symptomatic, non-fatal course
Supportive + symptomatic for stimulant withdrawal - no specific antidote; monitor mood and suicidality closely

Untreated alcohol/sedative-hypnotic withdrawal can progress to delirium tremens and death
Opioid withdrawal - non-fatal but drives relapse and overdose risk (loss of tolerance)
Stimulant withdrawal - protracted dysphoria is the main driver of relapse

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