alcohol withdrawal

**Pathophysiology** - Chronic alcohol enhances GABA-A inhibitory signaling (CNS depressant) and inhibits NMDA glutamate receptors. The brain compensates by downregulating GABA-A receptors and upregulating NMDA receptors. - Abrupt cessation unmasks this: reduced inhibition plus excess glutamatergic excitation leads to CNS hyperexcitability and sympathetic surge (increased norepinephrine, locus coeruleus firing). Kindling means repeated withdrawal episodes cause progressively more severe withdrawal.

**Timeline (classic board testable)** - 6-12 h: Minor withdrawal with tremor, anxiety, insomnia, nausea/vomiting, diaphoresis, tachycardia, hypertension, headache. - 12-48 h: Alcoholic hallucinosis, with visual (sometimes auditory or tactile) hallucinations and a *clear sensorium* with normal vitals. Withdrawal seizures are generalized tonic-clonic, usually brief, and peak at about 24 h. - 48-96 h: Delirium tremens (DTs), with global confusion/disorientation, fluctuating consciousness, vivid hallucinations, severe autonomic instability (fever, tachycardia, hypertension, diaphoresis), and agitation. It is a medical emergency, and mortality is about 1-5% with treatment (higher if untreated). Risk factors include prior DTs or seizures, concurrent illness, older age, a high last-drink-to-presentation delay, and high baseline alcohol use.

**Diagnosis** - Clinical diagnosis based on history of heavy use plus the timeline above. The CIWA-Ar score quantifies severity and guides dosing. - Check glucose, electrolytes (low Mg, K, phos), CBC, LFTs, and ECG. Consider a CT head if there is a focal deficit, trauma, or atypical course. - Labs suggesting chronic use: elevated GGT, AST:ALT >2:1, macrocytosis (high MCV), elevated CDT.

**Management** - First line is benzodiazepines (e.g., chlordiazepoxide, diazepam, lorazepam), titrated by symptom-triggered CIWA-Ar protocol. Use lorazepam or oxazepam (LOT: Lorazepam, Oxazepam, Temazepam, which avoid hepatic oxidation) in severe liver disease, elderly patients, or those with respiratory compromise. - Thiamine (B1) before glucose to prevent precipitating Wernicke encephalopathy (confusion, ophthalmoplegia/nystagmus, ataxia). Untreated, it can progress to Korsakoff syndrome (anterograde amnesia, confabulation; mammillary body damage). Also give folate, multivitamin, and replete Mg/K/phos. - Refractory DTs: high-dose benzodiazepines, phenobarbital, or propofol (ICU, intubation). Add dexmedetomidine only as an adjunct, since it does not prevent seizures or DTs. Antipsychotics (haloperidol) are only adjuncts for hallucinations/agitation because they lower the seizure threshold. - Seizures: benzodiazepines. Phenytoin is NOT effective for alcohol withdrawal seizures. - Mild withdrawal can be managed as an outpatient with a long-acting benzodiazepine, or with carbamazepine or gabapentin in selected patients.

**Long-term relapse prevention (alcohol use disorder)** - Naltrexone (opioid antagonist, reduces cravings; contraindicated with opioid use or acute hepatitis/liver failure). - Acamprosate (NMDA modulator/GABA effects, used for maintaining abstinence; renally cleared). - Disulfiram (inhibits aldehyde dehydrogenase, causing acetaldehyde accumulation with flushing, nausea, and tachycardia). - Also consider psychosocial support (AA, CBT, motivational interviewing).

**Key distinctions** - Alcohol withdrawal differs from intoxication, which causes CNS depression (slurred speech, ataxia, disinhibition). - Alcoholic hallucinosis has a clear sensorium and normal vitals, while DTs have delirium and autonomic instability. - Benzodiazepine and barbiturate withdrawal are clinically similar. Opioid withdrawal causes "flu-like" symptoms (mydriasis, rhinorrhea, diarrhea, piloerection) but is rarely life-threatening.