Alcohol Use Disorder & Withdrawal

Alcohol use disorder (AUD) is the most prevalent substance use disorder worldwide and a perennial NEET PG favourite. This note packs the high-yield triad you will be tested on: screening and diagnosis (CAGE, DSM-5), the time-locked withdrawal cascade (tremor → seizure → delirium tremens), and the pharmacology of detoxification and relapse prevention — plus Wernicke-Korsakoff syndrome, which examiners love to weave into clinical vignettes.

Definitions & key terminology

• Hazardous/at-risk drinking — pattern that increases risk of harm but no current diagnosis. (Roughly >14 standard drinks/week or >4/occasion for men; >7/week or >3/occasion for women.)
• Alcohol Use Disorder (AUD) — DSM-5 term that merged the older DSM-IV categories of alcohol abuse and alcohol dependence into a single spectrum disorder graded mild/moderate/severe.
• Standard drink (US) = 14 g of pure ethanol = 360 mL beer (5%) = 150 mL wine (12%) = 45 mL spirits (40%).
• Tolerance — need for increasing amounts to achieve effect.
• Withdrawal — characteristic syndrome on cessation/reduction, relieved by re-administration.
• CAGE, AUDIT — screening instruments (below).

High-yield: DSM-5 abolished the abuse vs dependence split. There is now ONE disorder — AUD — with 11 criteria, graded by number of criteria met. The term "dependence" is reserved physiologically (tolerance + withdrawal), not as a diagnosis.

Screening: CAGE & AUDIT

The CAGE questionnaire is the single most asked screening tool in Indian PG exams.

Letter	Question
C	Have you ever felt you should Cut down on drinking?
A	Have people Annoyed you by criticising your drinking?
G	Have you felt Guilty about drinking?
E	Do you need an Eye-opener (morning drink to steady nerves / cure hangover)?

• Each "yes" = 1 point. Score ≥ 2 is clinically significant (suggests problem drinking; sensitivity ~70-90% for ≥2).
• Limitation: poor at detecting early/binge drinking; insensitive in women and elderly.
• AUDIT (Alcohol Use Disorder Identification Test, 10 items, WHO) is more sensitive, detects hazardous use earlier; cut-off ≥ 8 indicates harmful drinking. AUDIT-C = first 3 (consumption) items.

High-yield: "Eye-opener" = the E in CAGE = a morning drink. The need for an eye-opener is the most specific item for dependence.

DSM-5 diagnostic criteria (≥2 of 11 in 12 months)

Grouped into four clusters — a useful exam framework:

1. Impaired control — (1) larger amounts/longer than intended; (2) persistent desire/unsuccessful efforts to cut down; (3) much time spent obtaining/using/recovering; (4) craving.
2. Social impairment — (5) failure to fulfil role obligations; (6) continued use despite social/interpersonal problems; (7) giving up important activities.
3. Risky use — (8) recurrent use in hazardous situations; (9) continued use despite physical/psychological harm.
4. Pharmacological — (10) tolerance; (11) withdrawal.

Severity: Mild = 2-3 criteria · Moderate = 4-5 · Severe = ≥ 6.

High-yield: Craving was a NEW criterion added in DSM-5 (absent in DSM-IV). Legal problems (a DSM-IV criterion) were REMOVED.

Pathophysiology

Ethanol is a CNS depressant acting chiefly through two channels:

• Potentiates GABA-A receptors → inhibitory tone, sedation, anxiolysis.
• Inhibits NMDA (glutamate) receptors → reduced excitation.

Chronic intake → adaptive down-regulation of GABA-A and up-regulation/sensitisation of NMDA receptors. When alcohol is abruptly withdrawn, GABA inhibition is lost while a hyper-excitable glutamatergic system runs unopposed → autonomic hyperactivity, tremor, seizures and delirium. This glutamate "rebound" excitotoxicity is the core of withdrawal.

Reinforcement/reward is mediated by mesolimbic dopamine (ventral tegmental area → nucleus accumbens), the basis for craving and the rationale behind naltrexone.

Flow: Chronic ethanol → ↓GABA-A + ↑NMDA (neuroadaptation) → abrupt stop → unopposed glutamate excitation → autonomic storm → withdrawal syndrome.

Alcohol withdrawal: the time-locked cascade

This timeline is the single most tested item in the whole topic. Learn the hours.

Syndrome	Onset after last drink	Features
Minor withdrawal / tremulousness	6–12 h	Tremor, anxiety, insomnia, nausea, sweating, tachycardia, HTN; normal sensorium
Alcoholic hallucinosis	12–24 h	Visual/auditory/tactile hallucinations with CLEAR sensorium & intact vitals
Withdrawal seizures ("rum fits")	24–48 h	Generalised tonic-clonic, usually single or few, self-limiting
Delirium tremens (DT)	48–96 h (2–4 days)	Clouded consciousness, disorientation, visual hallucinations, gross tremor, severe autonomic instability, fever

High-yield: Withdrawal seizures peak at 24–48 h; delirium tremens peaks at 48–96 h (classically day 3). Hallucinosis differs from DT by having a clear sensorium and normal vitals.

Delirium tremens (DT)

• Most serious form; medical emergency. Mortality up to 5–15% untreated, <5% with treatment.
• Triad to recall: clouding of consciousness + perceptual disturbance (visual hallucinations, e.g. Lilliputian/formication) + marked autonomic hyperactivity (fever, tachycardia, HTN, diaphoresis).
• Risk factors: prior DT, prior withdrawal seizures, concurrent illness/infection, high blood alcohol on admission, older age, abnormal liver function.

High-yield: Hallucinations of DT are characteristically visual (animals, insects — formication = "cocaine bugs" is classically cocaine but tactile insects can occur in DT). In contrast, schizophrenic hallucinations are characteristically auditory.

CIWA-Ar scale

The Clinical Institute Withdrawal Assessment for Alcohol, revised quantifies severity and guides symptom-triggered benzodiazepine dosing.

• 10 items scored 0–7 each (except orientation 0–4): nausea/vomiting, tremor, paroxysmal sweats, anxiety, agitation, tactile disturbances, auditory disturbances, visual disturbances, headache, orientation/clouding of sensorium.
• Maximum score = 67.
• Interpretation: < 8–10 = minimal/absent; 8–15 = mild; 16–20 = moderate; > 20 = severe (high DT/seizure risk).
• Symptom-triggered therapy (medicate when CIWA-Ar ≥ 8–10) uses less total benzodiazepine and shortens treatment vs fixed-schedule dosing.

High-yield: Maximum CIWA-Ar score is 67; treatment is typically initiated at a score of ≥ 8–10.

Management of withdrawal

Stepwise approach:

1. Benzodiazepines = drug of choice (cornerstone). They are cross-tolerant with alcohol (both GABA-ergic) and prevent seizures/DT.
   • Long-acting — chlordiazepoxide, diazepam — preferred for smooth, self-tapering course (active metabolites).
   • Short-acting / no active metabolites — lorazepam, oxazepam, temazepam ("LOT") — preferred in hepatic failure and the elderly (metabolised by conjugation, not oxidation; no accumulation).
2. Thiamine (vitamin B1) BEFORE any glucose — see Wernicke below.
3. Correct electrolytes — magnesium, potassium, phosphate; hydration.
4. Refractory DT — add adjuncts: phenobarbital, or propofol/dexmedetomidine in ICU.
5. Seizures — benzodiazepines treat and prevent; phenytoin is NOT effective for pure alcohol withdrawal seizures.

High-yield: In a patient with liver disease, use lorazepam/oxazepam (LOT drugs) — they bypass hepatic oxidative (CYP) metabolism and undergo only glucuronidation.

High-yield: Antipsychotics (haloperidol) LOWER seizure threshold and do NOT prevent withdrawal seizures — use only as adjunct for severe agitation/hallucinations after adequate benzodiazepines.

Wernicke–Korsakoff syndrome (WKS)

Caused by thiamine (B1) deficiency — a must-know complication.

Wernicke encephalopathy — acute, reversible. Classic triad (full triad in only ~10%):

Component	Feature
Ophthalmoplegia / nystagmus	Bilateral lateral rectus (CN VI) palsy, nystagmus
Ataxia	Wide-based gait
Confusion / encephalopathy	Global confusional state

• Mnemonic for the triad: "COAT" rack — Confusion, Ophthalmoplegia, Ataxia, due to Thiamine deficiency. (Also taught as CAN: Confusion, Ataxia, Nystagmus.)
• Neuropathology: lesions in mammillary bodies, periaqueductal grey, dorsomedial thalamus. MRI shows symmetrical T2 hyperintensity around the third ventricle/periaqueductal region.

Korsakoff psychosis — chronic, often irreversible amnestic syndrome:

• Anterograde + retrograde amnesia with confabulation, preserved consciousness and other cognition.

High-yield: ALWAYS give thiamine BEFORE glucose. A glucose load in a thiamine-deficient patient consumes residual thiamine (cofactor for transketolase/pyruvate dehydrogenase) and can precipitate or worsen Wernicke encephalopathy.

High-yield: Wernicke is reversible; Korsakoff (mammillary body/thalamic damage) is largely irreversible. Treat suspected Wernicke with high-dose IV thiamine (e.g. 500 mg IV TDS) — never oral alone in the acute setting.

Relapse prevention pharmacotherapy

Three FDA-approved anti-craving / aversive agents — high-yield to differentiate.

Drug	Mechanism	Key points / caution
Disulfiram	Inhibits aldehyde dehydrogenase → acetaldehyde accumulation → aversive reaction (flushing, nausea, vomiting, throbbing headache, tachycardia, hypotension)	Aversive agent; needs abstinence ≥12 h before start; avoid in CAD, psychosis, pregnancy. Patient must be motivated
Naltrexone	Opioid (μ) receptor antagonist → ↓ reward/craving, reduces heavy drinking	First-line. Contraindicated with opioid use (precipitates withdrawal) and in acute hepatitis/liver failure; long-acting IM available
Acamprosate	Modulates glutamate/NMDA (and GABA) → restores neurotransmitter balance, helps maintain abstinence	Renally excreted → safe in liver disease, avoid in renal failure; best for already-abstinent patients

• Topiramate and gabapentin are useful off-label options (topiramate has good evidence for reducing heavy-drinking days).
• Baclofen (GABA-B agonist) — option in patients with significant liver disease.

High-yield: Disulfiram blocks ALDEHYDE dehydrogenase (not alcohol dehydrogenase). The toxic culprit causing the reaction is acetaldehyde. Other drugs causing a disulfiram-like reaction: metronidazole, cefoperazone/cephalosporins with MTT side-chain, chlorpropamide, griseofulvin, procarbazine.

High-yield: In a patient with cirrhosis, prefer acamprosate (renal excretion, hepatically safe); avoid disulfiram and naltrexone.

Acute alcohol intoxication & overdose

• Dose-related CNS depression: disinhibition → ataxia/slurred speech → stupor → coma → respiratory depression.
• No specific antidote; supportive care, protect airway, thiamine + glucose, watch for hypoglycaemia and aspiration.
• Methanol/ethylene glycol poisoning (a frequent distractor): treat with fomepizole (or ethanol) which inhibit alcohol dehydrogenase; methanol → formic acid → optic neuropathy/blindness and high anion-gap metabolic acidosis.

Complications of chronic alcohol use

• Hepatic: fatty liver → alcoholic hepatitis → cirrhosis; AST:ALT ratio > 2:1 is characteristic.
• GI: gastritis, Mallory-Weiss tear, pancreatitis, varices.
• Haematological: macrocytosis (↑ MCV), megaloblastic anaemia (folate deficiency), thrombocytopenia.
• Neuro: peripheral neuropathy, cerebellar degeneration, central pontine myelinolysis (over-rapid Na+ correction), Marchiafava-Bignami disease (corpus callosum demyelination).
• Cardiac: dilated cardiomyopathy, "holiday heart" (atrial fibrillation), hypertension.
• Foetal: Foetal Alcohol Syndrome — growth retardation, smooth philtrum, thin upper lip, microcephaly, intellectual disability.
• Lab clue: elevated GGT (sensitive marker of heavy use) and CDT (carbohydrate-deficient transferrin) — most specific biomarker.

High-yield: Best biomarkers — GGT (sensitive) and CDT (most specific) for chronic heavy drinking; MCV rises with chronic use.

Key differentials

• Alcoholic hallucinosis vs DT — hallucinosis = clear sensorium, normal vitals; DT = clouded sensorium + autonomic storm.
• DT vs hepatic encephalopathy — HE has asterixis, raised ammonia, EEG triphasic waves, no autonomic hyperactivity; DT has tremor + autonomic storm.
• Withdrawal seizure vs epilepsy — withdrawal seizures are generalised, few, time-locked (24–48 h); focal seizures/status warrant imaging.
• Wernicke vs other causes of acute confusion — look for ophthalmoplegia + ataxia + nutritional context.
• Alcohol withdrawal vs sedative-hypnotic (benzodiazepine/barbiturate) withdrawal — clinically similar (both GABA-ergic); benzodiazepine withdrawal can also cause seizures.

Recently asked / exam angle

• Withdrawal timeline matching — match "tremor at 6–12 h," "seizures at 24–48 h," "DT at 48–96 h." Near-universal across NEET PG/INI-CET.
• Drug of choice for withdrawal/DT = benzodiazepine (lorazepam in liver disease) — recurrent single-best-answer.
• "Give thiamine before glucose" — clinical vignette of confused alcoholic; answer = thiamine first.
• Disulfiram mechanism = inhibits aldehyde dehydrogenase; identify disulfiram-like reaction drugs (metronidazole).
• CAGE = 4 items; ≥2 significant; E = eye-opener.
• Acamprosate safe in liver disease; naltrexone contraindicated with opioids.
• Wernicke triad (COAT/CAN) and irreversibility of Korsakoff.
• Maximum CIWA-Ar = 67, symptom-triggered dosing reduces benzodiazepine use.
• AST:ALT > 2:1 ratio identifies alcoholic liver disease.
• DSM-5: craving added, legal problems removed, abuse+dependence merged.

Rapid revision

1. CAGE — Cut down, Annoyed, Guilty, Eye-opener; ≥ 2 = significant.
2. DSM-5 AUD = ≥ 2 of 11 criteria/12 months; severity by number (2-3 mild, 4-5 moderate, ≥6 severe); craving added, legal criterion removed.
3. Ethanol = GABA-A agonist + NMDA antagonist; withdrawal = unopposed glutamate excitation.
4. Withdrawal clock: tremor 6–12 h → hallucinosis 12–24 h → seizures 24–48 h → DT 48–96 h.
5. Alcoholic hallucinosis = clear sensorium + normal vitals (vs DT).
6. DT = clouded sensorium + visual hallucinations + autonomic storm; emergency, mortality up to 15% untreated.
7. Benzodiazepines = drug of choice; lorazepam/oxazepam ("LOT") in liver disease & elderly.
8. Thiamine BEFORE glucose — glucose can precipitate Wernicke.
9. Wernicke (reversible): ophthalmoplegia + ataxia + confusion (COAT/CAN); lesions in mammillary bodies. Korsakoff = irreversible amnesia + confabulation.
10. Disulfiram → inhibits aldehyde dehydrogenase → acetaldehyde toxicity (metronidazole gives similar reaction).
11. Naltrexone = μ-opioid antagonist (avoid with opioids); acamprosate = NMDA modulator, safe in liver disease.
12. CIWA-Ar max 67, treat at ≥ 8–10; AST:ALT > 2:1; GGT/CDT markers; ↑ MCV in chronic use.