Nejm 1998;338:592; 1989;321:442

Cause:Multifactorial including genetic (cross-fostering studies—Nejm 1988;318:180) and/or behavioral characteristics leading to addiction. 1st-degree relatives have 3-4 fold higher prevalence (Psychol Med 1997;27:1381)

Pathophys:Mediated by the dopaminergic pathway from the ventral tegmental area to the nucleus accumbens. Long-term exposure leads to downregulation of inhibitory GABA receptors (Nejm 1999;340:1482). GI and pancreatic acute and chronic toxicity (Ann IM 1981;95:198). Withdrawal sx due to increased noradrenergic activity (Ann IM 1987;107:875) and long-term changes in GABA and glutamate receptors

M/F = 3:1; lifetime prevalence in US ~10%. Acute and chronic complications of alcohol may occur more often in women than men due not to size differences but to gastric mucosa alcohol dehydrogenase activity (Nejm 1990;322:95). 5% of those with alcohol dependence experience severe withdrawal complications (DTs, seizures)

Sx:
H/o significant trauma (70%—Ann IM 1984;101:847), eg, motor vehicle accident (Nejm 1987;317:1262)

Standardized questionnaires (Ann IM 1998;129:353; Jama 1998;280:166; 1994;272:1782) like MAST, AUDIT, TWEAK (Tolerance measured by ability to “hold” 6 drinks or “high” on 3 drinks; Worried friends; Eye-openers; Amnesia hx; Kut down plans), and the short test CAGE questions (have you tried to Cut down; are you Annoyed by criticism of your drinking; do you sometimes feel Guilty about your drinking; and do you sometimes have an Eye-opener drink in the morning?) (Jama 1984;252:1905). TWEAK score 2 is 87% sens and specif in women, 95% sens and 56% specif in men; scores 3, less sens and more specific. CAGE score 2 has 74% sens, 91% specif (Jama 1994;272:1782; Ann IM 1991;115:774).

Upper limit of alcohol consumption not assoc w problems is <4 drinks qd and <14-17/wk for men, and <3 drinks qd and <7-12/wk for women (Jama 1995;276:1964; Am J Publ Hlth 1995;85:823)

Si:Include nasal rosacea, palor, sequelae of portal hypertension, erratic behavior, missed appointments. Withdrawal si’s include autonomic reactivity with elevated HR and BP, tremor, nausea and vomiting, anxiety, psychomotor agitation, insomnia, hallucinations (DTs) and seizures.

Dependence develops gradually, onset typically in late teens and early twenties, usually a decade to diagnosis. Withdrawal sx typically begin 4-12 hours after last drink as serum level drops, peaks usually at 48-72 hrs, resolving by day 4-5 (Nejm 2003;348:1786)

Hypokalemia, hypomagnesemia, hypocalcemia, hypoglycemia, hypophosphatemia, ketoacidosis, respiratory alkalosis (Nejm 1993;329:1927)

Increased mortality from cirrhosis, accidents, cancer, respiratory illness when >4 drinks qd (Am J Publ Hlth 1993;83:805; Ann IM 1984;101:847); smoking-related mortality continues even if stop drinking (Jama 1996;275:1097)

Pneumonia, due to diminished macrophage function, ciliary action, and polymorphonuclear wbc responses (Nejm 1970;282:123)

Sudden death (arrhythmias) and strokes (Nejm 1986;315:1041; Curr Concepts Cerebro Dis 1986;21:24)

Suicidal ideation ~15% die by suicide over lifetime

Fetal alcohol syndrome

Delirium tremens (DTs) including prior h/o often, agitation, tremor, disorientation, delirium, hallucinations, seizures, hyperthermia (rectal temp); 10-20% mortality

Wernicke’s encephalopathy and Korsakoff’s psychosis (Wernicke's Encephalopathy)

Seizures, as often during drinking as in withdrawal? (Nejm 1988;319:666) whenever alcohol levels are rapidly falling

Vitamin A deficiency causing impaired night vision (Ann IM 1978;88:622)

Lab:

Hem:High MCV

Chem:Blood alcohol level >0.08 mg % = legal intoxication, but levels often exceed 0.2% in alcoholics w few overt si of intoxication; fatty acid ethyl esters pos up to 24 h later (Jama 1996;276:1152)

LFTs up, acutely GGTP, chronically AST (SGOT), GGTP, Alk phos

Xray:CT scan of head for alcohol seizures only if evident head trauma or focal si’s (Ann IM 1981;94:519)

Rx:

(rv—Nejm 2005;352:596)

Primary prevention: screen with GGTP, if >50 U/L, educate once, repeat in 1 month and 1 yr (Prev Med 1991;20:518); or ask how many drinks/wk—if >14 for men, >11 for women, then educate q 1 mo × 2; this strategy decr alcohol intake by 1/3 to 1/2 over 1 yr (Jama 1997;277:1040)

Secondary prevention (Am J Med 2000;108:263; Jama 1998;279:1230): structured treatment program should include anticipatory guidance by primary doctor, 12-step program (AA), and perhaps prophylaxis (Nejm 1999;340:1482) w

• Naltrexone (ReVia) (Nejm 2008;359:715; Jama 2005;293:1617; 2006;295:2003; Med Let 1995;37:64 vs not effective by DBCT—Nejm 2001;345:1734) 25-50 mg po qd for 3-4 mo, or 190-380 mg im q 1 mo; an opiate antagonist, hepatic metabolism, so monitor LFTs; $110/mo po, $700/mo im
• Disulfiram (Antabuse) 250 mg qd (Ann IM 1989;111:943); $22/mo
• Acamprosate (Campral) (Med Let 2005;47:1; Jama 1999;281:1318) 333-666 mg po tid; moderately effective (vs not—Jama 2006;295:2003); renal excretion; can use w disulfiram or naltrexone; $105/mo
• Topiramate (Topamax) 300 mg po qd, perhaps (DBCT—Jama 2007;298:1641)

Alcoholics anonymous (AA), detoxification programs, etc, equal in effectiveness to naltrexone (Jama 2006;295:2003); prognosis for rehabilitation better after motor vehicle accident (Nejm 1987;317:1262). If safe stable home situation, outpatient rx as good as inpatient (Nejm 1989;320:358). Nonhospital residential programs adequate and cheaper (Nejm 1990;323:844—Institute of Medicine recommendations re drug and alcohol rehab policies). Later-controlled drinking controversial, <2% can safely pull it off (Nejm 1985;312:1678)

Rx any depression (p91) (Jama 1996;275:761) w SSRIs

of withdrawal (Jama 1997;278:145):

of DTs: hospitalize, iv lorazepam 1 mg/5 min, or diazepam 1 mg/min until BP and agitation decr in order to decr the 5-15% mortality

of lesser degrees of withdrawal:

• Thiamine 100-200 mg im/iv bid × 3 d then po daily +
• Benzodiazepines
• Lorazepam (Ativan) 2 mg im q1h or po q 2 h to control si and sx, to 12 mg max
• Chlordiazepoxide (Librium) 100 mg po/im q 6 h × 4 doses, then q 8 h × 3 doses, then q 12 h × 2 doses, then hs once, then stop; or 25-100 mg po q 4-6 h prn scoring system like below results in hospital d/c >2 d sooner (Jama 1994;272:519); beware oversedation, which takes days to recover from since has a 36+ h half-life, or
• Oxazepam (Serax) 30 mg po q 6 h × 7 d (Am J Psych 1989;146:617); or 30 mg po q 4 h × 6 doses, then q 6 h × 4 doses, then q 8 h × 3 doses, then q 12 h × 2 doses, then hs once, then stop; or 0-45 mg po q 4 h (q 2 h if no improvement after last dose) based on various scoring systems (Br J Addict 1989;84:1353) that rate tachycardia (>100), hypertension (>140/90), sweating, tremor, fever (99.6°F), insomnia, agitation, disorientation, and hallucinations (Clin Pharmacol Ther 1989;34:822), or
• Diazepam (Valium) (Clin Pharmacol Ther 1983;34:822) 0-15 mg iv/im/po q 2-4 h based on a scoring system as above; long half-life like chlordiazepoxide
• Other meds:
• Carbamazepine
• Valproate
• MgSO₄ 50% solution, 2 cc iv/im q 8 h × 2 d
• Thiamine 100 mg po/im tid × 3 d

of seizures: lorazepam (Ativan) 2 mg iv after 1st seizure reduces recurrence rate within next 6 h from 25% to 3% and over 48 h from 32% to 4% (Nejm 1999;340:915)