- 1 Introduction and Terms
- 2 Physiology
- 3 Genetics and Epidemiology
- 4 Diagnosis
- 5 Chronic management
- 6 Diagnostic pearls
- 7 Pharmocological treatment
- 8 Clinical pearls
- 9 Further Reading
Introduction and Terms
- Blackout refers to a period of anterograde amnesia resulting from being intoxicated, while remaining awake. Alcohol-induced persisting amnestic disorder is known as Wernicke-Korsakoff syndrome.
- Psychological dependence refers to seeking pleasurable experience as the cause of increased drinking.
- Physiological dependence refers to developing a withdrawal syndrome with abstinence from alcohol.
- Behavioral tolerance is learning (through practice) how to perform tasks effectively while under the influence of alcohol.
- Pharmacokinetic tolerance is the metabolic adaptation, including ADH enzyme and MEOS, to rid the body of alcohol more rapidly.
- Cellular (pharmacodynamic) tolerance is an adaptation of the nervous system on cellular level so that it can function despite very high blood alcohol concentrations
Small amount is broken down in the stomach (particularly in men), most metabolized by alcohol dehydrogenase (rate-limiting step) to acetaldehyde. At higher blood-levels, some alcohol is metabolized by CYP450 system. Acetaldehyde is broken down further by ALDH; variation in ALDH lower risk of abuse in Asians, since acetaldehyde produces increased heart rate, nausea, and vomiting.
- acute alcohol intoxication increase dopamine and its metabolites
- serotonin increase in the synapse and upregulation serotonin receptors.
- GABA-a receptor is affected to produce sedation, anti-convulsive effect, and muscle relaxation.
- dampening of NMDA receptors during acute intoxication.
Alcohol intoxication effect on Sleep
- Decreased REM sleep
- Decreased stage 4 sleep
- Increased sleep fragmentation
Multiple other effects contribute to vitamin deficiency, peripheral neuropathy, cirrhosis and pancreatitis, WBC, platelet suppression, fetal alcohol syndrome, increased risk for GI, liver, and breast cancer, and cardiomyopathy. Red blood cells increase in MCV.
Genetics and Epidemiology
Alcoholism has a very strong genetic component, as supported by several lines of evidence:
- Children of alcoholic parents, adopted at young age by non-alcoholic families, have 4-fold increase in risk for alcoholism
- Close family members have 4-fold increased risk
- Identical twin risk > fraternal twin risk (K&S)
Lifetime prevalence of alcohol dependence is 10-15% in men and 3-5% in women.
Alcohol use in adolescents
According to large epidemiological study 35% of adolescents (12-17) had used alcohol in the last year; 16% of those who had used alcohol met criteria for an alcohol use disorder (abuse or dependence). Thus the prevalence of alcohol use disorders in adolescents is around 5%. By comparison, of the 13% of adolescents smoked marijuana, a quarter went to develop a drug use disorder. The prevalence of marijuana use disorder and analgesic opioids use disorders were (3.4%) and (1.2%) respectively. (1)
Diagnosis according to DSM-IV-TR
- The diagnostic criteria for abuse focus on impairment in social, legal, and occupational functioning in a patient who is not alcohol dependent. It's diagnosed with at least 1 of 4 criteria present during 12 months; alcohol dependence is diagnosed when at least 3 of 7 (more severe) criteria are present over 12 month.
- It is possible for a patient to meet some criteria for alcohol dependence without alcohol abuse; these diagnostic "orphans" are not adequately accounted for by the DSM IV.
- Alcohol intoxication is based on evidence of recent ingestion of alcohol with some impairment and at least one physiological manifestation of intoxication.
Diagnosis according to DSM-5
- DSM-5 combines 3 criteria for abuse ("legal problems" is thrown out) with 7 criteria for dependence, adds a criteria for cravings (supported by evidence from neuroimaging, etc).
- The criteria can be grouped in 4 domains (diminished control, social impairment, risk-taking, and pharmacological effects)
- Substance Use Disorder is diagnosed when 2 of 11 criteria are present over 12-month period.
Certain psychiatric disorders dramatically increase the risk of having alcohol problems
- Antisocial personality disorder (80% misuse alcohol)
- Schizophrenia (40% misuse alcohol)
- Bipolar and anxiety disorders also have significant comorbidity.
Elements of long-term treatment are intervention, detoxification, and rehabilitation/relapse prevention.
- Intervention involves engaging in treatment through motivational interviewing.
- Detoxification stage involves physical evaluation, hydration, addressing nutritional deficiencies, and prevention of withdrawal syndrome.
- Rehabilitation involves managing co-morbid psychiatric conditions, counseling, psychopharmocology, self-help groups (AA), and involving the family.
- Alcoholism is a strong chronic risk factor for suicide and 2.2-18% of patients with alcoholism end their lives(a 60-120x increase over general population)
- Acute intoxication is a strong acute risk factor (33-69% of suicide "completers" had a blood alcohol level)
Etiological subtypes (based on Cloninger’s Alcoholism Typology)
- Type 1 (also type A) alcoholism (75%) is characterized by adult onset and drinking to relieve depression and anxiety; alcoholics often feel guilty about drinking. Patients quickly develop behavioral tolerance
- Type 2 (also type B) alcoholism (25%) is characteized by early onset and antisocial and risk-taking behavior while intoxicated; it has been termed male-limited alcoholism due to perceived transmission from fathers to sons
- Markers of heavy use:
- GGT (same as GGTP) gamma-glutamyl transferase (or transpeptidase) - level >35 has sensitivity and specificity of 60% for heavy use within 2-4 weeks. GGT is also elevated in DM, HTN, chronic liver disease (low specificity)
- CDT (carbohydrate-deficient transferrin) >3% has sensitivity and specificity of 60-75% for heavy drinking.
- Elevated AST and ALT with classic ratio of 2:1
- Elevated MCV, a finding also seen in macrocytic and Folate/Vitamin B12 anemias
- Blood alcohol level (BAL)
Naltrexone (NTX) is a competetive opioid antagonist. It decreases cravings and prolongs time to relapse, compared to placebo, particularly in short-term studies.
- Important predictors of response to NTX include positive family history of alcoholism, high levels of cravings, and adherence.
- Includes a black box warning for the risk of liver damage.
- long-acting injection (Vivitrol) is available. IM administration reduces the serum fluctuations of NTX.
- includes a black box warning (liver toxicity), but may be safer as IM preparation does not undergo first-pass metabolism.(Franck)
Disulfiram inhibits the aldehyde dehydrogenase, thereby preventing the metabolism of alcohol's primary metabolite, acetaldehyde. Its accumulation produces headache, sweating, flushing, nausea and vomiting.
- On evaluation, it's important to distinguish between a "hangover" and withdrawal, since management is very different.
- Alcohol dependence is a chronic relapsing disorder with suicide rates >10%.
(1) Wu et.al. Racial/Ethnic Variations in Substance-Related Disorders Among Adolescents in the United States. Arch Gen Psychiatry. 2011;68(11):1176-1185 (2) Johan Franck. Pharmacotherapy for alcohol dependence: status of current treatments. Current Opinion in Neurobiology (2013);23(4):692–699
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