Alcohol and Alcohol Use Disorders¶
Chapter 464 | Part 13: Neurologic Disorders
KEY CLINICAL POINTS¶
- Alcohol use disorder (AUD) is defined by repeated alcohol-related difficulties in at least 2 of 11 life areas (DSM-5 criteria).
- Ethanol metabolism involves ADH and ALDH pathways, with MEOS contributing ~10% of oxidation at high concentrations.
- Chronic alcohol exposure causes neurochemical changes, including GABA receptor upregulation and NMDA receptor sensitization.
- Alcohol withdrawal symptoms include tremor, autonomic hyperactivity, and insomnia, with ~2% risk of seizures.
- Naltrexone and acamprosate are FDA-approved medications for AUD maintenance, while benzodiazepines are first-line for withdrawal.
1. DEFINITION & OVERVIEW¶
Alcohol use disorder (AUD) is a chronic relapsing condition characterized by impaired control over drinking, negative consequences, and compulsive use. Alcohol (ethanol) exerts widespread effects on neurochemical systems, with acute effects opposing those of withdrawal. The chapter emphasizes the importance of screening for AUD in all patients, as alcohol contributes to ~249 billion USD in annual costs in the U.S.
Table 464-1 Effects of Blood Alcohol Levels in the Absence of Tolerance¶
| BLOOD LEVEL, g/dL | USUAL EFFECT |
|---|---|
| 0.02 | Decreased inhibitions, a slight feeling of intoxication |
| 0.08 | Decrease in complex cognitive functions and motor performance |
| 0.20 | Obvious slurred speech, motor incoordination, irritability, and poor judgment |
| 0.30 | Light coma and depressed vital signs |
| 0.40 | Death |
1.1 Pathophysiology¶
Alcohol enhances GABA activity and inhibits NMDA receptors, leading to sedation and anticonvulsant effects. Chronic use alters dopamine pathways, contributing to reward and craving. Neurochemical changes include serotonin receptor upregulation and opioid receptor modulation.
1.2 Clinical Impact¶
Alcohol exacerbates medical conditions, interacts with medications, and causes direct organ damage. Acute effects include hypoglycemia, while chronic use leads to neuropathy, liver disease, and cardiovascular complications. Alcohol-related ketoacidosis mimics diabetic ketoacidosis with a large anion gap.
2. EPIDEMIOLOGY¶
Lifetime risk for AUD is ~10–20% in men and 5–10% in women. Rates are higher in populations with genetic predisposition (e.g., Native Americans, Maori) and lower in Mediterranean countries. U.S. prevalence increased 49% from 2001–2013, with women showing the highest growth. Alcohol-related problems are common in late teens to early 20s, with ~20% of patients meeting AUD criteria.
2.1 Demographics¶
Higher prevalence in individuals with comorbid psychiatric conditions (e.g., schizophrenia, PTSD). Cultural and genetic factors influence risk, with polygenic risk scores identifying multiple gene variations contributing to vulnerability.
2.2 Global Trends¶
Prevalence varies by region: higher in Ireland, Eastern Europe, and Scandinavia; lower in Mediterranean countries. Native American and Aboriginal populations show disproportionately high rates due to genetic and cultural factors.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Alcohol's effects are mediated through metabolic pathways (ADH, ALDH, MEOS) and neurochemical mechanisms. Chronic use leads to tolerance, withdrawal, and neuroadaptations. Genetic factors (e.g., ALDH2 polymorphisms) influence metabolism and risk for alcohol-related disorders.
Table 464-2 Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Classification of Alcohol Use Disorder (AUD)¶
| Criteria |
|---|
| Two or more of the following items occurring in the same 12-month period must be endorsed for the diagnosis of an alcohol use disordera: |
| Drinking resulting in recurrent failure to fulfill role obligations |
| Recurrent drinking in hazardous situations |
| Continued drinking despite alcohol-related social or interpersonal problems |
| Tolerance |
| Withdrawal, or substance use for relief/avoidance of withdrawal |
| Drinking in larger amounts or for longer than intended |
| Persistent desire/unsuccessful attempts to stop or reduce drinking |
| Great deal of time spent obtaining, using, or recovering from alcohol |
| Important activities given up/reduced because of drinking |
| Continued drinking despite knowledge of physical or psychological problems caused by alcohol |
| Alcohol craving |
3.1 Metabolism¶
Ethanol is metabolized to acetaldehyde via ADH, then to acetate via ALDH. MEOS contributes ~10% of oxidation at high concentrations. Acetaldehyde toxicity contributes to hangover symptoms and organ damage.
3.2 Neurochemical Changes¶
Chronic alcohol increases GABA receptor density, decreases NMDA receptor function, and alters dopamine pathways. These changes underlie tolerance, withdrawal, and compulsive drinking behaviors.
4. CLINICAL FEATURES¶
Acute effects include impaired cognition, motor coordination, and hypoglycemia. Chronic use leads to neuropathy, liver disease, cardiovascular complications, and cognitive deficits. Alcohol-related ketoacidosis presents with elevated ketones and a large anion gap. Psychiatric comorbidities include depression, anxiety, and psychosis.
4.1 Acute Effects¶
Low doses impair judgment and coordination; high doses cause coma or death. Alcohol-induced hypoglycemia occurs within 6–36 hours, with transient glucose intolerance. Acute intoxication increases dopamine and serotonin levels.
4.2 Chronic Effects¶
Peripheral neuropathy, liver cirrhosis, and cardiovascular disease are common. Cognitive deficits include memory impairment and
5. DIFFERENTIAL DIAGNOSIS¶
Alcohol-related conditions must be distinguished from other causes of neurological and psychiatric symptoms. Key differentials include diabetic ketoacidosis, psychiatric disorders, and medication side effects. Alcohol-induced psychosis mimics schizophrenia but resolves with abstinence.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis relies on clinical criteria (DSM-5) and laboratory tests. Key markers include elevated GGT, CDT, and MCV. Alcohol use is assessed via AUDIT questionnaire. Imaging may reveal brain atrophy in chronic users.
Table 464-3 The Alcohol Use Disorders Identification Test (AUDIT)a¶
| ITEM | 5-POINT SCALE (LEAST TO MOST) |
|---|---|
| 1. How often do you have a drink containing alcohol? | Never (0) to 4+ per week (4) |
| 2. How many drinks containing alcohol do you have on a typical day? | 1 or 2 (0) to 10+ (4) |
| 3. How often do you have six or more drinks on one occasion? | Never (0) to daily or almost daily (4) |
| 4. How often during the last year have you found that you were not able to stop drinking once you had started? | Never (0) to daily or almost daily (4) |
| 5. How often during the last year have you failed to do what was normally expected from you because of drinking? | Never (0) to daily or almost daily (4) |
| 6. How often during the last year have you needed a first drink in the morning to get yourself going after a heavy drinking session? | Never (0) to daily or almost daily (4) |
| ITEM | 5-POINT SCALE (LEAST TO MOST) |
|---|---|
| 7. How often during the last year have you had a feeling of guilt or remorse after drinking? | Never (0) to daily or almost daily (4) |
| 8. How often during the last year have you been unable to remember what happened the night before because you had been drinking? | Never (0) to daily or almost daily (4) |
| 9. Have you or someone else been injured as a result of your drinking? | No (0) to yes, during the last year (4) |
| 10. Has a relative, friend, doctor, or other health worker been concerned about your drinking or suggested that you should cut down? | No (0) to yes, during the last year (4) |
7. MANAGEMENT & TREATMENT¶
Treatment includes SBIRT (screening, brief intervention, referral, treatment), pharmacotherapy, and rehabilitation. Withdrawal management uses benzodiazepines, while naltrexone and acamprosate aid long-term abstinence. Cognitive-behavioral therapy and support groups (e.g., AA) are critical for relapse prevention.
8. PROGNOSIS & COMPLICATIONS¶
Chronic alcohol use shortens lifespan by ~10 years. Complications include liver cirrhosis, cardiovascular disease, and cognitive decline. Spontaneous remission occurs in ~20% of patients, but relapse rates remain high without structured support.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: Fetal Alcohol Spectrum Disorder (FASD) includes facial abnormalities, growth retardation, and cognitive deficits. Treatment: Abstinence is critical. Pediatrics: Alcohol-induced myopathy and growth retardation. Elderly: Increased risk of falls and drug interactions.
10. KEY POINTS & CLINICAL PEARLS¶
- Screen all patients for alcohol use using AUDIT or DSM-5 criteria. 2. Benzodiazepines are first-line for withdrawal, but avoid in patients with liver disease. 3. Naltrexone and acamprosate reduce relapse risk. 4. Cognitive-behavioral therapy and support groups are essential for long-term recovery. 5. Monitor for Wernicke-Korsakoff syndrome in chronic users.