Alcohol-related disorders

Alcohol-related disorders, including alcohol intoxication, alcohol use disorder (AUD), and alcohol withdrawal, are a group of conditions associated with disruptive patterns of alcohol use. Alcohol intoxication is the acute onset of behavioral and psychomotor impairment shortly after an episode of drinking. Alcohol use disorder (AUD) is characterized by clinically significant psychosocial and behavioral problems associated with alcohol use. Alcohol withdrawal develops after a sudden cessation or reduction of alcohol use in patients with a history of excessive drinking. The diagnosis of an alcohol-related disorder can be established using the DSM-5 criteria. The most important aspect of management for all alcohol-related disorders is the cessation of alcohol use. Therapeutic management is guided by the severity of the disorder.

See breakdown of ethanol for a review of alcohol metabolism pathways. See also “Alcohol withdrawal.”

• Definition: : a temporary condition in which excessive consumption of alcohol alters a person's consciousness, cognition, perception, judgment, affect, and/or behavior ^[1]
• Related terms
  • Standard drink: An alcoholic drink containing 14.0 g (0.6 oz) of pure alcohol
  • Excessive alcohol use: A pattern of alcohol use that involves binge drinking, heavy drinking, any alcohol use in pregnant women, and any alcohol use in individuals < 21 years of age.
  • Heavy drinking: a pattern of drinking that is associated with an increased risk of developing negative health consequences
    • ♀: consumption of > 7 standard drinks per week or > 3 standard drinks per day
    • ♂: consumption of > 14 standard drinks per week or > 4 standard drinks per day
  • Binge drinking
    • Consumption of > 4 standard drinks in women and > 5 standard drinks in men in 2 hours
    • A pattern of alcohol use that brings a person’s blood alcohol concentration (BAC) to above 0.08%
  • Low-risk drinking: Drinking levels associated with a low risk of developing alcohol use disorder:
    • ♀: consumption of < 3 standard drinks on any single day and < 7 standard drinks per week
    • ♂: consumption of < 4 standard drinks on any single day and < 14 standard drinks per week
• Pathophysiology
  • The majority of alcohol consumed is absorbed by the proximal small intestine. Only a small amount of alcohol gets absorbed by the oral, esophageal, and/or gastric mucosa. ^[2][3]
• Clinical features ^[4][5]

In the US, the maximum legal limit for driving under the influence of alcohol is a BAC of 0.08%.

Because alcohol has a long absorption time (approx. 40 min), patients with alcohol intoxication may deteriorate over time.

• Laboratory tests: See “Diagnostics” below.
• Treatment
  • Agitation and/or aggression management
    • Sedation with benzodiazepines or typical antipsychotics (e.g., haloperidol)
    • Mechanical restraints may be used for individuals who pose a danger to themselves and/or others if de-escalation and medication strategies have been unsuccessful.
  • Aggressive fluid therapy
  • Thiamine: for Wernicke encephalopathy prophylaxis or treatment
  • Correction of electrolyte disbalance, hypoglycemia, and hypothermia
  • Thorough assessment for occult trauma (e.g., imaging), if suspected

Haloperidol may worsen respiratory depression secondary to alcohol intoxication!

References:^[6][7]

AUD is a chronic condition in which an uncontrolled pattern of alcohol use leads to significant physical, psychological, and social impairment or distress. Symptoms of withdrawal emerge when drinking is discontinued. Not all individuals who drink heavily develop AUD, and not all individuals with AUD have a history of heavy alcohol use.

• Alcohol consumption results in > 3 million deaths worldwide per year.
• Prevalence ^[8]
  • US lifetime prevalence is ∼ 29%
  • More common in Native Americans and Alaska Natives
• Peak incidence: 21–34 years ^[9]
• Sex: ♂ > ♀ (2.5:1) ^[10]
• Associated comorbidities ^[11]
  • Childhood ADHD
  • Conduct disorder
  • Personality disorders (most commonly borderline personality disorder)
  • Anxiety, mood disorders (e.g., depression, bipolar disorder), and psychosis
  • Other substance-related disorders (e.g., stimulants, sedatives, cannabis, and other)
  • Cognitive dysfunction

References: ^{[8][12][13][14]}

• Genetic factors
• Neurobiological factors
• Psychosocial factors
  • Family history of AUD ^[15]
  • Environmental influence: e.g., social pressure to consume alcohol, economic disadvantage (e.g., unemployment), stressful life events

References:^[16][17]

Diagnosis of AUD begins with a screening test, which is followed by a confirmatory test based on patient history. Commonly used screening tests include AUDIT-C and CAGE tests. Diagnosis is confirmed if the patient history meets the DSM-V criteria for AUD.

Screening

• AUDIT-C test
  • Three questions based on the Alcohol Use Disorders Identification Test (AUDIT)
  • Evaluation
    • Every response is given a score from 0 to 4 points.
    • The total score can range from 0 to 12.
    • A positive test suggests the presence of an alcohol use disorder.
      • ≥ 4 in men
      • ≥ 3 in women

• CAGE test ; ^[18]
  • A series of four questions (CAGE) is used to screen for AUD
    1. Cut down drinking: Have you ever felt you should cut down on your drinking?
    2. Annoyed: Have people annoyed you by criticizing your drinking?
    3. Guilty: Have you ever felt guilty about drinking?
    4. Eye-opener: Have you ever felt you needed a drink first thing in the morning (eye-opener) to steady your nerves or to overcome a hangover?
  • Every “yes” response counts as one point.
  • The CAGE test is considered positive for AUD if ≥ 2 questions are answered in the affirmative.

Diagnostic criteria (according to DSM-5)

• 11 criteria based on the patient's history within the past 12 months
• A diagnosis of AUD is established once ≥ 2 criteria are met.
  1. Drinking more or over a longer period than intended
  2. Tried to cut down or stop more than once, but couldn't
  3. Spends a lot of time drinking or recovering from aftereffects
  4. Strong desire to drink alcohol
  5. Drinking has a negative impact on everyday function (social, work etc)
  6. Continued drinking despite social or interpersonal problems
  7. Given up interests and activities that were important because of drinking
  8. Drinking in physically hazardous situations more than once
  9. Continued drinking despite physical or psychological problems
  10. Increasing amount of drinks to maintain same effects as before
  11. Features of withdrawal when the effects of alcohol wear off (see alcohol withdrawal below)
• Severity
  • Mild: presence of 2–3 criteria
  • Moderate: presence of 4–5 criteria
  • Severe: presence of ≥ 6 criteria

Laboratory tests

AUD is a clinical diagnosis, and laboratory tests are not usually required, although they may provide evidence of problematic alcohol use in patients who cannot provide a conclusive history.

• Acute alcohol intoxication: high BAC
• Chronic alcohol intoxication
  • Liver damage
    • ↑ γ-GT (most sensitive marker of alcohol abuse)
    • ↑ ALT, ↑ AST (AST is only higher than ALT when liver parenchyma is significantly damaged)
  • Carbohydrate-deficient transferrin (CDT)
    • CDT is the most specific marker for AUD.
    • For CDT levels to become elevated, approximately 50–80 g of alcohol must be consumed daily for 1–2 weeks. ^[19][20]
  • Malnutrition and bone marrow damage
    • ↓ Folic acid, ↓ vitamin B₁₂ (cobalamin), ↓ vitamin B₁ (thiamine), ↓ vitamin B₆ (pyridoxine), ↓ vitamin D, ↓ vitamin K
    • Megaloblastic anemia (↓ Hb, ↑ MCV), thrombocytopenia

Don't be the lAST 2 hALT! (AST levels are at least 2 times higher than those of ALT in case of alcoholic hepatitis).

• See “Counseling on alcohol use disorder.”
• Psychosocial support (e.g., Alcoholics Anonymous): helps the patient maintain abstinence for longer periods and provides support to the patient's close family and friends.
• Pharmacotherapy (to promote alcohol cessation)
  • Naltrexone (first-line agent): reduces cravings for alcohol
  • Disulfiram: exacerbates intoxication symptoms and induces negative conditioning (only recommended in patients who show strong motivation and commitment for abstinence)
  • Acamprosate: blocks central glutamate receptors and reduces cravings for alcohol
  • Topiramate or gabapentin: for patients who do not tolerate or respond to other medications
• Vitamin supplementation
  • Vitamin B₁ (thiamine)
  • Vitamin B₆ (pyridoxine)
  • Vitamin B₁₂ (hydroxocobalamin)
  • Folic acid

References:^[21]

• Erosive gastritis
• Dilated cardiomyopathy
• Pancreatitis
• Alcoholic liver disease (e.g., steatosis, hepatitis, fibrosis) ^[22]
• Cirrhosis
• Testicular atrophy ^[23]
• Alcoholic cerebellar degeneration
  • Definition: degeneration of cerebellar vermis due to chronic alcohol use
  • Clinical features
    • Unsteady gait
    • Truncal ataxia
    • Gaze-evoked nystagmus
  • Diagnostics
    • CT or MRI: atrophy of the cerebellar vermis
• Marchiafava–Bignami disease
  • Definition: degeneration and necrosis of the corpus callosum, almost exclusively as a result of malnutrition due to chronic alcohol use
  • Clinical features
    • Behavioral changes
    • Cognitive impairment and dementia
    • Epileptic seizures
• Zieve syndrome
• Central pontine myelinolysis
• Meningitis
• Mood disturbance: anxiety, depression, irritability, aggression
• Vitamin deficiency
  • Vitamin B₁ deficiency (thiamine deficiency): Wernicke-Korsakoff syndrome
  • Vitamin B₆ deficiency: peripheral neuropathy
  • Vitamin B₉ deficiency (folate deficiency): megaloblastic anemia
  • Vitamin B₁₂ deficiency: subacute combined degeneration of spinal cord; (funicular myelosis), megaloblastic anemia
• Cytochrome P-450 induction
• In pregnancy: fetal alcohol syndrome

• Definition: elevated anion gap metabolic acidosis due to increased production of ketone bodies with normal or low glucose levels resulting from the combined effects of alcohol and starvation on glucose metabolism
• Etiology
  • Most commonly occurs in malnourished individuals with AUD
  • Associated with recent episodes of binge drinking complicated by poor food intake, dehydration, and vomiting
• Onset: typically occurs 1–2 days after cessation of drinking
• Pathophysiology: accumulation of ketone bodies (see ketogenesis) as a result of:
  • Depleted glycogen stores in the liver (malnutrition/decreased carbohydrate intake)
  • Increased lipolysis and free fatty acid release
    • Decreased energy intake (e.g., starvation) → decreased insulin secretion and excess secretion of glucagon, catecholamines, and cortisol
    • Increased NADH:NAD⁺ ratio: chronic alcohol intake ; → impaired hepatic gluconeogenesis → hypoglycemia → decreased insulin secretion
  • Volume depletion (e.g., vomiting, poor oral fluid intake) → impaired renal perfusion → decreased ability to excrete ketone bodies
• Clinical features
  • Nausea, vomiting, and abdominal pain
  • Tachypnea
  • Features of dehydration and electrolyte imbalance (e.g., hyponatremia, hypokalemia, hypophosphatemia), including hypotension and altered mental status
  • Features of alcohol withdrawal: e.g., tremors, seizures, tachycardia
• Diagnostics
  • Arterial blood gas analysis: elevated anion gap metabolic acidosis
  • Ketonemia (acetoacetate, β-hydroxybutyrate, acetone in blood) and ketonuria
  • Blood glucose: low, normal, or only moderately increased
  • Blood ethanol: not detectable or low
• Treatment
  • Initially: parenteral administration of thiamine to prevent Wernicke encephalopathy
  • Followed by: IV fluid therapy with 5% dextrose in 0.9% saline
  • Correction of electrolyte imbalances
  • Treatment of alcohol withdrawal and complications of chronic alcohol abuse (see alcohol withdrawal management in “Treatment” above)
• Prognosis: The condition is reversible with appropriate treatment.

In contrast to diabetic ketoacidosis, blood glucose levels are normal or low in alcoholic ketoacidosis.

References:^{[1][3][6][24]}

• One-Minute Telegram 58-2022-1/3: The trip to abstinence: Psilocybin improves outcomes in alcohol use disorder.

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