Alcohol (Ethanol) and Related Disorders

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Problematic pattern of alcohol use with clinically significant impairment or distress as manifested by at least 2 of the following, occurring within a 12-month period.

  1. Alcohol taken in larger amounts over a longer period of time than intended
  2. Persistent desire to cut down or unsuccessful efforts to cut down or control use
  3. A great deal of time spent in obtaining, using and recovering form effects
  4. Craving or strong desire or urge to use alcohol
  5. Recurring use resulting in a failure to fulfill major role obligations at work, school or home
  6. Continue use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of alcohol
  7. Important social, occupational or recreational activities are given up or reduced because of alcohol use
  8. Recurrent alcohol use in situations in which it is physically hazardous
  9. Alcohol use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by alcohol
  10. Tolerance, as defined by either of the following: A need for marked increase in the amount of alcohol consumed to achieve intoxication or desired effect; A markedly diminished effect with continued use of the same amount of alcohol
  11. Withdrawal as manifested by either of the following: Characteristic withdrawal syndrome for alcohol; Alcohol (or benzodiazepines) is taken to relieve or avoid withdrawal symptoms

Severity Specifier: Based on the number of items present

  • Ethanol is an alcohol that is absorbed in the stomach and duodenum
  • Ethanol readily diffuses across lipid membranes and therefore passively diffuses through the blood brain barrier (BBB)
  • Peak blood alcohol concentration (BAC) normally occurs within 30min but this can vary depending on rate of drinking, concentration of alcohol in beverages, gastric emptying time (i.e., food in stomach), hepatic first pass metabolism, and distribution into total body water (TBW)
  • NOTE: Gender differences in peak levels are due to differences in TBW (Woman have higher peak levels due to lower TBW)
  • Ethanol follows zero-order elimination kinetics: Constant amount of drug metabolized per unit time
  • Excretion of ethanol occurs via lungs and kidney and allows for detection using breathalyzer tests and urine tests (Urine ethyl glucuronide detectable for 4-6 days after use)
  • Normal adults metabolize ~ 7-10 g ethanol per hour (about one standard drink per hour) – One standard drink: 300ml beer, 105ml Wine, 30ml 80-proof spirits
  • Ethanol is metabolized in the liver via ADH (Alcohol Dehydrogenase) and ALDH (Aldehyde Dehydrogenase)



ADH (Alcohol Dehydrogenase)Enzyme located primarily in liver | Genetic variation (fast and slow metabolizers)

ALDH (Aldehyde Dehydrogenase): Mitochondrial enzyme | Genetic deficiency in activity in  ~50% of East Asians | Accumulation of high blood concentration of acetaldehyde causes the “hangover effect” (Flushing, nausea, headache, hypotension)

Ethanol readily crosses the Blood Brain Barrier (BBB) and levels equilibrate quickly. It takes approximately 20-40 minutes from initial drink to peak effects.


Approximate Blood Alcohol Concentration (BAC) and Effects:

0.02% to 0.04% BAC: Lightheaded, Relaxation

0.05% to 0.07% BAC:  Buzzed, euphoria, disinhibition

0.08% to 0.10% BAC:  Cerebellar and vestibular functions deteriorate, Slurred speech, ataxia, nystagmus, incoordination

0.11% to 0.15% BAC:  Drunk, agitation, inattention, gross motor impairment, judgement and perception impaired

0.16% to 0.19% BAC: Very Drunk, nausea, disorientation, vision impairment, memory impairment

0.2% or higher BAC: Blackouts, Respiratory depression, hypotension, lethargy, Stupor/coma, Death


Alcohol and Effects on Driving:




Blackouts are the result of anterograde amnesia (inability to form new memories) but immediate recall and long term memory remain intact. Mechanism is likely related to inhibition of NMDA-receptor-stimulated calcium influx in the hippocampus which leads to disruption of Long Term Potentiation and memory consolidation


Treatment of Alcohol Intoxication (Acute Alcohol Poisoning)

  • Haloperidol 2-10mg PRN for agitation
  • Emesis/Gastric Lavage
  • Cardiorespiratory support
  • Thiamine 500mg-1500mg IV/IM daily for 3-4 days then switch to PO 100mg-500mg PO Daily
  • Folate 1-5mg PO daily
  • Multivitamin tablet daily
  • Intravenous glucose (give thiamine first)
  • Dialysis in severe cases

Alcohol Withdrawal Syndrome

Four Major Clinical Features:


(1) Tremulousness/Tremors

  • 6-8 hrs after last drink
  • Worsens over the next 1-2 days
  • Associated with irritability, anxiety, and agitation

(2) Disordered perceptions

  • Parallel in time w/ tremors
  • Most pronounced at 24-36 hrs (clears in a few days)
  • Auditory hallucinations – can persist for weeks

(3) Convulsions

  • Within 1-2 days after reducing or stopping drinking
  • Multiple seizures are common and occur over 6-12 hours

(4) Delirium Tremens (Alcohol Withdrawal Delirium)

  • Agitation
  • Global confusion
  • Insomnia
  • Frightening hallucinations
  • Sympathetic overdrive (tachycardia, hypertension, tachypnea)
  • May occur 72 hours up to several days after last drink
  • Life threatening (5-15% mortality if left untreated)
  • Usually takes 10 years of heavy drinking to develop risk of DTs (but not always)
  • Previous DTs episodes increases risk for future DTs (Kindling?)
  • High BAC with symptoms/signs of withdrawal increases the risk for developing DTs


Neurotransmitters in Alcohol Withdrawal




Symptoms Neurotransmitters Treatment
Fine tremor
Decreased GABA GABA-agonists
Course Tremor
Increased Glutamate and Norepinephrine Beta-blockers, alpha agonists
Hallucinations Paranoia
Increased glutamate and Dopamine Dopamine Antagonists


Treatment of Alcohol Withdrawal and Alcohol Withdrawal Delirium (DTs):

  1. Conscious sedation is the goal
  2. Benzodiazepines (first line) such as Chlordiazepoxide (Librium) 25-50mg PO q2-6hrs | Lorazepam (Ativan) 2mg PO/IV q2-6h | Diazepam (Valium) 5-10mg PO q2-6h
  3. Sympatholytics (for autonomic hyperactivity) such as Clonidine, Propranolol, or dexmedetomidine
  4. Anticonvulsants (as augmentation) such as Gabapentin, Carbamazepine, and/or Valproic acid
  5. Antipsychotics (for hallucinations, delusions)Haloperidol 1mg-10mg PO TID
  6. Cardiorespiratory monitoring and Support if Needed (may need to intubate)
  7. Aggressive Fluid Replacement
  8. Thiamine Supplementation: 500mg-1500mg IV/IM daily for 3-4 days then switch to PO 100mg-500mg PO Daily
  9. Folate 1-5mg daily
  10. Correction of electrolyte imbalances such as Hypokalemia, Hypomagnesemia, Hypoglycemia
  11. Multivitamins (or Banana Bag IV)
  12. High Carbohydrate soft diet (3000-4000 calories/day
  13. Cooling blanket, if needed


  • Gastritis
  • Mallory Weiss Tears
  • Ulcer disease
  • Malabsorption/Diarrhea
  • Fatty Liver Disease
  • Hepatitis
  • Cirrhosis and it’s complications
  • Esophageal varices
  • GI bleed
  • Hepatorenal disease
  • Hepatic/Uremic/Ammonia Encephalopathy



  • Hepatocellular carcinoma
  • Colon Cancer
  • Pancreatic Cancer
  • Oral/pharyngeal/esophageal cancers
  • Breast cancer





  • A condition in which one or more fingers become permanently bent in a flexed position.
  • Multiple etiologies/risk factors: Alcoholism, Family History, smoking, thyroid disease, liver disease, diabetes, hand trauma, epilepsy (anticonvulsants), HIV
  • Usually begins as small hard nodules just under the skin of the palm, then worsens over time until the fingers can no longer be straightened.
  • Formation of abnormal connective tissue within the palmar fascia.
  • Usually painless (not always)
  • The ring finger followed by the little and middle fingers are most commonly affected
  • Diagnosis is clinical
  • Treatment options include Steroid Injections, Physical Therapy, Radiation therapy, Surgery (in that order)


Neurological Damage

  • Ethanol is neurotoxic and can directly damage neuronal tissue
  • Nutritional deficiencies associated with alcohol use play key role in many alcohol related neurological disorders
  • Serious nutritional deficiencies commonly associated with alcohol: Protein, Thiamine, Folate, Niacin, B-12


Wernicke-Korsakoff Syndrome 

  • Wernicke Encephalopathy and Korsakoff Psychosis are not two entirely separate entities and are usually referred to as Wernicke-Korsakoff Syndrome

  • Caused by a deficiency in thiamine (Vitamin B1)
  • Thiamine pyrophosphate is an important coenzyme in catabolism of carbohydrates and amino acids
  • Untreated mortality rate: 10-20%
  • Clinical Triad: Ataxia, Oculomotor abnormalities (e.g. nystagmus, Internuclear ophthalmoplegia, rectus palsies), Global Confusion
  • Other Signs: Hypotension, Hypothermia, Polyneuropathy
  • Ocular abnormalities may resolve within hours to a few days
  • Confusion and ataxia usually resolve more slowly

  • Demyelination, necrosis, gliosis, vascular proliferation seen in Mammillary bodies, Superior cerebellar vermis, Hypothalamus, and Gray matter regions of the diencephalon and brain stem
  • Most patients with Wernicke’s Encephalopathy (WE) are chronic alcoholics, but WE has also been found in patients with Persistent vomiting, Starvation, Renal dialysis, Iatrogenic malnutrition (e.g., malabsorption from GI surgery), Malignant neoplasms

Korsakoff Psychosis

  • A chronic amnestic disorder that occurs in most patients who survive Wernicke’s encephalopathy
  • Retrograde amnesia for recent memories
  • Anterograde amnesia (inability to learn new information)
  • Patients are usually disoriented to place and time
  • Patients are usually unaware of their deficit and confabulation is common
  • Remote memories & Immediate memory (recall) intact, but pts forget this information several minutes later
  • Alertness and other aspects of cognitive function are unaffected
  • Probable cause of memory deficits: Lesions in dorsal medial nuclei of thalamus
  • ~25% of pts never recover and require long-term care
  • ~20% recover completely over several months
  • Thiamine supplementation and healthy diet are first line treatment
  • Antipsychotics typically not effective for Korsakoff Psychosis


Cerebellar Degeneration

  • Alcoholic Cerebellar Degeneration
  • Clinical Features: Gait ataxia with lesser degrees of limb ataxia (in limb ataxia, legs are affected more than arms)
  • Occurs after several years of alcoholism and develops gradually
  • Loss of cerebellar cortical neurons particularly in the anterior and superior vermis
  • Cerebellar dysfunction frequently abates or stabilizes with abstinence and improved nutrition


Alcoholic Dementia & Cognitive Deficits

  • Cortical atrophy
  • Enlargement of the lateral ventricles
  • Loss of cortical neurons
  • Cerebral atrophy and cognitive deficits are partially reversible


Central Pontine Myelinolysis (CPM)

  • Rare disorder found most often in patients abusing alcohol
  • Preceded by hyponatremia
  • Aggressive correction of chronic hyponatremia appears to be the major precipitating factor in humans and animals
  • Bilaterally symmetrical focal destruction of white matter in the ventral pons.
  • 10% of pts have extra pontine lesions in the thalamus, basal ganglia, cerebellum, and cerebral white matter
  • Lesions exhibit a loss of myelin and a reduced number of oligodendroglia, with relative sparing of neurons and axons and no inflammation or vascular changes
  • Evolves over days to weeks
  • Mental confusion is prominent
  • Demyelination of pontine corticobulbar fibers may lead to
    • Dysarthria
    • Mutism
    • Dysphagia
    • Facial and neck weakness
    • Conjugate gaze palsies
    • Impaired tongue movement
  • Corticospinal tract lesions in the pons produce paraparesis or quadriparesis
  • In severe cases a “locked in” syndrome may develop
  • CSF fluid Studies: Normal or elevated pressure; Increased protein (including myelin basic protein)
  • Brain stem auditory evoked potentials may be abnormal and improve as patient recovers
  • Imaging Studies: MRI is more sensitive than CT for detecting pontine lesions
  • Treatment: Vigorous supportive treatment


Alcoholic Neuropathy

  • Polyneuropathy is the most common neurologic complication in alcoholism
  • Paresthesias, pain, and weakness, especially in the feet
  • Reduced pain and temp sensations
  • Distal muscle weakness and atrophy are common (legs>arms)
  • Reduced deep tendon reflexes
  • Absent ankle reflexes
  • CSF fluid protein levels: normal or slightly elevated
  • Axonal degeneration and demyelination due to direct neurotoxic effect of ethanol on peripheral nerves
  • Alcoholic persons frequently suffer entrapment or pressure neuropathies, particularly of ulnar and peroneal nerves
  • Recovery in abstinent patients is slow and often incomplete, requiring weeks to months


Acute alcoholic myopathy

  • A dramatic and life-threatening disorder that can develop after several days of heavy binge drinking
  • Pain, cramps, tenderness, proximal weakness, and swelling of the muscles (sometimes associated with cardiac arrhythmias)
  • Elevated blood creatine kinase levels – associated with rhabdomyolysis and myoglobinuria
  • May lead to hyperkalemia, renal failure, and death
  • Recovery usually occurs within days to weeks of abstinence, but residual weakness in proximal muscles may remain


Chronic alcoholic myopathy

  • A painless syndrome of proximal muscle weakness and atrophy that is often unrecognized~50% of asymptomatic persons with alcoholism probably have a skeletal myopathy
  • Myopathy can be mild or severe
  • Coexistent alcoholic peripheral neuropathy may contribute to the weakness
  • Alcoholic skeletal myopathy and alcoholic cardiomyopathy have been reported to develop simultaneously in well-nourished alcoholic persons
  • There is a direct correlation b/w amount of ethanol consumed and severity of the myopathies
  • Improvement usually occurs 2-3 months after discontinuing drinking
  • Myopathy is due to direct toxicity of ethanol, acetaldehyde, or other ethanol metabolites.