SUD 2: Alcohol Classification

SUBSTANCE-RELATED AND ADDICTIVE DISORDERS II:
THE ACTION & CLASSIFICATION OF ALCOHOL & ALCOHOL-RELATED DISORDERS
Ximena Sanchez-Samper, MD
Instructor Harvard Medical School
Medical Director Spring Hill Recovery Center
Board-Certified Addictions Psychiatrist
xsanchezmd@gmail.com
Question Based Learning

Lecture Modules
• The Action of Alcohol

• Classification of Alcohol-Induced Disorders
Module: The Action of Alcohol
Question: The American Medical Association’s Alcohol Consumption Guidelines state that women should
limit their weekly alcohol consumption to fewer than how many drinks?
A. 7
B. 14
C. 21
D. 28
E. 35
Psychiatry Review: Substance-Related and Addictive Disorders II: The Action & Classification of Alcohol & Alcohol-Related Disorders
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AMA Consumption Guidelines
• The Guidelines also note that some people should not drink alcohol at all, including
– Women who are or may be pregnant/breastfeeding
– People younger than age 21
– People w/ certain medical conditions or are taking certain medications that can interact with alcohol
– Recovering alcoholics or people unable to control the amount they drink
– Activities that require skill, coordination, and alertness such as driving a car
• For some conditions (i.e., breast cancer) and liver disease, there is no known safe level of alcohol
consumption
• Although past studies have indicated that moderate alcohol consumption has protective health benefits
(i.e., reducing risk of heart disease), recent studies show this may not be true. While some studies have
found improved health outcomes among moderate drinkers it’s impossible to conclude whether these
improved outcomes are due to moderate alcohol consumption or other differences in behaviors or
genetics between people who drink moderately and people who don’t
• Most U.S. adults who drink don’t drink every day That’s why it’s important to focus on the amount people
drink on the days that they drink
• Drinking at levels above the moderate drinking guidelines significantly increases the risk of short-term
harms (injuries), as well as the risk of long-term chronic health problems, such as some types of cancer
Alcohol Morbidity and Mortality

• ED admissions: 9%-31% of chief complaints
• 100,000 annual unexpected deaths
• 15% of all MVA’s; 50% of fatalities in MVA’s
• Liver cirrhosis: 8% of all deaths due to medical causes (50% alcohol
related)
• Suicide; domestic violence
• Abuse and neglect of minors
• Annual cost US economy: $249 bill; $26.3 bill health care
Alcohol Use in the United States
• Prevalence of Drinking: 2015 National Survey on Drug Use and Health (NSDUH)
– 86.4 percent of people ages 18 or older reported that they drank alcohol at some point in their lifetime
– 70.1 percent reported that they drank in the past year
– 56.0 percent reported that they drank in the past month
• Prevalence of Binge Drinking and Heavy Alcohol Use (2015)
– 26.9 percent of people ages 18 or older reported that they engaged in binge drinking in the past month
– 7.0 percent reported that they engaged in heavy alcohol use in the past month
Prevalence of Alcohol Use
Alcoholism Natural History
Source: Schuckit MA. In: Harrison’s Principles of Internal Medicine. New York: McGraw-Hill, 2001:2561-2566.
Module: Classification of Alcohol-Induced Disorders
Question: Delirium tremens is most likely to develop at what point in the intoxication-withdrawal cycle?
A. 12 hours after the last drink
B. 24 hours after the last drink
C. 3-10 days after the last drink
D. 10-14 days after the last drink
E. 14-28 days after the last drink
Alcohol-Related Disorders
• Alcohol intoxication
• Alcohol withdrawal
• Alcohol intoxication delirium
• Alcohol withdrawal delirium
• Alcohol-induced persisting neurocognitive disorder/dementia
• Alcohol-induced psychotic disorder
• Alcohol-induced depressive disorder
• Alcohol-induced anxiety disorder
• Alcohol-induced sexual disorder
• Alcohol-induced sleep disorder
Alcohol Intoxication Diagnosis

• Recent ingestion of alcohol
• Clinically significant problematic behavior/psychological changes
– Inappropriate sexual/aggressive behavior, poor judgment mood lability
• One or more
– Slurred speech
– Incoordination
– Unsteady gait
– Nystagmus
– Impairment in attention or memory
– Stupor or coma
Alcohol Assessment
• Lab tests: Complete blood count, MCV (macrocytosis), TGL, electrolytes, magnesium liver enzymes, (GGT,
AST >ALT), urine drug screen pregnancy test, and Breathalyzer or blood alcohol level
• Others: Skin test for tuberculosis, chest X-ray electrocardiogram, and tests for viral hepatitis HIV or other
STD’s
• *CDT, EtG
Carbohydrate-deficient Transferrin (CDT)

• Laboratory test used to help detect heavy ethanol consumption
• Physiology: Transferrin is a serum protein that carries iron through the bloodstream to the bone marrow
where red blood cells are manufactured, as well as to the liver and spleen. Structurally, transferrin is a
polypeptide with two N-linked polysaccharide chains. These polysaccharide chains are branched with sialic
acid residues. Sialic acid is a monosaccharide carbohydrate
Source: Bell, H.; Tallaksen, C.; Sjahelm, T.; Weberg, R.; Raknerud, N.; Orjasaeter, H.; Try, K.; Haug, E. (1993). "Serum Carbohydrate-Deficient
Transferrin as a Marker of Alcohol Consumption in Patients with Chronic Liver Diseases". Alcoholism: Clinical and Experimental Research. 17 (2): 246.
doi:10.1111/j.1530-0277.1993.tb00757.x.
Carbohydrate-deficient Transferrin (CDT)
• Various forms of transferrin exist, with differing levels of sialylation. The most common form is
tetrasialotransferrin, with four sialic acid chains. In persons who consume significant quantities of alcohol
(usually more than 4 or 5 alcoholic beverages a day for two weeks or more), the proportion of transferrin
with zero, one, or two sialic acid chains is increased These are referred to as carbohydrate-deficient
transferrin. These carbohydrate-deficient transferrin can be measured in the bloodstream, and are an
important marker for alcohol abuse
• CDT is elevated in the blood of heavy alcoholism but raised levels can also be found in a number of
medical conditions (liver disease, pregnancy)
Source: Bell, H.; Tallaksen, C.; Sjahelm, T.; Weberg, R.; Raknerud, N.; Orjasaeter, H.; Try, K.; Haug, E. (1993). "Serum Carbohydrate-Deficient
Transferrin as a Marker of Alcohol Consumption in Patients with Chronic Liver Diseases". Alcoholism: Clinical and Experimental Research. 17 (2): 246.
doi:10.1111/j.1530-0277.1993.tb00757.x.
Ethyl Glucuronide (EtG)

• Metabolite of ethanol which is formed in the body by glucuronidation usually from drinking alcoholic
beverages
• Used as a biomarker to test for ethanol use and to monitor alcohol abstinence in situations where drinking
is prohibited, such as by the military, in alcohol treatment programs, in professional monitoring programs
(health professionals, attorneys airline pilots in recovery from addictions), in schools liver transplant
clinics, or in recovering alcoholic patients
• A disadvantage of the test is that because EtG can be detected in samples at very low levels, it can also be
positive after exposure to alcohol from non-beverage sources, or incidental exposure, which can lead to
false positives (mouthwash foods, over-the-counter medications, and even from inhalation of alcohol
from topical use). It is impossible with this biomarker to distinguish small amounts of drinking from
extraneous exposure to alcohol
Source: Sharpe PC (November 2001). "Biochemical detection and monitoring of alcohol abuse and abstinence" Ann. Clin. Biochem. 38 (Pt 6): 652–64.
doi:10.1258/0004563011901064. PMID 11732647 Helander, A.; Peter, O.; Zheng, Y. (2012). "Monitoring of the Alcohol Biomarkers PEth, CDT and
EtG/EtS in an Outpatient Treatm. Setting". Alcohol and Alcoholism. 47 (5): 552–557. doi 10.1093/alcalc/ags065.
Alcohol Withdrawal Diagnosis

• Cessation or reduction in alcohol use
• Two or more within hours or days
– Autonomic hyperactivity (sweating; HR >100)
– Increased hand tremors
– Insomnia
– Nausea or vomiting
– Transient visual, auditory, tactile hallucinations
– Psychomotor agitation
– Anxiety
– Generalized tonic-clonic seizures
Alcohol Withdrawal Seizures

• Features
– Peak incidence at 24 hrs. of cessation/decrease
– Generalized (tonic-clonic) or partial
– Repeat within 3-6 hours
– Status epilepticus rare (<3%)
– 25%-33% of pts with significant withdrawal
– Outcome: 30%-50% progress to DTs
• Differential: Must consider other etiologies
– Head trauma, CNS infections, neoplasms
• Treatment: Benzo’s (or anticonvulsants)
– “Out The Liver”: Oxazepam / Temazepam / Lorazepam (Benzodiazepine)
Alcohol Withdrawal Delirium Diagnosis
• Disturbance of consciousness (ability to focus, sustain shift attention)
• Cognition impaired (memory, orientation, language perception)
• Acute and fluctuating course
• Consequence of substance withdrawal
Alcohol Withdrawal Delirium (Delirium Tremens): Presentation

• Onset 48-72 hours after cessation – 10 days after last drink
– Preceded by early withdrawal symptoms
• Masked or delayed by illnesses or medications
– 5% of hospitalized alcohol dependent patients
• Medical emergency!
– Mortality: Up to 20%
– Increases with delayed diagnosis, inadequate treatment and concurrent medical conditions
Alcohol Withdrawal Delirium Treatment

• Sympathetic hyperactivity
– Tachycardia, hypertension, fever, diaphoresis, hallucinations delusions
• Treatment: Prevention!
– Benzodiazepines, hydration, caution with neuroleptics and restraints, support
Predictors of Alcohol Withdrawal Delirium

• Prior history of severe withdrawal symptoms or DTs
• High blood alcohol level without signs of intoxication
• Withdrawal signs with high blood alcohol level
• Concurrent use of sedative-hypnotics
• Medical problems (hepatitis, pancreatitis)
• Daily heavy and prolonged ethanol consumption
• Greater number of days since last drink
• Older age, Hypokalemia, Thrombocytopenia Elevated blood level of homocysteine
Source: Risk assessment of moderate to severe alcohol withdrawal--predictors for seizures and delirium tremens in the course of withdrawal. Alcohol
Alcohol. 2011; 46(4):427-33 (ISSN: 1464-3502). Clinical predictors for delirium tremens in patients with alcohol withdrawal seizures. Am J Emerg Med.
2015; 33(5):701-4 (ISSN: 1532-8171).
Alcohol-Induced Persisting Neurocognitive Disorder

Wernicke’s Encephalopathy
• Delirium due to thiamine deficiency
• Rare <35 y.o.
• Acute symptoms
• Reversible with treatment
• Triad: Ataxia, nystagmus, ophthalmoplegia
• Tx: Thiamine 100 mg IM/IV x 3d; 100 mg PO tid x 2 wks
Korsakoff’s Syndrome
• Impaired short term memory – sequela of Wernicke’s
• Chronic condition
• 20% recovery rate
• Anterograde amnesia in alert, responsive pt
• +/- Confabulation
• Tx: 100 mg tid 3-12 months
Mammillary
bodies
The mammillary bodies are atrophic and discolored brown, which is associated with vitamin B1 (thiamine)
deficiency. Microscopically there is capillary proliferation, gliosis and, in severe cases, neuronal loss and
hemorrhage. It is commonly seen in chronic alcoholics but may also be found in other nutritionally deprived
populations
Answer Key
Question: The American Medical Association’s Alcohol Consumption Guidelines state that women should
limit their weekly alcohol consumption to fewer than how many drinks?
A. 7
B. 14
C. 21
D. 28
E. 35
Answer Explanation
• “Standard drink” = 14 grams ethanol
– 12-oz beer (5%)
– 5-oz wine (12%)
– 1.5-oz spirits (40%)
– If alcohol is consumed, it should be in moderation—up to 1 drink per day for women and up to 2 drinks
per day for men—and only by adults of legal drinking age
• Hepatic metabolism
– The average person metabolizes about 1 standard drink per hour
• Excessive Drinking
– Women: <7 per week or no greater than 4 max/day
– Men: <14 per week or no greater than 5 max/day
*Binge drinking: consumption within 2 hours of 4 or more drinks for women and 5 or more drinks for
men
Source: AMA Consumption Guidelines (2015-2020 Dietary Guidelines for Americans).
Question: Delirium tremens is most likely to develop at what point in the intoxication-withdrawal cycle?
A. 12 hours after the last drink
B. 24 hours after the last drink
C. 3-10 days after the last drink
D. 10-14 days after the last drink
E. 14-28 days after the last drink
Answer Explanation
• Delirium Tremens is the most severe form of alcohol withdrawal manifested by altered mental status
(global confusion) and sympathetic overdrive (autonomic hyperactivity), which can progress to
cardiovascular collapse. DTs is a medical emergency with a high mortality rate, making early recognition
and treatment essential
• It occurs 3-10 days following the last drink
Source: Risk assessment of moderate to severe alcohol withdrawal--predictors for seizures and delirium tremens in the course of withdrawal. Alcohol
Alcohol. 2011; 46(4):427-33 (ISSN: 1464-3502). Clinical predictors for delirium tremens in patients with alcohol withdrawal seizures. Am J Emerg Med.
2015; 33(5):701-4 (ISSN: 1532-8171).
References
• Centers for Disease Control and Prevention. Alcohol Use and Your Health. Available at
http://www.cdc.gov/alcohol/fact-sheets/alcohol-use.htm.
• Di Castelnuovo A, Costanzo S, Bagnardi V, Donati M, Iacoviello L, de Gaetano G. Alcohol Dosing and Total
Mortality in Men and Women. Arch Intern Med 2006;166(22):2437-45.
• Rehm J, Shield K. Alcohol consumption. In: Stewart BW, Wild CB, eds. World Cancer Report 2014. Lyon,
France: International Agency for Research on Cancer; 2014.
• U.S. Department of Health and Human Services and U.S. Department of Agriculture. 2015 – 2020 Dietary
Guidelines for Americans. 8th Edition, Washington, DC; 2015.
• Henley SJ, Kanny D, Roland KB, et al. Alcohol control efforts in comprehensive cancer control plans and
alcohol use among adults in the United States. Alcohol 2014;49(6):661-7.
• Chikritzhs T, Fillmore K, Stockwell T. A healthy dose of skepticism: four good reasons to think again about
protective effects of alcohol on coronary heart disease. Drug Alcohol Rev 2009;28:441–4.
• Andréasson S, Chikritzhs T, Dangardt F, Holder H, Naimi T, Stockwell T. Evidence about health effects of
“moderate” alcohol consumption: reasons for skepticism and public health implications.[PDF-9.44 MB] .
In: Alcohol and Society 2014. Stockholm: IOGT-NTO & Swedish Society of Medicine, 2014.
• Knott CS, Coombs N, Stamatakis E, Biddulph JP. All cause mortality and the case for age specific alcohol
consumption guidelines: pooled analyses of up to 10 population based cohorts. BMJ 2015;350:h384.
• Holmes MV, Dale CE, Zuccolo L, et al. Association between alcohol and cardiovascular disease: Mendelian
randomisation analysis based on individual participant data. BMJ 2014;349:g4164.
• Naimi TS, Brown DW, Brewer RD, et al. Cardiovascular risk factors and confounders among nondrinking
and moderate-drinking US adults. Am J Prev Med 2005;28(4):369–73.
• Naimi TS. “Gray area” alcohol consumption and the U.S. Dietary Guidelines: a comment on Dawson and
Grant. J Stud Alcohol Drug 2011;72:687.
• Vinson DC, Maclure M, Reidinger C, Smith GS. A population-based case-crossover and case-control study
of alcohol and the risk of injury. J Stud Alcohol Drugs 2003;64:358-66.
• Nelson DE, Jarman DW, Rehm J, et al. Alcohol-attributable cancer deaths and years of potential life lost in
the United States. Am J Public Health 2013;103(4):641-8.
End of Lecture

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SUD 2: Alcohol Classification

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SUBSTANCE-RELATED AND ADDICTIVE DISORDERS II:

THE ACTION & CLASSIFICATION OF ALCOHOL & ALCOHOL-RELATED DISORDERS

Question Based Learning

• The Action of Alcohol

Module: The Action of Alcohol

Alcohol Morbidity and Mortality

Prevalence of Alcohol Use

Alcoholism Natural History

Alcohol Intoxication Diagnosis

Carbohydrate-deficient Transferrin (CDT)

Ethyl Glucuronide (EtG)

Alcohol Withdrawal Diagnosis

Alcohol Withdrawal Seizures

Alcohol Withdrawal Delirium (Delirium Tremens): Presentation

Alcohol Withdrawal Delirium Treatment

Predictors of Alcohol Withdrawal Delirium

Alcohol-Induced Persisting Neurocognitive Disorder

Source: AMA Consumption Guidelines (2015-2020 Dietary Guidelines for Americans).

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