alcohol use disorder

Disulfiram: dose

between 125 to 500 mg/day

Disulfiram (continued): SE

- Drowsiness - Liver toxicity - Seizures - Arrhythmia - Peripheral neuropathy - Psychosis

Alcohol - Neurobiology

- Enhances inhibition at GABA synapses - Reduces excitation at glutamate synapses (inhibits glutamatergic release) - Some action at opioid synapses within the mesolimbic reward circuity **** Can also stimulate the release of endogenous opioids (encephalin)

alcohol withdrawal: CIWA SCALE

0 - 9 10-19 >/= 20

Diagnosing Alcohol Use Disorder - Laboratory Values: AST / ALT: normal values

0-50 U/L

Stats about withdrawal

70% of pts seeking treatment for AUD manifest sx of withdrawal DT's can occur in up to 5% of pts -mortality rate 1%

Alcohol Withdrawal: DT's begin

1-2 days after cessation of alc or precipitous drop in AL

alcohol use disorder: minor

1. Alcohol is often taken in larger amounts or over a longer period than was intended. 2. There is a persistent desire or unsuccessful efforts to cut down or control alcohol use. 3. A great deal of time is spent in activities necessary to obtain alcohol, use alcohol, or recover from its effects. 4. Craving, or a strong desire or urge to use alcohol. 5. Recurrent alcohol use resulting in a failure to fulfill major role obligations at work, school, or home. 6. Continued alcohol 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 markedly increased amounts of alcohol 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: - The characteristic withdrawal syndrome for alcohol. - Alcohol (or a closely related substance) is taken to relieve or avoid withdrawal symptoms.

MCV

1. Index of the average volume of erythrocytes 2. Elevated MCV is the most typical morphologic abnormality associated with excessive alcohol consumption 3. Elevates after 6 weeks of alcohol misuse and may remain elevated for up to 3 months after a person has stopped drinking 4. Not specific for alcohol; can be elevated in other disorders

Alcohol Use Disorders Identification Test (AUDIT): serious risk?

15 or more

Alcohol Use Disorder: MILD

2-3 SX

Topiramate: dosages

25 mg/day and increase over several weeks to 300 mg/day given in divided doses Reduce doses by 50% in patients with CrCl <70 mL/min

Alcohol Use Disorder: MOD

4-5 SX

Alcohol Use Disorder: SEVERE

6 OR MORE SX

Acamprosate: dosing

666 mg TID Reduce dose to 333 TID for pts w/ moderate renal insufficiency

Alcohol Use Disorders Identification Test (AUDIT): cut off score?

8 is moderate risk and requires some follow up

MCV: normal

80-100

GGT: numbers orrelate to alcohol consumption?

>30 U/L correlate with alcohol consumption >4 drinks per day

CDC and U.S. Surgeon General Recommendation of alc use in pregnancy

A pregnant woman should not drink alcohol during pregnancy A pregnant woman who has already consumed alcohol during her pregnancy should stop in order to minimize further risk. A woman who is considering becoming pregnant should abstain from alcohol Recognizing that nearly half of all births in the United States are unplanned, women of childbearing age should consult their physician and take steps to reduce the possibility of prenatal alcohol exposure Health professionals should inquire routinely about alcohol consumption by women of childbearing age, inform them of the risks of alcohol consumption during pregnancy, and advise them not to drink alcoholic beverages during pregnancy

alcohol use disorder: main

A problematic pattern of alcohol use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:

Benzodiazepines

A substantial body of evidence, including several meta-analyses, supports the use of benzodiazepines in the treatment of alcohol withdrawal Literature is less clear about a specific benzodiazepine or a specific protocol

AST and ALT: ratio?

AST:ALT ratio >2:1 = supports a suspicion of alcohol abuse More than 90% of patients with an AST:ALT ratio of 2:1 have alcoholic liver disease

How to Choose?: which for may help prevent relapse in abstient pts?

Acamprosate

Rates of the disorder are greater among

Adult men than adult women although: women may experience morbidity and mortality at a precipitous rate

DTs

Agitation Severe autonomic instability Seizures Severe confusion Hallucinations

Differential Diagnosis of DTs

Alcohol hallucinosis Wernicke's encephalopathy Korsakoff's syndrome

Medical Complications of Alcohol Use: GI

Alcohol hepatitis Cirrhosis of liver Pancreatitis Cancer of mouth, larynx, pharynx, esophagus, liver, colon, rectum, appendix

Epidemiology and Etiology of Alcohol Use Disorder: basics

Alcohol may be used to alleviate the unwanted effects of these other substances or to substitute for them when they are not available.

DD of DTs: Korsakoff's syndrome

Anterograde and retrograde amnesia Disorientation Poor recall Impairment of recent memory coupled with confabulation **Approximately 80% of patients with Wernicke encephalopathy also develop Korsakoff's syndrome

Topiramate: MOA

Anti-convulsant medication Potentiates GABA and inhibits excitatory glutamate transmission Potentially leads to decreased dopamine release in response to alcohol consumption - Helps with cocaine craving too

Alcohol Withdrawal: sx

Anxiety Agitation Tremor Autonomic instability Insomnia Confusion

Management of Alcohol Withdrawal: vitamins

B complex vitamins - Used to treat/prevent Wernicke's encephalopathy and Korsakoff syndrome - Thiamine 50-100 mg/day IM or IV usually after adequate fluids and glucose levels are maintainedoh s

Alcohol Withdrawal: begins

Begins 4 hrs to 2 days after cessation of alcohol or precipitous drop in BAL

Diagnosing Alcohol Use Disorder - Laboratory Values

Blood alcohol level (BAL) Mean corpuscular volume (MCV) Liver function tests (LFTs) - Aspartate aminotranferase (AST) - Alanine aminotranferase (ALT) - Gamma-glutamyltransferase (GGT)

DD of DTs: Wernicke's encephalopathy

CANON Clouded consciousness— - impaired orientation and inability to sustain attention to environmental stimuli Ataxia—primarily affecting gait Nystagmus Ophthalmoplegia—accompanied by lateral orbital palsy and gaze palsy, which is usually bilateral Neuropathy—mainly peripheral

Management of Alcohol Withdrawal: initial assessment: what labs?

CBC w/ diff blood glucose electrolytes renal and hepatic function tests

Management of Alcohol Withdrawal: when can they be safely managed in an ambulatory setting?

CIWA-Ar score less than 15 No past history of DTs or seizures Additionally... - Cognitively intact? - Able to take oral medications? - Able to attend frequent medical follow-ups

Naltrexone: dosage?

Can be dosed PO daily, or in an IM formulation given every 4 weeks (Vivitrol) à this can improve adherence

BAL

Can document alcohol intoxication Use is limited bc alcohol has a 4-hour half-life and an elimination rate of 7 grams per hour (1 drink per hr) - unable to identify alcohol dependent patients who abstain within 24 hrs of testing

Naltrexone: can result in & what should monitor?

Can result in hepatotoxicity must monitor LFTs - Particularly given that many patients with both alcohol use and opioid use disorders may have hepatic disease including Hepatitis A, B, or C Should monitor for suicidality

Medical Complications of Alcohol Use: CV

Cardiomyopathy HTN Ischemic heart disease Acute MI

Benzodiazepines

Chlordiazepoxide 50 to 100 mg TID Lorazepam 1 to 2 mg q 4 hrs Oxazepam 15 to 30 mg QID Diazepam 10 to 20 mg TID or QID The dose can usually be tapered over 3-5 days, with monitoring for reemergence of symptoms Emerging evidence for gabapentin (900 - 1200mg/day) These doses are for inpatient detox. Outpatient detox are lower dosages

Risk Factors for DTs

Comorbid medical illness - Electrolyte abnormalities - Poorly treated CV and respiratory conditions History of DTs BAL >300 mg/dl on presentation Older age Longer history of alcohol dependence Intense alcohol craving Abnormal liver functions

Disulfiram (continued): contraindications

Concurrent alcohol consumption Severe cardiac disease DM Psychosis Pregnancy

Epidemiology and Etiology of Alcohol Use Disorder (continued): age: risk factors

Cultural attitudes toward drinking and intoxication Availability of alcohol (including price) Acquired personal experiences with alcohol uStress levels 40%-60% of the variance of risk explained by genetic influences Trauma history and/or other mental health issues

Management of Alcohol Withdrawal: Oxazepam dosages

Day 1 - 30 mg every 6 hours Day 2 - 30 mg every 8 hours Day 3 - 30 mg every 12 hours Day 4 - 30 mg at night

Management of Alcohol Withdrawal: librium dosages

Day 1 - 50 mg every 6 to 12 hours Day 2 - 25 mg every 6 hours Day 3 - 25 mg twice a day Day 4 - 25 mg at night Be very clear that goal is that you are completely OFF the medication

Assessment of the Neonate/Child: issues?

Difficult to differentiate FASDs from other neurodevelopmental issues (autism spectrum disorders, ADHD), particularly if the mother is not forthcoming about alcohol use during pregnancy

How to Choose?: which for highly motivated patients with social support available to ensure medication adherence

Disulfiram

Medications for Alcohol Use Disorder: FDA-approved meds with evidence of efficacy

Disulfiram Naltrexone Acamprosate Topiramate (off-label) Gabapentin (off-label)

Topiramate: potential SE's

Dizziness, somnolence, poor concentration Paresthesia Weight loss Hyperammonemia when combined with VPA Can reduce effectiveness of oral contraceptives Nephrolithiasis

Gabapentin: doses

Doses between 900 and 1800 mg/day adjustment in individuals with renal impairment Gabapentin does not undergo metabolism and is excreted unchanged, predominantly in urine

Disulfiram (continued): SE: MOST COMMON

Drowsiness and liver tox

American Academy of Pediatrics Recommendation

During pregnancy: - no amount of alcohol intake should be considered safe - there is no safe trimester to drink alcohol - all forms of alcohol, such as beer, wine, and liquor, pose similar risk - binge drinking poses dose-related risk to the developing fetus

Diagnosing Alcohol Use Disorder - Laboratory Values: GGT: normal values

Females: 0-45 U/L Males: 0-53 U/L

Management of Alcohol Withdrawal: likely need inpt treatment if?

Fever Disorientation Drenching sweats Severe tachycardia Hypertension Pregnancy Concurrent substance use that could lead to withdrawal symptoms (eg, benzodiazepines) Markedly abnormal laboratory values

Gabapentin: problem

Growing concern for misuse

CAGE Questionnaire

Have you ever felt you should cut down on your drinking? Have people annoyed you by criticizing your drinking? Have you ever felt guilty about your drinking? Have you ever had a drink first thing in the morning (eye opener)? Score of 2 is recommended as a clinical cut-off score

The treatment of alcohol withdrawal has two major goals:

Help the patient achieve detoxification in a manner that is as safe and comfortable as possible Enhance the patient's motivation for abstinence and recovery

Diagnosing Alcohol Use Disorder - Physical Exam

Hepatosplenomegaly Spider angiomas/telangiectasis -red broken blood vessels often seen around nose Esophageal varices Low-grade hypotension Peripheral neuropathy -Their peripheral neuropathy is VERY well delineated, they can tell you where it starts and stops Dyslipidemia

Alcohol Use Disorders Identification Test (AUDIT):

How often do you have a drink containing alcohol? How many drinks containing alcohol do you have on a typical day when you are drinking? How often do you have six or more drinks on one occasion? How often during the last year have you found that you were not able to stop drinking once you had started? How often during the last year have you failed to do what was normally expected of you because of drinking? How often during the last year have you needed a first drink in the morning to get yourself going after a heavy drinking session? How often during the last year have you had a feeling of guilt or remorse after drinking? How often during the last year have you been unable to remember what happened the night before because of your drinking? Have you or someone else been injured because of your drinking? Has a relative, friend, doctor, or other health care worker been concerned about your drinking or suggested you cut down? How often during the last year have you had a feeling of guilt or remorse after drinking?

Assessment of the Neonate/Child: nuerodevelop assessment examine for

Impulsivity Hyperactivity Inattention, Oppositional behavior Intellectual impairments, such as learning difficulties or speech delays Other developmental deficits, such as fine and gross motor delays

Disulfiram: MOA

Irreversible aldehyde dehydrogenase inhibitor Disrupts alcohol-to-acetate metabolism which leads to acetaldehyde accumulation -It inhibits the enzyme that metabolizes alcohol. So if you cant metabolize it you get real bad effects!

Disulfiram: interactions?

Inhibits P450 2C9 Potential drug interactions with warfarin, metronidazole, and phenytoin

Fixed tapering dose vs. symptom-triggered

Inpatient you want symptom-triggered whereas outpatient is more fixed tapering Likely to use fixed tapering on an outpatient basis... however, patients can also be prescribed as-needed medications for breakthrough symptoms i.e. oxazepam 15mg Q6H if CIWA-Ar greater than 10 despite fixed dosing

Epidemiology and Etiology of Alcohol Use Disorder (continued): age?

Large majority of individuals who develop alcohol-related disorders do so by their late 30s

Management of Alcohol Withdrawal: initial assessment

Last drink? Frequency, volume of alcohol use History of withdrawal seizures of delirium tremens Number of prior supervised withdrawal episodes Laboratory evaluation Vital signs

GGT

MOST specific enzyme for alcohol Enzyme concentrated in the liver, bile ducts, and kidneys Remains elevated for 4-6 weeks after drinking cessation Useful for monitoring abstinence in treatment programs

Disulfiram (continued): SE: LIVER TOXICITY

Monitor LFTs at baseline; retest 10-14 days after starting Thereafter, monitoring every 3-6 months is generally sufficient

NIAAA Drinking Guidelines: MEN

More than 14 standard drinks per week OR More than 4 drinks on one occasion

NIAAA Drinking Guidelines: WOMEN

More than 7 standard drinks per week OR More than 3 drinks on one occasion

Non-Pharmacological Interventions for Substance Use

Motivational interviewing AA/NA (12 step facilitation) -Some AA/NA groups frown a little upon MAT, each group sort of have their own culture so try not to let pt get discouraged if they didn't like a certain group Family-based therapy Consider al-Anon for families Cognitive behavioral therapy Dialectical behavioral therapy Contingency management Tangible "rewards" to reinforce behavior - can be useful for patients with financial restraints or homelessness

How to Choose?: which for alcohol-dependent patients starting treatment and for relapse prevention

Naltrexone and less conclusively topiramate

Acamprosate: SE

Nausea Diarrhea Suicidal thoughts

Topiramate: indications

Not FDA approved for alcohol dependence but some data supports a reduction in drinking and increased abstinence

Cause of Withdrawal and DTs

Now evidence suggests multiple neuro-adaptive changes in the brain secondary to chronic alcohol exposure Brain seems to compensate for alcohol's enhancement of GABA by upregulating excitatory glutamatergic neurons - Withdrawing alcohol triggers an excitatory state until the brain can readjust the fine balance between excitation and inhibition Repeated alcohol withdrawal episodes can produce a kindling effect - Repeated alcohol withdrawal becomes harder to treat and eventually leads to seizures (detoxes become worse & worse - always find out # of times they have detoxed)

DD of DTs: Alcohol hallucinosis

Occurs in 3-10% of pts with severe alcohol withdrawal Characterized by auditory, visual, and tactile hallucinations with a clear sensorium Not fatal

Naltrexone: is

Opioid antagonist

Alcohol Intoxication: treatment

Primarily, treatment will occur in emergent or acute care settings Airway assessment, observation, and monitoring with oxygen as needed Hydration status and electrolyte correction (IV solution containing dextrose, magnesium, folate, thiamine, and multivitamins) Anti-emetic medications can be used for management of nausea/vomiting (Zofran, Compazine, etc.) Sedation, if necessary, but not advised (Haldol, etc.) Restraints also not advised Must screen for alcohol use disorder when a patient presents with alcohol intoxication

SBIRT

Screening should be universal in the primary care setting as an effective secondary prevention strategy Screening should occur on a continuum - thus, a negative screen during a discrete point does not discount the importance of continued, longitudinal screening You should screen at LEAST annually

Disulfiram (continued): SE: DROWSINESS

Self-limiting; dose in the evening

Acamprosate: contraindications

Severe renal disease - Cr clearance <30 mL/min

Alcohol Intoxication: s/s

Slurred speech Incoordination Unsteady gait Nystagmus Impairment in attention or memory Stupor or coma Amnestic events can occur ("blackouts") à important to assess for history of blackouts in those with alcohol use disorders

Acamprosate: MOA

Structurally similar to GABA and is thought to inhibit the glutamatergic system

Disulfiram: can still have reaction

if combined with alcohol up to 2 weeks after discontinuing disulfiram

what increase the likelihood of a complicated withdrawal syndrome

The presence of a co-occurring medical disorder

Medical Complications of Alcohol Use: neurologic

Wernicke's encephalopathy Korsakoff syndrome Cognitive decline Decreased gray and white matter; increased ventricular volume Peripheral neuropathy

Diagnosing Alcohol Use Disorder - Patient Interview

When was the last time you drank alcohol? What happened before you started drinking? Where were you at the time? How were you feeling on that day? At what moment did you realize that you wanted to drink? What sort of feelings did you experience while you were drinking? What about after the incident was over? What consequences (positive and negative) arose because of the drinking?

Naltrexone: MUST EDUCATE?

about the potential for overdose should relapse occur... opioid receptors can down-regulate during periods of abstinence - Decrease in the number of opioid receptors = overdose potential increasee && this neurobiological finding may be more profound with opioid antagonism so for harm reduction be sure to tell them hey if you use, use a smaller amount

alcohol withdrawal: CIWA SCALE: 0-9

absent or minimal withdrawal

substance use disorders: substances

alcohol Caffeine (only intoxication and withdrawal) Cannabis Phencyclidine (and other hallucinogen-related disorders) Inhalant Opioid Sedative, hypnotic, or anxiolytic à very similar to alcohol in intoxication and withdrawal symptoms Stimulant (amphetamine, cocaine, etc.) Tobacco Gambling disorder

Epidemiology and Etiology of Alcohol Use Disorder: sx of ____ accompany/precede AUD?

conduct problems, depression, anxiety, and insomnia

What to do with the results of the screen: If + & meets criteria for AUD?

consider referral to treatment via a warm hand-off

Alcohol Use Disorder: early remission

criteria not met for 3-12 months (with the exception of craving)

Alcohol Use Disorder: full, sustained remission

criteria not met for greater than 12 months (with the exception of craving)

Disulfiram: problem?

doesn't really nip anything *********** It doesn't help cravings but it can be effective

Peripartum- and Pediatric-Specific Issues - Fetal Alcohol Spectrum Disorders (FASDs): FASD spectrum encompassing

fetal alcohol syndrome (FAS) alcohol-related neurodevelopmental disorder (ARND) alcohol-related birth defects (ARBDs) neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE)

Gabapentin: assoc w/

increased rate of abstinence and a reduction in heavy drinking days in a 12-week double-blind, randomized, placebo-controlled, dose ranging study

Disulfiram: SE?

ingestion of alc causes the following: - Diaphoresis - Hypotension and tachycardia - Flushing - Nausea, vomiting, headache Reaction's severity is proportional to the dose of disulfiram and amount of alcohol consumed

Acamprosate: indication

relapse prevention in patients with alcohol dependence who have stopped drinking

Management of Alcohol Withdrawal: chose librium when?

long half-life, reducing the risk of breakthrough withdrawal symptoms Librium can be issue in elderly with toxicity

FASDs consequences & sequelae

low body weight poor coordination hyperactivity poor attention and memory learning disabilities speech and language delays delays in fine and gross motor development intellectual disabilities impulsivity, vision and hearing problems && cardiac, renal, or skeletal malformations

Disulfiram: indicated for

maintaining sobriety in pts with chronic alcohol dependence

alcohol withdrawal: CIWA SCALE: 10-19

mild to moderate withdrawal

If a pregnant woman needs treatment for AUD.. what is option?

naltrexone the risks of heavy alcohol consumption likely exceed the risks of naltrexone

Prazosin

often used for nightmares for PTSD - some evidence that prazosin can be used off label for alcohol use disorder, if you have someone with alcohol use issue and nightmares from PTSD it is a good option

Naltrexone: Before starting?

patients must be completely withdrawn and abstinent - for at least 5 days from a short-acting opioid such as heroin - or 7 days from a longer-acting opioid such as methadone Can do "naloxone challenge" before initiating naltrexone

In those gender-fluid, non-binary, or transgender, standard drink guidelines are

per sex assigned at birth

MCV: other disorders can be elevated

pernicious anemia & folate & B12 deficiency

FASDs: 100%?

preventable!! Consider women who may not know they are pregnant in the early weeks of pregnancy - certainly, we are not "prohibitionists" that expect all women of childbearing age to abstain from alcohol, but should be counseling on the importance of adequate contraception Women who are actively trying to get pregnant should also be counseled to eliminate alcohol consumption

What to do with the results of the screen: If negative screen

provide positive reinforcement and education in regards to appropriate drinking levels... also, plan for future screening (annually would be appropriate)

alcohol withdrawal: CIWA SCALE: >/= 20

severe withdrawal

Assessment of the Neonate/Child: PE of face should evaluate

short palpebral fissure length smooth philtrum thin upper lip

Disulfiram: begin treatment when?

uafter patients abstain from alcohol for > 12 hrs and have a serum alcohol concentration of 0

Management of Alcohol Withdrawal: chose diazepam when?

ugenerally avoided, can be somewhat reinforcing due to rapid onset of action

Management of Alcohol Withdrawal: chose lorazapam / oxazepam when?

useful for patients with hepatic impairment, delirium, or dementia

What to do with the results of the screen: If +?

utilizing motivational interviewing techniques to assess motivation for change assist with change planning - if the patient is ready and agreeable utilization of readiness/confidence rulers

Acamprosate: most effective for?

when used to maintain abstinence and less effective to initiate abstinence