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
