AUD Pharmacology - Crouse

Learning Objectives

• List impact of alcohol on other medical and psychiatric disorders

• Recognize screening tools used in alcohol use disorder and alcohol withdrawal

• Describe symptoms and timeline of alcohol withdrawal

• Summarize treatment strategies (including medication, target symptoms, routes of admin) for acute withdrawal and prevention of complications (BZDs vs MVI, Folate, Thiamine)

• Classify severity of alcohol use disorder based on DSM5

• Compare FDA approved medications for AUD

• Select treatment strategies

Some conditions that Alcohol can impact or worsen

Heartburn

Suicide ideation

Hypertension

Insomnia, anxiety

additive CNS depression

How much alcohol in ALCOHOL types

12 oz beer - 5%

8-9 oz malt liquor - 7%

Wine - 12%

Gin, rum, tequila, vodka — 40%

What is a good screening tool for alcohol?

CAGE questionnaire

scores of > 2 signify potential problem

DSM-5 criteria for Alcohol Withdrawal

Cessation (or reduction in) prolonged and heavy use of alcohol AND

2 or more of the following symptoms within hours to days of alcohol cessation/reduction

• Autonomic hyperactivity

• Hand/tremor

• Insomnia

• N/V

• Hallucinations

• Psychomotor agitation

• Anxiety

• Seizuers

Who is AT RISK for Alcohol withdrawal ?

• History of alcohol WD delirium or WD seizures

• numerous WD episodes

• Co-morbid medical or surgical illness

• Age >65 years

• Long duration of regular/heavy alcohol consumption

• Seizures during current episodes

• Presenting with autonomic hyperactivity

• Physiological dependence on BZDs or barbiturates

Who MAY be at RISK for Alcohol withdrawal ?

• use of other substances of misuse

• Positive Blood alcohol level (BAL) with symptoms of WD

• Co-occurring psychiatric disorder

Easy to understand pathophysiology of alcohol intoxication

Increased GABA + alcohol activity

Less glutamate activity

Pathophysiology of alcohol WITHDRAWAL

• Unregulated receptors of glutamate INCREASED due to consistent GABA depression

• More glutamate activity as a REBOUND once alcohol is stopped —- withdrawal symptoms

Timeline of alcohol withdrawal

6 to 36 hours - tremors, anxiety, GI upset - mental status normal

6 to 72 hours - seizures risk (1/3 seizures will become Delirium tremens)

12 to 48 hours - halluconosis, visual, auditory, tactile - resolves within 24-48 hours

48 to 72/96 hours - Delirium Tremens

If Delirium Tremens is UNTREATED — Wernickes Encephalopathy

If WE untreated ——— 80-90% progress to Korsakoff Psychosis

Points about Delirium tremens

Extreme hyperactivity of the autonomic nervous system

Altered mental status, hallucinations, tachycardia, HTN, hyperthermia, agitation

Life threatening

Seizures points relating to AWD

• Tonic clonic seiures

• 90% of alcohol withdrawal related seizures occur within 48 hours after last drink

• Likelihood of seizures increases with the number of past withdrawals

• Life threatening

Points about Wernicke-Korsakoff

• related to thiamine deficiency

• Severe cognitive impairment, delirium, gait, disorientiation, paralysis of certain eye muscles

• Can leave patients with Korsakoff syndrome which is characterized by abnormal gaze, ataxia, disabling memory disorder, psychosis

What is in a Banana Bag?

Thiamine, Magnesium, Folic acid, Vitamins

Withdrawal assessment (CIWA Ar) points

• N/V

• Tremor

• Paroxysmal sweating

• Anxiety

• Agitation

• Tactile disturbances

• Visual disturbances

• Auditory disturbances

• Headache

• Orientation

Score of <8 = mild

score of 8-14 = moderate

score of >15 = severe

What is used to treat Alcohol withdrawal Syndrome?

benzodiazepines or barbiturates

Librium

diazepam

lorazepam

KNOW THESE 3^^^!!!

• still good to know the class of BZDs as well

and remember that Lorazepam, Oxazepam, and Temazepam can only be used in liver impairment (important for alcohol disorders)

Order that we should use/choose medications for Alcohol Withdrawal symptoms

1. Benzodiazepines

2. Barbiturates

Goals of treatment in AWD

• Prevent severe withdrawal

• Prevent DTs

Non-pharmt treatments for Alcohol USE disorder (not

• CBT

• Short term residential programs

• outpatient treatment

• Alcoholics Anonymous

Goals of treatment for AUD

• Decrease number of days drinking

• Decrease number of days with heavy drinking

• Decrease # of drinks per day

• Minimize physical, psychological financial and social harm

The TWO agents for first line AUD treatment pharmacologically

Naltrexone

Acamprosate

Naltrexone points for AUD

MOA: Opioid Antagonist

Use in AUD: Reduce craving goal to reduce heavy drinking // Reduce reward

Adverse effects: Nausea, sedation, pain at injection site (IM)

Considerations: Caution in hepatic impairment “benefit often outweighs risk in hepatic impairment” '// abstinence is NOT required // contraindicated with opioids

Acamprosate points for AUD

MOA: Glutamate Modulator

Use in AUD: Maintain abstinence, reduce cravings

Adverse effects: GI Adverse effects

Considerations: Requires renal dosage adjustment // Works better if patient has completed alcohol withdrawal

Some important points about Naltrexone formulations for AUD

2 peak concentrations

• initial peak - 2 hours after injection

• 2nd peak 2-3 days later

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~14 days after dosing concentrations slowly decline

• Measurable levels > 1 month

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Naltrexone is NOT metabolized by the CYP system, so there are lower incidences of DDIs

Second and third line options for AUD treatment

1. Disulfiram

2. Gabapentin

3. Topiramate

Disulfiram points in treatment of AUD

• 2nd/3rd line

Use in AUD: Aversive “negative” reinforcement —- AVOID DRINKING!!!

Adverse effects: Facial flushing, N/V, HA, dizziness/palps/tachy — monitor LFTs

Cannot drink with other Alcoholic agents - caution in hepatic disease

Gabapentin points in treatment of AUD

• 2nd/3rd line

Use in AUD: Cravings

Adverse effects: CNS sedation/dizziness

Considerations: Comorbidities - used for anxiety // neuropathic pain —- renal dose adjustment

Topiramate points in treatment of AUD (off label)

• 2nd/3rd line

Use in AUD: Cravings

Adverse effects: Cognitive slowing // kidney stones // Paresthesias

Considerations: Comorbidities - PTSD [1st comorbidity] !!!! // migraine // cocaine use DO —- renal dose adjustment

Main lecture takeaways

• Alcohol withdrawal symptoms can range from severe to mold ad can be deadly (peaking within 3-5 days)

• Preferred management strategy includes symptom triggered dosing utilizing benzodiazepines

• Supportive care includes: multivitamins, thiamine, folic acid, in addition to electrolytes and fluids as needed

• FDA approved meds for AUD include naltrexone, acamprosate, and disulfiram

• Future directions - GLP1s