Alcohol Use Disorder

is alcohol use disorder (AUD) heritable

• yes

• 50% of first-degree relatives of individuals with alcohol use disorder become alcohol-dependent

(chronic) alcohol impacts which systems of the body

• cardiac

• GI

• cancer

• immune system

• neurologic

how does (chronic) alcohol impact cardiac system

• hypertension

• coronary artery disease

• stroke

• CARDIOMYOPATHY

• arrhythmias

how does (chronic) alcohol use impact the GI system

• liver disease

  • alcoholic hepatitis

  • cirrhosis

• pancreatitis

how does (chronic) alcohol use impact cancer

• breast cancer

• oral/esophageal cancer

• liver cancer

• colon cancer

how does (chronic) alcohol use impact the immune system

• impairs the immune system

• increases risk of infection

  • ex., pneumonia

• damages GI lining = increased bacteria able to get in

how does (chronic) alcohol use impact neurologic system

• dementia

• learning/memory issues

• depression

• anxiety

alcohol ‘drug class’ & its effects

CNS depressant:

• causes sedation that can progress:

  • sleep

  • unconsciousness

  • coma

  • surgical anesthesia

  • fatal respiratory depression

• affects endogenous opiates and NTs in the brain

  • GABA

  • glutamine

  • dopamine

• activates (increases) GABA, calms (decreases) glutamate = constant state of sedation

sobriety BAC

0 - 0.05

what BAC stage/level is the beginning danger point?

confusion (0.18 to 0.30)

sx of danger point in stages of alcohol intoxication

• blacking out

• alcohol poisoning

what is alcohol poisoning

• occurs when large quantities of alcohol beverages are consumed rapidly

• doesn’t occur with sustained drinking of moderate amounts of alcohol

why doesn’t alcohol poisoning occur with sustained drinking of moderate amounts of alcohol

since the person will pass out before toxic dose is consumed, or vomit

how are fatal BACs achieved

1. person has a moderate amount of alcohol → if they don’t vomit, they pass out

2. falling asleep or passing out without vomiting allows continued GI absorption → achievement of fatal BACs (allows toxicity to remain in body)

how is AUD screened

• CAGE questionnaire

  • 2+ positive responses suggests alcohol abuse

• AUDIT

CAGE questionnaire

• used to screen for AUD

• consists of 4 questions:

  • 1. C - Have you ever felt the need to cut down on your drinking?

  • 2. A - Have people annoyed you by criticizing your drinking?

  • 3. G - Have you ever felt guilty about your drinking?

  • 4. E - Have you ever had a drink first thing in the morning? (an eye opener)

AUDIT

• a method for screening for AUD

• 10 question screening tool to screen for:

  • alcohol dependence

  • alcohol use problems

  • the amount/frequency of alcohol consumption in adults in the outpatient setting

what is a standard drink

KNOW!

(in the U.S.): any drink that consists of 14 g of pure alcohol

• 14 g = ~0.6 fl oz or 1.2 tbsp

how much alcohol is in 121 oz of beer

KNOW

~5%

how much alcohol is in 5 oz of wine

KNOW

~12%

how much alcohol is in 8 oz of malt liquor

KNOW

~8%

how much alcohol is in 1.5 oz of spirits

KNOW

~40%

initial signs of alcohol withdrawal

• intoxication

• slurred speech and ataxia

• sedated or unconscious

• nystagmus

  • “a condition characterized by rapid, involuntary, and rhythmic eye movements—side-to-side, up-and-down, or circular”

clinical presentation of BAC levels decreasing during alcohol withdrawal

• tachycardia

• diaphoresis

• hypertension

• hyperthermia

• N/V

• tremors

• hallucinations

• SEIZURES and delirium tremens

  • switching from an excitatory state to… not to so much (bad)

  • excitatory state = increased GABA, decreased glutamate

sx 6-12 hrs after alcohol cessation

• insomnia

• tremors

• anxiety

• GI upset

• h/a

• diaphoresis

• palpitations

• anorexia

sx 12-24 hrs after alcohol cessation

hallucinations

sx 24-48 hrs after alcohol cessation

• withdrawal seizures

  • generalized tonic-clonic seizures

sx 48-72 hrs after alcohol cessation

• delirium

• hallucinations

• disorientation

• tachycardia

• hypertension

• low-grade fever

• agitation

• diaphoresis

how long can alcohol withdrawal last if untreated

up to weeks

when is the worst time (peak sx) for/of alcohol withdrawal

1-3 days post cessation

what should be used for alcohol withdrawal sx? for how long?

• CIWA-Ar (Clinical Institute Withdrawal Assessment for Alcohol)

• should be used for up to 1 week following alcohol cessation

laboratory tests to monitor in AUD

• BAC

• CBC

• CMP

• complete toxicologic screening

how is BAC usually reported

KNOW!

in mg/dL

• ex., 100mg/dL is 0.1% BAC

why is a CBC drawn for AUD

to assess anemia

components of CBC

• Hb

• Hct

• PLT

components of CMP

• electrolytes

• blood glucose

  • long-term alcohol can → hypoglycemia

• BUN

• SCr

• LFTs

why is a toxicology screening drawn in AUD

to rule out other substances

can a pt experience withdrawal with an elevated BAL

yes!

revised CIWA-Ar - sx

• N/V

• tactile disturbances

  • aka hallucinations

  • ex., *feel* bugs crawling under skin

• tremor

• auditory disturbances

• anxiety

• h/a, fullness in head

• agitation

• orientation and clouding of sensorium

revised CIWA-Ar - what does it assess?

indicates severity of withdrawal sx on a scale from 0 to 67

• less than 10 = suggest MILD withdrawal; don’t typically require therapy

• 10-18 = suggests moderate withdrawal

• 19+ = suggests severe withdrawal

  • over 20 = probs ICU

• higher scores = WORSE withdrawal sx and outcomes

how many oz of pure alcohol is in a standard drink

KNOW!

~0.5 oz

alcohol absorption

• most absorbed in the small intestine

  • some absorption in the stomach

• slower if there is food or water in the stomach

• faster in the presence of carbonated beverages

  • ex., rum + coke, not just rum

alcohol distribution

• assessed by BAC

• distributed throughout body fluids

• not distributed throughout fatty tissues

  • a lean person will have a lower BAC than a fatter person of the same weight

what is BAC

• measure of the concentration of alcohol in blood

• expressed as a percentage in terms of grams per 100 mL

rate of alcohol metabolism

liver metabolizes abt 0.25 oz of alcohol per hr

when/how is BAC stable

if rate of intake = rate of metabolism

how/when does BAC increase

if rate of intake exceeds rate of metabolism, BAC increases

alcohol metabolism

• ~90% metabolized in liver

• ~2% excreted unchanged through:

  • breath

  • skin

  • urine

alcohol metabolism pathway

alcohol → acetaldehyde → acetic acid

• alcohol → acetaldehyde via alcohol dehydrogenase

• acetaldehyde → acetic acid via aldehyde dehydrogenase

• acetaldehyde = hangover (body takes longer to metabolize = acetaldehyde build up)

what is alcohol metabolism based on

based on a stable rate

• exercise

• coffee

other strategies do not speed up the rate of metabolism

how does the liver respond to chronic intake of alcohol

by increasing enzyme activity → contributes to tolerance among heavy users

in heavy alcohol users, when alcohol is present, metabolism of other drugs is ______ (slower/faster)

in heavy alcohol users, when alcohol is present, metabolism of other drugs is slower

in heavy alcohol users, when alcohol is not present, metabolism of other drugs is _____ (slower/faster)

in heavy alcohol users, when alcohol is not present, metabolism of other drugs is faster

sex differences in AUD

• women may be more susceptible than men to the effects of alcohol after consuming the same amount

• this is due to absorption & metabolism

how absorption contributes to sex differences in alcohol intake

• women tend to weigh less & have higher proportion of body fat

  • thus, women absorb a greater proportion of the alcohol they drink

how metabolism contributes to sex differences in alcohol intake

alcohol dehydrogenase is less active in women

MOA of alcohol

• CNS depressant

• exact MOA is unclear

• affects CNS

• enhances inhibitory effect of GABA @ GABA-A receptor

  • similar to barbiturates and benzos

• @ high doses, alcohol blocks glutamate

• also affects:

  • dopamine

  • serotonin

  • acetylcholine neurons

sx of alcohol withdrawal syndrome

• tremors

• tachycardia

• hypertension

• insomnia

• hallucinations

• seizures

why are inpatient medical settings often required for alcohol detoxification

due to medical risks

what medication class is typically used for/during alcohol detoxification

benzos

• reduce autonomic hyperactivity

• prevent seizures

• best choices = those with a slow onset of action

benzos used for alcohol detoxification

• benzos typically used

  • lorazepam

  • oxazepam

  • chlordiazepoxide

  • diazepam

solubility lorazepam

• less lipophilic than other benzos

• adequate aqueous solubility for formulation

metabolism of lorazepam

inactive metabolites

oxazepam metabolism

inactive metabolites

diazepam solubility

very lipophilic

diazepam metabolism

metabolized into active and inactive metabolites

common ADRs of benzos (class wide ADRs)

• CNS depression

• cognitive impairment

• psychomotor impairment

• other sx

  • h/a

  • rate: paradoxical agitation/excitement

CNS depression sx in benzos

• drowsiness

• sedation

• fatigue

• dizziness

cognitive impairment sx in benzos

• confusion

• mental clouding

• impaired concentration/judgement

• anterograde amnesia

psychomotor impairment sx in benzos

• ataxia

• impaired coordination

• muscle weakness

significant risks of benzos

• respiratory depression

  • increased risk with other CNS depressants

• dependence/tolerance/withdrawal

• falls - especially elderly

benzo DDIs

additive CNS depression with:

• opioids

• alcohol

• other sedatives

special populations to consider in benzo use

• elderly

• hepatic impairment

• hx of substance use disorder

• pregnancy

elderly patients taking benzos pearls

increased sensitivity → confusion, falls

hepatic impairment in benzo use pearls

• prefer LOT drugs

  • lorazepam

  • oxazepam

  • temazepam

drugs for maintenance of AUD

• disulfiram (Antabuse)

• naltrexone

• acamprosate

when is the maintenance phase of AUD

after withdrawal (refers to longer-term maintenance)

how does disulfiram (Antabuse) help with maintenance

• inhibits aldehyde dehydrogenase

• causes unpleasant sx if alcohol is consumed

how does naltrexone help the maintenance phase

• reduces:

  • alcohol craving

  • rate of drinking

  • rate of relapse

• may block opioid receptors and reinforcing effects of alcohol

how does acamprosate help with alcohol maintenance

• normalizes basal GABA concentrations

• blocks the glutamate increases during alcohol withdrawal

• recently approved - effectiveness hasn’t been determined

MOA of disulfiram

• inhibits aldehyde dehydrogenase → leads to many hangover side effects

• causes many unpleasant sx if alcohol is consumed

disulfiram is considered _____-line tx for AUD

disulfiram is considered second-line tx for AUD

unpleasant sx if alcohol is consumed while on disulfiram

• flushing

• throbbing head/neck

• throbbing h/a

• respiratory difficulty

• N/V

• sweating

• thirst

• chest pain

• palpitation

• dyspnea

• hyperventilation

• increased HR

• lower BP

• fainting

• uneasiness

• weakness

• vertigo

• blurred vision

• confusion

• respiratory depression

• CV collapse

• abnormal heart rhythms

• heart attack

• congestive heart failure

• unconsciousness

• convulsions

• death

how long can effects of disulfiram last

up to 14 days after last dose

considerations for disulfiram

• must abstain from alcohol for at least 12 hrs before administration

• risk of accidental disulfiram-alcohol rxn

  • use extreme caution in pts with:

    • T2DM

    • hypothyroidism

    • seizure disorders

    • cerebral damage

    • chronic/acute nephritis

    • hepatic cirrhosis

    • abnormal EEG

    • multiple drug dependence

side of effects of disulfiram (when alcohol isnt present)

• h/a

• metallic/garlic taste in mouth

• hepatotoxicity

• neurotoxicity

disulfiram DDIs

• acetaminophen (paracetamol)

• theophylline

• caffeine

naltrexone MOA

• not fully known

• may block opioid receptors → reinforces effects of alcohol

• reduces:

  • alcohol craving

  • rate of drinking

  • rate of relapse

naltrexone clinical pearls

• must avoid use of opioids for 7-10 days prior to starting

• pharmacotherapy typically used in conjunction with behavioral/psychosocial treatments

• take once a day, with or without food

when is best outcome of naltrexone seen

when used for 3+ months

naltrexone common ADRs

• N/V/D

• H/A

• dizziness

• nervousness

• insomnia

• drowsiness

• anxiety

naltrexone less common but more severe ADRs

• hepatotoxicity

• hypersensitivity

• suicidal thoughts

• hallucinations

• blurred vision

• swelling in face, feet, legs

• SOB

acamprosate MOA

• normalizes basal GABA concentrations

• blocks the glutamate increases during alcohol withdrawal

• NMDA receptor antagonist

does acamprosate treat or prevent alcohol withdrawal sx

no

acamprosate ADRs

• allergic rxns

• abnormal heart rhythms

• hypo/hypertension

• H/A

• insomnia

• impotence

• diarrhea

acamprosate CI

kidney impairment

general goals of alcohol withdrawal tx

• prevent or treat acute withdrawal sx and medical or psychiatric complications

• long-term abstinence after detoxification

• entering a medical and alcohol dependent tx program

non pharm tx for alcohol withdrawal

• during acute alcohol withdrawal, non pharm interventions are NOT RECOMMENDED

• alcohol withdrawal can be a life-threatening condition

standard of care drug for acute alcohol withdrawal

benzos

• long acting preferred, but short acting often used in practice

benzos MOA

enhances inhibitory effect of GABA at GABA-A receptors