Alcohol
Table of Contents
1. Overview
- in 2015, 130M people >12yo used illicit drugs
- most common marijuana and hashish
- ICD-10 includes "harmful use"
2. Alcohol
- 20-30% of middle-class men and 15% of women seeking medical care
- 50% will develop anxiety/depression (temporary)
- 90% of american have consumed alcohol at least once
- >60% of students have been intoxicated
- male 1.3:1 female
- higher risk for dep, anx, antisocial, schiz.
- higher edu/income, jewish, irish, inuit/indigenous: higher level of use
- almost 50% of drinkers experience temporary alcohol-related problems
2.1. Properties
- standard drink: 10-12g of ethanol
- one drink in a 70kg male raises blood alcohol by 15-20mg/dL
- roughly the same amount metabolized in 1 hour
- faster absorption if empty stomach and carbonated
- roughly the same amount metabolized in 1 hour
- most metabolized in liver -> ADH (rate limiting, needs NAD+) -> acetaldehyde -> ALDH (rapid) -> excretion
- acetaldehyde releases histamines and catecholamines -> changes in BP and nausea/vomiting
- alcohol is a depressant, along with benzo and barbiturates
- have cross-tolerance and can be fatal in overdose
- most prominent effect on GABA-A receptor: sedating, sleep-inducing, anticonvulsant, and muscle-relaxing properties
- also impacts NMDA: dampened stimulatory effects during intoxication and heightened activity during withdrawal
- acutely increases dopamine: intoxication and craving
- chronic: changes in pleasure centers in ventral tegmental area
- increases serotonin
- Lower brain levels of serotonin may be associated with a less intense response to alcohol and with consuming more alcohol per occasion
- acutely enhances the functioning of the opioid-related brain systems and impacts adenosine, acetylcholine, and cannabinoid 1 (CB1) receptors
- tolerance
- behavioural
- pharmacokinetic (cellular level)
- pharmacodynamic (nervous system adaptation)
2.2. Medical issues
- sleep
- suppresses REM sleep
- inhibits stage 4 sleep
- associated with frequent alternations between sleep stages (fragmentation)
- more intense and disturbing dreams
- may not return to normal for 3-4 months post-abstinence
- cerebellar degeneration
- ethanol, acetaldehyde, vitamin deficiency
- unlikely to completely recover
- thiamine deficiency
- alcohol-induced major NCD, amnestic confabulatory type, persistent
- include 6th nerve palsy: Wernicke's
- anterograde amnesia out of proportion to level of confusion: Korsakoff's
- Wernicke-Korsakoff
- Wernicke encephalopathy
- prominent ataxia and 6th nerve palsy
- reverses rapidly with vitamin supplementation
- Korsakoff syndrome
- permanent in 50% of affected people
- pronounced anterograde and retrograde amnesia
- and impairment in visuospatial, abstract, and other types of learning
- in most cases, level of recent memory loss is out of proportion to confusion
- patients who recover generally respond to 500mg IV thiamine, 2-3x/day for 3-5 days or 100mg thiamine per day orally for many months
- Wernicke encephalopathy
- alcohol-induced major NCD, amnestic confabulatory type, persistent
- peripheral neuropathy
- GI issues
- esophageal inflammation
- esophageal varices
- cirrhosis
- pancreatitis
- fatty liver
- alcoholic hepatitis
- CV
- high BP
- raise LDL and tryglycerides
- alcoholic cardiomyopathy
- alcohol is a striated muscle toxin
- leading cause of death in AUD is heart disease
- 4-8 drinks reduces WBC production
- Cancer
- head, neck, esophagus, stomach, liver, colon, lung, breast
- likely alcohol-related immune suppression
2.3. Etiology
- genetics 60% risk
- ADH and ALDH variants, impulsivity and disinhibition, other psychiatric disorders, level of response to alcohol
- initiation linked with religion, personality, social factors
- stress, expectations of alcohol, perceived pattern of drinking among peers
2.4. AUD
- repeated + at least 2/11 impairments related to alcohol
- mild(2-3), moderate(4-5), severe(6+)
- highest risk of relapse in 3-12 months of recovery
- early remission when none of the 11 criteria are met (except craving) x3 months
- sustained remission x12 months
- lifetime risk of AUD male 15%, female 10%
- early onset associated with worse prognosis
- up to 80% with AUD report temporary sadness or anxiety during course of illness
- 40% can become intense and persistent to meet MDD or panic criteria
- alcohol-induced issues don't have same prognosis and don't need same pharm treatments
- can diminish in 1w-1m of abstinence
2.5. Intoxication
Level (mg/dL) | Impairment |
---|---|
20-30 | Slowed motor performance and decreased thinking ability |
30-80 | Increases in motor and cognitive problems |
80-200 | Increases in coordination |
Mood lability | |
Deterioration in cognition and judgement errors | |
200-300 | Nystagmus, marked slurring of speech, and blackouts |
>300 | Impaired vital signs and possible death |
2.6. Withdrawal
- opposite of intoxication
- coarse tremor of the hands, insomnia, anxiety, and increased blood pressure, heart rate, body temperature, and respiratory rate
- start 8h, peak 2-3d, diminish 4-5d
- symptoms persist in milder form 3-6 months
- protracted withdrawal
- contributes to relapse
- signs
- Increased pulse, blood pressure, and/or sweating
- Tremor of the hands
- Problems sleeping
- Gastrointestinal upset
- Hallucinations
- Inability to sit still
- Nervousness
- Seizures
- delirium
- <5%
- meet criteria for both delirium and intoxication or withdrawal
2.7. Alcohol-induced psych disorders
- dep, anx, psychosis
- chronological history
- If a review of the timelinereveals no evidence that the additional psychiatric syndromes either clearly antedated the severe alcohol problems or persisted for a month or more after abstinence, an AUD is the major disorder.
2.8. Scales and Investigations
- AUDIT (Alcohol Use Disorder Identification Test)
- GGT >35 U/L; CDT >3%; MCV >91; uric acid > 6.4mg/dL for men and >5mg/dL for women; AST >45; ALT 45
2.9. Prognosis
- fewer than 50% ever receive treatment
- good outcomes for those without antisocial PD, in context of job and family contacts: 60% chance for >1y abstinence
2.10. Treatment
- intervention
- motivational interviewing
- discuss presenting problems and how alcohol affects them
- can repeat
- FRAMES
- Feedback
- Responsibility
- Advice
- Menu of options
- Empathy
- Self-efficacy
- motivational interviewing
- detoxification
- control withdrawal
- any depressant can work, but benzodiazepines are safe and cheap
- for severe or DT: high dose benzo + haloperidol for agitation and hallucination
- if not treated, ICU propofol or dexmetedomidine (arousable deep sleep)
- can have 1 generalized tonic clonic seizure
- needs neuro evaluation
- if no seizure disorder, no anticonvulsant is needed
- protracted withdrawal
- can last for months
- sadness, mood swings, anxiety, insomnia
- little benefit for antidepressants for sadness and mood swings for no independent psychiatric disorder
- acamprosate (NMDA antagonist) can help with mood swing and anxiety
- 2g divided tid
- 15-20% benefit with mild GI side effects
- control withdrawal
- rehabilitation
- maintaining motivation for change
- counselling
- help to readjust to new lifestyle
- counselling
- relapse prevention
- counselling
- medication
- acamprosate (NMDA antagonist)
- naltrexone (long-acting opioid antagonist)
- decreased activity in ventral tegmental area
- 15-20% improved outcome vs placebo
- mild GI upset and lethargy
- 50mg/d oral or 380mg/m injection
- disulfiram (ADH inhibitor)
- not really more effective than placebo
- ondansetron, baclofen, sertraline
- maintaining motivation for change