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
  • 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
  • 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

  1. intervention
    • motivational interviewing
      • discuss presenting problems and how alcohol affects them
      • can repeat
    • FRAMES
      • Feedback
      • Responsibility
      • Advice
      • Menu of options
      • Empathy
      • Self-efficacy
  2. 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
  3. rehabilitation
    1. maintaining motivation for change
      • counselling
    2. help to readjust to new lifestyle
      • counselling
    3. 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

Author: Armin

Created: 2022-08-23 Tue 19:17