B6.041 Prework 3: Alcohol Use Disorder Flashcards
standard drink
14-15 g of EtOH
alcoholic content of common beverages
beer 3-6%
wine 8-14%
fortified wine 20%
liquor 40-90%
absorption of alcohol
rapidly absorbed
primarily absorbed in duodenum
rate is extremely variable
factors that influence BAC
amt and alcohol concentration of beverage
rate of drinking
food consumption and composition
gastric emptying and gastric metabolism
patient’s use of meds w interaction effects
major pathway of ethanol metabolism
ethanol> acetaldehyde> acetate> acetyl CoA > CO2 + H2O + energy (7 kcal/gm)
- alcohol dehydrogenase
- aldehyde dehydrogenase
- TCA cycle
location of metabolism of alcohol
90-98% in liver
kinetics of alcohol metabolism
alcohol dehydrogenase saturates at low to moderate BACs
0 order kinetics @ moderate BACs
-7 g per hour elimination
-15 mg% per hour disappearance
accumulation of acetaldehyde
aldehyde dehydrogenase usually not rate limiting
symptoms: headache, gastritis, nausea, dizziness (hangover)
can be caused by inhibition of aldehyde dehydrogenase
CNS effects of alcohol
CNS depressant
apparent stimulatory effects result from depression of inhibitory control mechanisms in the brain
characteristic response: euphoria, impaired thought processes, decreased psychomotor efficiency
what is a reinforcer
substance whose pharmacological effects drive the user to continue to use it
positive reinforcing effects of alcohol
euphoria
altered consciousness
relief of anxiety and other negative emotions
relief of withdrawal symptoms
what neural system is implicated in alcohol reinforcement
mesocorticolimbic system
- prefrontal cortex
- nucleus accumbens
- VTA
animal models of alcohol reinforcement
animals can be selectively bred to self administer alcohol in preference to other usually reinforcing liquids
- intra cranial injections into VTA
- different neurotransmitter levels in mesocorticolimbic system compared to non-alcohol preferring animals
neurotransmitter effects of alcohol
increases dopamine in mesocorticolimbic system
activated opioid peptide system
facilitates GABA transmission
blocks NMDA receptors
euphoria/pleasure
increased dopamine
increased opioids
anxiolysis/ataxia
increased GABA
sedation/ amnesia
increased GABA
decreased NMDA
withdrawal symptoms (neurotransmitters)
decreased GABA
increased NMDA
craving
decreased opioids
effects of alcohol on GI tract
increased incidence of cancer (esophagus, stomach, liver) gastritis malabsorption pancreatitis liver disease
clinical symptoms of acute alcoholic gastritis
anorexia
epigastric pain
vomiting (w or w/o hematemesis)
effects of ethanol on small intestine
decreased absorption (folate, thiamine, B12) increased absorption (iron)
symptoms of acute alcoholic pancreatitis
constant epigastric pain
pain worse after eating
low grade fever
epigastric tenderness
complications of pancreatitis
acute, recurrent, or chronic abscess or pseudocyst formation exocrine insufficiency endocrine insufficiency hemorrhagic pancreatitis
manifestations of alcohol liver disease
fatty liver
hepatitis
cirrhosis
alcoholic fatty liver
liver tender and may be enlarged 2-3x normal
GGTP, AST, and ALT usually elevated moderately
reversible in several weeks with abstinence
alcoholic hepatitis
jaundice
low grade fever
enlarged tender liver
persistently elevated AST, ALT, alk phos
alcoholic cirrhosis
jaundice: elevated AST, ALT, bilirubin ascites, peripheral edema decreased albumin gynecomastia, testicular atrophy hard, nodular liver; enlarged spleen easily bruised, elevated PT, decreased platelets spider angiomata
major complications of cirrhosis
portal HTN -esophageal varices and bleeding -bleeding hemorrhoids -encephalopathy hepatoma
causes of anemia in alcoholism
blood loss -gastritis, varices -decreased platelets -elevated PT hypersplenism decreased folate absorption decreased EPO
effects of alc on cardiovascular system
cardiomyopathy
HTN
stroke
acute CNS effects of alc
intoxication
blackouts
coma
alcohol intoxication symptoms
euphoria assertiveness irritability loss of behavioral inhibitions dysarthria ataxia
alcoholic blackout
intoxicated, alert
new learning (memories) not recorded
retrograde amnesia for period of blackout
duration usually several hours
related to rate of increase in BAC, not in absolute level
alcoholic coma
leads to death by respiratory depression
lethal BAC 500-700%
literally tolerance to lethal BAC
lethal synergism with other sedative hypnotics
hyperosmolarity becomes a problem with these levels
chronic CNS effects of alc
depression polyneuropathy W-K syndrome tolerance withdrawal alcohol dementia central pontine myelinosis marchiafava-bignami syndrome
pscyh illness correlations with alcoholism
antisocial personality -20% of male alcs -5% of female alcs affective disorder -20% of female alcs -5% male alcs
alcohol induced depression
symptoms identical to major depressive disorder
occurs after several weeks to months of heavy drinking
resolves 2-21 days after cessation of alcohol
wernicke’s encephalopathy
clinical features: -6th nerve paralysis/palsies -truncal ataxia -confusion due to thiamine deficiency give high dose of thiamine cerebellar degeneration often prominent and may occur as isolated finding
Korsakoff’s syndrome
often occurs w Wernicke's inability to retain new information usually irreversible -50% perm disables -25% partial recovery w abstinence
alcoholic dementia
memory impairment
cognitive dysfunction
cerebral atrophy common
what % of patients in general medical practice are drinking at a hazardous level
20%
at risk drinking
directly harmful or correlated w greater risk of health problems
at risk drinking- men
> 14 per week
4 or more per occasion
at risk drinking - women
> 7 per week
4 or more per occasion
BAC in diagnosing alcoholism
> 300% anytime
150% in patient not obviously intoxicated
100% in patient during routine exam
MCV
elevated in 40-95% of actively drinking alcs
associated w folate def in 1/3 of alcoholics
more marked in alcs who smoke
returns to normal with 2-4 months of abstinence
GGTP
elevated in 75% of alcs with evidence of liver disease
AST
elevated in 30-75% of alcs
ALT
elevated in 50% of alcs
AST/ALT
> 1
AST + ALT < 300 identifies 90% of patients w alcohol liver disease and 77% of patients with nonalcohol liver disease
CDT
> 20 indicated heavy use for several months
CXR in alcs
30% have old or new rib or vertebral fractures compared to 1% of controls
treatment of minor withdrawal
benzos
GABA agonists
treatment of major withdrawal (DTs)
supportive GABA agonists antipsychotics phenobarbital gabapentin a2 agonists
pharm options for ttx of alcoholics
disulfram (Antabuse)
naltrexone (revia)
Acamprosate (campral)
disulfram
inhibits metabolism of acetaldehyde
naltrexone
opioid antagonist
perhaps better for attenuating relapse than maintaining abstinence
Acamprosate
? GABA agonist and glutamate receptor antagonist
perhaps better for abstinence than relapse
other treatments for alcohol use disorder
AA education groups cognitive therapy MET (motivational enhancement therapy) psychodynamic therapy marital and fam therapy pharm
