EtOH Flashcards
PK
absorption
- 10% from stomach
- peak ___ - ___ min
- limited by gastric emptying (slowed by food)
- alcohol increases acid release - induces ___ /GERD
distribution
- distributed in total body water
- men ___ ethanol more
- 30-90
- ulcers
- dilut
PK
elimination
- ___ order kinetics at or above 10-20 mg/dL
- __ rate limiting step
- zero
- ADH
ADH = alcohol dehydrogenase
metabolism
metabolism
- 90% in liver
- ADH
- microsomal ethanol oxidizing system (MEOS) - only at ___ alcohol concentration, involves CYP ___ , ___ affinity for alcohol
glucuronidation
- ALDH
glucuronidation
- test used to monitor alcohol consumption - too sensitive
- ethyl glucuronide has very ___ t 1/2
- useful for student athletes - if they party on friday, can detect on monday
- high, 2E1, LOW
- long
metabolism
1) alcohol is metabolized by alcohol dehydrogenase
- enzyme found in liver, brain, and stomach
fomepizole (Antizol)
- antifreeze antidote
- ___ inhibitor - alcohol can be used as well
- ethylene glycol, MeOH poisoning
- slow formation of ___ and toxic metabolites
- liver has more time to further metabolize toxic metabolites
- ADH
- formaldehyde
2) acetaldehyde is metabolized by aldehyde dehydrogenase
- ALDHB1 and ALDH2 isozymes are important for alcohol metabolism
- 50% of asians only have ___
- SNP in ALDH2 ___ activity (ALDH2*2)
heterozygouse ALDH2*2
- reduced metabolic activity
- ___ and increase skin temp
- can still consume EtOH
homozygous ALDH2*2
- deficient in the ability to metabolize ___
- neurotoxic
- strong hangover
disulfiram (Antabuse_
- ___ inhibitor
- effects persist up to ___ days
- ALDH2
- reduces
- flushing
- acetaldehyde
- 14
MOA of Alcohol
many targets and actions
- alcohol is a very ___ drug
dirty
many targets and actions
ligand-gated ion channels
- ___ receptors ( ___ activator of inhibitory neurotransmitters)
- ___ receptor (inhibitor)
- alpha 7 nicotinic receptors
neurotransmitter release
- ___ (enkephalins) - dopamine
- serotonin, NE
- ACh
- increases CNS and blood ___ levels
- GABA A, allosteric
- NMDA
- opioid
- ACTH
T or F: blood alcohol level is independent of behavioral tolerance
TRUE
blood alcohol
- 0.10% is equal to 100 mg/dL or 22 mmol/L
- Mg% = mg of ethyl alcohol in 100 mL (1 dL) of blood
- 0.1% = 100 mg/dL = 100 mg%
- USA, ___ mg% = legal driving limit
80mg%
PCol of low levels of alcohol
- euphoria, disinhibition, talkative (__ - __ mg/dL)
- analgesia ( ___ - ___ mg/dL)
- CNS stimulation ( __ - ___ mg/dL) - mood swings, aggression
- CNS depression ( ___ - ___ mg/dL) slurred speech, ataxia, sedation, loss of motor control, irrational behaviour
- coma-death ( ___ - ___ mg/dL)
- 30-60
- 60-90
- 80-120
- 100-200
- 300-500
people have survived 1000-1500 mg/dL
CV effects induced by alcohol
acute
- vaso ___
- warm, flush
- ___ BP
- ___ HR
moderate use
- ___ risk of CAD
- increases HDL
heavy/chronic use
- cardio ___
- arrhythmias
- HTN (5% of all cases)
- hemostasis
- vasodilation
- decrease
- increase
- reduced
- cardiomyopathy
physiological effects of alcohol consumption
thermoregulation
- ___
- moderate in man
- possibly lethal with cold temp and large dose
GI
- EtOH is a ___ - increased HCl secretion
- chronic gastritis in alcoholics
- low dose: appetite ___
- high dose: appetite ___
- hypothermia
- secretagogue
- stimulant
- depressant
alcohol consumption causes
Liver
- increase fat metabolism (promote ___ synthesis from FFA)
- ___ liver leading to ___ is comon in abusers
- vitamin deficiencies; ___ reduced
- small intestine damage leading to ___
- can cause ascites, ___ , effusions
Blood
- mild ___
- gastritis, chance for blood loss
- alcohol related ___ acid deficiency
Cancer
- liver
- along route of ingestion
- mouth larynx, esophagus, stomach
- triglyceride
- fatty, cirrhosis
- glutathione
- diarrhea
- edema
- anemia
- folic
drug-drug interactions
CNS depressants
- ___ , antipsychotics, anti-histamines, sedative hypnotics
Aldehyde dehydrogenase inhibitors
- ___ , antimicrobials (metronidazole, cephalosporins), sulfonylureas hypoglycemics (tolbutamide)
acetaminophen
- increase toxic metabolite ( ___ )
- alcohol upregulates CYP ___
- treat with ___ to detoxify
aspirin
- increased ___ and GI ___
- opioids
- disulfiram
- NAPQI
- CYP2E1
- n-acetylcysteine
- ulcers, bleeding
alcohol is toxic and teratogenic
acute intoxication management
- prevent ___ depression
- aspiration of vomit
teratology
- fetal alcohol syndrome
- facial dysmorphology
- low birth weight
- decreased brain size
- mental retardation
lower __ and ___ quality
- respiratory
- testosterone, sperm
