Ethanol pharmacology Flashcards
ETOH absorption
rapid, fastest in small intestine. rapid ingestion –> rapid absorption. Slowed by food
ETOH distribution
evenly distributed. Areas with high blood flow (brain, liver, kidney, lung) –> more rapid distribution
Time for initial CNS effect
5 minutes
Gender differences in distribution
women = more fat, less water per kg body weight –> higher BAC for same dose as a man
volume of distribution of ETOH [r] in men
0.68
volume of distribution of ETOH [r] in women
0.55
BAC calculation
(alcohol in body g/100ml)/[r]
ETOH metabolism
hepatic
location of first pass metabolism
gastric mucosa. Female less than male
Rate of metabolism
constant rate of 0.015-0.020% per hour
ETOH metabolic pathway
ETOH + NAD + alcohol dehydrogenase –> acetaldehyde + NADH
Acetaldehyde + NAD + aldehyde dehydrogenase –> acetate + NADH
Acetate + CoA + ATP –> Acetyl CoA + AMP + PP
Acetyl CoA –> fatty acids, cholesterol, CO2, H2O, energy
Effect of fructose in ETOH metabolism
fructose –> more rapid NADH conversion to NAD –> increased metabolic rate
Role of NADH in ETOH metabolism
must be oxidized to NAD
Disruptions in oxidation of NADH
increased blood lactate (–> acidosis, behavioral disturbances), increased Mg excretion ( –> convulsions), decreased uric acid excretion ( –> gout attacks), increased acetyl CoA ( –> increased fatty acid synthesis, decreased fat breakdown –> fatty liver), increased NADH ( –> decreased Krebs cycle activity, decreased gluconeogenesis –> hypoglycemia)
ETOH tolerance
limited compared to opioids
Early/minor withdrawal
mild agitation, anxiety, restlessness, tremor, anorexia, insomnia. Seizures possible within 6-48h after onset of withdrawal
Late/major withdrawal
extreme overactivity, disorientation, confusion, disordered sensory perception. No seizures
ETOH effects on CNS
sedation, analgesic, emetic, hangover,
initially anticonvulsive –> later CNS withdrawal hyperexcitability –> precipitate convulsions
BAC = 0.05-0.08
impaired reaction time, impaired judgment, impaired driving ability, ataxia
BAC = 0.08 - 0.2
staggering gait, inability to operate a motor vehicle
ETOH effects on liver
initially reversible
later: cell death –> collagen replacement (cirrhosis) in 20% of chronic alcoholics
regeneration and enlargement –> pressure on veins –> decreased venous return, ascites, esophageal varicies, increased bleeding time
ETOH effects on kidney
BAC rising –> Blocked secretion of ADH –> diuresis
Stable BAC –> antidiuresis
ETOH GI effects
irritation –> gastric secretions –> gastric ulcers (especially with aspirin), pancreatitis
High doses –> blocked absorption of amino acids, glucose, folate, thiamine, B12
Criteria for fetal alcohol syndrome
pre/postnatal growth retardation and altered morphogenesis (facial) and CNS involvement (mental retardation)
Fetal alcohol syndrome incidence
1/1000 to 1/300
Heavy drinkers: 1/3
ETOH effects by trimester
1st: morphologic abnormality
2nd: increased risk of spontaneous abortion
3rd: decreased fetal growth
Acute ETOH DDIs
additive effects with CNS depressants
DDIs in chronic ETOH use, with tolerance
cross-tolerance to sedative-hypnotic drugs and general anesthetics
Alcoholic with normal liver function
faster metabolism, reduced concomitant drug effect, potentiated acetaminophen toxicity
alcoholic with mild liver disease
normal metabolism
alcoholic with severe liver disease
slower metabolism due to enzyme loss, increased effect of concimitant drugs
management of acute ETOH intoxication
respiratory support, IV fluids, glucose, thiamine, K and Mg
management of ETOH withdrawal
Benzos (action at GABA receptors block CNS hyperexcitability)
Clonidine (a2 agonist) for signs of autonomic hyperactivity
Strategies for reduction of ETOH consumption
Disulfiram (antabuse), naltrexone,
NMDA receptor modulation (Acamprosate) –> reduced ETOH craving and relapse rates in combination with psychotherapy
