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)
