Lecture 17: Pharmacology of Ethanol Flashcards
What is alcohol?
oxygen + proton functional group
EtOH is water-soluble and crosses membranes
How much EtOH is in one drink?
1 oz. contains ~23.3 g of ethanol
one drink contains: 23.3g EtOH/oz. x 0.6 oz. = 13.98 g
What are the different levels of alcohol use?
abstinent
moderate
bingeing –> 5 or 4 drinks on one occasion in the last 30 days for men or women, respectively
heavy (alcoholic)
Where is EtOH mostly absorbed?
EtOh is mostly absorbed in the small intestine
low pH does not alter ethanol
BAC after one drink is higher in females
How does food affect alcohol absorption?
drinking on a full stomach slows absorption and lowers peak BAC
How does EtOh distribution affect BAC over time?
ethanol is distributed throughout tissues
BAC = mg EtOH/100 mL of blood (100 mL is a decilitre, dL)
larger people have lower BAC –> greater body volume
leaner people have lower BAC –> greater water volume within body volume
small size allows passage into brain
gender differences: females tend to be smaller and less lean
What are the acute effects in the brain of EtOH consumption?
inhibited decision-making and judgments
unstable mood and heightened emotions
decreased anxiety
increased aggression
increased addiction
What are the acute effects in the eyes of EtOH consumption?
reduced time to fall asleep, less deep sleep, less REM sleep
impaired memory
impaired balance and coordination
vision impeded and inhibited taste and smell
reduced perception of pain
What are the acute effects in the blood vessels of EtOH consumption?
dilated blood vessels of skin
reduced blood clotting
increased HDL levels
How does zero order kinetics describe ethanol metabolism?
0 order kinetics –> linear elimination curve
alcohol dehydrogenase and aldehyde dehydrogenase are main enzymes for metabolism
saturate quickly, enzymes need NAD+ to operate, 7-8 g/hr max on average
0.015 BAC elimination per hour
amount of alcohol exhaled is ~1/2200th of BAC
How does zero order kinetics describe ethanol metabolism differences between genders?
male: 0.020 - 0.015 = 25% of ethanol left
female: 0.030 - 0.015 = 0.015 = 50% of ethanol left
In what ways are the acute effects of EtOH biphasic?
- BAC rises –> stimulant
- BAC declines –> depressant
what causes the phases? –> administration and metabolism
increased sociability, deceased anxiety especially in adolescent animals
How does alcohol affect perception?
alcohol affects perceptions because in interacts with brain receptors
EtOH modulates glutamate (Glu) and gamma-amino butyric acid (GABA) receptor activity
tilts balance of neuronal activation towards hyper-polarization = inhibition
What is the mechanism of EtOH action?
reduced electrical activity
strong potentiation of GABAA receptors at lower [EtOH]
inhibition of Glu-NMDA receptors and voltage-gated Ca channels at higher [EtOH]
overall effect -> neuronal inhibition, sedative-like effects
asphyxiation at lethal doses (0.4-0.5 BAC) via depressed activity in autonomic centers
What are GABAA receptors?
Cys-loop ligand-gated channel superfamily
heterotetrametric receptors: most contain 2 alpha subunits + 2 beta subunits + 1 other
conduct negative chloride current into neurons
What are NMDA receptors?
ionotropic Glu receptor superfamily
heterotetrametric receptors: all contain 2 NR1 subunits + either 2 NR2 ir 2 NR3 subunits
conduct positive currents into neurons –> depolarizating
Why is alcohol addictive?
alcohol is addictive because it releases dopamine in the brain
What are the physiological effects of EtOH?
vasodilation gives sensation of warm skin but decreased core temperature –> autonomic brainstem nuclei
loss of stomach mucosal lining –> ulcers
What is the mechanism of “the spins” which are a common side effect of drinking?
EtOH permeates endolymph and cupula
BAC starts to decline
EtOH diffuses out of cupula before endolymph
Cupula is now more dense than endolymph and does not stabilize when lying down
sensory fibers are activated
brain interprets activity as motion
What is the mechanism of metabolic tolerance?
mechanism of metabolic tolerance is due to liver adaption
tolerance can occur at behavioral and/or cellular levels
the more you drink, the more you can drink
metabolic –> up-regulation of enzymes, especially in heavy drinkers
What are the symptoms of alcohol withdrawal, or the hangover?
symptoms are physical and psychological
physical –> headache, diarrhea, fatigue, restlessness, nausea
psychological –> haziness, slower thought/cognition, impaired reaction times, poor reasoning
symptoms peak as BAC reaches 0
exact causes are not known, not explained by dehydration alone
may have immune component –> increased cytokine production via thromboxane pathway
How do different types of alcohol cause different hangover severity?
beer before liquor, you’ve never been sicker
liquor before beer, you’re in the clear
congener: a minor chemical constituent, especially one that gives a distinctive character to w wine or liquor or is responsible or some of its physiological effects
substances that flavor and color drinks
increase hangover severity
What is acetate in the metabolism of ethanol?
acetate contains a lot of calories
EtOH is calorie-dense which can be a problem in heavy drinkers who can simultaneously suffer from malnutrition
plus complex carbohydrates, especially in beer
can account for 50%+ of caloric intake in heavy drinkers
very easy to put on weight –> beer belly
accompanied by metabolic changes in energy usage –> causes the brain to metabolize acetate, not glucose
most alcoholic beverages have no nutritional value
What is fetal alcohol spectrum disease?
developmental stages are adversely affected
3rd trimester most vulnerable, synaptogenesis, facial development
What are the facial characteristics of fetal alcohol spectrum disease?
small head
epicanthal folds
flat midface
smooth philtrum
underdeveloped jaw
low nasal bridge
small eye openings
short nose
thin upper lip
What are the gross changes in brain heath and appearance?
ethanol metabolite, acetaldehyde, is reactive
modifies proteins, causes dysfunction
e.g., affects glucose metabolism, protein synthesis, myelin formation –> all of which damage neurons and cause cell death
In what ways does ethanol increase cancer risk?
upper GI tract susceptible because microflora contribute to EtOH metabolism
acetaldehyde can reach 10-100x higher concentrations than in the blood
poor hygiene increases microbe count
smoking increases acetaldehyde production
acetaldehyde interferes with DNA synthesis and repair
What is the effect of ethanol on overall mortality?
safest level of drinking = 0
compare to Canada safe guidelines – 136 and 204 per week for women and men, respectively
relative risk for every 100000 who drink 1/day/year 918 will experience alcohol-related issue
914 abstinent will experience issue
at 2 drinks/day/year, 977
