Lecture 17: Pharmacology of Ethanol

Question 1

What is alcohol?

Answer 1

oxygen + proton functional group

EtOH is water-soluble and crosses membranes

Question 2

How much EtOH is in one drink?

Answer 2

1 oz. contains ~23.3 g of ethanol

one drink contains: 23.3g EtOH/oz. x 0.6 oz. = 13.98 g

Question 3

What are the different levels of alcohol use?

Answer 3

abstinent

moderate

bingeing –> 5 or 4 drinks on one occasion in the last 30 days for men or women, respectively

heavy (alcoholic)

Question 4

Where is EtOH mostly absorbed?

Answer 4

EtOh is mostly absorbed in the small intestine

low pH does not alter ethanol

BAC after one drink is higher in females

Question 5

How does food affect alcohol absorption?

Answer 5

drinking on a full stomach slows absorption and lowers peak BAC

Question 6

How does EtOh distribution affect BAC over time?

Answer 6

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

Question 7

What are the acute effects in the brain of EtOH consumption?

Answer 7

inhibited decision-making and judgments

unstable mood and heightened emotions

decreased anxiety

increased aggression

increased addiction

Question 8

What are the acute effects in the eyes of EtOH consumption?

Answer 8

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

Question 9

What are the acute effects in the blood vessels of EtOH consumption?

Answer 9

dilated blood vessels of skin

reduced blood clotting

increased HDL levels

Question 10

How does zero order kinetics describe ethanol metabolism?

Answer 10

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

Question 11

How does zero order kinetics describe ethanol metabolism differences between genders?

Answer 11

male: 0.020 - 0.015 = 25% of ethanol left

female: 0.030 - 0.015 = 0.015 = 50% of ethanol left

Question 12

In what ways are the acute effects of EtOH biphasic?

Answer 12

1. BAC rises –> stimulant
2. BAC declines –> depressant

what causes the phases? –> administration and metabolism

increased sociability, deceased anxiety especially in adolescent animals

Question 13

How does alcohol affect perception?

Answer 13

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

Question 14

What is the mechanism of EtOH action?

Answer 14

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

Question 15

What are GABAA receptors?

Answer 15

Cys-loop ligand-gated channel superfamily

heterotetrametric receptors: most contain 2 alpha subunits + 2 beta subunits + 1 other

conduct negative chloride current into neurons

Question 16

What are NMDA receptors?

Answer 16

ionotropic Glu receptor superfamily

heterotetrametric receptors: all contain 2 NR1 subunits + either 2 NR2 ir 2 NR3 subunits

conduct positive currents into neurons –> depolarizating

Question 17

Why is alcohol addictive?

Answer 17

alcohol is addictive because it releases dopamine in the brain

Question 18

What are the physiological effects of EtOH?

Answer 18

vasodilation gives sensation of warm skin but decreased core temperature –> autonomic brainstem nuclei

loss of stomach mucosal lining –> ulcers

Question 19

What is the mechanism of “the spins” which are a common side effect of drinking?

Answer 19

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

Question 20

What is the mechanism of metabolic tolerance?

Answer 20

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

Question 21

What are the symptoms of alcohol withdrawal, or the hangover?

Answer 21

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

Question 22

How do different types of alcohol cause different hangover severity?

Answer 22

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

Question 23

What is acetate in the metabolism of ethanol?

Answer 23

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

Question 24

What is fetal alcohol spectrum disease?

Answer 24

developmental stages are adversely affected

3rd trimester most vulnerable, synaptogenesis, facial development

Question 25

What are the facial characteristics of fetal alcohol spectrum disease?

Answer 25

small head
epicanthal folds
flat midface
smooth philtrum
underdeveloped jaw
low nasal bridge
small eye openings
short nose
thin upper lip

Question 26

What are the gross changes in brain heath and appearance?

Answer 26

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

Question 27

In what ways does ethanol increase cancer risk?

Answer 27

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

Question 28

What is the effect of ethanol on overall mortality?

Answer 28

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