Lecture 14 - Pharmacology of alcohol

Question 1

What is alcohol

Answer 1

• oxygen and proton functional group
• EtOH is water soluble and crosses membranes

Question 2

Where is ethanol absorbed?

Answer 2

small intestine

Question 3

How does drinking on a full stomach affect absorption

Answer 3

• slows absorption and lowers peak BAC

Question 4

How is BAC calculated

Answer 4

mg EtOH/100ml of blood

Question 5

How is BAC different between larger and leaner people?

Answer 5

• larger people have lower BAC -> greater body volume
• leaner people have lower BAC -> greater water volume within body volume

Question 6

What are gender differences with BAC absorption

Answer 6

females tend to be smaller and less lean -> higher BAC after one drink

Question 7

What are acute effects of EtOH consumption

Answer 7

• inhibited decision making and judgement
• unstable mood and heightened emotions
• decreased anxiety
• increased aggression
• increased addiction
• reduced time to fall asleep
• impaired memory
• impaired balance and coordination
• vision impeded + inhibited taste + smell
• reduced perception of pain
• dilated blood vessels of skin
• reduced blood clotting
• increased HDL levels

Question 8

What is zero order kinetics

Answer 8

• linear elimination curve
• 0.015 BAC elimination/hour
• amount of alcohol exhaled is 1/2200 of BAC

Question 9

What are acute effects of EtOH

Answer 9

• biphasic
• phases are caused by metabolism
• increased sociability, decreased anxiety especially in adolescent animals

Question 10

What receptors does EtOH modulate?

Answer 10

• glutamate and GABA receptor

Question 11

What does the interaction of EtOH with receptors do?

Answer 11

• tilts the balance of neuronal activation towards hyper-polarization = inhibition

Question 12

What is the mechanism of EtOH action

Answer 12

• strong potentiation of GABAa receptors at lower [EtOH]
• inhibition of Glu-NMDA receptors + 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 centres

Question 13

What are GABAa receptors

Answer 13

• cys-loop ligand gated channel superfamily
• heteropentameric receptors
• conduct negative chloride currents into neurons

Question 14

What are NMDA receptors

Answer 14

• ionotropic Glu receptor superfamily
• heterotetrameric receptors
• conduct positive currents into neurons -> depolarizing

Question 15

What are the physiological effects of EtOH

Answer 15

• vasodilation gives sensation of warm skin, but decreased core temperature -> autonomic brainstem nuclei
• loss of stomach mucosal lining -> ulcers

Question 16

What are spins

Answer 16

• common side effect of drinking excess EtOH can cause a feeling like vertigo
• EtOH permeates endolymph and capula
• BAC starts to decline
• EtOH diffuses out of capula before endolymph
• capula becomes much denser and doesn’t stabolize when lying down
• causes brain to interpret activity as motion

Question 17

What is the mechansism of metabolic tolerance

Answer 17

• due to liver adaptation
• tolerance can occur at behavioural/cellular levels
• more you drink, more you can drink
• metabolic -> up-regulation of enzymes, especially in heavy drinkers

Question 18

What is the metabolism of alcohol?

Answer 18

• can be calorie dense so problem with those who suffer from malnutrition
• can account for 50%+ of calories in heavy drinkers
• very easy to put on weight -> beer belly
• causes brain to metabolize acetate, not glucose

Question 19

What is fetal alcohol spectrum disease

Answer 19

• developmental stages are adversely affected
• 3rd trimester most vulnerable, synaptogenesis, facial development

Question 20

What are gross changes in brain health + appearance

Answer 20

• modifies proteins, causes dysfunction
• affects glucose metabolism, protein synthesis, myeline formation -> all of which damage neurons + cause cell death