Lecture 14 - Pharmacology of alcohol Flashcards
What is alcohol
- oxygen and proton functional group
- EtOH is water soluble and crosses membranes
Where is ethanol absorbed?
small intestine
How does drinking on a full stomach affect absorption
- slows absorption and lowers peak BAC
How is BAC calculated
mg EtOH/100ml of blood
How is BAC different between larger and leaner people?
- larger people have lower BAC -> greater body volume
- leaner people have lower BAC -> greater water volume within body volume
What are gender differences with BAC absorption
females tend to be smaller and less lean -> higher BAC after one drink
What are acute effects of EtOH consumption
- 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
What is zero order kinetics
- linear elimination curve
- 0.015 BAC elimination/hour
- amount of alcohol exhaled is 1/2200 of BAC
What are acute effects of EtOH
- biphasic
- phases are caused by metabolism
- increased sociability, decreased anxiety especially in adolescent animals
What receptors does EtOH modulate?
- glutamate and GABA receptor
What does the interaction of EtOH with receptors do?
- tilts the balance of neuronal activation towards hyper-polarization = inhibition
What is the mechanism of EtOH action
- 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
What are GABAa receptors
- cys-loop ligand gated channel superfamily
- heteropentameric receptors
- conduct negative chloride currents into neurons
What are NMDA receptors
- ionotropic Glu receptor superfamily
- heterotetrameric receptors
- conduct positive currents into neurons -> depolarizing
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 are spins
- 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
What is the mechansism of metabolic tolerance
- 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
What is the metabolism of alcohol?
- 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
What is fetal alcohol spectrum disease
- developmental stages are adversely affected
- 3rd trimester most vulnerable, synaptogenesis, facial development
What are gross changes in brain health + appearance
- modifies proteins, causes dysfunction
- affects glucose metabolism, protein synthesis, myeline formation -> all of which damage neurons + cause cell death
