14 - Ethanol Flashcards
What is the permeability of ethanol (EtOH)?
EtOH is water-soluble and crosses membranes
How does stomach acid alter EtOH?
Has no affect
EtOH is not altered by low pH
Drinking on a full stomach ______ absorption and _______ peak BAC
Drinking on a full stomach slows absorption and lowers peak BAC
Where does most ethanol absorption occur?
Small intestine.
Starts in the stomach but most absorption occurs in the SI
How is BAC measured?
BAC = mgEtOH/100mL of blood
Ethanol is distributed throughout _______
Tissues
Why do females tend to reach higher BAC?
They are smaller and less lean
___ order kinetics describe metabolism of EtOH, what does this mean?
0 order kinetics describe metabolism of EtOH, what does this mean?
- Linear elimination curve
- Regardless of dose, there is a linear relation curve
What are the two main enzymes for EtOH metabolism?
- Alcohol dehydrogenase
- Aldehyde dehydrogenase
Because alcohol dehydrogenase and aldehyde dehydrogenase ______ quickly and require ____ to operate, the max rate of metabolism is:
Because alcohol dehydrogenase and aldehyde dehydrogenase saturate quickly and require NAD+ to operate, the max rate of metabolism is: 8g/hr
= 0.015 BAC elimination/hour
Where is alcohol metabolized?
***** needs editing
Liver primarily
Oral mucosa (Breath AC)
Filtered in Kidney
Absorbed in GI tract
EtOH modulates _____ and _______ receptor activity in the brain
- Tilts the balance of neuronal activation towards:
EtOH modulates Glutamate (Glu) and GABA (gamma-aminobutyric acid) receptor activity in the brain
- Tilts the balance of neuronal activation towards: hyperpolarization = inhibition
Strong potentiation of _______ receptors at lower [EtOH]
Strong potentiation of GABAA receptors at lower [EtOH]
Inhibition of ________ receptors and ________ channels at higher [EtOH]
Inhibition of Glu-NMDA receptors and voltage-gated Ca2+ channels at higher [EtOH]
What is the overall effect of EtOH action on brain receptors?
neuronal inhibition, sedative-like effects
- Asphyxiation at lethal doses (0.4-0.5 BAC) via depressed activity in autonomic centres
To which superfamily of channels do GABAA receptors belong?
Cys-loop ligand-ligand channel superfamily
-
heteropentameric receptors
- 2 alpha subunits, 2 beta subunits and 1 other
- Conduct negative chloride current INTO neurons
GABAA receptors conduct _______ into neurons
GABAA receptors conduct Cl- into neurons
To which receptor superfamily do NMDA receptors belong?
Ionotropic Glu receptor superfamily
- Heterotetrameric receptors
- Contain 2NR1 subunits and either 2 NR2 or 2 NR3 subunits
- Conduct positive currents into neurons = depolarizing
- NMDA receptors belong to the ________ receptor superfamily.
- They are Heterotetrameric and contain 2 _______ and either 2 _______or 2 _______
- They conduct ________ into neurons
- NMDA receptors belong to the Ionotropic Glu receptor superfamily.
- They are Heterotetrameric and contain 2 NR1 and either 2 NR3 or 2 NR3
- They conduct Positive currents (Ca2+ / Na+) into neurons = depolarizing
Alcohol is addictive because it releases ____ in the brain
Alcohol is addictive because it releases dopamine in the brain
________ gives the sensation of warm skin but the core temperature is _______
Vasodilation gives the sensation of warm skin but the core temperature is decreased = Autonomic Brainstem nuclei
How can alcohol contribute to gastric ulcer formation?
Through the loss of mucosal lining
Why does alcohol give the “spins” and at what BAC would you get this effect?
- BAC ~0.04
- EtOH permeates endolymph and cupula
- BAC starts to decline
- EtOH diffuses out of the cupula before the endolymph
- Cupula is now denser than endolymph and does not stabilize when lying down
- activates sensory fibres
- Brain interprets this as motion
How is metabolic tolerance achieved?
Up-regulation of enzymes in heavy drinkers
What are some hangover symptoms? Physical and psychological?
When do these symptoms PEAK?
- Physical:
- headache
- diarrhea
- fatigue
- restlessness
- nausea
- Psychological
- haziness
- slower cognition
- impaired reaction times
- poor reasoning
- Symptoms peak as BAC reaches 0
What is the possible immune component involved in causing hangover?
Increased cytokine production via thromboxane pathway
What is a Congener?
Minor chemical constituent, especially one that gives a distinctive character to a wine or liquor or is responsible for some of its physiological effects
- substances that flavour and colour drinks
- More congeners = worse hangover
Heavy drinking can cause the brain to metabolize ________ instead of ______
Heavy drinking can cause the brain to metabolize acetate instead of glucose
what stage of fetal development is most vulnerable to fetal alcohol spectrum disease? What does FASD affect?
Third trimester
- synaptogenesis
- Facial development
How can EtOH change brain health?
- Metabolite of ethanol, acetaldehyde, is reactive
- Modifies proteins = causes dysfunction
- eg affects glucose metabolism, protein synthesis, myelin formation, all of which damage neurons and cause cell death
- Modifies proteins = causes dysfunction
What are four regions that are at an increased risk for cancer with EtOH use?
- Upper GI tract
- Colorectal
- Liver
- Breast
Why is the upper GI tract susceptible to cancer with high alcohol use?
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
How is acetaldehyde linked with cancer?
Acetaldehyde interferes with DNA synthesis and repair
