Alcohol Flashcards
Why is it easier to understand dose of alcohol
Because its legal
Safe level of alcohol consumption?
<14 units/week
Where can Alcohol can be absorbed from ? % of absorption in each place?
Usually oral
- Alcohol can be absorbed from the stomach (20%) and the intestines (intestines designed for absorption) (80%)
How does drinking on a full stomach influence your blood alcohol level?
Much more alcohol is absorbed in the small intestine- if you drink on a full stomach, gastric emptying is delayed, and alcohol is less effectively absorbed
What % of alcohol is metabolised and where’s the rest of it
90% is metabolised- 10% doesn’t change at all, it’s just excreted, some of which is via the lungs and is what the breath test measures
Where is alcohol metabolised? What % where?
85% liver
15% GIT (stomach):
What enzymes metabolises alcohol
- Alcohol dehydrogenase (metabolises 75%) and mixed function oxidase (25%) convert alcohol into acetaldehyde (this is toxic)
What is the metabolite of alcohol
acetaldehyde
what order kinetics of metabolism is alcohol
Zero order
What does alcohol metabolism depend on
first pass hepatic metabolism and saturation of liver enzymes
What causes tolerance to alcohol
upregulation of mixed function oxidase enzymes
Difference between men and women re. alcohol dehydrogenase
Females have much less of this enzyme in their stomach compared to men
Where can you find alcohol dehydrogenase
Stomach and liver
Why can alcohol diffuse across lipid membranes
its tiny size, it can just squeeze through the gaps in the membrane.
- A man and a woman of similar height and weight share a bottle of wine. Explain why the blood alcohol levels in the woman are likely to be higher.
Because women metabolise it less effectively in stomach, they have 50% less alcohol dehydrogenase in the stomach wall than men so more alcohol enters the blood stream, and it is then less well diluted/distributed across body tissues (more concentrated so more potent effect)
- Acetaldehyde is broken down by….
aldehyde dehydrogenase
Acetaldehyde is broken down into …
inert acetic acid (acetate)
What is disulfiram
aldehyde dehydrogenase inhibitor
An aldehyde dehydrogenase inhibitor?
Disulfiram
use of aldehyde dehydrogenase inhibitor
alcohol aversion therapy
Use of disulfiram
Alcohol aversion therapy
Potency of alcohol?
Low
Low potency of alcohol means what regarding drug targets
has a weak effect on a lot of targets (low potency)
What makes the potency of alcohol low
- Weak affinity and low efficacy
Why are alcohol ACUTE EFFECTS DIFFICULT TO FIGURE OUT
CNS IS COMPLEX AND ETHANOL HAS LOW POTENCY + SELECTIVITY (because its so low in potency there is no specific target for alcohol)
Effect of alcohol on GABA
- Positive effect on GABA receptors:
Directly effects the GABA receptor post-synaptically, causing increase in function
Also evidence that it acts pre-synaptically to increase release of allopregnenolone which binds to GABA receptors to increase their effect
Effect of alcohol on NMDA receptors
- Decreases NMDA receptor activation- NMDA receptor = excitatory
Effect of alcohol on Ca channels
- Decreases Ca2+ channel opening and impacts neurotransmitter release in general
Euphoric effect of alcohol? Similar to what drug? What dose is needed
- At high dose can behave like heroine and morphine
- Binds to opioid receptor and switches off GABA inhibitory signal, increasing firing rate of dopaminergic neurones
Effect of alcohol on corpus callosum
Alcohol interferes with coordination of the sides of the brain
Effect of alcohol on HYPOTHALAMUS
Effects appetite, emotions etc.
Effect of alcohol on RETICULAR ACTIVATING SYSTEM
Alcohol impairs consciousness
Effect of alcohol on HIPPOCAMPUS
Alcohol impairs memory
Effect of alcohol on CEREBELLUM
Alcohol impairs coordination
Effect of alcohol on BASAL GANGLIA
Alcohol impairs time perception
Effect of alcohol on arterioles
Red face caused by increased acetaldehyde- interferes with smooth muscle function in the arterioles (vasodilation):
- Impaired calcium entry
- Increased prostaglandin release
Effect of alcohol on heart
Tachycardia, Due to depressant effect on baroreceptors- stops them from enhancing parasympathetic fucntion and inhibiting sympathetic function
Effect of alcohol on kidney
Diuresis Acetaldehyde inhibits production of ADH (vasopressin)- less aquaporins inserted into collecting duct- lose more fluid (polyuria)
How does alcohol cause dementia
Alcohol causes cortical atrophy and decreased volume of cerebral white matter, confusion (encephalopathy) and oculomotor symptoms
How does alcohol cause ataxia
Cerebellar cortex degeneration - gait
How does alcohol cause WERNICKE-KORSAKOFF SYNDROME
Due to thiamine deficiency- alcoholics have a very poor diet and carbohydrates are needed to get thiamine- without it you get acidosis, excessive glutamate production etc.- neurones don’t work
2 parts of WERNICKE-KORSAKOFF SYNDROME?
- WERNICKE’S ENCEPHALOPATHY
and
- KORSAKOFF’S PSYCHOSIS
Describe - WERNICKE’S ENCEPHALOPATHY
This part is reversible
3rd ventricle and aqueduct damaged
Ataxia, eye problems, confusion
Describe - - KORSAKOFF’S PSYCHOSIS
This is irreversible
Dorsomedial thalamus damaged
Memory problems from hippocampus damage
Confabulation, eventually death
What do you use to metabolise alcohol to acetaldehyde
NAD+
First things you see when someones been binge drinking? Why
After binging alcohol you lose ability to metabolise fats and lipids, a fatty liver containing lots of triacylglycerol is one of the first things you see when binge drinking alcohol.
this is because NAD+ is needed for glycolysis, making Acetyl-CoA, Krebs cycle etc.
How does binge drinking cause liver acidosis/ketosis
Lack of NAD+ causes pyruvate to be converted to lactate and Acetyl-CoA to be converted to ketones
Alcohol acute liver effect?
Fatty liver
Alcohol chronic liver effect? (2) cause?
Liver inflammation and hepatitis from leaked free oxygen radicals
Where do leaked free radicals come from
Mixed function oxidase system overuse
Longer chronic effect of alcohol on liver? (2)
FIBROBLAST INFILTRATION & CIRRHOSIS
When does liver damage become irreversible (2)
AFTER FIBROBLAST INFILTRATION & CIRRHOSIS
Beneficial effects of low chronic use of alcohol (4)
- Decreased mortality from coronary artery disease (men 2-4 units/day)
- Increased HDLs
- Increased tPA levels and decreased platelet aggregation
- Are polyphenols protective (found in red wine)?
ALCOHOL CHRONIC EFFECTS- GIT: (2)
- Damage to gastric mucosa due to toxic acetaldehyde (can lead to ulceration etc.)
- Carcinogenic effect
ALCOHOL - CHRONIC EFFECTS- ENDOCRINE (2)
- Increased ACTH secretion (and cortisol production)
- Decreased testosterone production
Hangover headache caused by…
Vasodilation
Hangover nausea caused by…
Irritant, vagus, vomiting centre
