Alcohol Flashcards
How many units should you drink in a week?
< 14 units/week
What is binge drinking?
Drinking more than 8 units in one sitting
Where is ethanol absorbed?
20% in stomach
80% in intestines
What affects speed of onset of effects of ethanol?
Speed of onset of effects is proportional to SPEED OF GASTRIC EMPTYING
Why does drinking on an full stomach decrease speed of onset of effects?
On a full stomach, stomach is metabolising food so gastric emptying is reduced
Slower rate of absorption because alcohol is retained in stomach rather than going into SI where it’s absorbed more easily
The liver is good at metabolising ethanol, but what problem does the liver have when doing so?
Enzymes can be saturated
1 large dose saturates metabolic enzymes –> higher blood [ethanol]
4 smaller doses: enzymes metabolise 1/4 of dose at a time - allows time for liver to recover between doses
Where is ethanol metabolised?
Body metabolises 90% of ethanol dose
10% unmetabolised
85% of 90% to acetaldehyde in LIVER
15% to acetaldehyde in STOMACH
How does the ethanol breath test work?
Body metabolises 90% of ethanol dose
10% unmetabolised - excreted via lungs and measured
What enzymes are involved in metabolising ethanol?
In liver: to acetaldehyde
- Alcohol dehydrogenase (75%)
- Mixed function oxidase (25%)
In stomach: to acetaldehye
1. Alcohol dehydrogenase
When is mixed function oxidase induced? Why is this relevant?
Continual alcohol exposure
Alcohol tolerance - liver becomes more effective at metabolising alcohol tf can drink the same amount without feelings effects
Enzymes return to normal if you stop drinking
Why must acetaldehyde also be cleared from the body?
Toxic metabolite of ethanol
Many of the negative consequences of drinking are due to acetaldehyde
How is acetaldehyde metabolised?
To acetic acid
By aldehyde dehydrogenase
How does disulfiram work?
Alcohol aversion therapy Aldehyde dehydrogenase inhibitor Inhibits acetaldhyde --> acetic acid Acetaldehyde accumulates and you feel really bad Less keen to drink again
Why can women drink less than men?
Women are 50% water vs men 59% in terms of accessible fluid in body for alcohol to be dissolved in
AND men are usually larger, so more volume anyway
Women have less alcohol dehydrogenase in stomach
Less alcohol is metabolised
Alcohol is very water soluble, so the greater the volume of body water, the more dilute the alcohol will be in plasma
As plasma [alcohol] is lower in an vs woman, they are better able to tolerate alcohol
How does alcohol cause a response despite it’s very low pharmacological potency?
If you throw enough alcohol at a receptor, you’re still likely to get some response
Need a lot more alcohol vs other drugs to produce response though
Why can alcohol bind with several different receptors?
Ethanol is a very simple chemical
Why does alcohol has very low pharmacological potency?
Low affinity and low efficacy for any target
What kind of drug is alcohol?
Generally, a depressant - slows down cellular activity
But at low dose, CNS agitation may occur
As you increase the dose of alcohol, on what do the effects depend?
- Degree of CNS excitability
a. Environment
b. Personality
Social setting w/lots of sensory info, low dose –> CNS excitation (not depressant)
High dose = depressant
What are the major targets of alcohol?
GABA receptors
NMDA receptors
Calcium channels
How does alcohol affect GABA function?
Enhances it
Tf alcohol is a depressant
What are the pre-synaptic and post-synaptic effects of alcohol?
- Increases allopregnenolone production - allosteric modulator of Cl channels, facilitates channel opening, increases Cl influx = depressant
- Decreases NMDA receptor function
- Negative impact on Ca channels - decreases Ca influx, decreases NT exocytosis
None of the effects are very powerful
Why is there confusion over how alcohol causing euphoria?
Enhances GABA - inhibits dopamine release
Switches off NMDA - stimulates dopamine release
Counter-intuitive in terms of causing euphoria
What parts of the brain does alcohol affect?
Corpus callosum - passes info between L (rules, logic) + R (impulse, feelings)
Hypothalamus - appetite, emotions, temp, pain
Reticular activating system - consciousness
Hippocampus - memory
Cerebellum - mvmt + coordination
Basal ganglia - time perception
Cortical region - motor + sensory fn
How does alcohol affect the CVS?
- Vasodilation - flushing (acetaldehyde, reduced Ca entry, prostaglandins)
- Tachycardia - decreases baroreceptor firing rate, reduced parasymp stimulation decreases HR, reduced inhibition of symp stimulation increases HR - overall increases HR
How does alcohol affect the endocrine system?
Powerful diuretic
Acetaldehyde effect
Acts on neurohypophysis
Inhibits vasopressin release
How does chronic alcohol use contribute to dementia?
Cortical atrophy - decreases volume of cerebral white matter
What is Wernicke-Korsakoff syndrome?
Due to thiamine deficiency
Chronic alcoholics get most calories from alcohol –> bad diet –> thiamine deficient
ATP formation is very dependent on thiamine (important co-factor)
Impairs Krebs –> oxidate stress builds up in cell
Increased oxidative stress in parts of brain –> mitochondrial injury –> apoptosis
What is Wernicke’s encephalopathy?
Part of W-K syndrome
3rd ventricle and aqueduct
Some mitochondrial injury
What is Korsakoff’s pschyosis?
Part of W-K syndrome
Dorsomedial thalamus
Progressed from mitochondrial injury to apoptosis in brain
Irreversible and patient will probably die from this cellular injury
Associated w/hippocampus - memory problems
What are the chronic effects of alcohol on the liver?
- Depletion of NAD+ and increase in NADH - NAD+ needed for ethanol –> acetaldehyde by alcohol DH
a. Instead alcohol metabolised by CYP450 –> makes oxygen free radicals –> damage cell –> mitochondrial injury + inflamm changes –> hepatitis
b. Persistent inflammation –> fibroblasts recruited –> lay down CT –> cirrhosis - Increased NADH
a. inhibits beta oxidation of lipids –> fat builds up in liver (reversible)
b. interferes w/Krebs –> less ATP
What are the beneficial effects of alcohol?
Chronic alcohol at safe levels is good for CVS
- Increase in HDL
- Decrease in platelet aggregation
Anti-atherogenic effects –> reduced mortality
Polyphenols in red wine?
What are the chronic effects of alcohol on the GIT?
Very damaging, esp to stomach
Chronic drinking - toxic acetaldehyde builds up in stomach
Directly damages gastric mucosa –> ulcerations
May be carcinogenic in stomach
What are the chronic effects of alcohol on the endocrine system?
Cushing’s type symptoms
Increases ACTH secretion
Reduces testosterone secretion
What are the symptoms of a hangover?
Symptoms peak as BAC –> 0
Nausea: irritant –> vagus –> vomiting centre
Headache: vasodilation
Fatigue: 1. sleep deprivation, 2. rebound
Restlessness and muscle tremors: rebound
Polyuria, polydipsia: decreased ADH
Rebound = alcohol is depressant, so as conc –> 0, depressant effect is lost and CNS becomes v active - why you become sleep deprived
