Alcohol

Question 1

How many units should you drink in a week?

Answer 1

< 14 units/week

Question 2

What is binge drinking?

Answer 2

Drinking more than 8 units in one sitting

Question 3

Where is ethanol absorbed?

Answer 3

20% in stomach

80% in intestines

Question 4

What affects speed of onset of effects of ethanol?

Answer 4

Speed of onset of effects is proportional to SPEED OF GASTRIC EMPTYING

Question 5

Why does drinking on an full stomach decrease speed of onset of effects?

Answer 5

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

Question 6

The liver is good at metabolising ethanol, but what problem does the liver have when doing so?

Answer 6

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

Question 7

Where is ethanol metabolised?

Answer 7

Body metabolises 90% of ethanol dose
10% unmetabolised
85% of 90% to acetaldehyde in LIVER
15% to acetaldehyde in STOMACH

Question 8

How does the ethanol breath test work?

Answer 8

Body metabolises 90% of ethanol dose

10% unmetabolised - excreted via lungs and measured

Question 9

What enzymes are involved in metabolising ethanol?

Answer 9

In liver: to acetaldehyde

1. Alcohol dehydrogenase (75%)
2. Mixed function oxidase (25%)

In stomach: to acetaldehye
1. Alcohol dehydrogenase

Question 10

When is mixed function oxidase induced? Why is this relevant?

Answer 10

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

Question 11

Why must acetaldehyde also be cleared from the body?

Answer 11

Toxic metabolite of ethanol

Many of the negative consequences of drinking are due to acetaldehyde

Question 12

How is acetaldehyde metabolised?

Answer 12

To acetic acid

By aldehyde dehydrogenase

Question 13

How does disulfiram work?

Answer 13

Alcohol aversion therapy
Aldehyde dehydrogenase inhibitor
Inhibits acetaldhyde --> acetic acid
Acetaldehyde accumulates and you feel really bad
Less keen to drink again

Question 14

Why can women drink less than men?

Answer 14

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

Question 15

How does alcohol cause a response despite it’s very low pharmacological potency?

Answer 15

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

Question 16

Why can alcohol bind with several different receptors?

Answer 16

Ethanol is a very simple chemical

Question 17

Why does alcohol has very low pharmacological potency?

Answer 17

Low affinity and low efficacy for any target

Question 18

What kind of drug is alcohol?

Answer 18

Generally, a depressant - slows down cellular activity

But at low dose, CNS agitation may occur

Question 19

As you increase the dose of alcohol, on what do the effects depend?

Answer 19

1. Degree of CNS excitability
   a. Environment
   b. Personality

Social setting w/lots of sensory info, low dose –> CNS excitation (not depressant)
High dose = depressant

Question 20

What are the major targets of alcohol?

Answer 20

GABA receptors
NMDA receptors
Calcium channels

Question 21

How does alcohol affect GABA function?

Answer 21

Enhances it

Tf alcohol is a depressant

Question 22

What are the pre-synaptic and post-synaptic effects of alcohol?

Answer 22

1. Increases allopregnenolone production - allosteric modulator of Cl channels, facilitates channel opening, increases Cl influx = depressant
2. Decreases NMDA receptor function
3. Negative impact on Ca channels - decreases Ca influx, decreases NT exocytosis

None of the effects are very powerful

Question 23

Why is there confusion over how alcohol causing euphoria?

Answer 23

Enhances GABA - inhibits dopamine release
Switches off NMDA - stimulates dopamine release

Counter-intuitive in terms of causing euphoria

Question 24

What parts of the brain does alcohol affect?

Answer 24

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

Question 25

How does alcohol affect the CVS?

Answer 25

1. Vasodilation - flushing (acetaldehyde, reduced Ca entry, prostaglandins)
2. Tachycardia - decreases baroreceptor firing rate, reduced parasymp stimulation decreases HR, reduced inhibition of symp stimulation increases HR - overall increases HR

Question 26

How does alcohol affect the endocrine system?

Answer 26

Powerful diuretic
Acetaldehyde effect
Acts on neurohypophysis
Inhibits vasopressin release

Question 27

How does chronic alcohol use contribute to dementia?

Answer 27

Cortical atrophy - decreases volume of cerebral white matter

Question 28

What is Wernicke-Korsakoff syndrome?

Answer 28

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

Question 29

What is Wernicke’s encephalopathy?

Answer 29

Part of W-K syndrome
3rd ventricle and aqueduct
Some mitochondrial injury

Question 30

What is Korsakoff’s pschyosis?

Answer 30

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

Question 31

What are the chronic effects of alcohol on the liver?

Answer 31

1. 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
2. Increased NADH
   a. inhibits beta oxidation of lipids –> fat builds up in liver (reversible)
   b. interferes w/Krebs –> less ATP

Question 32

What are the beneficial effects of alcohol?

Answer 32

Chronic alcohol at safe levels is good for CVS

1. Increase in HDL
2. Decrease in platelet aggregation

Anti-atherogenic effects –> reduced mortality

Polyphenols in red wine?

Question 33

What are the chronic effects of alcohol on the GIT?

Answer 33

Very damaging, esp to stomach
Chronic drinking - toxic acetaldehyde builds up in stomach
Directly damages gastric mucosa –> ulcerations
May be carcinogenic in stomach

Question 34

What are the chronic effects of alcohol on the endocrine system?

Answer 34

Cushing’s type symptoms
Increases ACTH secretion
Reduces testosterone secretion

Question 35

What are the symptoms of a hangover?

Answer 35

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