Alcohol

Question 1

What equation is used to determine the absolute amount of alcohol/number of grams of alcohol per 100 ml?

Answer 1

ABV% x 0.78 = g/100 mL

ABV = alcohol by volume

Question 2

What equation is used to calculate the number of units in a given volume of alcohol?

Answer 2

ABV% x volume (ml)/1000

Question 3

What is the recommended weekly allowance (low risk) of alcohol for men and women?

Answer 3

<14 units

Question 4

What is the legal driving limit for blood alcohol content?

Answer 4

80 mg/100 ml

Question 5

Where is alcohol absorbed in the GI tract, and in what proportions?

What determines the speed of onset of the effects of alcohol?

Answer 5

20% - stomach
80% - small intestine

The speed of onset of the effects of alcohol is proportional to the rate of gastric emptying

Question 6

What proportion of alcohol is metabolised?

Out of the alcohol that is metabolised, what proportion is metabolised in the liver? Where does the rest of the metabolism take place?

Answer 6

90% (the remaining 10% is excreted unmetabolised)

85% - Liver
15% - Stomach

Question 7

State two enzymes in the liver that are involved in metabolising alcohol. State alcohol is converted to.

Answer 7

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

These both convert alcohol to acetaldehyde

Question 8

What is an important feature of mixed function oxidase?

Answer 8

It can be induced if you constantly expose yourself to alcohol – it is the reason for alcohol tolerance

Question 9

Why would one large dose of alcohol give a higher plasma ethanol concentration than several small doses?

Answer 9

The liver enzymes that are responsible for metabolising alcohol are saturable
Giving a large dose at once is more likely to saturate the enzymes => more unmetabolised alcohol avoiding first pass metabolism and entering systemic circulation

Question 10

Describe the metabolism of alcohol in the stomach. How does this differ in women compared to men?

Answer 10

The stomach contains alcohol dehydrogenase, which is responsible for15% of alcohol metabolism
Women have 50% less alcohol dehydrogenase in their stomachs than men

Question 11

State one other reason why women, in general, can’t tolerate alcohol as well as men?

Answer 11

Women have a body water composition of about 50%
Men have a body water composition of about 59-60% so a given amount of alcohol will be more dilute in a man compared to a woman

Question 12

Describe the metabolism of acetaldehyde.

Answer 12

Acetaldehyde is toxic and must be metabolised further

It is metabolised by aldehyde dehydrogenase to produce acetic acid

Question 13

Name a drug that is used as an alcohol aversion therapy. Explain why it is used for this purpose.

Answer 13

Disulfiram – it is an aldehyde dehydrogenase inhibitor so it promotes the build up of acetaldehyde, which is responsible for most of the negative feelings associated with drinking

Question 14

Why do some people (particularly Asians) tend to tolerate alcohol badly?

Answer 14

Common genetic polymorphism in the aldehyde dehydrogenase gene meaning that some people (particularly Asians) can’t convert acetaldehyde to acetic acid as efficiently so acetaldehyde builds up and makes them feel bad

Question 15

Describe the pharmacological potency of alcohol.

Answer 15

Low pharmacological potency (so need a relatively higher dose)

Question 16

What are the three major CNS targets of alcohol and what effects does alcohol have on these targets?

Answer 16

1. GABA – alcohol increases pre- and post-synaptic allopregnenolone production (which facilitates the opening of chloride channels) – thus enhancing GABA action
2. NMDA – alcohol decreases NMDA receptor function
3. Ca2+ channels – alcohol reduces Ca2+ channel function => less calcium influx, which negatively affects neurotransmitter exocytosis

Question 17

How does alcohol cause euphoria?

Answer 17

Inhibition of the GABA inhibitory control of dopaminergic neuronal firing (via binding to the opiate receptor)

Question 18

Name a few specific parts of the brain that are affected by alcohol and state how they are responsible for features of alcohol intoxication.

Answer 18

Hypothalamus – controls appetite, emotions, temperature
Reticular activating system – impairs consciousness
Hippocampus – amnestic effects
Cerebellum – movement and coordination
Basal ganglia – perception of time

Question 19

Describe and explain the effects of alcohol on cutaneous vasculature.

Answer 19

Alcohol causes vasodilation (this is thought to be due to acetaldehyde)
It causes decrease calcium influx and increased prostaglandins => vasodilation

Question 20

Describe and explain the effects of alcohol of alcohol on heart rate.

Answer 20

Alcohol decreases the sensitivity of baroreceptors
This means decreased baroreceptor firing –> decreased parasympathetic firing + decreased inhibition of sympathetic firing => INCREASED HEART RATE

Question 21

Describe the acute effects of alcohol on the endocrine system.

Answer 21

Alcohol inhibits vasopressin release from the neurohypophysis (via acetaldehyde?)
This means that alcohol is a powerful diuretic

Question 22

State an important syndrome that is caused by chronic alcohol use. What is it characterised by?

Answer 22

Wernicke-Korsakoff Syndrome - due to thiamine (vit B1) deficiency
Wernicke’s encephalopathy – (hypothalamus/thalamus)
Korsakoff’s psychosis – (deep brain; irreversibe neuronal cell death e.g. hippocampus)

Question 23

Describe and explain how chronic alcoholism can cause this syndrome.

Answer 23

Chronic alcoholics tend to have a bad diet (=> thiamine deficiency)
Thiamine is an important cofactor in the generation of ATP within cells
The lack of thiamine impairs the Krebs’ cycle and pentose phosphate shunt, leads to the build up of oxidative stress within the cells
The oxidative stress can cause mitochondrial damage and apoptosis, especially in brain regions with high metabolic demand

Question 24

How can chronic alcohol abuse lead to dementia?

How can chronic alcohol abuse lead to ataxia?

Answer 24

Chronic alcohol causes cortical atrophy and a loss of cerebral white matter

Chronic alcohol can cause cerebellar cortex degeneration

Question 25

What are the chronic effects of alcohol on the liver?

Answer 25

Alcohol metabolism in the liver uses up NAD+ so it depletes the liver’s NAD+ stores and increases NADH
This inhibits beta-oxidation of lipids in the liver so you get an accumulation of fat in the liver
It also interferes with the Krebs’ cycle because, without NAD+, glucose can’t be converted to pyruvate, and pyruvate can’t be converted to Acetyl CoA
Pyruvate is converted to lactate
Acetyl CoA is converted to ketone bodies

Question 26

How can chronic alcohol abuse cause hepatitis?

Answer 26

Chronic use of cytochrome P450 enzymes in metabolising alcohol can generate oxygen free radicals, which can cause mitochondrial injury and inflammatory changes (increased IL-6, TNF-alpha)

Question 27

How can chronic alcohol abuse cause cirrhosis?

Answer 27

If the inflammation persists, fibroblasts could be recruited, which lay down connective tissue and cause cirrhosis

• deceased hepatocyte regeneration
• decreased active liver tissue

Question 28

What are the potentially beneficial effects of chronic alcohol use at moderate levels?

Answer 28

Decreased mortality from coronary artery disease
Increase HDL
Increase tPA/decreased platelet aggregation
NOTE: it is thought that polyphenols are responsible for these effects

Question 29

Describe the chronic effects of alcohol on the GI tract.

Answer 29

The acetaldehyde can directly damage the gastric mucosa leading to ulceration
There is some evidence that alcohol can be carcinogenic in the stomach

Question 30

Describe the chronic effects of alcohol on the endocrine system.

Answer 30

Alcohol can increase ACTH secretion (causes Cushing’s type appearance)

Decreases testosterone

Question 31

Why do you get the following symptoms when hungover:

a. Nausea
b. Headache
c. Restlessness and muscle tremors
d. Polyuria and polydipsia

Answer 31

a. Nausea
Gastric irritation --> vagus --> vomiting centre
b. Headache
Vasodilation
c. Restlessness and muscle tremors
Rebound increase in CNS activity once the alcohol (depressant) wears off
d. Polyuria and polydipsia
Inhibition of ADH secretion

Cure - sleep, drink water?