Alcohol

Question 1

Describe the epidemiology of alcohol usage

Answer 1

There is heavy alcohol use in Western Europe. The worst place in the world in terms of the amount of alcohol drunk per capita is Ireland.

Question 2

How is the absolute amount of alcohol (g) calculated?

Answer 2

% ABV x 0.78 = grams of alcohol/100ml (ABV = alcohol by volume)

Question 3

How are the units of alcohol calculated?

Answer 3

%ABV x actual volume (ml)/1000

Question 4

What is one unit of alcohol?

Answer 4

10ml or 8g of absolute alcohol

Question 5

What is the amount of alcohol that is safe to drink per week?

Answer 5

14 units or less per week for men and women

low risk means there is a low chance of having alcohol related problems in life

Question 6

What is binge drinking defined as?

Answer 6

drinking > 8 units in one sitting

Question 7

What is approximately the legal drinking limit?

Answer 7

1-2 drinks bu depends on weight as if you are heavier you can handle more alcohol

Question 8

What is the risk of drinking alcohol on driving?

Answer 8

More risk of having an accident even in low amounts

Question 9

How much alcohol is absorbed from the stomach and intestines?

Answer 9

S - 20%

I - 80%

Question 10

How does drinking on a full stomach affect its absorption?

Answer 10

• Alcohol is far more effectively absorbed from the small intestine
• Therefore, in order to absorb alcohol quickly, it needs to get into the intestine as quickly as possible
• The method for doing this is to drink on an empty stomach (fluid stimulates gastric emptying)
• Drinking on a full stomach delays gastric emptying (this houses the alcohol in the stomach, where it is far less effectively absorbed)

Question 11

How much alcohol is metabolised?

Answer 11

90% - the remaining 10% doesn’t change at all

Question 12

Where is some alcohol lost?

Where is the majority of alcohol metabolised?

Answer 12

• We excrete some of it through our lungs unchanged (e.g. breath test assesses amount of alcohol)
• Once alcohol is absorbed, the first place it goes to is the liver (85% of the 90% is metabolised here)

Question 13

What are the 2 main groups of enzymes that metabolise alcohol?

Answer 13

The liver metabolises alcohol in many ways, but there are 2 major groups of enzymes that predominate

• Alcohol dehydrogenase (75%)
• Mixed function oxidase (25%)

Question 14

How does alcohol tolerance come about?

Answer 14

• Tolerance to alcohol: comes about by upregulation of mixed function oxidase enzymes by the liver
• Hence, you need to drink more alcohol to get the same effect

Question 15

What happens when alcohol is taken in large amount in one go compared to if it is taken in smaller quantities many times?

Answer 15

• If you add a lot of alcohol in one go, the liver enzymes can metabolise a certain amount of it
• But if there is too much, lots of alcohol gets through the liver and into the blood
• The liver enzymes become saturated with alcohol
• Breaking it down into doses over several hours allows the liver to metabolise and recover
• Less alcohol gets into the systemic circulation

Question 16

Where does the remaining 15% of alcohol metabolism occur?

How does this differ in females?

Answer 16

• If 85% of total amount metabolism is via the liver, the other 15% is somewhere else
• This is predominantly the stomach (there is alcohol dehydrogenase in the stomach)
• As the alcohol is absorbed across the stomach, it is metabolised by stomach enzymes to a certain degree
• Females tend to have a lot less stomach alcohol dehydrogenase
• So in females, this arm of metabolism isn’t as effective

Question 17

Why does alcohol have a more powerful effect on women than on men?

Answer 17

• Alcohol is very water-soluble
• Men generally have more body water than women
• Blood alcohol levels in the woman are higher because they metabolise it less effectively (less alcohol dehydrogenase in the stomach)
• More alcohol gets across into the bloodstream
• Once in the blood, alcohol is less well diluted and distributed
• Hence more powerful effects in women

Question 18

What is the first step in alcohol metabolism and which enzymes doe this?

What is important to note about the metabolite produced?

Answer 18

Alcohol dehydrogenases and oxidases convert alcohol -> acetylaldehyde

Acetaldehyde is a very toxic, so we don’t want it building up in the blood

Question 19

What is the second step in alcohol metabolism?

Where does this occur and what does it produce?

Answer 19

An enzyme, aldehyde dehydrogenase, converts acetaldehyde -> acetic acid

• This reaction occurs both in the liver and the stomach to produce an inactive product

Question 20

What is a common polymrophism affecting alcohol metabolism, what does it result in and which people is it common in?

Answer 20

• In the aldehyde dehydrogenase enzyme
• Very common in Asian populations
• This polymorphism results in ineffective metabolism of acetaldehyde -> build up -> toxicity (nausea)

Question 21

What is the name of a drug that blocks aldehyde dehydrogenase?

What is its use?

Answer 21

Disulfiram

If this is given to alcoholics, whenever they drink alcohol, acetaldehyde builds up -> puts them off

Question 22

What is the pharmacological target of alcohol?

Answer 22

It has many targets as it is not very potent and is a simple molecule so can fit into many targets (hence you have to drink a lot to get an effect)

Question 23

What are the acute effects of alcohol on the CNS?

Answer 23

• Alcohol is primarily a depressant
• CNS agitation may occur (CNS excitation is only seen at a very low dose)
• CNS excitation also depends on your personality and the environment (social/non-social setting)

Question 24

How can alcohol interact with different receptors in the CNS?

Answer 24

• Alcohol can interact with GABA receptors (seems to have a positive effect on GABA receptors)
• Alcohol may directly affect the GABA receptor itself -> increase function
• There is evidence for alcohol acting pre-synaptically, to increase allopregnenolone (indirect effect)
• Allopregnenolone can bind to a GABA receptor to increase its effect
• Alcohol may decrease NMDA receptor activity
• Alcohol may interfere with calcium channel opening (-> impacts general NT release)

Question 25

Does alcohol cause euphoria? If so how?

Answer 25

- Alcohol behaves a bit like heroine when it comes to euphoria - Many people use versions of alcohol that are inhalable, which can cause euphoria - In this case, it binds to the opioid receptors in the CNS - Alcohol switches off the GABA receptor via the opioid receptor (as opposed to cannabinoid receptors in cannabis) - GABA is switched off -> increased firing rate of dopaminergic neurones

Question 26

What are the effects of alcohol in the brain?

Answer 26

Alcohol affects all these tissues hence interferes with these processes - Corpus Collosum: Passes info from left brain (rules, logic) to right brain (impulse, feelings) and vice versa - Hypothalamus: Controls appetite, emotions, temperature, and pain sensation - Reticular Activating System: Consciousness - Hippocampus: Memory - Cerebellum: Movement and coordination - Basal Ganglia: Perception of time

Question 27

What are the effects of alcohol on the blood vessels and why?

Answer 27

- Anyone who drinks enough alcohol might see a degree of redness (cutaneous vasodilation) - This is thought to be due to increased acetaldehyde - Acetaldehyde interferes with smooth muscle function in the arterioles - Calcium entry is impaired and prostaglandins are promoted -> vasodilation

Question 28

Why does alcohol cause tachycardia?

Answer 28

- Alcohol causes tachycardia (due to a depressant effect on the baroreceptors) - Baroreceptors, if firing well, enhance parasympathetic function and inhibit sympathetic function - Alcohol depresses baroreceptors -> no stimulation of PNS + loss of inhibition of SNS

Question 29

What effect does alcohol have on vaospressin, cortisol, testosterone and any other endocrine effects?

Answer 29

- Increased diuresis (polyuria) is related to increased acetaldehyde - Acetaldehyde inhibits vasopressin production -> less AQPs in the collecting ducts -> loss of fluid - Alcohol increases cortisol production (can produce ‘Cushing’s like’ syndrome as alcohol increases ACTH) - Alcohol has a negative effect on testosterone secretion (can have feminisation symptoms)

Question 30

How can alcohol severely affect the CNS?

Answer 30

Dementia – Cortical atrophy/decreased volume cerebral white matter Ataxia – Cerebellar cortex degeneration

Question 31

What is Wernicke's Korsakoff Syndrome? | What causes it and why?

Answer 31

Due to thiamine deficiency - seen in chronic alcoholics. Two seperate conditions that can occur together 1. Wernicke's encephalopathy (3rd ventricle & aqueduct, reversible reversible part) 2. Korsakoff’s psychosis (dorsomedial thalamus, irreversible part) - Thiamine deficiency is indirectly related to chronic alcohol use due to an alcoholic’s poor diet - You need carbohydrate to obtain thiamine – your neurones need thiamine to function - If you don’t have thiamine, you see acidosis and excessive glutamate production

Question 32

What happens to the liver due to NAD+ being used up?

Answer 32

- A consequence of alcohol binging is the depletion of NAD+ - If you drink too much alcohol, lots of NAD+ is used up - NAD+ is needed for many stages in aerobic metabolism - As a result, if you are chronically abusing alcohol: Pyruvate starts getting converted to lactate Acetyl CoA starts getting converted to ketones Your liver is now being exposed to lactic acid (acidosis) and ketones (ketosis). The ability of the liver to metabolise fats and lipids is impaired -> build up of fat in the liver. If the mixed function oxidase system is used a lot, free oxygen radicals begin to be released into the blood

Question 33

Why do alcoholics end up with fatty livers? | Is it reversible or not?

Answer 33

- Acutely, after going on an alcohol binge, one of the things seen is fatty liver - This is the acute presentation of liver problems related to alcohol - This is related to the inability to sufficiently metabolise fats and lipids - They just store in the liver.- This is reversible, and not particularly dangerous in isolation - Instead of glycerol and fatty acids being directed towards the mitochondria, they are directed to the liver to produce triacylglycerols

Question 34

Hepatitis of the liver (noninfective): what causes it, what is it and is it reversible?

Answer 34

- If alcohol is being abused long-term, the Krebs cycle is being permanently disrupted. - There is a permanent generation of acidosis, ketosis and oxygen free radicals in the liver - This creates a very pro-inflammatory environment - Hepatitis describes the changes associated with chronic alcohol use (increased ketones, lactic acid, free radicals) - These all promote WBC influx. In hepatitis, we see both blood and hepatic cytokine changes - We see an increase in IL-6 and TNF alpha - Hepatitis is still reversible

Question 35

Cirrhosis of the liver: what is it and is it dangerous and why?

Answer 35

- Long term, if the inflammatory profile of the liver remains, there can be some real problems - Fibroblasts may begin to infiltrate the liver - Fibroblasts increase the amount of connective tissue being laid down, in place of active liver tissue - The end form of alcohol-induced liver damage is where the inflammatory environment is so bad, that active liver tissue begins to be replaced (cirrhosis) - Decreased hepatocyte regeneration, increased fibroblasts and decreased active liver tissue - At some point, there is so little left of active liver tissue, that a liver transplant is required

Question 36

What are some GIT problems caused by chronic alcohol abuse?

Answer 36

- If you drink alcohol chronically, GIT problems may arise - Due to stomach alcohol dehydrogenase, chronic use of alcohol results in exposure of stomach tissue to acetaldehyde - Acetaldehyde can lead to damage to gastric mucosa - Ulceration is common in chronic alcoholics – strongly associated with acetaldehyde - Stomach cancer risk increases in alcoholics – carcinogenic effects

Question 37

What are some beneficial effects of alcohol use? | Why may this be?

Answer 37

- There is evidence that low levels of alcohol semi-regularly protects against CVS - E.g. a glass or red wine may have a protective effect against coronary artery disease - It may be that there are compounds in the alcohol, as opposed to the type of alcohol being drank - E.g. Polyphenols in alcohol may be beneficial - There is a positive CVS profile (increased HDLs, increased tPA levels, decreased platelet aggregation) - In men who drank 2-4 units a day there was a decrease in mortality from CAD

Question 38

When do hangover symptoms peak?

Answer 38

As blood alcohol concentration reaches 0

Question 39

What are some hangover symptoms? What causes them?

Answer 39

Nausea: Alcohol is an irritant -> Vagus -> Vomiting centre Headache: vasodilation Fatigue: 1. Sleep deprivation, 2. ‘Rebound’ Restlessness and muscle tremors: ‘Rebound’ Polyuria and polydipsia: ↓ ADH secretion

Question 40

What is the cure for a hangover?

Answer 40

Try to counter the rebound effect by going back to sleep. Sleeping yourself through the rebound effect will make you feel better.

Question 41

What is rebound effect?

Answer 41

- Rebound excitation occurs as blood alcohol levels decrease, - It means that certain physiological variables (e.g., sleep variables, such as the amount of REM sleep) change in the opposite direction to the changes induced by alcohol and even exceed normal levels once alcohol is eliminated from the body