Alcohol

Question 1

What is absolute amount?

Answer 1

% ABV x 0.78 = grams of alcohol/100ml

*ABV = alcohol by volume

Question 2

What are units?

Answer 2

%ABV x actual volume (ml)/1000

1 unit = 10ml or 8g of absolute alcohol

Question 3

What is a safe level of alcohol?

Answer 3

low risk for men and women is consuming 14 units OR LESS per week

• Binge drinking (dangerous alcohol use) is defined as drinking > 8 units in one sitting

Question 4

How do you calculate blood alcohol level?

Answer 4

0.01% = 10mg/100ml blood

Question 5

How can alcohol be absorbed?

Answer 5

from the stomach (20%) and intestines (80%)

Question 6

How does drinking on a full stomach affect blood alcohol levels?

Answer 6

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 7

How is alcohol metabolised?

Answer 7

90% of total alcohol dose is metabolised

The 10% of alcohol that isn’t metabolised doesn’t change at all - 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)

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

• ALCOHOL DEHYDROGENASE (75%)
• MIXED FUNCTION OXIDASE (25%)

1. enzymes convert ALCOHOL -> ACETALDEHYDE (VERY TOXIC PRODUCT)
2. An enzyme (ALDEHYDE DEHYDROGENASE) converts acetaldehyde -> ACETIC ACID (inert)

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

Question 8

How do you build up tolerance to alcohol?

Answer 8

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 9

How does timings of doses affect the effects of alcohol?

Answer 9

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 10

How does body water differences in men and women affect distribution of alcohol?

Answer 10

Alcohol is very water-soluble. Men generally have more body water than women (around 60% c.f. 50%) -the alcohol will be diluted more effectively in the man.
Therefore, it is more concentrated in the woman than in the man. It will have a more powerful effect in women.

Question 11

What does a common genetic polymorphism in aldehyde dehyrogenase cause?

Answer 11

very common in Asian populations (Asian flush)

results in ineffective metabolism of acetaldehyde -> BUILD UP -> toxicity (nausea)

Question 12

What is disulfiram?

Answer 12

a drug that BLOCKS aldehyde dehydrogenase – it is used in alcohol aversion therapy

If this is given to alcoholics, whenever they drink alcohol, acetaldehyde builds up -> PUTS THEM OFF

Question 13

Describe the pharmacological potency of alcohol

Answer 13

low
very simple molecule so fits in many targets but will have a weak effect in them -> you have to drink quite a lot to get an effects

• Nicotine: 20ng/ml
• cocaine: 200ng/ml
• alcohol: 200μg/ml

Question 14

What are the acute effects of alcohol on the CNS?

Answer 14

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))

Alcohol can interact with GABA receptors (generally seems to have a positive effect on GABA receptors) - increase function (direct effect)

There is evidence for alcohol acting pre-synaptically, to increase allopregnenolone (indirect effect) - can bind to a GABA receptor to increase its effect

Alcohol may DECREASE NMDA RECEPTOR ACTIVATION (binds to receptor – allosteric modulation)

Alcohol may interfere with CALCIUM CHANNEL OPENING (-> impacts general NT release)

Question 15

How does alcohol cause euphoria?

Answer 15

Alcohol behaves a bit like heroine when it comes to euphoria.

Many people use versions of alcohol that are inhalable, which can cause euphoria - 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 16

What tissues in the brain does alcohol interfere with?

What functions are impaired?

Answer 16

• 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 17

What are the acute effects of alcohol in the CVS?

Answer 17

Anyone who drinks enough alcohol might see a degree of redness (CUTANEOUS VASODILATION)

• 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

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 18

What are the acute effects of alcohol in the endocrine system?

Answer 18

believed that 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) – alcohol increases ACTH

Alcohol has a negative effect on testosterone secretion (can have feminisation symptoms)

Question 19

What are the chronic effects of alcohol on the CNS?

Answer 19

• 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

brain regions with high metabolic demand - impaired metabolism, NMDA excitotoxicity, ROS

• Dementia – Cortical atrophy/decreased volume cerebral white matter - confusion (encephalopathy), oculomotor symptoms
• Ataxia – Cerebellar cortex degeneration - gait

Wernicke-Korsakoff syndrome (due to thiamine deficiency) – SEEN IN CHRONIC ALCOHOLICS

• Wernicke’s encephalopathy – (3rd ventricle & aqueduct) – reversible part
• Korsakoff’s psychosis – (dorsomedial thalamus) – irreversible part

Question 20

What are the chronic effects of alcohol in the liver?

Answer 20

A consequence of alcohol dehydrogenase 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.

fatty liver -> hepatitis ( inflammation) -> cirrhosis

Question 21

What would you see in the liver acutely after going on an alcohol binge?

Answer 21

FATTY LIVER - inability to sufficiently metabolise fats and lipids

Instead of glycerol and fatty acids being directed towards the mitochondria and hepatocytes, they are directed to the liver to produce triacylglycerol

*This is reversible, and not particularly dangerous in isolation.

Question 22

What is hepatitis?

Answer 22

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.

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 is still reversible.

Question 23

How does chronic alcohol abuse cause cirrhosis?

Answer 23

Long term, if the inflammatory profile remains (hepatitis) 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 24

What are the effects of alcohol in the gut?

Answer 24

chronic alcohol drinking -> GIT problems

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 (which is proportional to dose).

• Ulceration is common in chronic alcoholics – strongly associated with acetaldehyde
• Stomach cancer risk increases in alcoholics – carcinogenic effects

Question 25

What are some beneficial effects of alcohol?

Answer 25

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)

Question 26

What causes the symptoms of a hangover?

Answer 26

Hangover symptoms tend to PEAK as blood alcohol concentration reaches 0 -> rebound excitation

• 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

THE CURE FOR A HANGOVER: Try to counter the rebound effect by going back to sleep. Sleeping yourself through the rebound effect will make you feel better.