14. Alcohol Flashcards
1
Q
What is the worst country in the world in terms of the amount of alcohol consumed per capita?
A
Ireland
2
Q
What is ABV?
A
Alcohol by volume
3
Q
How do you calculate absolute amount?
A
%ABV x 0.78 = grams of alcohol/100ml
4
Q
How do you calculate units of alcohol?
A
[%ABV x actual volume (ml)] / 1000
5
Q
How much alcohol is there in 1 unit?
A
10ml or 8mg of absolute alcohol
6
Q
What considered the low risk level of alcohol for men and women?
A
14 units or less per week
7
Q
What does ‘low risk’ refer to when talking about alcohol?
A
Risk of alcohol-related problems in life
8
Q
What is binge drinking defined as?
A
Drinking >8 units in one sitting
9
Q
Which part of the population does the binge drinking category mainly relate to?
A
18% of 16-24 year olds on a weekly basis
10
Q
What does 0.01% blood alcohol mean?
A
10mg alcohol / 100ml blood
11
Q
What is the UK drink driving limit?
A
- 0.08%
- 80mg alcohol / 100ml blood
- Usually 1-2 drinks depending on weight
12
Q
Where is alcohol absorbed in the body?
A
- Stomach (20%)
* Intestines (80%)
13
Q
What is the speed of onset of alcohol proportional to in the stomach?
A
Gastric emptying
14
Q
How does drinking on a full stomach influence blood alcohol levels?
A
- Delayed gastric emptying
- Alcohol housed in the stomach
- Absorption is less effective here than in the intestines
- Therefore, longer onset and lower bioavailability
15
Q
How much alcohol is metabolised and where?
A
- 90% is metabolised, 10% doesn’t change
- Some excreted through lungs unchanged
- 85% of the 90% is metabolised in the liver (many ways)
- 15% of the 90% is mainly metabolised in the stomach to a certain degree (alcohol dehydrogenase)
- Females have 50% less stomach alcohol dehydrogenase
16
Q
Describe how the liver enzymes metabolise alcohol
A
- Alcohol => acetaldehyde [alcohol dehydrogenase (75%) and mixed function oxidase - CYP450 (25%)]
- This is a very toxic product - don’t want it building up
- Acetaldehyde => acetic acid [aldehyde dehydrogenase]
- Happens in the liver and stomach to produce an inert product
17
Q
How relevant is the solubility of alcohol in absorption?
A
- Alcohol is very water soluble so you would expect poor absorption
- However, it is really small and can easily diffuse across the lipid membrane through gaps
- Water/lipid solubility becomes irrelevan
18
Q
Outline the distribution of alcohol in men and women?
A
- Men generally have more body water than women
- Therefore, alcohol is more concentrated and has a more powerful effect in women
- Women also metabolise alcohol less effectively, so blood alcohol levels are higher
19
Q
What causes asian flush?
A
- Very common genetic polymorphism in the aldehyde dehydrogenase enzyme
- Ineffective metabolism of acetaldehyde
- Build up
- Toxicity (nausea)
20
Q
What is disulfiram and how does it work?
A
- Drug that blocks aldehyde dehydrogenase
- Used in alcohol aversion therapy
- Acetaldehyde builds up whenever they drink
- Puts them off drinking
21
Q
How potent is alcohol?
A
- Low pharmacological potency
- Very simple molecule
- Therefore, fits many targets but has a weak effect in them
- Consequence: have to drink a lot to have an effect - 200μg/ml (nicotine/cocaine are 20/200ng/ml)
22
Q
Can you identify a pharmacological target for alcohol?
A
Not really, it has many targets
23
Q
Describe the affinity and efficacy for the targets of alcohol
A
Not very good, weak for both
24
Q
What is the primary acute effect of alcohol on the CNS
A
- High dose - depressant
- Low dose - CNS excitation
- Also depends on personality and environment (higher excitation in social environment caused by disinhibition)
25
What are the 3 main CNS receptor targets of alcohol and how does it effect them?
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GABA receptors (inhibitory NT)
• Direct - increases function of the receptors
• Indirect - acts pre-synaptically, increasing allopregnenolone, which can bind to a GABA receptor
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NMDA receptors (memory and excitement)
• Decrease of receptor activation
• Binds to receptor - allosteric modulation
Calcium channels
• Interference with opening
• General NT release from neurones impacted
26
How can alcohol cause a euphoric effect?
* Alcohol binds to the opioid receptors in the CNS
* This switches off the GABA receptors
* Firing rate of dopaminergic neurones is increased
27
Which tissues are interfered with and impaired by alcohol?
* Corpus callosum - passes info from left brain (rule, logic) to right brain (impulse, feelings) and vice versa
* Hypothalamus - controls appetite, emotions, temp, pain
* Reticular activating system - consciousness
* Hippocampus - memory
* Cerebellum - movement and coordination
* Basal ganglia - perception of time
28
Why does alcohol cause redness?
• Increased acetaldehyde
• Interference with smooth muscle function in arterioles
- calcium entry impaired and prostaglandins promoted
• Cutaneous vasodilaiton
29
What acute effect can alcohol have on the heart?
* Alcohol depresses baroreceptors
* No stimulation of PNS, loss of inhibition of SNS
* Tachycardia caused
30
What acute effects does alcohol have in the endocrine system?
* Acetaldehyde inhibits vasopressin production
* Less aquaporins in collecting ducts
* Increased diuresis (polyuria)
* Increased ACTH
* Increased cortisol production
* Can produce 'Cushing's like' syndrome
* Negative effect on testosterone secretion
* Can have feminisation symptoms
31
How does alcohol have an effect on dementia?
* Chronic use
* Cortical atrophy
* Decreased volume of cerebral white matter
* Confusion (encephalopathy)
* Oculomotor symptoms
32
How does chronic use of alcohol affect gait?
* Ataxia
| * Cerebellar cortex degeneration
33
What is Wernicke-Korsakoff syndrome and it's relation to alcohol?
* Vision changes, ataxia, impaired memory
* Chronic alcohols get a lot of their calories from alcohol - bad diet
* Thiamine (B1) deficiency
* Important co-factor in ATP formation
* Impaired Kreb's cycle - oxidative stress in brain
* Mitochondrial injury and eventual apoptosis
34
What is affected in Wernicke's encephalopathy?
* Affects 3rd ventricle and aqueduct
* Some mitochondrial injury
* Apoptosis
35
What is affected in Korsakoff's psychosis?
* Progression from mitochondrial injury to cell apoptosis in the brain
* Irreversible
* Patient will probably die
* Particularly associated with the hippocampus - problems with memory
36
How does the chronic consumption of alcohol affect aerobic metabolism?
• Alcohol dehydrogenase causes the depletion of NAD+
• As a result:
- pyruvate starts getting converted to lactate
- acetyl CoA start getting converted to ketones
• Liver now exposed to acidosis and ketosis
• Ability of 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
37
How does an acute alcohol binge cause a fatty liver?
• Inability to sufficiently
metabolise fats and lipids
• Stored in the liver
• Glycerol and fatty acids are directed to the liver to produce triacylglycerols instead of the mitochondria and hepatocytes
38
How does chronic alcohol consumption cause hepatitis?
* Kreb's cycle permanently disrupted
* Generation of acidosis, ketosis and oxygen free radicals in the liver
* Creates a pro-inflammatory environment
* All promote WBC influx
* Increase in IL-6 and TNF alpha
* Reversible
39
How does chronic alcohol consumption cause cirrhosis?
* If an inflammatory profile remains, fibroblasts may begin to infiltrate the liver
* Increased connective tissue laid down in place of active liver tissue
* Reduce metabolic capacity
* At some point, there is so little active tissue that a transplant is required
40
What GIT problems can arise from chronic alcohol consumption?
• Exposure of stomach tissue to acetaldehyde
• Damage of gastric mucosa
- ulceration is common
- stomach cancer risk (carcinogenic effect)
41
What positive effect is there on the CVS of men who drink 2-4 units of alcohol a day?
Decrease in mortality from coronary artery disease
42
What positive effect can polyphenols in alcohol have on the CVS profile?
Positive
• Increased HDLs
• Increased tPA
• Decreased platelet aggregation
43
When do hangover symptoms tend to peak?
* As blood alcohol concentration reaches 0
| * Rebound excitation - depressant effect is lost and CNS becomes very active
44
```
What causes the following symptoms of a hangover:
• nausea
• headache
• fatigue
• restlessness and muscle tremors
• polyuria and polydipsia
```
* Nausea - alcohol is an irritant => vagus => vomiting centre
* Headache - vasodilation (pressure) and acetaldehyde
* Fatigue - sleep deprivation, rebound causing poor quality sleep
* Restlessness and muscle tremors - rebound
* Polyuria and polydipsia - lower ADH secretion
