14. Alcohol Flashcards
What is the worst country in the world in terms of the amount of alcohol consumed per capita?
Ireland
What is ABV?
Alcohol by volume
How do you calculate absolute amount?
%ABV x 0.78 = grams of alcohol/100ml
How do you calculate units of alcohol?
[%ABV x actual volume (ml)] / 1000
How much alcohol is there in 1 unit?
10ml or 8mg of absolute alcohol
What considered the low risk level of alcohol for men and women?
14 units or less per week
What does ‘low risk’ refer to when talking about alcohol?
Risk of alcohol-related problems in life
What is binge drinking defined as?
Drinking >8 units in one sitting
Which part of the population does the binge drinking category mainly relate to?
18% of 16-24 year olds on a weekly basis
What does 0.01% blood alcohol mean?
10mg alcohol / 100ml blood
What is the UK drink driving limit?
- 0.08%
- 80mg alcohol / 100ml blood
- Usually 1-2 drinks depending on weight
Where is alcohol absorbed in the body?
- Stomach (20%)
* Intestines (80%)
What is the speed of onset of alcohol proportional to in the stomach?
Gastric emptying
How does drinking on a full stomach influence blood alcohol levels?
- Delayed gastric emptying
- Alcohol housed in the stomach
- Absorption is less effective here than in the intestines
- Therefore, longer onset and lower bioavailability
How much alcohol is metabolised and where?
- 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
Describe how the liver enzymes metabolise alcohol
- 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
How relevant is the solubility of alcohol in absorption?
- 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
Outline the distribution of alcohol in men and women?
- 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
What causes asian flush?
- Very common genetic polymorphism in the aldehyde dehydrogenase enzyme
- Ineffective metabolism of acetaldehyde
- Build up
- Toxicity (nausea)
What is disulfiram and how does it work?
- Drug that blocks aldehyde dehydrogenase
- Used in alcohol aversion therapy
- Acetaldehyde builds up whenever they drink
- Puts them off drinking
How potent is alcohol?
- 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)
Can you identify a pharmacological target for alcohol?
Not really, it has many targets
Describe the affinity and efficacy for the targets of alcohol
Not very good, weak for both
What is the primary acute effect of alcohol on the CNS
- High dose - depressant
- Low dose - CNS excitation
- Also depends on personality and environment (higher excitation in social environment caused by disinhibition)
What are the 3 main CNS receptor targets of alcohol and how does it effect them?
GABA receptors (inhibitory NT) • Direct - increases function of the receptors • Indirect - acts pre-synaptically, increasing allopregnenolone, which can bind to a GABA receptor
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
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
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
Why does alcohol cause redness?
• Increased acetaldehyde
• Interference with smooth muscle function in arterioles
- calcium entry impaired and prostaglandins promoted
• Cutaneous vasodilaiton
What acute effect can alcohol have on the heart?
- Alcohol depresses baroreceptors
- No stimulation of PNS, loss of inhibition of SNS
- Tachycardia caused
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
How does alcohol have an effect on dementia?
- Chronic use
- Cortical atrophy
- Decreased volume of cerebral white matter
- Confusion (encephalopathy)
- Oculomotor symptoms
How does chronic use of alcohol affect gait?
- Ataxia
* Cerebellar cortex degeneration
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
What is affected in Wernicke’s encephalopathy?
- Affects 3rd ventricle and aqueduct
- Some mitochondrial injury
- Apoptosis
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
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
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
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
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
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)
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
What positive effect can polyphenols in alcohol have on the CVS profile?
Positive
• Increased HDLs
• Increased tPA
• Decreased platelet aggregation
When do hangover symptoms tend to peak?
- As blood alcohol concentration reaches 0
* Rebound excitation - depressant effect is lost and CNS becomes very active
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
