Alcohol Flashcards
How to work out grams of alcohol in a drink
%ABV *0.78 = grams of alcohol per 100ml
Or for unit (%ABV *volume)/1000
What is low risk and what is binging
Low is less than 14 units
Binge drinking is 8 units or more in one sitting
18% of 18-24 year olds per year
How much alcohol in the blood if blood alcohol concentration is 0.01%
10mg/100ml blood
Where is alcohol absorbed
ORAL
20% stomach
80% small intestine
What is the speed of onset of alcohol related to
Gastric emptying…. so drinking on a full stomach will make blood alcohol level increase more slowly…..
Stomach keeps hold of food and churns so alcohol will stay there if you’ve eaten (where it is absorbed very slowly)…. if you drink on full stomach then gastric emptying is slower, and alcohol passes into the small intestine more slowly….
If on an empty stomach, passes the straight through the to the intestine, where it is absorbed much better
What proportion of alcohol is metabolised, and where does this metabolism occur
90% metabolised, but the rest is excreted as pure alcohol, unmetabolised (the breath test is based on the pure alcohol… so alcohol excreted off the lungs is unmetabolised)
85% of the 90% that is metabolised is metabolised in the liver (other 15% is metabolised in the GIT)
Which enzymes metabolise the alcohol
Alcohol dehydrogenase (75%) and mixed function oxidase (i.e. the cytochrome p450 system) (25%)
Note alcohol dehydrogenase presnet in the liver and the stomach, and mixed function oxidase only in the liver
What is the product of alcohol metabolism
Acetaldehyde… which has many toxic side effects
Why can alcohol be tolerated through time
Upregulation of the mixed function cytochrome oxidase system
It will stop being upregulated if you stop drinking
What will effect blood ethanol levels when drinking alcohol
Speed of drinking….
If you administer all at once it will saturate the liver ezyme system
If you administer a bit at a time if won’t saturate the liver and your blood alcohol concentration reaches a lower peak blood concentration … this allows your enzymes to recover
Why does alcohol diffuse across memenrame despife being really hydrophilic
Cos it’s tiny.. hydrophilic but this is irrelevant cos it’s so small (opposite of cannabis)
What else can break down alcohol
The stomach wall also has alcohol dehydrogenase (this makes up 15%)
Differentiate metabolism of alcohol in male and female
Females have a 50% lower concentration of alcohol dehydrogenase enzyme IN THE STOMACH WALL compared to men
How is the alcohol diluted more in female than males
Because they have more body fat and less body water compared to man and alcohol is really water soluble
Man has higher body water than woman (59% in male, 50% in female)
So the alcohol is well distributed and more dilute in males
Outline why women have high blood concentration than men end on the same dose
Less alcohol dehydrogenase in stomach wall
And less body water in the female so less water to dilute the alcohol.. more concentrated in the female
How is acetaldehyde brokendownn and where
Aldehyde dehydrogenase in stomach wall and liver (NOTE DIFFERENT TO ALCOHOL DEHYDROGENASE)
breaks acetaldehyde down to acetic acid
alcohol dehydrogenase (ADH) = CYTOSOLIC aldehyde dehydrogenase (ALDH2) = MITOCHONDRIAL.
Both enzymes use NAD+ as a cofactor, producing a reducing equivalent NADH in both steps
Npte that this is an oxidation reaction –> ALCOHOL DEHYDROGENASE= ZERO ORDER KINETICS
Why is there differences in effects of acetaldehyde between race
Asian have genetic polymorphism of acetaldehyde dehydrogenase…. Higher blood concentration of acetaldehyde which has all the toxic effects so drinking is lower in this population
Why can disulfiram be used as alcohol aversion
Aldehyde dehydrogenase inhibitor….. so you get build up of acetaldehyde…. and the negative effects associated with it
tries to put alcoholic off of drinking
(it’s like it turns alcoholics Asian)
What is the potency of alcohol and why
Low potency… such a simple molecule no specific targets
So much higher levels needed than other drugs
Outline the affinity and efficacy of alcohol
Poor affinity and poor efficacy for lots of receptors.
Acts on lots of receptors
What does the effect of alcohol depend on
CNS excitability…. environment (social settings etc.) and personality
What is the drug class of alcohol and what does it cause
Depressant, and causes CNS agitation (well, more disinhibition)
What does receptors can alcohol act on
GABA- DIRECTLY stimulates GABA receptor to increase Cl- entry, and also INDIRECTLY increases release of allopregnenolone pre-synaptically which also acts on GABA receptors to increase Cl- on the post synaptic membrane (INCREASES GABA mediated inhibition)
NMDA- it REDUCES activation of this glutamate receptor and ion channel protein by inducing ALLOSTERIC CHANGE
Ca2+ channel opening- it REDUCES Ca2+ to prevent influx of calcium and the exocytosis of neurotransmitter than follows
Why is it difficult to determine the acute effects of alcohol on the CNS,
- CNS is functionally complex
- Ethanol has low potency and low selectivity- so it’s working on so many receptors it’s hard to determine which receptor is causing the effect
How might alcohol work to induce euphoria as an acute CNS effect
It might act on opioid receptor (like heroin!)
to reduce the GABA neurones which inhibit the dopaminergic neurons which have cell bodies in the VTA
SO INCREASED DOPAMINE RELEASE
Alcohol has effects on all the following systems, explain how these could explain the effect of alcohol
Corpus callosum
Hypothalamus
Reticular activating system
Hippocampus
Cerebellum
Basal ganglia
Corpus Collosum - Passes info from the left brain (rules, logic)
to the 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
What is the effect of alcohol on the CVS
- CUTANEOUS VASODILATION
2. Increased heart rate
Why might asian flush occur
Because asians have genetic polymorphism and break down acetaldehyde much more poorly, you get more cutaneous vasodilation
Why does alcohol cause cutaneous vasodilation
ACETALDEHYDE
• Calcium entry into pre-capillary sphincters is impaired and prostaglandins are promoted –> VASODILATION
Kind of explains asian flush (asians have less aldehyde dehydrogenase so the increased acetaldehyde causes fliushing)
Why does alcohol cause tachycardia
Depresses the baroreceptors
This means that reduced firing rate leads to reduced PNS and reduced inhibition of SNS
So you actually get sympathetic effect to the heart
‘Centrally mediated decrease in baroreceptor sensitivity leads to an acute increase in heart rate and chronic alcohol may be associated with an increased blood pressure’
What are the acute effects of alcohol on the endocrine system
- Acetaldehyde suppresses ADH (negative effect on post pit)
What are the chronic effects of alcohol
Brain and liver
What is the chronic effect of alcohol on CNS
LOSS OF THIAMINE
Important for metabolism (it’s a co factor for many enzymes in energy metabolism)… so affects brain regions with high metabolic demands the most
Impaired metabolism (due to the lack of thiamine cofactor) –> excitotoxicity
In addition there is poorly functioning mitochondria –> ROS–> apoptosis –> cell death
Thiamine acts as an essential coenzyme to the TCA cycle and the pentose phosphate shunt
So brain regions with high metabolic demands cannot have access to the energy they need
What is thiamine intake related to. Why might it be reduced in alcoholics
thiamine requirement for healthy individuals is related to their carbohydrate intake and is between 1–2mg per day: this requirement increases with alcohol misuse.
Why do alcoholics not become immdiateyl thiamien deficient
The body can only store between 30–50 mg of thiamine, thus body stores of individuals on a thiamine deficient diet are likely to be depleted in four-to-six weeks.
Outline 2 CNS diseases relating to alcohol misuse
Wernicke’s encephalopathy (WE)… reversible. Overwhelming metabolic demands to brain cells deficint in thiamine… cellular energy deficit, acodisis, increase in glutamate (i.e excitotoxicity) and cell death.
TRIAD: ophthalmoplegia, ataxia, and confusion
Injury caused by thiamine deficiency:
- oxidative damage,
- mitochondrial injury leading to apoptosis, and
- directly stimulating a pro-apoptotic pathway.
Korsakoffs psychosis is associated with polyneuritis, and is characterized by an impaired ability to acquire new information and by a substantial, but irregular memory loss for which the patient often attempts to compensate through confabulation. Irreversible – neuronal cell death.
What brain areas do wernicke’s encephalopathy and korsakoff’s psychosis affect
Wernicke’s encephalopathy – (hypothalamus/thalamus and brainstem, causing ophthalmoplegia due to cranial nerve problems )
Korsakoff’s psychosis – (deep brain e.g. hippocampus)
What does aldehyde dehydrogenase break acetaldehyde down into
In the liver, alcohol is primarily metabolized by cytosolic alcohol dehydrogenase (ADH) to acetaldehyde, which is further metabolized to acetate by mitochondrial aldehyde dehydrogenase (ALDH2).
Which two problems are associated with chronic alcohol use in the CNS
Dementia – Cortical atrophy/reduced volume cerebral white matter confusion (encephalopathy),
oculomotor symptoms
Ataxia – Cerebellar cortex degeneration - gait
These are associated with wernicke’s encephalopathy
Memory deficit is associated with the Korsakoff’s
What is the effect of alcohol in the liver, including why there can be acidosis
If lots of alcohol needs to be metabolised, NAD+ is used up (to oxidise the alcohol… in both alcohol dehydr. and aldehyde dehydr.)
If NAD+ is lacking, disruption of many dehydrogenase-related reactions in the cytoplasm and mitochondria [i.e. the tricarboxylic acid cycle (TCA) and β-oxidation of fatty acids], thereby suppressing energy supply and fatty acid oxidation, which in turn results in alcoholic fatty liver
With alcohol using up NAD+, then pyruvate must be converted to lactate to generate NAD+ for glycolysis, and pyruvate itself cannot be used in TCA because this needs NAD+.
Acetyl coA unable to enter TCA are transformed to ketones.
What happens after an alcohol binge
NAD+ depletion, so TAG builds up in fat droplets within the liver. Not broken down by liver mitochondrial enzymes.
Glycerol and fatty acids do not get broken down by hepatocyte mitochondria, it is stored as TAG
What is the effect of chronic alcohol use on the liver
Differentiate hepatitis and cirrhosis
- Hepatitis (reversible):
- reduced NAD+ leads to deranged metabolic processes whcih leak ROS cause tissue damage and inflammation (IL6 and TNFa)
- acetaldehyde too causes inflammation - Cirrhosis (irreversible) inflammatory response –> fibroblasts.
Fibroblasts then lay down connective tissue due to reduced hepatocyte regeneration, reducing the active liver tissue
What are the beneficial effects of chronic alcohol
Reduced mortality from coronary heart disease (in men 2-4/day)- particularly with polyphenol (which is high in wine- so is it just other things in the wine?)
Increased HDL
and increased tPA levels/reduced platelet aggregation
What is the effect of chronic alcohol use on GIT
Acetaldehyde can lead to damage to gastric mucosa (which is proportional to dose).
Due to stomach alcohol dehydrogenase, chronic use of alcohol results in exposure of stomach tissue to acetaldehyde.
- Ulceration is common in chronic alcoholics – strongly associated with acetaldehyde
- Stomach cancer risk increases in alcoholics – carcinogenic effects
Chronic alcohol effects on endocrine
Increased ACTH secretion (cushings like)
Decreased testosterone secretion (feminisation)
What causes the hangover
Nausea Irritant Vagus Vomiting center
Headache Vasodilation
Fatigue 1. Sleep deprivation, 2. ‘Rebound’
Restlessness and muscle tremors ‘Rebound’
Polyuria and polydipsia ↓ ADH secretion
When does alcohol provide CNS excitation
Only at a very low dose, after this provides CNS agitation
