15: Drugs of Abuse: Alcohol Flashcards
What is one unit of Alcohol?
1 unit = 10ml or 8g of absolute alcohol
How would you calculate one unit of alcohol?
(%Alcohol x V(ml))1000
What is currently considered the “safe level” of alcohol consumption per week?
What is binge drinking?
Men & Women; = 14 units/week LOW RISK
Binge drinking i.e. > 8 units in one sitting)
What is the ROA of Alcohol?
Oral
Explain the effects of a full/ empty stomach on the pharmacokinetics of Alcohol
- 20% of alcohol is absorbed in the stomach
- 80% in the small intestine
With full stomach: gastric emptiing is slow –> slower absorbtion on the stomach and small intestine
How much of the total alcohol in the body gets metabolised?
What happens to the rest?
90% gets metabolised in body, 10% gets directly excreted
Where does phase 1 of Metabolism of Alcohol happen?
85% in the liver
15% directly in GI tract
Explain Step 1 in Alcohol metabolism
In the liver (85%)
- Alcohol dehydrogenase (75%)
- Mixed function oxidases (25%)
In the GI tract (15%)
- Alcoholdehydrogenase
Into: Acetaldehyde
Why do women have a lower alcohol tolerance than men?
Mainly 2 reasons
- less Alcoholdehydrogenase (in GI tract)
- Less total body water –> same amount is more concentrated in women
Explaint Step 2 in the Metabolism of Alcohol
Acetaldehyde – Aldehydedehydrogenase –> Acetic Acid
Name a drug that can be used in alcohol conversion therapy
Explain why it might work
Disulfiram can be used –> inhibits Aldehydedehydrogenase and therefore causes a buid up of Acetaldehyde
- Acetaldehyde is the toxic component that makes you feel bad from drinking –> feel effects from drinking
What is the concept behind the “Asian Flush”?
There are genetic polymophisms in the enzxme Aldehydedehydrogenase that cause an build up of Acetaldehyde in some popoulation groups
Explain the potency of alcohol
It is a small, simple molecule –>
- low potency
- but binds weakly to many targets
High dose required to see effects!
What is the pharmacological use of alcohol?
Why?
Ther is no use for it–> because it is very very unspecific
What are the primary effects of Alcohol on the body?
Overally: it has a depressant effect (but CNS agitation might occur at low doses –> increased CNS exitability)
- +ve on GABA
- -ve on NMDA receptors
Why do people get talkative with alcohol, though its overall effects are depressant?
Which factors influence this?
- It can cause CNS agitation + increased exitability at low doses, dependant on
- personaltiy
- environment
- social/ non-social setting
What are the effects of Alcohol on GABA ?
It has a pre+post synaptic increasing effects on GABA
- Pre-synaptic: Increase Neuro-active steroids that enhance GABA function (Allopregnelone)
- Post-synatpit: interacts with GABA receptors (Cl-influx when binding to it)
What are the effects of Alcohol on NMDA receptors?
It binds to NMDA receptors and inhibits them
–> Decrease
What are the effects of Alcohol on Calcium channels?
Decreasing effect on Calcium influx –> decreased neurotransmitter efflux
–> inhibitory
Explain how Alcohol can induce Euphoria
- It binds to opioid receptors
- Endogenous opioids switch off GABA–>
- causing disinhibiton of the reward system
- Euphoria
- causing disinhibiton of the reward system
Summaris the effects Alcohol has on the CNS
Slowing down of:
- Corpus Collosum - decreased rules and logic+ impulse retardation
- Hypothalamus - Controls appetite, emotions, temperature, and pain sensation.
- Reticular Activating System –Consciousness
- Hippocampus - Memory
- Cerebellum - Movement and coordination
- Basal Ganglia – Perception of time
What are the effects of Alcohol on the vasculature
- Causes Vasodilation
- decreased Ca2+ influx –> SM relaxation –> cutaneous vasodilation
- increase in prostaglandins (possibly due to Acetaldehyde)
Explain the effects of Alcohol on HR
It increases HR due to an decrease in Baroreceptor fiering
Explain the endocrine effects of Alcohol
It Supresses the secretion of ADH – >polyuria
Explain the effects of chronic alcohol abuse on the CNS
Main issue: Thiamine reduce (due to lack of thiamine in diet, because many calories got from Alcohol)
Mainly damaging things build up in regions with high metabolic demand in brain
- Dementia – Cortical atrophy/¯ volume cerebral white matter
- confusion (encephalopathy), oculomotor symptoms
- Ataxia – Cerebellar cortex degeneration - gait
What is Wernicke-Korsakoff syndrome?
Explain its backround
Associated with Thiamine defficiency due to chroinic alcohol abuse –>
- Wernicke’s encephalopathy – (hypothalamus/thalamus) (acute+ reversible)
- agitation, ataxia and ophtalmoplegia
- Korsakoff’s psychosis – (deep brain e.g. hippocampus (irreversible)
- Anterograde+ Retrograde amnesia
- might lead to confabulation (filling memory gaps with stories)
Via
Neurological injury due to cellular energy deficienty
- oxidative damage,
- mitochondrial injury leading to apoptosis,
- and directly stimulating a pro-apoptotic pathway
Explain the effects of chronic alcohol abuse on the liver
- Alcohol metabilism required NAD+ for metabolism –> used up and not there for other processes like
- Triglyceride metabolism (increased NADH leads to production of fatty acids, low NAD+ leads to reduced fatty acid acitvation)
- Fatty liver (reversible)
- Other liver metabolism (e.g. lack of pyruvate in Krebs cycle)
- Acidosis
- Ketocis
- Induces: Oxidative stress
- Triglyceride metabolism (increased NADH leads to production of fatty acids, low NAD+ leads to reduced fatty acid acitvation)
-
Hepatitis
- due to accumulation of free radicals and cytokine changes
- Acetaldehyde –> Forms acetaldehyde adducts –> immunogenic and can upregulate transcription of collagen I directly + transforming growth factor-beta 1 (TGF-beta1).
- Cirrhosis (due to fibroblast repari of damaged hepatocytes)
What is Liver Cirrhosis?
How is it connected to chronic alchol abuse?
In cirrhosis: fibroblasts replace hepatocyted and causes a
- decrease in active liver tissue
- decrease in heüatpcyte regeneration
What are the beneficial effects of alcohol on the CVS?
Only in low doses : 2-4 units/day –>
- increase in HDL
- decreased risk of mortality from coronary artery disease
- tPA levels/¯ platelet aggregation
Thought to be mediated via Polyphenols
What are the effects of Alcohol on the GI tract?
Carciogenic:
- Damage to the Mucusa via metabolism in GI tract–> Acetaldehyde in mucosal wall of GI tract
What are the damaging effects of Alcohol on the Endocrine system?
It
- increases ACTH
- Decreases Testosterone
Explain the Symptoms of a Hangover
- Nausea
- Acetaldehyde –> Irritant –> Vagus –> Vomiting center
- Headache
- Acetaldehyde –> Vasodilation
- Fatigue
- Sleep deprivation,
- ‘Rebound’
- Restlessness and muscle tremors ‘Rebound’
- Polyuria and polydipsia ↓ ADH secretion
