Alcohol Flashcards

Question

How might alcohol work to induce euphoria as an acute CNS effect

Answer 1

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

Answer 2

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

Answer 3

1. CUTANEOUS VASODILATION | 2. Increased heart rate

Answer 4

Because asians have genetic polymorphism and break down acetaldehyde much more poorly, you get more cutaneous vasodilation

Answer 5

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)

Answer 6

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'

Answer 7

* Acetaldehyde suppresses ADH (negative effect on post pit)

Answer 8

Brain and liver

Answer 9

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

Answer 10

thiamine requirement for healthy individuals is related to their carbohydrate intake and is between 1–2mg per day: this requirement increases with alcohol misuse.

Answer 11

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.

Answer 12

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: 1. oxidative damage, 2. mitochondrial injury leading to apoptosis, and 3. 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.

Answer 13

Wernicke’s encephalopathy – (hypothalamus/thalamus and brainstem, causing ophthalmoplegia due to cranial nerve problems ) Korsakoff’s psychosis – (deep brain e.g. hippocampus)

Answer 14

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).

Answer 15

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

Answer 16

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.

Answer 17

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

Answer 18

1. Hepatitis (reversible): - reduced NAD+ leads to deranged metabolic processes whcih leak ROS cause tissue damage and inflammation (IL6 and TNFa) - acetaldehyde too causes inflammation 2. Cirrhosis (irreversible) inflammatory response --> fibroblasts. Fibroblasts then lay down connective tissue due to reduced hepatocyte regeneration, reducing the active liver tissue

Answer 19

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

Answer 20

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

Answer 21

Increased ACTH secretion (cushings like) Decreased testosterone secretion (feminisation)

Answer 22

Nausea Irritant  Vagus  Vomiting center Headache Vasodilation Fatigue 1. Sleep deprivation, 2. ‘Rebound’ Restlessness and muscle tremors ‘Rebound’ Polyuria and polydipsia ↓ ADH secretion

Answer 23

Only at a very low dose, after this provides CNS agitation