15. Alcohol

Question 1

how can the total amount of alcohol in a drink be proved?

Answer 1

absolute amount: %ABV (alcohol by volume) x 0.78 = grams of alcohol/100ml

units: %ABV x actual volume (ml)/1000

Question 2

what volume does 1 unit of alcohol equal?

Answer 2

10ml of absolute alcohol

Question 3

what is considered the safe levels of alcohol?

Answer 3

14 units or less/week

Question 4

what is binge drinking defined as?

Answer 4

> 8 units in 1 sitting

Question 5

how does drinking on a full stomach influence your blood alcohol level?

Answer 5

alcohol is mostly absorbed from the SI so drinking on an empty stomach is most effective because fluid stimulates gastric emptying whereas a full stomach delays gastric emptying

Question 6

how is alcohol metabolised?

Answer 6

• 90% is metabolised, 85% metabolised in the liver
• 10% is excreted unchanged: through lungs (hence breath test)
• liver metabolises alcohol by alcohol dehydrogenase (75%) and mixed function oxidase (25%)

Question 7

how do liver enzymes metabolise alcohol and what is the effect?

Answer 7

• enzymes convert alcohol –> acetaldehyde

acetaldehyde is a toxic product that we don’t want building up in the blood

Question 8

what does alcohol tolerance come from?

Answer 8

upregulation of mixed function oxidase enzymes by the liver - drinking more alcohol gives the same effect

Question 9

why is dosing of alcohol important?

Answer 9

saturation of the liver and first pass metabolism: flooding with alcohol means the liver enzymes can’t metabolise a lot of it and it goes straight to the blood

Question 10

where does the remaining 15% of metabolism occur?

Answer 10

stomach - alcohol dehydrogenase, alcohol is absorbed across the stomach

females have a lot less so metabolism isn’t as effective

Question 11

why is water solubility relevant in alcohol distribution?

Answer 11

• alcohol is very water soluble
• men have more body water than women so alcohol is more diluted in men
• there is a more powerful effect in women

Question 12

what does aldehyde dehydrogenase do?

Answer 12

converts acetaldehyde –> acetic acid (inert)

occurs in liver and stomach

Question 13

what does a genetic polymorphism in the aldehyde dehydrogenase enzyme result in?

Answer 13

• common in asian populations

- polymorphism results in ineffective metabolism of acetaldehyde –> build up –> toxicity (nausea)

Question 14

what does disulfiram do?

Answer 14

blocks aldehyde dehydrogenase

often given to alcoholics in alcohol aversion therapy so that when they drink alcohol acetaldehyde builds up, putting them off

Question 15

describe the potency of alcohol

Answer 15

• low pharmacological potency
• simple molecule
• fits in many targets but with weak effects
• have to drink a lot to get an effect

Question 16

what are the acute effects of alcohol in the CNS?

Answer 16

• depressant effect
• CNS agitation depending on degree of CNS excitability –> environment (non-social setting/social setting) and personality

Question 17

what does alcohol interact with and what are the effects of these interactions?

Answer 17

• acts on GABA receptors –> increases function (direct effect)
• acts pre-synaptically –> increases allopregnenolone –> allopregnenolone binds to GABA receptors (indirect effect)
• decreases NMDA receptor activation
• interferes with calcium channel opening

Question 18

why is alcohol said to behave like heroin when inhaled/at high dose?

Answer 18

alcohol binds to the opioid receptors in the CNS

it switches off the GABA receptor via the opioid receptor –> increased firing rate of dopaminergic neurones

Question 19

what areas of the brain does alcohol impact and what are the effects?

Answer 19

• corpus callosum: rules, logic, impulse, feelings
• hypothalamus: appetite, emotions, temperature, pain sensation
• reticular activating system: consciousness
• hippocampus: memory
• cerebellum: movement and coordination
• basal ganglia: time perception

Question 20

what are the acute effects of alcohol in the CVS?

Answer 20

• redness (cutaneous vasodilation) –> due to increased acetaldehyde
• acetaldehyde interferes with smooth muscle function in the arterioles
• calcium entry is impaired and prostaglandins are promoted –> vasodilation

Question 21

what is the effect of alcohol on HR?

Answer 21

causes tachycardia:

- alcohol depresses baroreceptors –> no stimulation of PNS + loss of inhibition of SNS

Question 22

what are the acute effects of alcohol in the endocrine system?

Answer 22

• diuresis (polyuria) due to increased acetaldehyde
• acetaldehyde inhibits vasopressin production –> less AQPs in the collecting duct –> loss of fluid
• increases ACTH –> increases cortisol
• negative effect on testosterone

Question 23

what are the chronic effects of alcohol on the CNS?

Answer 23

THIAMINE DEFICIENCY (thiamine is necessary for the production of ATP in brain regions of high metabolic demand) LEADS TO:

• dementia: cortical atrophy/decreased volume of cerebral white matter
• ataxia: cerebellar cortex degeneration

Question 24

what is wernicke-korsakoff syndrome?

Answer 24

seen in chronic alcoholics due to thiamine deficiency

wernicke’s encephalopathy: confusion, oculomotor symptoms, gait (reversible)

korsakoff’s psychosis: memory deficits (irreversible)

Question 25

what are the chronic effects of alcohol on the liver?

Answer 25

alcohol uses too much of the NAD+ (depleting it) which the liver needs for b-oxidation of fat (leading to fatty build up), and metabolic pathways (e.g. TCA cycle: pyruvate and acetyl coA can’t be cycled into TCA cycle)

pyruvate starts getting converted to lactate and acetyl coA starts getting converted to ketones resulting in acidosis and ketosis in the liver

Question 26

what is fatty liver?

Answer 26

impaired b-oxidation of fats

glycerol and fatty acids cannot be broken down and are stored as fat droplets (triacylglycerol)

this is REVERSIBLE

Question 27

if alcohol is abused long-term what happens?

Answer 27

the krebs cycle is permanently disrupted, there is permanent generation of acidosis, ketosis and oxygen free radicals in the liver

a pro-inflammatory environment is created

Question 28

what is hepatitis?

Answer 28

• hepatitis is the changes associated with chronic alcohol use (increased ketones, lactic acid, free radicals)
• these promote WBC influx
• there are both blood and cytokine changes in hepatitis –> increased IL-6 and TNF-a

THIS IS REVERSIBLE

Question 29

what is cirrhosis?

Answer 29

• fibroblasts infiltrate the liver and increase the amount of connective tissue being laid down in place of active liver tissue
• decreased hepatocyte regeneration
• liver transplant may be required

Question 30

what is the effect of chronic alcohol use in the gut?

Answer 30

chronic use may result in the exposure of stomach tissue to acetaldehyde leading to:

• ulceration
• stomach cancer

Question 31

what are the beneficial effects of alcohol?

Answer 31

low levels of alcohol seem to semi-regularly protect against coronary artery disease –> increased HDLs, increase tPA levels, decreased platelet aggregation

Question 32

what causes a hangover and what are the signs?

Answer 32

hangover symptoms peak as blood alcohol concentration reaches 0 causing:

• nausea: alcohol is an irritant –> vagus –> vomiting centre
• headache: vasodialtion
• fatigue: sleep deprivation
• restlessness and muscle tremors
• polyuria and polydipsia