Ethanol Flashcards

1
Q

describe ethanol

A

very powerful drug
Legal in north america for most of history
Was banned once but not good
Highly advertised = Sales of alcohol enormous - huge profit

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2
Q

describe ethanol stats

A

8 million canadians with alcohol use disorder
Many people in world have it
Many side effects
Commonly consumed
240 million people across globe consume alcohol problematically
15 million people around the world use injection drugs
Long term and short term toxicity

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3
Q

describe general effects of ethanol

A

Acts on nervous system
Effects increases as increase dose
General depressant of CNS

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4
Q

describe general effects of ethanol low vs high dose

A

Low dose = depress a few excitatory type areas
People feel release from anxiety and disinhibition

As increase dose =
Sedated, hypnosis - sleep
Point where they pass out/sleep = dangerous because close to lethal level

Depresses more and more circuits until gets to areas vital for life

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5
Q

name 5 concepts of cns depressants

A

1- Additive effects when combined
2 - Cannot reverse effects with stimulants
3 - General depressants not totally general
4- Chronic use will lead to rebound excitation if stop
5- All general CNS depressants cause tolerance

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6
Q

describe 5 concepts of cns depressants - 1= additive

A

Sedatives, antidepressants, anticonvulsants, anti anxiety, opioids
If take more than one = combine
Ex alcohol and sleeping meds

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7
Q

describe 5 concepts of cns depressants - 2= reverse

A

Myth = give people coffee after they’ve had drinks
Does not oppose effects of CNS depressant - does not matter how much coffee

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8
Q

describe 5 concepts of cns depressants - 3= general

A

Many differences
At high doses = knockout everything

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9
Q

describe 5 concepts of cns depressants - 4= chronic

A

If taking all the time = get adaptation if suddenly stop = rebound in other direction
so excitation

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10
Q

describe 5 concepts of cns depressants - 1= tolerance

A

If take repeatedly over time = body counteracts with mechanisms and end up taking more and more
Often cross tolerance
Serious alcoholic = may need modification for anaesthesia for procedure

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11
Q

describe ethanol at low doses

A

At low concentrations = first start affect emotions, judgement, voluntary motor skills (ability to drive)
As increase dose = affects other systems vital for life and start to get at dangerous level
Low doses = disinhibition and relaxation
Less anxiety

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12
Q

describe ethanol at high doses

A

cns depression
Can pass out
Cannot leave anyone alone after pass out = can quickly reach point as death because they are still absorbing alcohol from GI tract
Need to wake up them up or call 911 if do not wake up

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13
Q

describe legal limit

A

Legal limit = low, after more than one drink = not safe to drive

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14
Q

what are common side effects of ethanol

A

amnesia
delusions
blackouts

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15
Q

describe partial amnesia

A

Fragmentary loss of memory, person later unaware of memory gaps, universal, dose related
Remember general stuff but not detail
More drinks = more memory loss

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16
Q

describe blackouts

A

Total loss of memory for specific time, person later aware of 0 memory, susceptibility varies
Do not happen to everyone
Wake up somewhere and have no idea how got there

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17
Q

describe alcohol stats

A

> 30% dead drivers, majority of dead pedestrians
⅓ of dead drivers
½ of dead pedestrians =
Driver or drunk pedestrian walks out into street

~25% private plane crashes, home accidents
Private boats = easy to get into accidents
Half of boating fatalities related to ethanol

Another 18% of deaths due to THC

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18
Q

should you drive with ethanol in system

A

Should not drive with any ethanol
Depends on country
Most provinces = 0.05
Other countries = 0.02 in europe, 0.05 in france and 0.08 in north america

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19
Q

describe BAC for canada 2024

A

0.00 for commercial drivers or less than 21
0.05 = licence can be suspended, penalties if mixed with cannabis
0.08 = criminal charges

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20
Q

describe blood alcohol and death stats

A

Impaired driving = 0.04 or 0.05
Criminal charges = 0.08
Risk of fatal crash = 2x at 0.05, 3x at 0.08
For every death, 10x more are seriously injured
Death rate pretty high in canada
Criminal limit may soon change to 0.05

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21
Q

where in canada do people drink the most

A

Consumption of ethanol varies depending on part of country
Northern parts = most drinking
Also the case of all the recreational drugs

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22
Q

describe risk of accidents

A

Risk of accidents varies by time of day
Highest in evening
Much higher on friday an saturday night
Higher after work

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23
Q

describe ethanol epidemiology - harvard study

A

> 10,000 students
100 campuses

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24
Q

describe ethanol epidemiology - NIH

A

1,519 deaths
Many from overdose and few from accidents
699,000 assaults
Binge drinking = 28%
1 in 5 college women experience sexual assault during time in college
Majority of sexual assaults in college involve alcohol or other substances

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25
Q

describe ethanol epidemiology - Substance use among university and college students in canada 2019-2020

A

77% of people consumed alcohol in past moth
Almost half (40%) drink frequently
Drinking pattern
Binge drinking = consuming 4.5 - 5 drinks in a day and some drink more
Problems = Physical harms to health, Trouble with school = missed lectures, Signs of alcohol dependence

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26
Q

when does brain stop developing

A

Brain continues to develop until mid 20s = 25
New synapses and remodel brain
15 year old
Heavy drinker = marked difference from kid who does not drink
Brain activity while performing memory task

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27
Q

why is binge drinking an issue

A

Memory of binge drinker lower and scoring on test
Significant effect
Lose certain fraction of students from ethanol
Die
Or drop out = fail courses

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28
Q

name the places where ethanol acts in brain

A

Acts in many locations
Cerebellum = coordination
Cortex = judgement
Various regions related to memory, vision, sensations
Acts on reward pathway too

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29
Q

what receptors does ethanol target

A

receptors = ion channels
And ion channels themselves
Na, K, Ca
ALSO acts on ion channels
GABA receptors and glycine receptors = inhibitory pathways
Glutamine and 5HT, Ach = excitatory pathways

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30
Q

describe ethanol effects on ligand gated ion channels

A

Has very prominent effect on specific types of GABA(a) and glycine = Mainly inhibitory
Major effector on NMDA type of glutamate receptor = Inhibits excitation and enhances inhibition
Combination very powerful = unconscious and dying

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31
Q

describe gaba a receptor

A

Ligand gated ion channel
Normal agonist = GABA, Opens up channel and mainly have chloride flowing through
Inhibitory response
Has recognition site for ethanol
Also other CNS depressants = barbiturates and benzodiazepines

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32
Q

describe how ethanol affects gaba a

A

not just situation on postsynaptic side under nerve terminal
Lots of them
Multiple types, locations and functions

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33
Q

describe how ethanol affects gaba a - extrasynaptic receptors

A

GABA released from terminal drifts over to extrasynaptic region
Not broken down easy in this region
Tonic effect that goes on all the time from GABA released
Tonic level of inhibition from GABA release all the time
Also prominent phasic reaction when impulse comes down nerve ending and have post synaptic effectdescribe how ethanol affects gaba a - extrasynaptic receptors

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34
Q

describe how ethanol affects gaba a - postsynaptic receptors

A

Acts on postsynaptic= inhibition and acts on extrasynaptic = creates tonic inhibition
Ethanol acts on both
Increases GABA inhibition
More than one receptor type
Ethanol = releases glycine, enhances postsynaptic response to glycine
Enhances inhibition

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35
Q

what does ethanol block

A

excitation
Blocks glutamate transmission
On glutamate receptor = NMDA
Impairs intellectual function

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36
Q

describe effects of ethanol - on nts

A

Increased inhibition = GABA
Decrease excitation = NDMA

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37
Q

describe ethanol blocking nmda

A

acute effect
With time if keep drinking = get upregulation
Chronic intermittent alcohol
Mechanism of adaptation of drugs
Upregulate excitatory receptors = neuron trying to counteract inhibitory effect of the ethanol

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38
Q

overview of ethanol nts

A

Inhibits excitation = glutamate receptors
Potentiates inhibition = GABA and glycine receptors
Lowers release of acetylcholine, serotonin
Facilitates release of dopamine, opiate neuropeptides

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39
Q

describe how ethanol affects ion channels

A

Blocks voltage gated calcium channels
Interferes with process of transmitter release
Also particularly for sodium

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40
Q

describe effect of ethanol on serotonin

A

Impulsiveness and aggression noted during intake of ethanol

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41
Q

what does block of ach by ethanol do

A

problems of amnesia and cognitive impairment

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42
Q

describe effect of ethanol - dopaminergic neuron

A

Dopaminergic neuron in ventral tegmental area and releases dopamine in nucleus accumbens
Lowers GABA inhibition
Stimulates release of glutamate
= Increases dopamine release
Many other proposed actions, research ongoing

43
Q

what is ethanol

A

Simple molecule
CH3CH2OH

44
Q

describe absorption of ethanol - gen

A

Lipid soluble = easily absorbed from GI tract

45
Q

describe absorption of ethanol - peak

A

Rapid - detect in 5 mins
Detect in blood
On empty stomach
Strong Drink

Peak = 30-90 min
Depends on what is it in stomach

46
Q

describe absorption of ethanol - organs

A

Stomach = START
SMall intestine = most

47
Q

what increases rate of ethanol absorption

A

increases by carbonation
Beer, champagne, sparkling wine
On empty stomach especially
Dumps liquid into intestines fast

48
Q

what decreases rate of ethanol absorption

A

by food: fat
More food in stomach = high fat food delays gastric emptying
Some ethanol absorbed through stomach - most is through SI
If eating with drink = food in stomach will delay alcohol from getting to intestines
Slower absorption

49
Q

the faster the rate of absorption…

A

Faster the rate of absorption = higher the blood alcohol level will be because have not had time to metabolize much

50
Q

how much ethanol absorbed in stomach

A

About 20% absorbed in stomach
High level ADH in gastric mucosa
Alcohol dehydrogenase = metabolized ethanol in gastric mucosa
Some inactivated
Turned into aldehyde
Side effects = gastritis

51
Q

describe ethanol being absorbed by intestines

A

Large surface area, designed for absorption
Intestine = in 10 mins absorbs 64% ethanol
Absorb most
Vs stomach = 38% in one hour

52
Q

describe absorption of ethanol on empty stomach

A

On empty stomach = blood alcohol rises way more than with stomach containing food

53
Q

describe distribution of ethanol

A

Ethanol = small passes through membrane
Distributed everywhere

54
Q

describe distribution of ethanol - HOW

A

Distributed in total body water
Apparent volume of distribution ethanol = ~total body water

55
Q

describe distribution of ethanol - differences

A

In males vs females
Larger total body water in males = 68% - More diluted in males because of larger amount of body water
Females = 55% - Higher concentration of ethanol in blood
Difference gets smaller as age

56
Q

describe Apparent volume of DISTRIbution = AVD

A

Amount of drug in body/concentration of drug in circulation
Greater protein binding = high concentration in blood = LOW AVD
Greater tissue binding = low concentration in blood = HIGH AVD

57
Q

what is AVD~

A

total body water

58
Q

where does ethanol go - rapidly

A

High blood flow to brain =
Ethanol enters brain rapidly
Ethanol stimulates CTZ = vomiting

59
Q

describe drinking too much - ctz

A

If drink too much or drink a lot
Designed to protect you
Often saves life
If consumed lethal amount of ethanol
Acts in brain but also in periphery
Because it’s a irritant and stimulates receptors in periphery = sends signals to brain to trigger vomiting

60
Q

describe biotransformation of ethanol

A

Saturates enzyme quickly
First order
Once large amount = zero order kinetics

61
Q

describe biotransformation of ethanol - zero order kinetics

A

Can only metabolize given quantity not fraction
Case with ethanol = anything above small doses
Can take much time to get rid of it if consumed many drinks
½ drink per hour = can properly metabolise
After = enzyme saturated

62
Q

describe Result on blood alc level

A

drink rapidly increases blood level
Increases rate absorption
Decreases rate metabolism

63
Q

how metabolize alc

A

Small molecule
In liver and bit of gastric mucosa = alcohol dehydrogenase= Changed it to acetaldehyde (Pretty toxic)
Then have acetaldehyde dehydrogenase in liver = converts to acetic acid, Body can easily get rid of it
Easily saturated
Many variations between people - For both enzymes

64
Q

how metabolize alc - step 1

A

alcohol dehydrogenase
Homodimer, 7 genes encode subunits
Ethanol →acetaldehyde
Genetic variations in metabolism

65
Q

how metabolize alc - step 2

A

aldehyde dehydrogenase
Homotetradimer or homodimer, 19 genes encode subunits
Acetaldehyde → acetate
VERY Extensive genetic variation = less active form in around 50% of some populations = For that person = enzyme will not get rid of acetaldehyde = side effects

66
Q

describe side effects of Acetaldehyde

A

can cause flushing, headache, vomiting, hypotension, sweating
If have low active form
Protected from becoming alcoholics because of uncomfortable side effects

67
Q

what else metabolizes ald

A

Some metabolism by p450s
Inducible
CYP2E1 - induction with chronic use
People who drink a lot = less reaction to alcohol because breaking it down more rapidly

68
Q

describe where all alc goes

A

80% = alcohol dehydrogenase
Greater than or equal to 10% = CYE2E1, microsomal enzymes
2-10% = dose dependent elimination (breath 5%, sweat, urine)

69
Q

describe Alcohol impairment chart

A

female / male difference in ethanol pharmacokinetics
Female = lower alcohol dehydrogenase in wall of stomach and liver = slower metabolism

70
Q

why do females have lower metabolism of alc

A

Lower body size and % body water = higher blood level
Can drink less than male and still be above legal limit
5 drinks = binge drinking
Level in blood higher for female than male

71
Q

describe alc excretion

A

Around 5% excreted in kidney
Lipid soluble so have reabsorption
Goes through glomerulus and can be reabsorbed from tubules

72
Q

describe acute toxicity of ethanol

A

Problem
Lethal level/recreational level = only 4
Ratio
Put drug in animal and clinical trials
And saw that dose required for killing is 4 times recreational or therapeutic effect = would never get it into clinical trials in humans
Unless no other option
Narrow difference

73
Q

can acute dose be fatal

A

yuhhhh

74
Q

compare therapeutic index of ethanol to other drugs

A

Benzodiazepines = therapeutic index 500= Slow curve - rises
Barbiturates = steeper curve so benzos replaced them = relieve anxiety and for sleep
Ethanol = therapeutic index 4 =Steepest curve

75
Q

montreal children’s Hospital

A

Montreal children’s hospital treats an average of one severely intoxicated teen per week
Intensive care

76
Q

describe st thomas uni

A

St thomas university = hazing party preceded death of student
Found at bottom of stairs of apartment building

77
Q

describe acadia uni

A

Acadia university = alcohol poisoning leads to death of first year student - binge drinking

78
Q

describe queens uni

A

Deaths of 2 queen’s university students were alcohol related, coroner finds
Person fell from buildings while intoxicated

79
Q

describe athena gervais

A

teen that died linked to sugary alcoholic drinks
Consumed most of 3 568ml cans of a beverage called FCKD UP
Equivalent of 12 glasses of wine
In span of half an hour
Fell into local stream and drowned
Changed law = 568 ml can now only contain 4.5% alcohol instead of 11.9%

80
Q

describe alcohol teratogenic effects

A

Dangerous to fetus
Transferred to fetus
Fetal alcohol syndrome - spectrum disorders
Safe level of alcohol during pregnancy = NONE
Not a rare event

81
Q

describe fetal alc syndrome

A

spectrum disorders
300,000 people around in canada
Can consume alcohol before they even know they are pregnant

Mild to severe issues =
Impaired function of cardiovascular system
Facial deformity
Severe intellectual impairment
Emotional crises

82
Q

describe chronic toxicity of ethanol

A

2 main targets = biggest targets for alcohol induced toxicity
Brain
Liver

83
Q

does the type of drink matter for chronic toxicity

A

NOOOO

84
Q

describe effects of chronic drinking

A

Chronic drinker = liver
hepatitis , fatty liver and then end up with cirrhosis = serious scarring type of disorder of liver, Can kill you
Mortality from cirrhosis = goes up in straight line the more you drink , Same in all countries
GI, vascular effects also go up in straight line

85
Q

name alc long term effects on liver and brain - gen

A

Intellectual impaired if drinks lot
Affects cardiovascular system
Lungs
Sexual response = People become impotent
Often have inflammation of stomach because irritates lining of stomach
Pancreatitis common
Changes muscles and skins
Epidemiological studies = causes 7 different types of cancer

86
Q

describe effects of ethanol - Epidemiological studies - cancer

A

Recent report in canada
Alcohol = carcinogen causes 7 types of cancer
Including breast cancer
Myth = low doses protect against heart disease = NOT TRUEEE, 100 different cohort studies = 4.8 million participants, Prove its a myth
Reality = regular use increases heart attacks and strokes
RISK Of dying goes up in proportion to amount of alcohol person drinks

87
Q

name alc long term effects on liver and brain - cns

A

on brain
Neurodegeneration= Potentiated by vitamin B deficiency
Gives people = Dementia, cerebellar ataxia, psychiatric illness, depression, balance problems

88
Q

name alc long term effects - cardiovascular

A

Arrhythmias even following social drinking
Hypertension
Stroke
Cardiomyopathy = damage to structural components of heart

89
Q

name alc long term effects - pancreas

A

Chronic pancreatitis
More you drink = more at risk

90
Q

name alc long term effects - esophagus

A

Esophageal cancer
Combo of smoking and drinking
Huge increase in risk of esophageal cancer

91
Q

name alc long term effects - liver damage

A

induced liver damage
19 human aldehyde isozymes
ALDH2 = main enzyme for ethanol derive acetaldehyde
Acetaldehyde is cytotoxic = Variation between people of how much acetaldehyde accumulates in live before got rid of it
Portal circulation altered
Blood flow impaired = shunts sideways = end up with increased pressure in portal circulation
Fluid leaks out of portal circulation into abdominal cavity = Ascites (Fluid in abdominal cavity)

92
Q

name alc long term effects - cirrhosis

A

Loss of ability of liver to detoxify things that are going through it
Somethings go straight through liver and reach brain
Portal obstruction= doesn’t go through liver first = So many things directly into circulation when should not be
Reasons for hepatic encephalopathy = Liver no detoxifying things properly and gets to brain and injures it

93
Q

name alc long term effects - neurons

A

Ethanol can impair neurons directly
Impairs mitochondrial function = Impaired motility, impaired function of neurons and eventually neuronal death

94
Q

name alc long term effects - brain damage

A

irreversible brain damage
Very notable
Brain smaller = shrunk and lost many neurons
Unable to function at full capacity intellectually or emotionally

95
Q

if stop drinking when serious alcoholic = probably will

A

Increases survival for most

96
Q

describe acute tolerance to ethanol

A

Acute tolerance to ethanol = effect at the same blood level is lower during decline than the rise
Effect less as blood level falls than as it rises

97
Q

describe acute tolerance to ethanol - pharmacodynamics

A

Ethanol inhibits excitatory NMDA glutamate receptors (memory)
Chronic use → upregulation of glutamate receptor, WithDrawal hyperexcitability
More receptors

98
Q

what happens when withdrawal from ethanol if chronic user

A

If withdraw from ethanol = have hyperexcitability
Big problem with anxiety, insomnia, tremors, withdrawal seizures, hallucinations when withdrawing from ethanol
Delirium tremens
Should go to detox center
Level of severity of withdrawal depends on level of addiction
More they drink everyday = worse the withdrawal will be

99
Q

describe Delirium tremens

A

not in right mind
Weird beliefs and sensations
Tachycardia, hypertension, low grade fever, tremor, diaphoresis, delirium, agitation
Can go on for several days

100
Q

what can happens when withdrawal - hyperexcitability

A

can cause neuronal death
Treatment center = treat acute withdrawal with other CNS depressants and slowly get them off ethanol

101
Q

describe strategy for treating ppl when go through withdrawals

A

treating people after gone through withdrawal = give them drug that will block alcohol dehydrogenase
So when drink = immediately get higher levels of acetaldehyde= not pleasant
Discourage from drinking

102
Q

describe strategy for treating ppl when go through withdrawals - other drugs

A

NMDA receptor antagonist = lowers abstinence symptoms = Acamprosate, Deals with excess excitation
OPIOID receptor antagonist = lowers ethanol rewarding effect = Naltrexone

103
Q

describe cycle of addiction

A

problem
Hard to break
Need help in stopping
Much research on drugs that might help better

104
Q

what is one way to help someone get off addiction of ethanol

A

Psychological support = very helpful
AA = alcoholics anonymous
Many people around world go to it
Get help they need psychologically
Better than any of the drugs