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PHAR 300 > Ethanol > Flashcards

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
describe ethanol epidemiology - Substance use among university and college students in canada 2019-2020
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
26
when does brain stop developing
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
27
why is binge drinking an issue
Memory of binge drinker lower and scoring on test Significant effect Lose certain fraction of students from ethanol Die Or drop out = fail courses
28
name the places where ethanol acts in brain
Acts in many locations Cerebellum = coordination Cortex = judgement Various regions related to memory, vision, sensations Acts on reward pathway too
29
what receptors does ethanol target
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
30
describe ethanol effects on ligand gated ion channels
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
31
describe gaba a receptor
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
32
describe how ethanol affects gaba a
not just situation on postsynaptic side under nerve terminal Lots of them Multiple types, locations and functions
33
describe how ethanol affects gaba a - extrasynaptic receptors
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
34
describe how ethanol affects gaba a - postsynaptic receptors
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
35
what does ethanol block
excitation Blocks glutamate transmission On glutamate receptor = NMDA Impairs intellectual function
36
describe effects of ethanol - on nts
Increased inhibition = GABA Decrease excitation = NDMA
37
describe ethanol blocking nmda
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
38
overview of ethanol nts
Inhibits excitation = glutamate receptors Potentiates inhibition = GABA and glycine receptors Lowers release of acetylcholine, serotonin Facilitates release of dopamine, opiate neuropeptides
39
describe how ethanol affects ion channels
Blocks voltage gated calcium channels Interferes with process of transmitter release Also particularly for sodium
40
describe effect of ethanol on serotonin
Impulsiveness and aggression noted during intake of ethanol
41
what does block of ach by ethanol do
problems of amnesia and cognitive impairment
42
describe effect of ethanol - dopaminergic neuron
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
what is ethanol
Simple molecule CH3CH2OH
44
describe absorption of ethanol - gen
Lipid soluble = easily absorbed from GI tract
45
describe absorption of ethanol - peak
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
describe absorption of ethanol - organs
Stomach = START SMall intestine = most
47
what increases rate of ethanol absorption
increases by carbonation Beer, champagne, sparkling wine On empty stomach especially Dumps liquid into intestines fast
48
what decreases rate of ethanol absorption
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
the faster the rate of absorption...
Faster the rate of absorption = higher the blood alcohol level will be because have not had time to metabolize much
50
how much ethanol absorbed in stomach
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
describe ethanol being absorbed by intestines
Large surface area, designed for absorption Intestine = in 10 mins absorbs 64% ethanol Absorb most Vs stomach = 38% in one hour
52
describe absorption of ethanol on empty stomach
On empty stomach = blood alcohol rises way more than with stomach containing food
53
describe distribution of ethanol
Ethanol = small passes through membrane Distributed everywhere
54
describe distribution of ethanol - HOW
Distributed in total body water Apparent volume of distribution ethanol = ~total body water
55
describe distribution of ethanol - differences
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
describe Apparent volume of DISTRIbution = AVD
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
what is AVD~
total body water
58
where does ethanol go - rapidly
High blood flow to brain = Ethanol enters brain rapidly Ethanol stimulates CTZ = vomiting
59
describe drinking too much - ctz
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
describe biotransformation of ethanol
Saturates enzyme quickly First order Once large amount = zero order kinetics
61
describe biotransformation of ethanol - zero order kinetics
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
describe Result on blood alc level
drink rapidly increases blood level Increases rate absorption Decreases rate metabolism
63
how metabolize alc
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
how metabolize alc - step 1
alcohol dehydrogenase Homodimer, 7 genes encode subunits Ethanol →acetaldehyde Genetic variations in metabolism
65
how metabolize alc - step 2
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
describe side effects of Acetaldehyde
can cause flushing, headache, vomiting, hypotension, sweating If have low active form Protected from becoming alcoholics because of uncomfortable side effects
67
what else metabolizes ald
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
describe where all alc goes
80% = alcohol dehydrogenase Greater than or equal to 10% = CYE2E1, microsomal enzymes 2-10% = dose dependent elimination (breath 5%, sweat, urine)
69
describe Alcohol impairment chart
female / male difference in ethanol pharmacokinetics Female = lower alcohol dehydrogenase in wall of stomach and liver = slower metabolism
70
why do females have lower metabolism of alc
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
describe alc excretion
Around 5% excreted in kidney Lipid soluble so have reabsorption Goes through glomerulus and can be reabsorbed from tubules
72
describe acute toxicity of ethanol
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
can acute dose be fatal
yuhhhh
74
compare therapeutic index of ethanol to other drugs
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
montreal children’s Hospital
Montreal children's hospital treats an average of one severely intoxicated teen per week Intensive care
76
describe st thomas uni
St thomas university = hazing party preceded death of student Found at bottom of stairs of apartment building
77
describe acadia uni
Acadia university = alcohol poisoning leads to death of first year student - binge drinking
78
describe queens uni
Deaths of 2 queen’s university students were alcohol related, coroner finds Person fell from buildings while intoxicated
79
describe athena gervais
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
describe alcohol teratogenic effects
Dangerous to fetus Transferred to fetus Fetal alcohol syndrome - spectrum disorders Safe level of alcohol during pregnancy = NONE Not a rare event
81
describe fetal alc syndrome
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
describe chronic toxicity of ethanol
2 main targets = biggest targets for alcohol induced toxicity Brain Liver
83
does the type of drink matter for chronic toxicity
NOOOO
84
describe effects of chronic drinking
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
name alc long term effects on liver and brain - gen
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
describe effects of ethanol - Epidemiological studies - cancer
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
name alc long term effects on liver and brain - cns
on brain Neurodegeneration= Potentiated by vitamin B deficiency Gives people = Dementia, cerebellar ataxia, psychiatric illness, depression, balance problems
88
name alc long term effects - cardiovascular
Arrhythmias even following social drinking Hypertension Stroke Cardiomyopathy = damage to structural components of heart
89
name alc long term effects - pancreas
Chronic pancreatitis More you drink = more at risk
90
name alc long term effects - esophagus
Esophageal cancer Combo of smoking and drinking Huge increase in risk of esophageal cancer
91
name alc long term effects - liver damage
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
name alc long term effects - cirrhosis
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
name alc long term effects - neurons
Ethanol can impair neurons directly Impairs mitochondrial function = Impaired motility, impaired function of neurons and eventually neuronal death
94
name alc long term effects - brain damage
irreversible brain damage Very notable Brain smaller = shrunk and lost many neurons Unable to function at full capacity intellectually or emotionally
95
if stop drinking when serious alcoholic = probably will
Increases survival for most
96
describe acute tolerance to ethanol
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
describe acute tolerance to ethanol - pharmacodynamics
Ethanol inhibits excitatory NMDA glutamate receptors (memory) Chronic use → upregulation of glutamate receptor, WithDrawal hyperexcitability More receptors
98
what happens when withdrawal from ethanol if chronic user
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
describe Delirium tremens
not in right mind Weird beliefs and sensations Tachycardia, hypertension, low grade fever, tremor, diaphoresis, delirium, agitation Can go on for several days
100
what can happens when withdrawal - hyperexcitability
can cause neuronal death Treatment center = treat acute withdrawal with other CNS depressants and slowly get them off ethanol
101
describe strategy for treating ppl when go through withdrawals
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
describe strategy for treating ppl when go through withdrawals - other drugs
NMDA receptor antagonist = lowers abstinence symptoms = Acamprosate, Deals with excess excitation OPIOID receptor antagonist = lowers ethanol rewarding effect = Naltrexone
103
describe cycle of addiction
problem Hard to break Need help in stopping Much research on drugs that might help better
104
what is one way to help someone get off addiction of ethanol
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

PHAR 300 (22 decks)

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