alcohol 3 Flashcards
1
Q
what are bed spins (simple defintion)
A
positional alcohol vertigo
2
Q
what is altered physiologically that causes bed spins
A
buoyancy of the cupula with respect to surrounding endolymph fluid
3
Q
what is the cupula
A
inner ear component
4
Q
what happens to the ear at BAC around 0.04
A
ethanol diffuses into cupula and makes it lighter than surrounding endolymph
5
Q
what BAC is required for ethanol to diffuse into cupula
A
0.04
6
Q
what happens to cupula when alcohol enters
A
it makes it lighter than surrounding endolymph
7
Q
how long does it take to get BAC to 0.04
A
30min
8
Q
what happens to ear when drinking increases (3-5hrs, more than 0.04)
A
endolymph is also affected by ethanol, so now its density matches cupula
9
Q
what happens when drinking stops to ear
A
ethanol diffuses out of cupula first, so it is heavier than endolymph (hangover, 5-10hours)
10
Q
what causes the bed spins (physiologically)
A
difference in density of cupula (heavier) than endolymph (lighter) tricks brain into thinking its spinning
11
Q
in bed spins, what is affected(enter) by ethanol first
A
cupula
12
Q
in bed spins, what is affected(enter) by ethanol second
A
endolymph
13
Q
in bed spins, where does alcohol LEAVE first
A
cupula
14
Q
in bed spins, where does alcohol LEAVE second
A
endolymph
15
Q
is bed spins caused by a more dense endolymph or cupula
A
more dense cupula
16
Q
what places are most likely to get cancer from ethanol
A
GI tract, liver, colorectal, breast
17
Q
what % of upper GI cancer is caused by alcohol
A
50%
18
Q
what are the main culprits of ethanol caused cancer
A
acetaldehyde and reactive oxygen species
19
Q
what is the safe threshold for drinking
A
non for some cancers (esophagus)
20
Q
what type of cancer is most prominent with ethanol use
A
esophagus
21
Q
order these cancers in descending order with cancer and alcohol intake
- colorectal
- oral cavity/pharynx
- pancreas
- larynx
- esophagus
A
- esophagus
- oral cavity/pharynx
- larynx
- colorectal
- pancreas
22
Q
what does acetaldehyde do to DNA repair enzymes
A
binds to and inactivates them
23
Q
what does acetaldehyde do to DNA bases
A
covalently modify
24
Q
what happens when acetaldehyde inactivates DNA repair enzymes and modifies DNA bases
A
mutations and chromosomal abnormalities
25
which base can be modified by acetaldehyde 2 ways
deoxygaunosine
26
is it ethanol or acetaldehyde that modifies deoxyguanosine + how did they find out
it was the acetaldehyde because they used an ADH inhibitor to figure it out
27
what are the two types of reactions that happen with acetaldehyde and deoxyguanosine
one with 1 and one with 2 acetaldehydes
28
what is made with 1 acetaldehyde and 1 deoxyguanosine
N^2 ethylidene - deoxyguanosine
29
what is made with 2 acetaldehyde and 1 deoxyguanosine
propano-deoxyguanosine
30
what happens if the propano-deoxyguanosine ring does close and aldehyde group remains
it can form covalent links with other DNA strands and/or proteins (DNA interstrand crosslinks or DNA-protein crosslinks)
31
why is there so much cancer in the upper-digestive tract
ethanol is metabolized to acetaldehyde by microbes in saliva (10-100X higher conc of acetaldehyde in saliva than blood)
32
how does the concentration of acetaldehyde compare to in the blood
10-100X higher in saliva
33
what does poor dental hygiene do to acetaldehyde amounts + Why
increases the concentration as there are more microbes with worse hygiene
34
what does smoking to do the microbes in mouth
shifts the types of microbes to the types that produce high (50%) acetaldehyde levels`
35
what causes ethanol induced liver cancer
ROS from CYP2E1 and catalase, activated from immune cells
36
what does ROS do to cause cancer
lipid damage creates reactive lipid species which covalently modify DNA - mutagenic
37
what is the role of retinoic acid/ vitamin A
negative regulator of malignant cells (prevent proliferation)
38
what metabolizes retinoic acid/ Vit A
CYP2E1
39
what does low retinoic/VIit A cause
less RA receptors, so a change in levels of proteins involved in gene regulation and proteins involved in liver cell proliferation (whole pathway less active, bad bad)
40
what 6 things cause brain damage from alcohol
acetaldehyde, ROS, nutritional deficiency, head trauma, neuroinflammation, excitotoxicity (Ca influx-excess glutamatergic)
41
what causes excitotoxiticy
hyperactivity of glutamatergic system-excess calcium influx causing inappropriate activation of calcium-sensitive signalling pathways and cell death
42
why does nutritional deficiency happen a lot in alcoholics
no nutritional value in ethanol
43
what is wernickes disease
B1 (thiamine) deficiency
44
is wernickes disease reversible
partially
45
what causes wenickes disease
bad B1/thiamine absorption from GI due to inflammation
46
what is thiamine/B1 involved in
myelin formation, glucose utilization and amino acid production
47
what are symptoms of wenickes disease
confusion, ataxia, abnormal eye movement (shaky or paralyzes eyes)
48
what is korsakoffs psychosis symptoms
short and long term memory loss, inability to learn new info
49
is korsakoffs psychosis reversivle
no
50
what causes korsakoffs psychosis
neuronal loss - progression of wernikes
51
what can help reverse wernickes
increase B1 intake
52
what does low ethanol dose do to HDL
increases it (its the good cholesterol)
BUT only really in cell culture
53
what does low ethanol dose do to platelet aggregation and coagulation
decreases (less likely to have clots) (but this data is kinda not sure if real)
54
what does low ethanol dose do to blood vessel inflammation
decrease (kinda weird and contradictory...)
55
what does low ethanol dose do to endothelial function, in what way is it changed
improved balance between blood vessel constriction and dilation
56
are the cardioprotective effects of alcohol real? do they translate into a measureable clinical benefit?
not really, there is an increase in moderate/heavy users of heart issues like BP
57
what does high dose of ethanol do to heart
toxic-cardiomyopathy (disease of heart muscle)
58
what does alcohol do directly to the myocardium
directly depresses it
59
what does acetaldehyde do to myocyte function and how
inhibits by altering calcium homeostasis and myocardial protein synthesis
60
how does acetaldehyde change calcium homeostatis
ca release from SR is inhibited - negative effect on calcium sensitive contractility proteins
61
what does ethanol metabolites do to mitochondria
causes dysfunction and poor energy usage
62
what was the main issue with the study that claimed alcohol was fine in moderation
that the abstainer group included previous drinkers and alcoholics (got so sick that they quit)
63
how many people (that drink 1 drink a day) out of 100 000 with experience 1 of 23 alcohol related issues
918
64
how many people (that drink 0 drink a day) out of 100 000 with experience 1 of 23 alcohol related issues
914
65
how many people (that drink 2 drink a day) out of 100 000 with experience 1 of 23 alcohol related issues
977`
66
what is the leading cause of brain damage in USA
fetal alcohol spectrum disorder (1 in 10 births) (i think 1 in 10 of brain damage births)
67
what is fetal alcohol syndrome
the severe end of the spectrum
68
what week in human development does the face and forebrain develop
week 3
69
what are the ways kids with FASD look different
thin upper lip
small head
small eye openings
no ridge b/w nose and lips
70
what are some symptoms of FASD
poor impulse control&planning, impaired mental function, seizures
71
when does synaptogenesis occur
third trimester
72
when is fetal alcohol exposure most harmful to brain and why
third trimester because thats when synaptogenesis occurs
73
what happens to the neurons in the third trimester with alcohol there
they dont form synapses-they may just go to the wrong place or never make connections
74
what can binge exposure of ethanol do to fetus
massive apoptosis (programmed cell death)
75
were all brain regions sensitive to ethanol at the same times
no, different regions are sensitive to ethanol during different stages within the time period (diff timing of the development and making connections between regions)
76
is the hypothalamus sensitive to early mid or late third trimester ethanol exposure
early
77
is the PFC sensitive to early mid or late third trimester ethanol exposure
late
78
is the thalamus sensitive to early mid or late third trimester ethanol exposure
mid
79
rank thalamus, hypothalamus and PFC in order of early to late in trimester most likely to die with ethanol
hypothalamus, thalamus, PFC
80
is severity of apoptosis linked to total dose or peak concentration
peak concentration
81
what BAC triggered apoptosis (and for how long) in rat embryo experiment
0.2 for 4 hours
82
what causes ethanol induced apoptosis
combination of GABA A receptor activation and NMDA receptor block
83
when does most of the ethanol induced apoptosis occur
third trimester
84
what is MK-801
NMDA receptor antagonist
85
what is phenobarbital
GABA-A receptor activator
86
how did they use phenobarbital and MK-801 to see what causes apoptosis
MK-801 antagonizes NMDA receptor,
| phenobarbital activates GABA -A receptor, so both of those effects combined showed the same results as ethanol exposure
87
what does ethanol do to ERK and cause does this cause
causes a lack in ERK phosphorylation - mitochondrial damage
88
what does ERK do normally
help cause neuroplasticity
89
what do caspase 3 and 9 do
enzymes that trigger apoptosis
90
what does ethanol do to caspase 3 and 9
activates them, which triggers apoptosis
91
is there more or less caspase 3 and 9 when theres ethanol around
more
92
what does prenatal ethanol do to surviving neurons
alters their migration
93
what are heterotopias
clumps of neurons in the wrong part of the brain
94
genes for which receptors are affected by prenatal ethanol
thyroid hormone and retinoid acid
95
what does the affected genes with thyroid hormone and retinoid acid cause
increased biological reactions to stress-poor coping, anxiety and depression
96
what is in stage 1 withdrawal (6)
tremors, rapid HR, hypertension, sweating, no appetite, insomnia
97
what is in stage 2 withdrawal (1)
hallucinations
98
what is in stage 3 withdrawal (4)
delusions, delirium, disorientation, amnesia
99
what is in stage 4 withdrawal (1)
seizures
100
what is mortality rate in alcohol withdrawal when not supervises/treated
1/7
101
what are delirium tremens
stage 3,4
| -delusions, delirium, disorientation, amnesia, seizures
102
when do delirium tremens occur
peak 3-4 days after last drink
103
how can benzodiazepines help with withdrawal
prevent stages 3 and 4 - especially seizures
104
what is clonidine
agonist and alpha2 receptors (adrenergic)
105
how can clonidine help with withdrawal
prevents excessive NT release
106
what is propranolol
beta adrenergic antagonist
107
how can propranolol help with withdrawal
blocks excess sympathetic activity, slows HR and reduces tremors
108
what are 2 drugs +1 drug class used for withdrawal
clonidine, propranolol, benzos (sedatives)can
109
what is disulfiram/how does it work
prevents aldehyde dehydrogenase from working
110
when is disulfiram used./why
to prevent alcohol use-makes you throw up, nausea
111
what does disulfiram do
results in high levels of acetaldehyde (prevents aldehyde dehydrogenase from working)
112
does disulfiram work long term
questionable
113
does disulfiram stop cravings
no!
114
what is naltrexone
mu-opioid receptor antagonist
115
what does naltrexone do
prevents beta endorphin from activating presynaptic receptors
116
what does naltrexone do to GABA release in VTA
prevents inhibition of GABA release in VTA
117
can naltrexone help with cravings
some studies say yes
118
what is a downside of naltrexone
may cause negative mood
119
what does alcohol do to endorphin and where
increases it in VTA and NA
120
what is acamprosate
glutamate receptor antagonist
121
how does acamprosate work
prevents glu acting at its receptors, stops the hyperexcitability due to glu up-regulation (esp in withdrawal)
122
what does acamprosate do to craving
helps prevent
123
when is acamprosate best and why
in withdrawal because it prevents glu binding to its receptor and causing hyperexcitability (due to gluR upregulation)
