Alcoholism I

Question 1

alcohol is a drug that alters brain metabolism through ___ -___ interactions

Answer 1

NT-etOH interactions.

Question 2

ACOA

Answer 2

adult children of alcoholics

Question 3

two facets of alcohol that contribute to DISEASE BURDEN

Answer 3

1) average volume of etOH consumption

2) pattern of drinking (esp. heavy binge drinking) contribute to disease burden

Question 4

4 diseases alcohol is linked to

Answer 4

1) alcohol dependence
2) cancer
3) cardiovascular disease
4) liver cirrhosis

Question 5

lifetime risk of alcohol use disorders for men (AUD)

Answer 5

20%

Question 6

countries with the highest consumption

Answer 6

eastern european countries and Russia

Question 7

how has women etOH consumption been changing?

Answer 7

men consume more etOH than women, but women have been increasing. Aka, the PROFILE of drug use is changing.

Question 8

___% of men and ___% of women do NOT drink

Answer 8

45% of men and 66% of women abstain.

Question 9

most deaths by etOH were related to ___, ___, ____ disease and _____ ____. Deaths prevented by etOH were in the ____ category.

Answer 9

most deaths by etOH were related to INJURY, CANCER, CARDIO disease and LIVER CIRRHOSIS. Deaths prevented by etOH were in the CARDIOVASCULAR category.

Question 10

___% of global burden of disease/injury is attributal to etOH

Answer 10

5.1

Question 11

etOH now accounts for higher proportion of deaths worldwide than ___, ____, ___ and ____ combined

Answer 11

etOH now accounts for higher proportion of deaths worldwide than HIV, AIDS, VIOLENCE and TB combined

Question 12

TF: Harmful drinking is on the rise among young men and women

Answer 12

TRUE. 43% of boys under 15 have been drunk at least once.

Question 13

EtOH is ___ leading risk for death and disability global in 2010

Answer 13

3rd leading risk for death and disability globally in 2010. this is up from 6th in 1990.

Question 14

T/F alcohol is the leading reason for hospitalization due in WHOLE or in PART to alcohol

Answer 14

TRUE. 3.3 billion for direct health costs.
14bil. in economic costs of etOH related harm in canada.

there is more hospitalization for etOH than for heart attacks.
77,000 hospitalization entirely caused by alcohol (HECA)vs 75000 for heart attacks.

Question 15

Low risk alc consumption for men

Answer 15

15 drinks/wk and not more than 3 a day

Question 16

low risk alc consumption for women

Answer 16

10 drinks/wk and not more than 2 per day.

Question 17

which gender has a higher HECA in adolesencts? (hospitalization entirely caused by alcohol)

Answer 17

between ages 10-19, girls have higher HECA than boys (in canada)

Question 18

how does SES relate to HECA? (hospitalization entirely caused by alcohol)

Answer 18

low SES/ low income neighborhoods have higher (2.5x higher) rates of hospitalization than in higher income neighborhoods.

BUT there is an alcohol harm paradox: lower income is associated with a lower prevalence of heavy drinking, but had higher rates of hECA. relates to be a greater susceptibility to consequences of lower SES. – high stress levels, level of support systems, poor diet etc.

Question 19

What is the alcohol harm paradox.

Answer 19

lower income is associated with a lower prevalence of heavy drinking, but had higher rates of HECA. relates to be a greater susceptibility to consequences of lower SES

Question 20

Discrepancy in the health care system about doctors talking to their patients about alcohol

Answer 20

in a 2016 clinical survey: when Canadians were asked if they have talked with their doctor about alcohol use in the last year, majority have not. 25% of males and 22% of females were asked about their alcohol usage.

• saskatchewan had the lowest percentage.

Question 21

Studies have shown that alcohol causes cancer of the ___, ___, __, and ____

Answer 21

mouth, esophagus, larynx and liver. basically any thing thats involved in the digestive system and accessory organs.

Question 22

how does etOH consumption relate to cancer in women?

Answer 22

low/moderate etOH consumption increases the risk of cancers in women.

• less than 3 drinks a day (average was 1 drink a day) still put women at risk.
• 10% of all cancer cases in men, and 3% in women are attributable to etOH consumption.
• etoH consumption above 2 drinks/day for men and 1 drink/day for women seemed to account for a significant portion of these cancer cases.

Question 23

____% of all cancer cases in men, and __% in women are attributable to etOH consumption.

Answer 23

• 10% of all cancer cases in men, and 3% in women are attributable to etOH consumption.
• etoH consumption above 2 drinks/day for men and 1 drink/day for women seemed to account for a significant portion of these cancer cases.

Question 24

in 2011, Chen et. al surveyed 75000 nurses about the correlation to alcohol and breast cancer. what did they find?

Answer 24

• saw that there was a positive correlation between alcohol consumed by female nurses and breast cancer.
• even at LOW LEVELS (3-6 glasses a week)
• concluded that there is NO SAFE threshold for alcohol consumption.
• drinking both earlier and later in life both independently associated with increased risk.

Question 25

biggest factor for the protective effect of alcohol

Answer 25

biggest factor is individual differences. Researchers have also established that moderate alcohol consumption has a protective effect on cardiovascular disease and reduced mortality. this is strange because even lower consumption may result in a predisposition for cancer.

Question 26

some researchers say alcohol is protective against cardiovascular disease. What did Hansel et al 2010 see otherwise?

Answer 26

they noticed that moderate etOH drinkers display a more favorable clinical biological profile that is consistent with decreased CV health risk. Ie/ individual differences were playing a hand as to why the alcohol drinking cohort were not experiencing heart disease.
- people are arguing that etOH is protective, but its the people with superior health status that have low cardiovascular disease and just happen to drink.

• others have said that even with biological profiles as a confounding effect, moderate alcohol consumption still shows a significant association with lower mortality risk

Question 27

relationship between Gin, red wine and BP

Answer 27

Gin consumption did not significantly affect BP.
Red Wine consumption did not significantly affect BP, BUT Deacoholized red wine consumption DECREASED BP. Issue now of red wine polyphenols and antioxidants is the reason behind supposedly-enhanced cardiovascular health effects of alcohol.

Question 28

What is resveratrol

Answer 28

a polyphenol found in grapes, red wine, chocolate etc. has anti-inflammatory effects, assocaited with reduced mortality and reduced risk of CV disease.

Contrary to expectations, resveratrol was not predictive of longevity or inflammation. CHALLENGES the notion that red wine has health benefits

Question 29

Rantakomi et. al., 2014: findings of alcohol and stroke mortality

Answer 29

strong association between frequency of EtOH and stroke mortality. Risk of stroke death was increased in men who consumed etOH greater than 2-5 drinks a week.

• after a 43 year follow up, middlife alcohl consumption increased risk of stroke by 34%. Moderate etOH consumption in women (1-2 drinks/day) showed a similar harmful effect.

Recommendations after these findings: men should consume no more than 2 drinks per day, and women should dink no more than 1 drink/day

Question 30

Note: basically, after all these study, it is (Lancet) realized that any potential benefit is offset by risk of low levels of consumption and cancer. Main conclusion: there is no “safe” level.

Answer 30

etOH accounts for close to 10% of death among 15-49 year olds

Lancets study has clinical significance criticism. The lancet 2018 study says for every 100000 people who drink 1 drink per day/year, 918 can expect to experience alcohol-related problems. BUT for those who do not dirnk 914 can expect to experience a problem. in other words, 99082 are unaffected and 914 will have an issue no matter what.
-hence, only 4 in 100,000 people who consume 1 dirnk a day may have a problem caused by drinking.

At 2 drinks/day, the number of people experiencing a problem rises to 977, aka (63/100,000). The point is that while the risks of 102 drinks per day are real, the risk is much smaller than many other risks in life.

Question 31

a study that showed effects of etOH on NTs in rabbits had results of:

Answer 31

found a whole brain DECREASE in NE after injection with etOH.

• but in reality, results are all over the place. studies have been published to show that there is no effect, decrease, or increase in catecholamines.

Question 32

How does etOH interact with limbic DA system?

Answer 32

• alcohol promotes release of DA in ventral striatum (part of the mesolimbic dopaminergic system) by reversing DA uptake. Alcohol actively interferes with reuptake.

it is therefore seen that etOH activates the limbic DA system. Acute etOH = increased DA release.

• tracking studies show that this mechanism may be similar to how amphetamine may increase DA release.

Question 33

alcohol promotes release of DA in ventral striatum (part of the mesolimbic dopaminergic system) by:

Answer 33

alcohol promotes release of DA in ventral striatum (part of the mesolimbic dopaminergic system) by reversing DA uptake. Alcohol actively interferes with reuptake.

Question 34

etOH is an ____ of ____ subtype of glutamate receptors

Answer 34

etOH is an INHIBITOR of NMDA subtype of glutamate receptors.

acute etOH depresses the responsiveness of NMDA receptors to released glutamate. Even small amounts of etOH interfere with glutamate.

Question 35

possible mechanism for etoH induced blackout

Answer 35

NMSA receptors are involved with memory and encoding and may account for the alcoholic blackout because they are easily inhibited by etOH

Question 36

how is the glutmate-etOH interaction possibly responsible for withdrawal symptoms

Answer 36

chronic etOH = compensatory up-regulation of NMDA receptors. Results in increased excitation. When etOH is removed, excess excitatory receptors from upregulation would result in more neuronal firing and can induce withdrawal signs, including seizures.

Question 37

How does GABA affect the brain

Answer 37

it is an inhibitory NT. GABA binds to its receptor so that it lets in Cl- into the cell. results in neuronal hyperpolarization and AP inhibition. Results in sedation, inhibition of cognitive and motor skills, and anti-anxiety effect.

Question 38

etoH is a GABA ___

Answer 38

gaba agonist. Causes an increase in inhibition and neuronal hyperpolarization

Question 39

short term vs chronic effects of alcohol in NTs

Answer 39

short term: GABA agonist (inhibitory), NMDA antagonist (further inhibition) results in sedation and cognitive/motor impairmnet

longterm: NMDA receptor upregulation: can INCREASE GLUT sensitivity, resulting in increased excitation. Even more NMDA receptors get activated at a lower level of NT
- when etOH is removed and no longer affecting GABA inhibitory system, there is still NMDA upregulation occurring. This results in increased excitation. It takes time to modify receptor regulation. This can cause withdrawal: this imbalance is thought to cause tremors, hallucinations, insomnia, agitation, seizures.

Question 40

cause of withdrawal symptoms of etOH

Answer 40

-when etOH is removed and no longer affecting GABA inhibitory system, there is still NMDA upregulation occurring. This results in increased excitation. It takes time to modify receptor regulation. This can cause withdrawal: this imbalance is thought to cause tremors, hallucinations, insomnia, agitation, seizures.

Question 41

Why is etOH considered a neurotoxin?

Answer 41

because of oxidative stress. OS is a general term to descrive the steady state of damage in a cell, tissue, or organ caused by reactive oxygen species. They are naturally produced during metabolism, and produced even more when trying to breakdown toxin, such as alcohol. OS are free radicals that can break down and affect the cells.

Question 42

which regions of the brain are atrophied and damaged after chronic excessive etoH consumption?

Answer 42

atrophy of the;

1) cerebral cortex
2) cerebellum
3) frontal lobe
4) hippocampus

increase in volume of ventricles (cerebrospinal fluid space)

Question 43

note: effects of EtOH on the brain

Answer 43

alcohol + fMRI

-examined rewarding and anxiolytic effects of etOH using functional mRI. Alcohol activates the striatal reward areas, esp. the ventral striatum. Increasing firing rate of DA neurons is SECONDARY to the effects seen through GABA and glutamate in the VTA. Alcohol attenuated the response to emotionally threatening stimuli by Increasing GABA, reducing excitatory glut, and stimulating the dopaminergic reward limbic system. Related to the anxiolytic effect of etOH.

Question 44

What were the findings of Makris et al 2008 who examined the volumetric changes in the reward network in brains of abstient alcoholics? aka of people who’ve had chronic exposure to alcohol?

Answer 44

Volume reduction was most pronounced in right dorsolateral-prefrontal cortex, right anterior insula, and right NAc, as well as left amygdala.

• therefore, the reward system is altered in alcoholism. There may also be a predisposition to alcohol dependence as a result of a genetic deficit in reward circuitry.
• long term alcoholism damages reward circuitry and may lead to a cycle of ACCELERATED DEPENDENCE ON ALCOHol
• ie/ alcohol –> damage –> hard to get pleasure because of mesolimbic DA damage –> more alcohol

In alcoholics, NAc and anterior insula volumes increased with length-of-abstinence, and total reward-network and amygdala volumes correlated positively with memory scores

Question 45

there is a significant ___ ____ relationship between alcohol consumption and total cerebral brain volume (TCBV)

Answer 45

there is a significant NEGATIVE LINEAR relationship between alcohol consumption and total cerebral brain volume (TCBV)

• HIGHER LEVELS OF ETOH CONSUMPTION ASSOCIATED WITH SMALLER BRAIN VOLUME AND LARGER VENTRICLE SIZE.EtOH does not have any protective effect on brain volume.
• there is more white matter in alcohlics than grey matter. indicative of cell death and brain damage.

Question 46

in contrast, how does alcohol affect the elderly

Answer 46

those 65 and older shoewd increased cognitive functioning with low to moderate alcohol consumption

Question 47

describe the laterl hypothalamus (LH) rat study and the results

Answer 47

• naive rats were fitted with an electrode directly into the LH. electrode stimulation results in more APs in the LH. the LH contains high concentrations of catecholeamines. Naive rats put in individual cage, food, H2O and alc available. Alc was free choice. animals could choose when to consume the alc.

results: 1) etOH consumped is significantly increased when following LH stimulation
2) etOH consumption remained elevated AFTER LH stimulation. The rats “remained addicted”

• suggests a role of CA’s (DA and NE) in the mediation of the positive reinforcing properties of etOH

Question 48

While LH stimulated rats seemed to have increased EtOH intake because of increased concentrations of Da and NE, how does 5HT play a role in the intake of EtOH?

Answer 48

studies have shown that BLOCKING 5ht REUPTAKE (ie increase 5HT concentration) REDUCED EtOH intake. Increased 5HT availability in synapse reduces alcohol intake.

• hence, 5HT interferes with PRP (Positive reinforcing properties) of etoH. Increased 5HT= decreased etOH

Question 49

It is seen that increased 5HT results in decreased etOH consumption. Why?

Answer 49

the 5Ht/DA interaction.

Question 50

___ DA/NE = ____ etOH consumption

____5HT = _____ etOH consumption

Answer 50

increased DA/NE = increased etOH consumption
decreased DA/NE = decreased etOH consumption
increased 5HT = decreased etOH consumption

Question 51

outline the 5Ht-DA interaction

Answer 51

5HT may have an inhibitory effect on DA receptors, primarily in the mesocortico-limbic pathways. Hence; increased 5HT = decreased DA = decreased etOH. Implicates the role of DA in etOH intake and addiction.

Question 52

alcohol promotes release of DA in ___ ____ (part of the mesolimbic dopaminergic system) by :

Answer 52

alcohol promotes release of DA in ventral striatum (part of the mesolimbic dopaminergic system) by reversing DA uptake. Alcohol actively interferes with reuptake.

Question 53

OS is a general term to describe the ____ ____ of damage in a cell, tissue, or organ caused by ___ ____ ____

Answer 53

OS is a general term to descrive the steady state of damage in a cell, tissue, or organ caused by reactive oxygen species. (ROS)