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Jason's GI Block > Liver Detox & Alcohol > Flashcards

Liver Detox & Alcohol Flashcards

1
Q

Cytochrome P450 oxidises all foreing chemicals with MW of?

A

<5000

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2
Q

Which Cytochrome P450 metabolises paracetomol?

A

Cytochrome P450 2E1

CYP2E1

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3
Q

Where do you find Cytochrome P450 enzymes in the cell?

A

Endoplasmic reticulum

mitochondria

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4
Q

What is the formula for Cytochrome P450 monoxygenase catalyse?

A

RH + NADPH + H+ + O2 –> ROH + H2O + NADP+

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5
Q

What happens if CYP 2D6 is deficient?

A

failure to convert codeine to morphine

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6
Q

What does the initial alternation in Cytochrome P450 involve?

A

addition of -OH group and then a sugar to make it soluble

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7
Q

where is Cytochrome P450 located on the ER?

A

Microsomes

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8
Q

Cytochrome P450 is an enzyme? or a pigment?

A

Enzyme

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9
Q

P450 is in the microsomes? or the ER?

A

ER

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10
Q

What colour are Microsomes?

A

PInk

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11
Q

What are the P450 in mitochondria used for?

A

oxidising steroids esp. in adrenals

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12
Q

Cytochromes (not P450) also function in what?

A

oxidative phosphorylation

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13
Q

Food toxins do what to your P450?

A

promotes variants of P450, can train your liver to metabolize more toxins slowly

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14
Q

how many P450 genes in humans?

A

57

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15
Q

CYP 2A6

What is CYP, 2, A, 6?

A

CYP: P450
2: family
A: subfamily
6: Form

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16
Q

Each family in P450 share ___% same sequence?

A

40%

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17
Q

Each subfamily in P450 share ___% same sequence?

A

> 55%

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18
Q

what does the hydrophobic protein foot of P450 enzymes do?

A

anchors P450 to a membrane eg. ER

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19
Q

are P450s inducible?

A

yes if substrates are persistently present

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20
Q

what makes P450 pink?

A

haem prosthetic group

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21
Q

What anchors the haem to the protein in P450?

A

cysteine anchor

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22
Q

P450 is a mono or di or tri-oxygenase?

A

mono-oxygenase

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23
Q

how does P450 get collateral damage during oxidation?

A

reactive O2 species don’t always hit their mark, since they are immediately next to substrate, it may damage P450 in process

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24
Q

peroxide usually attacks substate to form R-OH but when it doesn’t, what does it create?

A

epoxide

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25
Q

epoxides from P450 reaction gone awry does what?

A

highly reactive with DNA

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26
Q

imipramine is a tricyclic what? discovered how?

A

antidepressant, from a TB drug trial

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27
Q

What is the Ames test?

A

to see if your product has dioxins which are carcinogenic

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28
Q

aflatoxin from corn and nuts fungus contributes what severity of ?

A

kwashiorkor

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29
Q

kwashiorkor children have low what?

A

low albumin and high oedema

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30
Q

Drugs what induce P450 can do 3 things:

A

activate the gene dioxin/phenobarbital
stabilise mRNA
protect P450 from turnover

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31
Q

dioxin induces CYP ____ leading to what?

A

CYP 1A1

cancer, birth defects, immunocompromise

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32
Q

how much dioxins needed to cause problems?

A

picogram quantities

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33
Q

What was agent orange?

A

dioxins and benzopyrenes

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34
Q

Phenobarbital used for? acts where?

A

anesthetic by vets

acts on DNA

35
Q

Some drugs where poor metabolisers have adverse reactions due to P450 polymorphisms include?

A

warfarin
opioids
fluorouracil
diazepam

36
Q

If CYP 2D6 is inactive what happens?

A

poor metabolism of codeine = no analgesic action

37
Q

test for CYP 2D6 in patients how?

A

PCR with a kit

38
Q

Is cirrhosis reversible?

A

Nope

39
Q

how many Australians have health problems related to risky alcohol intake?

A

2-3 million

40
Q

Aldehyde dehydrogenase converts acetaldehyde to acetate, what is acetate used for? 2 things

A

oxidised for energy or converted into fat

41
Q

how fast to most people clear alcohol from their system?

A

1 standard drink per hour

42
Q

should we completely abstain from alcohol?

A

no. moderate amounts confers better health and longevity

43
Q

Fermenting to make alcohol was univeral to all civilisations except”

A

aboriginal australians

44
Q

compare ethanol to fat

A

almost identical in energy content

45
Q

how does alcohol depress nervous function?

A

ethanol disrupts membrane fats and make them more leaky and harder to fire properly

46
Q

High risk to health, how many drinks for men and women?

A 
Men = 6+
Women = 4+
47
Q

FAS features?

A

small irreversibly shrunken brains affecting their entire lives

48
Q

Alcoholic signs include? from head to toe

A 
neuro
jaundice
altered breath
esophageal varices
gynecomastia
Heart disease and arrythmia
scarred liver
portal hypertension
capat medusa
ascites
hand tremor
hypogonadism
bruisibility
muscle wasting
osteoporosis
edema
49
Q

How fast does fatty liver develop? reversible or irreversible?

A

rapid development and reversible

50
Q

3 presentations of alcohol induced liver damage?

A

fatty liver
alcoholic hepatitis with inflamm
alcoholic cirrhosis

51
Q

50% of heavy drinkers present with fever and jaundice and abdo pain, what is the likely diagnosis?

A

alcoholic hepatitis with widespread inflamm

52
Q

15-30% of heavy drinkers with extensive fibrosis and distorted internal liver structure are diagnosed with?

A

alcoholic cirrhosis

53
Q

How much of your liver do you need to function normally?

A

40%

54
Q

How much alcohol entered system through stomach vs. gut?

A

stomach: 30%
Gut: 70%

55
Q

how much of the alcohol is metabolized in liver? in lungs and kidneys? the rest?

A

90%
<2% in lungs and kidneys
rest by stomach

56
Q

what percentage of alcohol do you lose consciousness?

A

0.3%

57
Q

ethanol>acetylaldehyde>Acetate gets converted to what and then fed where?

A

acetyl CoA then into Krebs cycle

58
Q

why do you feel faint if you have alcohol on an empty stomach?

A

Alcohol Dehydrogenase makes NADH which represses gluconeogenesis and leads to hypoglycemia = faintness

59
Q

what is MEOS? how do it get activated?

A

microsomal ethanol oxidising system.
due to chronic alcohol: induces CYP2E1 four fold
Catalase is minor pathway

60
Q

why are women affected by alcohol more?

A

alcohol does not distribute into fat as in men

61
Q

three quick drinks raises you alcohol to?

A

0.05%

62
Q

How much alcohol in % can your liver clear per hour?

A

0.015

63
Q

Why is alcohol clearance so slow?

A

alcohol dehydrogenase kinetics maxes out very fast

64
Q

alcohol breath tests over or underestimates?

A

underestimates

65
Q

alcohol has 2 effects on drugs?

A

prevents drug clearance due to competition

promotes drug clearance due to elevated CYP 2E1

66
Q

one really important drug alcohol affects

A

warfarin

67
Q

warfarin + alcohol =

A

a bad day…..

68
Q

Hepatocytes are damaged via alcohol because 4 reasons

A

1 more free-radical damage due to decrease glutathione
2 dietary neglect
3. MEOS increases free radicals
4. increase iron catalyst for free radicals

69
Q

Wernicke Korsakoff syndrome cause? and symptoms?

A

thiamine deficiency

wide step, nystagmus, confusion, hypothermia, amnesia, confabulation

70
Q

what is ALDH2?

A

acetylaldehyde dehydrogenase II in the mitochondrias and most important

71
Q

acetylaldehyde dehydrogenase II inherited as recessive or dominant?

A

dominant

72
Q

acetylaldehyde dehydrogenase II missing in ____% of Asians?

A

40%

73
Q

What is disulfiram/antabuse used for

A

inhibites aldehyde dehydrogenase = nausea, vomiting with alcohol consumption

74
Q

Which could be a reward centre in the brain for alcohol?

A

Dopamine D2 receptor regulates reward reinforcement

75
Q

What are Naltrexone, Nalmefene, Tiapride, Acamprosate used for?

A

neurological Rx to decrease craving and ease withdrawal with alcohol

76
Q

Physical signs during examination for alcoholism?

A

spider naevi, palmar erythema, gynecomastia, change in body hair, peripheral neuropathy

77
Q

Gamma-glutamyltranspeptidase (GGT) is what?

A

elevated in almost any liver disease, but could be increased in heavy drinkers even without liver damage or inflamm

78
Q

is ALT elevated in alcohol liver damage?

A

yes

79
Q

what is carbohydrate deficient transferrin? when is it elevated?

A

marker for alcohol consumption greater than 4-5 drinks per day

80
Q

why does alcohol cause dehydration

A

alcohol interferes with pituitary, less vasopression>less reabsorption of water>more peeing>dehydration

81
Q

Alcohol causes most problems when in pregnancy?

A

in utero, first trimester

82
Q

FAS features?

A

small irreversibly shrunken brains affecting their entire lives

83
Q

definition of binge drinking?

A

more than 10 standard drinks in one sitting

84
Q

alcohol help with cancer?

A

NOPE.

Jason's GI Block (32 decks)

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