Exam 1- lectures 5,6,&7 Flashcards Preview

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Flashcards in Exam 1- lectures 5,6,&7 Deck (63):
1

PM

poor metabolizers

2

EM

extensive metabolizers

3

What phase of metabolism are CYP enzymes?

Phase I

4

what phase of metabolism are NAT, UGT & GST?

Phase II

5

CYP450 oxidizes drugs by adding:

an -OH group

6

CYP4 is mainly used for

lipid metabolism

7

CUP1A2

caffeine, melatonin, theophylline

8

CYP2A6

Coumarin, Nicotine

9

CYP2B6

buproprion, efavirenz, S-mephenytoin

10

CYP2C8

paclitaxel, pioglittazone

11

CYP2C19

omeprazole, S-mephenytoin

12

CYP2D6

dextromethorphan, debrisoquine, metoprolol

13

CYP3A

midazoleam, cortisol

14

CYP3A4

- largest form expressed in the liver
- metabolizes 45-60%
- NO grapefruit juice
- 18 variants
- erythromycin, nifedipine, cyclosporin, midazolam

15

CYP2C9

- 20% of liver P450
- warfarin, phenytoin, losartan, fluvastain, NSAIDs
- 2 major variants
- mainly caucasians

16

CYP2C9*2

cys 144 instead of Arg 144; fairly small effects

17

CYP2C9*3

leu 359 instead of Ile 359; pronounced reduction in catalytic activity; PM

18

CYP2C19

-S-mephenytoin
- 9 variants
- many drugs are metabolized by other P450
- Caucasians lowest
- chinese highest

19

CYP2D6

- PM autosomal recessive- so need to be homo
- 4 groups of metabolizers
- debrisoquine- dextromethorphan, codeine, oxycodone, TCAs, SSRIs, beta blockers

20

phase I enzymes convert drug to what form?

may be active or inactive

21

phase II enzymes convert drug to what form?

usually inactive

22

phase II drugs

improve drugs water solubility & prepare it for elimination

23

glucuronyl transferase (UGT) MOA

-takes UDP-glucuronic acid & transfers the sugar group to drug
- conjugates bilirubin
- imp. for NSAIDs & tylenol & inrinotecan

24

crigler-najjar disease

deficiency of UGTA1 & leads to jaundice

25

gilbert's syndrome

associated with UGT1A1 deficiency
- compromised bilirubin elimination

26

UGT1A6 deficiency

can lead to acetominophen sensitivity

27

glutathione-S-Transferase (GST)

- conjugates drugs through formation of thioester linkage
- highly expressed in liver
- 4 classes: A,M,P,T

28

N-Acetyl Transferase (NAT)

- acetylators

29

where is NAT1 found?

in most tissues

30

where is NAT2 found?

in liver & gut
significant polymorphisms

31

wild type NAT

probably rapid acetylatos

32

isoniazid-phenytoin interaction

slow acetylators show higher [] of isoniazid which inhibits hydroxylationof phenytoin, increasing its []->toxicity

33

PM effects

- < first pass metabolism
- > oral bioavailability
- < metabolic clearance
- > half life
- > drug effects & toxicity
- < metabolits
- possible inhibition of metabolism of other drugs

34

ultra-rapid metabolizer effetcs

- > first pass metabolism
- < oral bioavailibility
- > metabolic clearance
- < half life
- < therapeutic effects
- > metabolites

35

GPCRs

beta adrenergic receptor, serotonin receptor, mu-opiod receptor (beta-blockers, antipsycotics/antidepressants, opioid analgesics)

36

Transporters & ion channels

sodium channel, K channel, serotonin transporter (antiarrhythmics, antipsycotics/antidepressents)

37

nuclear hormone receptors

estrogen receptor, androgen receptor, glucocorticoid receptor (hormone therapy, glucocorticoids)

38

enzymes

angiotensin converting enzyme (ACE),(ACEI)

39

beta-agonist

reactive airway disease

40

beta-blockers

cardiovascular disease

41

beta 1

heart

42

beta 2

lungs

43

enhanced receptor down regulation in response to beta2 agonist

less efficacy

44

resistant to receptor down regulation

better efficacy

45

reduced affinity for some beta2 agonist

less binding, less efficacy

46

activatio of 5-LOX receptor produces:

leukotrienes

47

decreased expression of ALOX5

less responsive to leukotriene inhibitors-> disease not mediated by leukotrienes

48

increased expression of ALOX5

more responsive to leukotriene inhibitors->leukotrienes play a major role in disease

49

what is clozapine used to treat and where does it act?

acts on 5-HT2A receptors to treat schizophrenia

50

mutation in 5-HT2A receptor

his->Tyr

51

side effects of clozapine

agranulocytosis, seizures, mycarditis

52

CYP2D6 role in opioids

codeine->morphine (active)

53

UGT role in opioids

morphine->metabolites

54

QT prolongation risk factors

female, concomitant meds, long QT syndrome (LQTS)- mutations in various ion channels

55

LQT1

potassium ion
most common

56

LQT2

potassium ion
second most common
drug induced

57

LQT3

sodium ion

58

LQT5 &6

potassium ion
rare

59

LQT1&2 treatment

K supplementation & K channel openers

60

LQT3 treatment

Na channel openers

61

abacavir genotype

HLA-B*5701 (MCH class I)
can be fatal

62

carbamazepine genotype

HLA-B*1502
stevens-johnson syndrome
can be fatal

63

allopurinol genotype

HLA-B*5801