Drug Metabolism, Cology, James

Front 1

the most common pharmcological activity due to biotransformation

Back 1

active drug to inactive metabolite

Front 2

phy-chem proper after biotransformation

Back 2

water solubility increased

Front 3

the --- and ---- of biotransformation will affect the duration of action of the drug

Back 3

rate

extent

Front 4

which is more predictable toxicity r/t to pharm activity or unrelated

Back 4

r/t

Front 5

an example of toxicity r/t pharm activity

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too much antiHTN leading to hypotension

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main organ of biotransfomation

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liver

Front 7

what part of gi tract metabolizes

Back 7

upper intestine

important for ORAL meds

Front 8

what parts participates in entero-hepatic cycling of glucuronides

Back 8

liver

upper intestine

Front 9

name some intrinsic factors

Back 9

age

genetic make up

Front 10

name some extrinsic factors

Back 10

nutritional status

diet

drugs (including herbal)

disease state

Front 11

some things that affect metabolism

Back 11

xenobiotics

cofactors/cosubstrates

drug metabolizing enzyme

affinity to enzyme

molecular structure

Front 12

name some things r/t genetic polymorphism

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protein structure affected

affinity of enzyme to drug

altered expression of affected enzyme

Front 13

CYP2D6 affected -- containing drugs

Back 13

N

Front 14

low #'s of -------- are poor metabolizers of n containing drugs.

this affects 1-15 % of the population

Back 14

CYP2D6

Front 15

this enzyme is lacking in many orientals, but not in caucasians

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CYP2C19

polymorphism: less active drug expressed or enzyme different due to change in a.a. of the active site

Front 16

genetic variation in ---- family lead to low rates of conjugation of bilirubin and certain drugs

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UGT1

Front 17

genetic variation in UGT1 family lead to low rates of conjugation of ------ and certain drugs

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bilirubin

Front 18

inability of person to form GLUCORONIDE conjugates of bilirubin

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gilbert's syndrome

Crigler-Nager syndrom

Front 19

what gets rid of bilirubin

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glucoronide

Front 20

newborns have low levels of -----

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UGT

hence jaundice in many babies

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as you get older metabolism slows/speeds down/up

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slows down after age 65

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enzymes increase until age --

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65

Front 23

alteration in genes prevent expression of an ---- -----

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active protein

Front 24

what part of the gene may exhibit polymorphism

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promoter

Front 25

which region controls enzymes

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promoter

Front 26

a variation in the promoter region will cause a variation in the enzyme ----

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action

Front 27

1st recognized genetic polymorphism

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NAT-2

Front 28

what drug does NAT-2 metabolize

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isoniazid

Front 29

what drug does CYP2C19 metobolize

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mephenytoin

Front 30

which ethnic group has low incidence of slow acetylators

have high incidence

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asian and native americans

swedish

Front 31

how many americans are slow acetylators

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about 50%

Front 32

toxicity is a concern if the pt is a slow/rapid acetylators

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slow

w/ rapid ineffectiveness is a concern

Front 33

how can CYP2D6 be have low activity?

high activity?

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unstable: low activity

extra copies: high activity

Front 34

omeprazole

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CYP1A

also responsible for caffeine, theophylline, cigarette smoke

Front 35

phenobarbital, carbamazepine, isoniazid

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CYP 2 and 3

Front 36

isoniazid

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CYP2E1

Front 37

Clofibrate

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CYP 4

Front 38

Rifampin

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CYP3A4 and 5

Front 39

what detoxes and the enzyme?

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olitpraz induces GST which detoxifies by inducing glucothione

Front 40

CYP 1 and 2

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PCBs

DDT

Front 41

Ethanol

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CYP2E1

Front 42

tobacco, charcoal-broiled food

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CYP1A2

also theophylline, caffeine

so if a pt has asthma med will not be as effective due to increase metabolism

need increased amounts of med

Front 43

CYP3A4

Back 43

St. John's wort

Front 44

CYP2E1

Back 44

ETHANOL

ISONIAZID

Front 45

what can downregulate during an infection

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cytokines

Front 46

what can downregulate CYP2 and 3 family members

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interferons

Front 47

cirrhosis can lead to increased/lowered drug metabolizing enzymes

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lowered

Front 48

if more than 50 fold variation what's it due to

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genetics

Front 49

less than 50 fold due to

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exposure to something that can cause upregulation of CYP

Front 50

which one's higher UGT 1 or PAPS

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UGT 1

that's why glucoronidation is a major pathway

Front 51

what's higher in high conc in the liver

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GSH

NADPH

NADH

UGT 1

Front 52

poor nutrition can lead to lower ---- conc

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GSH

Front 53

protein calorie malnutrition leads to lower free aa and reduced ---- conjugation

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aa

Front 54

A person on a protein-poor diet is likely to have less ------ in their cells than someone who eats meat daily.

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glutathione (GSH)

cuz less aa

Front 55

what lowers NADPH and reduces drug monooxygenation

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ethanol

Front 56

cocktails for hiv work how?

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by one drug binding w/ the highest affinity and the others circulating and having antiviral effects

less dose needed: cheaper

Front 57

how do you prevent toxicity due to lack of oxygenation

Back 57

giving meds at different times

Front 58

what does grapefruit juice inhibit

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CYP3A

important efflux transporter in enterocytes, MDR1

usu limits how much gets into bloodstream

Front 59

what inhibits CYP3A4

what induces it?

Back 59

inhibits: bioflavonoids

induces: St. John's Wort