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Flashcards in drug metabolism Deck (25):
1

what is the purpose of metabolism of drugs?

increases water solubility so as to aid excretion
deactivation of compounds

2

can drugs be activated following metabolism?

yes

3

what are some effects of metabolism?

loss of pharmacological activity
decrease in activity, with metabolites that show some activity
increase in activity, more active metabolites
activation of a prodrug
production of toxic metabolites
change to different pharmacological properties

4

what reactions are involved in phase 1 metabolism?

hydrolysis, oxidation or reduction

5

what are the most important family of metabolising enzymes?

cytochrome p450

6

what families of cytochrome p450 are important in drug metabolism?

CYP1
CYP2
CYP3

7

what is the major constitutive enzyme in the human liver?

CYP3A4

8

what does CYP2D6 metabolise?

some antidepressants, antipsychotics, also responsible for the conversion of codeine to morphine

9

what can the CYP2D6 enzyme be induced be?

smoking

10

what can CYP1A2 be induced by?

smoking

11

what is the effect of conjugation and where does it occur?

increases water solubilty and enhances excretion
happens in phase 2 metabolism

12

what factors can affect the rate of metabolism?

other drugs
genetics
hepatic blood flow
liver disease
age
sex
ethnicity
pregnancy

13

what is enzyme induction?

increased synthesis of the enzyme, which results in increased activity

14

what is the effect of enzyme induction?

decreased drug effect

15

what factors can cause enzyme inhibition?

commonly used drugs can cause enzyme inhibition through a range of mechanisms including reversible and irreversible binding to the enzyme

16

what can gene mutations cause with regard to enzymes that metabolise drugs?

can cause deficiencies or complete absence of enzymes required to metabolise drugs
less commonly there may be multiple expressions of a particular metabolising enzyme, which increases enzyme activity, reduces drug effect

17

what effect does decreased enzyme activity have?

increased drug toxicity

18

in the fetus/infant, what is the state of drug metabolising enzymes?

often deficient/reduced

19

what four phenotypic populations of metabolizers are there?

poor metabolisers
intermediate metabolisers
exstensive metabolizers
ultrarapid metabolizers

20

what are some enzymes that exhibit genetic variation?

pseudocholinesterase
N- acetyltransferase
cytochrome p450 2D6
cytochrome p450 2C19

21

what is the rate of metabolism in puberty compared to adulthood?

greater

22

what is the effect of pregnancy on drug metabolism?

some enzymes are induced during second and third trimester

23

why are the elderly more likely to be on multiple drug therapy?

chronic disease is more common

24

what effect does ethnicity have on drug metabolism?

many incidences of racial differences in the genetic expression of cytochrome p-450 isoforms

25

why is ADME important?

determines how to:
get the drug to its site of action
determines the dose and frequency
making sure the drug is present in an effective dose whilst avoiding toxicity
making changes in drug therapy based on other drugs, illness or physiological factors.