drug metabolism

Question 1

what is the purpose of metabolism of drugs?

Answer 1

increases water solubility so as to aid excretion

deactivation of compounds

Question 2

can drugs be activated following metabolism?

Answer 2

yes

Question 3

what are some effects of metabolism?

Answer 3

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

Question 4

what reactions are involved in phase 1 metabolism?

Answer 4

hydrolysis, oxidation or reduction

Question 5

what are the most important family of metabolising enzymes?

Answer 5

cytochrome p450

Question 6

what families of cytochrome p450 are important in drug metabolism?

Answer 6

CYP1
CYP2
CYP3

Question 7

what is the major constitutive enzyme in the human liver?

Answer 7

CYP3A4

Question 8

what does CYP2D6 metabolise?

Answer 8

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

Question 9

what can the CYP2D6 enzyme be induced be?

Answer 9

smoking

Question 10

what can CYP1A2 be induced by?

Answer 10

smoking

Question 11

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

Answer 11

increases water solubilty and enhances excretion

happens in phase 2 metabolism

Question 12

what factors can affect the rate of metabolism?

Answer 12

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

Question 13

what is enzyme induction?

Answer 13

increased synthesis of the enzyme, which results in increased activity

Question 14

what is the effect of enzyme induction?

Answer 14

decreased drug effect

Question 15

what factors can cause enzyme inhibition?

Answer 15

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

Question 16

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

Answer 16

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

Question 17

what effect does decreased enzyme activity have?

Answer 17

increased drug toxicity

Question 18

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

Answer 18

often deficient/reduced

Question 19

what four phenotypic populations of metabolizers are there?

Answer 19

poor metabolisers
intermediate metabolisers
exstensive metabolizers
ultrarapid metabolizers

Question 20

what are some enzymes that exhibit genetic variation?

Answer 20

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

Question 21

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

Answer 21

greater

Question 22

what is the effect of pregnancy on drug metabolism?

Answer 22

some enzymes are induced during second and third trimester

Question 23

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

Answer 23

chronic disease is more common

Question 24

what effect does ethnicity have on drug metabolism?

Answer 24

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

Question 25

why is ADME important?

Answer 25

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.