pharmacokinetics -drug metabolism

Question 1

drug metabolism

Answer 1

biochemical modification of pharmaceutical substances by living organisms usually through specialized enzymatic activity.

Question 2

what does metabolism do to lipid soluble and

non-polar drugs?

Answer 2

converts them into water soluble and polar substances which are able to be excreted

Question 3

what are prodrugs?

Answer 3

drugs that are activated by metabolism

Question 4

what is the purpose of metabolism?

Answer 4

• increase water solubility and so aid excretion.

- deactivates compounds

Question 5

examples of prodrugs

Answer 5

codeine, enalapril, simvastatin, sacubitril

Question 6

effects of metabolism in a drug

Answer 6

• Loss of pharmacological activity.
• Increase in activity, more active metabolites (prodrugs)
• Production of toxic metabolites

Question 7

what are the effects of toxic metabolites of a drug

Answer 7

• direct toxicity
• carcinogenesis
• teratogenesis (production of congenital abnormalities in an embryo or fetus)

Question 8

phase 1 of drug metabolism

Answer 8

drug is either activated or inactivated by oxidation, reduction or hydrolysis

Question 9

what does phase 1 do to the polarity of an organism?

Answer 9

increases it

Question 10

what is the most important enzyme family for phase 1 metabolism?

Answer 10

cytochrome P-450

Question 11

CYP3A4

Answer 11

the major constitutive enzyme in the liver, also found in the gut so responsible for pre-systemic metabolism

Question 12

CYP2C6

Answer 12

resposible for the metabolism of some antidepressants and codeine to morphine

Question 13

CYP1A2

Answer 13

induced by smoking and is important in the metabolism of theophylline

Question 14

phase 2 of metabolism

Answer 14

involves conjugation, this increases water solubility which enhances excretion of metabolised compound.

Question 15

factors which affect metabolism

Answer 15

• Other drugs/herbals/natural substances
• Genetics
• Hepatic blood flow
• Liver disease
• Age
• Sex
• Ethnicity
• Pregnancy

Question 16

what is induction of drug metabolising enzymes?

Answer 16

increased synthesis and therefore increased activity of an enzyme

Question 17

what effect does enzyme induction have on drug effect?

Answer 17

decreases it as there is increased metabolism

Question 18

examples of enzyme inducers

Answer 18

• alcohol
• smoking
• other drugs
• herbal drugs

Question 19

what are drug enzyme inhibitors?

Answer 19

reduce the activity of drug metabolising enzymes

Question 20

examples of drug enzyme inhibitors

Answer 20

grapefruit juice
clarithromycin
cimetidine
ketoconazole
calcium channel blockers

Question 21

how can genetic variation affect drug metabolism?

Answer 21

-individuals may express different forms of a drug metabolising enzyme
-may also have abnormal levels of an enzyme. too high- reduced effect
too low- drug toxicity

Question 22

what will lack or decreased activity of an enzyme result in ?

Answer 22

increased toxicity

Question 23

how does drug metabolism differ in children?

Answer 23

• often deficient of metabolising enzymes in fetus and premature infant renal function is reduced so drugs can build up.
• by two children can metabolise many drugs more rapidly than adults

Question 24

how does drug metabolism differ in the elderly?

Answer 24

plasma protein, lean body mass and liver weight can be significantly decreased