Drug Metabolism

Question 1

What is metabolism

Answer 1

Biochemical modification of pharmaceutical substances through enzyme activity

Question 2

What happens to lipid soluble substances instead of getting excreted?

Answer 2

Passively reabsorbed from renal or extra renal excretory sites back into the blood

Question 3

What are the important sites of metabolism

Answer 3

Liver
Gut lumen
Kidney
Lungs

Question 4

Purpose of metabolism?

Answer 4

To increase water solubility and so aid excretion

or to deactivate compounds (may involve a number of steps).

Question 5

What are prodrugs?

Answer 5

Drugs activated by metabolism

Question 6

What are the effects of metabolism

Answer 6

Loss of pharmological activity

Production of toxic metabolite

Question 7

What are phase 1 reactions of metabolism?

Answer 7

OXIDATION
REDUCTION
HYDROLYSIS

Question 8

What does phase 1 metabolism involve

Answer 8

Increased polarity of compound provides active site for Phase 2
Cytochrome P450 metabolising enzymes
P450 determines drug specificity

Question 9

What are the functions of CYP1
CYP2
CYP3

Answer 9

CYP1- metabolises theophylline
CYP2- metabolism of antis, converts codeine-> morphine
CYP3- Enzyme in liver, gut, presystemic metabolism of many drugs

Question 10

What is the main role of the CYP1-3 families (contained within the P-450 family)

Answer 10

Important in oxidative drug metabolism

Question 11

Where are enzymes found that are responsible for the breakdown of SOME drugs

Answer 11

CYP3A4 - Liver + Gut
Omeprazole

Question 12

Why may 5-10% of the population may be immune to the analgesic actions of codeine?

Answer 12

Reduced expression of the enzyme responsible for conversion of codeine to morphine

Question 13

Why do smokers require a higher dose of theophylline than non-smokers?

Answer 13

Enzyme responsible for the metabolism of theophylline is induced by smoking

Question 14

What does phase 2 metabolism involve?

Answer 14

Conjugation

Attachment of glucoronic acid, glutathione, sulphate or acetate to the metabolite generated by phase 1 metabolism

Usually results in inactivation

Question 15

What does conjugation increase

Answer 15

Water solubility

Excretion of metabolised compound

Question 16

What factors affect metabolism?

Answer 16

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

Question 17

What is the effect of induction of drug metabolising enzyme on metabolism?

Answer 17

Increased enzyme synthesis
increased activity
Decreased drug effect

Question 18

What is the effect of inhibition of drug metabolising enzyme on metabolism?

Answer 18

Reversible or irreversible binding to the enzyme

Metabolism decreased

Question 19

What is the effect of decreased enzyme activity on drug metabolism?

(can be as a result of genetic polymorphism)

Answer 19

Increased drug toxicity

Question 20

What are the four phenotype subpopulations of metabolizers?

Answer 20

Poor metabolizers (PM)
Intermediate metabolizers (IM)
Extensive metabolizers (EM)
Ultrarapid metabolizers (UM)

Question 21

Describe the prevalence of drug metabolising enzymes in the fetus or premature infant?

Answer 21

Deficient or reduced
renal function deficient so drug metabolites rapidly build up to toxic levels.

Question 22

Who metabolises drugs faster - a teenager at puberty or an adult?

Answer 22

At puberty

Question 23

What can affect the metabolism of drugs in a pregnant woman?

Answer 23

The trimester she is in

Hormonal changes

Question 24

What factors brought about in old age alter drug metabolism?

Answer 24

Plasma protein
Lean body mass
Liver weight

DECREASE

Other drugs taken to treat chronic illness

Question 25

Which cytochrome P450 is responsible for the genetic variation in the metabolism of warfarin?

Answer 25

CYP2C9

Question 26

Metabolism of Paracetamol by which cytochrome P450

Answer 26

CYP2E1