Drug Metabolism

Question 1

What is the effect of metabolism

Answer 1

limits the life of a substance in the body, by rendering lipid soluble and non-polar compounds to water soluble and polar compounds so that they can be excreted

Production of toxic metabolites (direct toxicity, carcinogenesis)

Loss of pharmalogical activity

Increase in prodrug

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

Purpose of metabolism?

Answer 3

To increase water solubility and so aid excretion
or to deactivate compounds (may involve a number of steps).

Question 4

What are prodrugs?

Answer 4

Drugs activated following metabolism

Question 5

What are phase 1 reactions of metabolism?

Answer 5

OXIDATION
REDUCTION
HYDROLYSIS

Question 6

What is the purpose of phase 1 metabolism?

Answer 6

Increases polarity of the compound

Provides active site for phase 2 metabolism

Question 7

What is the most important super family of metabolising enzymes?

Answer 7

Cytochrome P-450 enzymes

Question 8

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

Answer 8

Important in oxidative drug metabolism

Question 9

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

Answer 9

CYP3A4 - Liver + Gut

Question 10

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

Answer 10

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

Question 11

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

Answer 11

Enzyme responsible for the metabolism of theophylline is induced by smoking

Question 12

What does phase 2 metabolism involve?

Answer 12

Conjugation

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

Usually results in inactivation

Question 13

What factors affect metabolism?

Answer 13

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

Question 14

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

Answer 14

Increased synthesis of the enzyme - increased activity - Decreased drug effect

Question 15

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

Answer 15

Reversible or irreversible binding to the enzyme

Metabolism decreased

Question 16

What is the effect of decreased enzyme activity or lack of an enzyme responsible for drug metabolism?

(can be as a result of genetic polymorphism)

Answer 16

Increased drug toxicity

Question 17

What are the four phenotype subpopulations of metabolizers?

Answer 17

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

Question 18

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

Answer 18

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

Question 19

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

Answer 19

At puberty

Question 20

What areas in drug response does disparity occur between genders?

Answer 20

Absorption
Distribution
Metabolism
Eliminiation

Question 21

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

Answer 21

The trimester she is in

Hormonal changes

Question 22

What factors brought about in old age alter drug metabolism?

Answer 22

Plasma protein
Lean body mass
Liver weight

DECREASE

Other drugs taken to treat chronic illness