Metabolism and Pharmacokinetics

Question 1

main organ involved in drug metabolism is

Answer 1

the liver

Question 2

main route of drug conjugation is by

Answer 2

glucuronidation

Question 3

metabolism can be divided into

Answer 3

two phases

Question 4

phase 1 metabolism involves

Answer 4

• oxidation
• reduction
• hydrolysis

which leads to activation/inactivation of drug

Question 5

phase 2 metabolism involves

Answer 5

conjugation/glucurodination which produces conjugation products

Question 6

what is family of enzymes are responsible for the majority of drug oxidation

Answer 6

cytochrome p450

Question 7

cytochrome p450 consists of

Answer 7

a number of isozymes with differing substrate specificity and regulatory mechanisms

Question 8

Drug metabolism =

Answer 8

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

Question 9

water-soluble substances undergo

Answer 9

excretion

Question 10

lipid soluble substances are

Answer 10

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

Question 11

where are drugs metabolised

Answer 11

• LIVER,
• lining of the gut
• the kidneys
• the lungs.

Question 12

where are drugs metabolised

Answer 12

• LIVER,
• lining of the gut
• the kidneys
• the lungs.

Question 13

Purpose of metabolism:

Answer 13

• to increase water solubility and so aid excretion

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

Question 14

what are prodrugs

Answer 14

drugs that are activated following metabolism.

Question 15

prodrug example

Answer 15

• codeine
• enalapril
• simvastatin
• sacubitril

Question 16

Production of toxic metabolites can cause

Answer 16

• direct toxicity
• carcinogenesis
• eratogenesis

Question 17

Effects of Metabolism

Answer 17

• production of toxic metabolites
• loss of pharmacological activity
• decrease in activity with metabolites that show some activity
• increase in activity, more active metabolites
  - prodrug activation

Question 18

enzymes that are divided into families or subfamilies have

Answer 18

wide substrate specificity and one drug can be metabolised more than one enzyme

Question 19

phase one metabolism steps

Answer 19

• polar groups are exposed to introduced to a molecule
• involves hydrolysis, oxidation or reduction
• this increases the polarity of compound and provides active site for phase 2 metabolism

Question 20

cytochrome p450 and isoforms involved in oxidative drug metabolism

Answer 20

CYP1A2 = theophylline
CYP2D6 = codine
CYP3A4 - cyclosporin

Question 21

relative drug specificity is determined by

Answer 21

isoform of cytochrome p450

Question 22

major constitutive enzyme in human liver

Answer 22

CYP3A4 = cyclosporin

• contributes to the metabolism of a wide range of drugs
• also found in the gut and is responsible for the pre-sysytemic metabolism of several drugs.

Question 23

responsible for the metabolism of some antidepressants, antipsychotics

Answer 23

CYP2D6 = codeine

• converts codeine into morphine
• Induction by cigarette smoking may be important in psychiatric patients
• 5-10% of the population may be immune to the analgesic actions of codeine

Question 24

important in the metabolism of theophylline

Answer 24

CYP1A2 = theophylline

• induced by smoking
• smokers require higher dose than non smokers

Question 25

conjugation increases

Answer 25

water solubility and enhanced excretion of metabolised compound.

Question 26

conjugation involves

Answer 26

attachment of

Question 27

conjugation involves

Answer 27

attachment of glucuronic acid, glutathione, sulphate or acetate into metabolite generated by phase 1 metabolism

Question 28

conjugation usually results in

Answer 28

inactivation but a small number of rug metabolites may be active.

Question 29

in phase 2 metabolism a molecule endogenous

Answer 29

to the body donates a portion of itself to the foreign molecule.

Question 30

Factors Which Affect Metabolism

Answer 30

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

Question 31

Induction of an enzyme involves

Answer 31

increased synthesis and therefore increased activity.
- The most common enzyme inducers include alcohol and smoking.
-

Question 32

Many commonly used drugs herbal medicines and food stuffs may

Answer 32

conversely inhibit drug metabolising enzymes.
- May be reversible or irreversible binding to the enzyme.
eg - grapefruit, cimetidine, erythromycin

Question 33

Grapefruit Juice Increases

Answer 33

Felodipine Oral Availability in Humans by Decreasing Intestinal CYP3A Protein Expression

Question 34

Lack or decreased activity of an enzyme often results in

Answer 34

increased drug toxicity.

Question 35

Dose adjustments are required for

Answer 35

drugs in individuals who have the mutant enzymes

Question 36

Drug metabolising enzymes are often deficient or reduced in

Answer 36

the fetus or premature infant.

- Renal function is also deficient so drug and metabolites rapidly build up to toxic levels

Question 37

By the age of two years children can metabolise

Answer 37

many drugs more rapidly than adults.

Question 38

By puberty the rate of metabolism is

Answer 38

greater than that of adults

Question 39

Hormonal changes during development have a profound effect on

Answer 39

drug metabolism

Question 40

In the elderly parameters such as

Answer 40

plasma protein, lean body mass and liver weight decrease significantly and so alter drug metabolism.
- Chronic disease is also more common and so the elderly are likely to be on multiple drug therapy

Question 41

Metabolism is an important process in

Answer 41

eliminating drugs from the body.