Drug metabolism

Question 1

define Drug metabolism

Answer 1

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

Question 2

Where are drugs usually metabolised

Answer 2

The liver

Question 3

What happens to lipid soluble drugs instead of excretion

Answer 3

passively reabsorbed from renal filtrate and absorbed back into the blood

Question 4

What is the purpose of drug metabolism and

what else can occur from the process that can cause an adverse reaction

Answer 4

increase water solubility to aid excretion
deactivate compounds
Toxic metabolites

Question 5

What are pro drugs (example)

Answer 5

drugs activated following metabolism e.g. codeine

Question 6

What is the most important metabolising enzyme family in the liver

Answer 6

Cytochrome P450

Question 7

What are the two ways metabolising enzymes can be expressed

Answer 7

constitutively -continuously

or Induced in the presence of substrate

Question 8

What process occur in phase 1 metabolism and what is the purpose of the processes

Answer 8

Oxidation Reduction Hydrolysis

To increase polarity

Question 9

How is drug specificity determined in the liver

Answer 9

isoform of cytochrome P450

Question 10

What are the three isoforms of cytochrome P450

Answer 10

CYP1A2
CYP2D6
CYP3A4

Question 11

What are the drug substrates for
CYP1A2
CYP2D6
CYP3A4

Answer 11

CYP1A2 - theophyline - respiratory diseases
CYP2D6 - codeine - pain relief
CYP3A4 - cyclosporine - immunosuppressant drug

Question 12

What is the purpose of CYP2D6 and what induces the enzyme

Answer 12

metabolises antidepressant

smoking

Question 13

What would happen if someone who smokes and takes antidepressants stops smoking

Answer 13

Induced levels go away but level of drug concentration remains this causes an accumulation of the drug resulting in toxicity

Question 14

What would happen to people that don’t have CYP2D6 enzyme and take codeine

Answer 14

Cant metabolise to morphine so don’t receive any pain relief

Question 15

What enzyme is a major constitutive enzyme

Answer 15

CYP3A4

Question 16

How is it easy to cause toxicity giving smoking patients theophlyine

Answer 16

As smoking induces enzyme CYP1A2, therefore if patient was to stop smoking the concentration of the drug would be to high as enzymes level decrease, the accumulation causes toxicity

Question 17

What are the factors affecting metabolism

Answer 17

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

Question 18

What are the most common enzyme inducers

Answer 18

alcohol and smoking

Question 19

What is enzyme induction and

how long does it take to take an effect

Answer 19

Increase synthesis of enzymes therefore increases the metabolism of a drug
Is a slow process = progressive loss of drugs affect

Question 20

How long does it take for enzyme inhibition to occur

Answer 20

Immediate response

Question 21

What ar common enzyme inhibitor drugs

Answer 21

cimetidine - inhibits stomach acid production
erythromycin - antibiotic 
clarithromycin - antibiotic 
ketoconazole - fungal infections 
grapefruit

Question 22

what is pharmacogenetics and what is the problem

Answer 22

A branch of pharmacology concerned with effects of genetic factors
You will over treat or under treat some patients

Question 23

wha is the consequences genetic variation in pharmacology

Answer 23

therapeutic failure or an adverse drug reaction

Question 24

How is genetic variation tackled

Answer 24

Wide variability in the response to drugs between individuals
Drug metabolising enzymes are often expressed in multiple forms

Question 25

Gene mutations resulting in lack or decreased activity of an enzyme results in what

Answer 25

Increased drug toxicity

Question 26

Gene varriation or mutation resulting in multiple expressions of a particular metabolising enzyme results in what

Answer 26

enhanced metabolism and reduced drug effect or drug resistance

Question 27

What are the Four phenotype subpopulations of metabolizers

Answer 27

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

Question 28

When is the rate of metabolism the best in humans

Answer 28

at puberty

Question 29

What are the levels of drug metabolising enzymes in children

Answer 29

deficient or reduced

Question 30

What happens to metabolising in pregnancy

Answer 30

is induced

Question 31

What are the factors that effect drug metabolism in elderly patients

Answer 31

``` plasma protein, lean body mass decreased liver weight More likely to have chronic disease so on multiple drug therapy renal functions aren't as efficient ```

Question 32

How might ethnicity effect drug metabolism

Answer 32

due to racial differences in the genetic expression of cytochrome P-450 isoforms.