Lecture 5- Variability In Drug Response

Question 1

What are the factors affecting Drug Metabolism?

Answer 1

Drug Interaction Age Gender
Genetic differences
Diet (components/status) Environment Disease state

Question 2

Self-serving

Answer 2

A drug inducing it’s own breakdown enzymes

Question 3

Half life

Answer 3

Time it takes to reduce a drug circulating concentration to one half of that when the drug concentration was initially assayed

Question 4

What do clear majority of drugs have?

Answer 4

Exponential decay

Question 5

What is Rifampicin inducing?

Answer 5

Enzymes responsible for the metabolism of warfarin

Question 6

What are the 2 drugs used for the treatment of depression?

Answer 6

Fluvoxamine Cimetidine

Question 7

Where is CYP3A4 most ubiquitously found?

Answer 7

Liver

Question 8

Age

Answer 8

Hepatic function is lower at birth and in old age

Question 9

What does the use of Chloramphenicol cause?

Answer 9

Grey baby syndrome

Question 10

What does Diazepam cause in the elderly?

Answer 10

Significant confusing effect

Question 11

What is total body water a component of?

Answer 11

Total body fluid (consider total body fat)

Question 12

What toxicants alter cytochrome P450 function?

Answer 12

Inducers/Inhibitors

Question 13

What are some examples of toxicants that alter cytochrome P450 function?

Answer 13

Tobacco Heavy metals Industrial pollutants
Solvents (polychlorinated biphenyls)
Pesticides/Herbicides

Question 14

What are 2 examples of liver disease?

Answer 14

Hepatitis or biliary cirrhosis

Question 15

What happens if microsomal oxidases are markedly affected?

Answer 15

Decreased capacity to Metabolise drugs

Question 16

What does migraine cause?

Answer 16

Gastric stasis

Question 17

What does Kinsey problem cause?

Answer 17

Affected renal function and the level at which drug can be excreted (urine production) Chronic disease: heart failure, nephrotic syndrome

Question 18

What did Bailey et al first note?

Answer 18

Grapefruit juice altered the oral bioavailability of felodipine

Question 19

What has GFJ been used for?

Answer 19

Mask the taste of ethanol (efficacy of felodipine)

Question 20

What did the plasma concentration of felodipine show?

Answer 20

5-cold higher after oral administration If taken with grapefruit juice

Question 21

What enzymes does the basis of GFJ-felodipine Interaction appear?

Answer 21

CYP3A4

Question 22

What is GFJ affecting?

Answer 22

The absorption of felodipine or the break down of felodipine

Question 23

What does statins work to reduce?

Answer 23

Circulating levels of Lipids in bloodstream - reducing the risk of atherosclerosis

Question 24

What do Brussel sprouts do?

Answer 24

Diminish the drug effect instead of prolonging it

Question 25

Where does Furanocoumarins act on?

Answer 25

Cytochrome P450 to slow down its activity

Question 26

What can activity of certain cytochrome P450 be increased by?

Answer 26

Presence of glucosinolates

Question 27

What is pharmacogenomics?

Answer 27

The branch of genetics concerned with determining the likely response of an individual to therapeutic drugs

Question 28

What are genetic differences often due to?

Answer 28

Single nucleotide polymorphisms

Question 29

Nortriptyline

Answer 29

Treatment of depression

Question 30

What are the 4 phenotypes identifies within European population?

Answer 30

1. Poor metabolisers 2. Intermediary Metabolizers 3. Extensive metabolizers 4. Ultra-rapid metabolizers

Question 31

Poor metabolizers

Answer 31

Such individuals lack the functional enzyme Drugs can have more than one route of elimination Elevated levels or drug

Question 32

Intermediary metabolizers

Answer 32

Such individuals are heterozygous for one functional allele or have two partially defective alleles encoding the enzyme

Question 33

Extensive metabolizers

Answer 33

Have two normal alleles

Question 34

Ultra-rapid metabolizers

Answer 34

Carry duplicates or multi-duplicated functional CYP2D6 genes

Question 35

Majority of population (80-65%)

Answer 35

Dose range between 100-200mg

Question 36

5-10% poor metabolizers

Answer 36

Dose range will be low between 20-50mg because Nortriptyline hangs around in the body for a longer period

Question 37

What does Warfarin have?

Answer 37

Narrow therapeutic window Wide variation in dose requirements High incidence of adverse events

Question 38

What patient genotype does gene-guided dosing consider?

Answer 38

CYP2C9 and VKORC1

Question 39

What is vitamin K involved in?

Answer 39

Coagulation process

Question 40

What is N-acetyltransferase 2 responsible for?

Answer 40

Metabolism of Isoniazid - can enhance effect of drug

Question 41

How does Isoniazid metabolism occur?

Answer 41

Acetylation

Question 42

Fast Acetylators

Answer 42

UK 40%

Question 43

Slow acetylators

Answer 43

UK 60%

Question 44

What is Isoniazid?

Answer 44

Inherited characteristics

Question 45

Isoniazid

Answer 45

Bi-modal distribution depending if you are fast or slow acetylators

Question 46

What is salicylate?

Answer 46

Compound related to aspirin Used as anti-inflammatory (treatment of fever) Unimodal distribution - less variation in metabolic processes

Question 47

What can affect drug response?

Answer 47

Receptor polymorphism

Question 48

What receptor is associated with weight gain?

Answer 48

5-HT2C - affect patient compliance

Question 49

What can sex hormones change?

Answer 49

Expression pattern