Lecture 1 Introduction to Personalised Medicine

Question 1

What is meant by mutlimorbitidy

Answer 1

The presence of two or more chronic medical conditions in an individual

Question 2

What is meant by the term pharmacogenomics

Answer 2

The study of how a person’s genome influences their response to medications

Question 3

Give examples of the benefits of personalised medicine in the clinic

Answer 3

Can reduce trial and error prescribing avoid adverse reactions increase patient compliance reveal additional uses control costs of health care

Question 4

What development lead to major advances in the pharmacogenomic realm of medicine

Answer 4

Completion of the human genome project

Question 5

Give an example of a pharmacogenomic drug that is targeted to patients with a particular disease in the right genomic background

Answer 5

Plavix /Clopidogrel is a drug that inhibits platelet aggregation. The drug is metabolised to its active form by the Cyp2c19 family of enzymes. If these enzymes contain polymorphisms they may be unable to metabolise it and the patient will be resistant to the drug. Hence this is only given to patients after a genetic test reveals their responsiveness to the drug

Question 6

What is meant by inter-individual variation

Answer 6

Variations in concentrations of the drug at the site of action or different responses to the same concentration of a drug

Question 7

What is meant by pharmacokinetics

Answer 7

Where the drug concentration changes in the different compartments of the body

Question 8

What are some of the main causes of variability in drug responses

Answer 8

Age ethnicity genomics immunological factors concomitant disease and other drug interactions

Question 9

How does drug elimination change with age

Answer 9

Drug elimination is less efficient in new-borns and older people

Question 10

What is significant about GFR in terms of the excretion of drugs

Answer 10

GFR in new-borns is 20% of the adult value

Question 11

How can the half-life of digoxin vary across different ages

Answer 11

In new-borns the half-life of digoxin is 200h whereas in adults in only 40hrs. This does however decrease to 80hrs in the elderly

Question 12

Give of example of a factor that can contribute to the altered activity of a drug in the elderly and in new-borns

Answer 12

In new-borns the drug metabolising enzymes are altered this accounts for their slower metabolism of compounds. Meanwhile in the elderly body composition has changed which alters the way drugs act

Question 13

How can ethnicity alter drug action

Answer 13

There are variations in genetics between ethnicities as well as differing environmental factors like diet

Question 14

Some ethnicities can receive increased benefit to drugs over the normal responses T or F

Answer 14

T

Question 15

Give an example of where a patient’s ethnicity impacts the metabolism of a drug

Answer 15

Ethanol metabolism is less efficient in Chinese patients

Question 16

What is meant by a polymorphism

Answer 16

An alternative sequence at loci within the DNA strand

Question 17

What is the most common form of an SNP

Answer 17

C-T base change

Question 18

Inherited thrombophilia is a genetic condition associated with an SNP where is this found

Answer 18

The SNP is found in the coagulation factor V

Question 19

Concomitant disease is another issue to consider in the variation of individuals in their response to a drug which organs are drug-modifying disease often seen

Answer 19

Kidney and liver

Question 20

Give an example of a concomitant disease that means that patients will be resistant to a particular drug

Answer 20

Familial hypercholesterolaemia is an inherited high cholesterol condition leading to a lack of function in LDLR receptor. Statins are therefore not effective in lowering cholesterol in these patients

Question 21

What kind of interactions need to be considered when administering a drug

Answer 21

Interactions with other drugs and with chemicals

Question 22

Give an example of a drug whose interaction with another drug needs to be considered

Answer 22

The vasodilator sildenafil’s mechanism of action potentiates organic nitrates and as a result should not be given in combination with these drugs as it can lead to severe hypotension

Question 23

What two genes does the warfarin genetic test look at

Answer 23

CYP29C - the enzyme that metabolises warfarin and VKORC – a gene that encodes the target of warfarin

Question 24

Describe the warfarin genetic test

Answer 24

The warfarin genetic test looks for specific genomic variants in the CYP2C and VKORC genes. This determines the dose of warfarin that the patients receives as too much for some genotypes can cause bleeding whereas too little in other patients can cause thrombosis

Question 25

How many different genotypes of CYP2C are there

Answer 25

3

Question 26

How many different genotypes of VKORC are there

Answer 26

3