1. Personalising Medicine

Question 1

Define personalised medicine.

Answer 1

Personalised medicine aims to customise healthcare with decisions and treatments tailored to each individual patient

Question 2

What is pharmacogenomics?

Answer 2

Pharmacogenomics is the study of how a person’s genome influences his/her response to medications

Question 3

What impacts can personalised medicine have?

Answer 3

• Reduce trial and error prescribing
• Avoid adverse reactions
• Increase patient compliance
• Reveal additional uses
• Control costs of healthcare

Question 4

What is the allomap test?

Answer 4

Allomap test uses 20 genes to predict risk of heart transplant rejection

Question 5

What is the brandname of Clopidogrel?

What is Clopidogrel used to treat?

Answer 5

• Plavix

- Used to inhibit platelets from forming aggregates in arteries

Question 6

What genetic factor can affect how the body breaks down Clopidogrel?

Answer 6

• CYP2C19 encodes enzyme that metabolises Clopidogrel into its active metabolite
• Genetic polymorphisms can reduce CYP2C19 activity so Clopidogrel is not metabolised into its active metabolite and is therefore less effective

Question 7

How could Clopidogrel treatment be tailored to specific patients?

Answer 7

Genotype CYP2C19 to see if drug will be effective

Question 8

Define inter-individual variation.

Answer 8

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

Question 9

Define pharmacokinetics.

Answer 9

How drug concentrations change over time in body regions depending on drug absorption

Question 10

How are individualised responses adjusted in pharmacodynamic variation?

Answer 10

By monitoring physiological endpoints e.g. blood pressure, platelet aggregation

Question 11

What are the main causes of variability in drug responses?

Answer 11

• Age
• Ethnicity
• Genetics/Genomics
• Immunological factors - patients develop anti-drug antibodies
• Concomitant disease
• Drug interactions

Question 12

How does age cause variation in drug response in newborns and the elderly?

Answer 12

• Drug response and elimination is less efficient in newborns as organs are not well developed
• Drug response is less efficient in elderly as the body composition changes with age and changes in volume of drug distribution

Question 13

Give an example of how a drug shows different responses in different age groups.

Answer 13

Digoxin - used in heart failure to increase strength and efficiency of heart contraction

• Digoxin t1/2 in newborn = 200h
• Digoxin t1/2 in adult = 40h
• Digoxin t1/2 in elderly = 80h

Question 14

Give an example of how a specific ethnicity may receive increased benefit over normal responses.

Answer 14

Hydralazine - used to treat heart failure and is very effective when used in combination with nitrate in African Americans

Question 15

What is a mutation?

Give an example of how a mutation causes variation in drug response.

Answer 15

• Mutation is a heritable change in DNA

- Slow/Fast acetylators (hepatic acetyl transferase)

Question 16

What is a polymorphism?

Give an example of how a polymorphism causes variation in drug response.

Answer 16

• Alternative sequence at loci within the DNA strand (allele), single nucleotide polymorphisms are very common and influence drug efficacy and interactions
• Inherited thrombophilia - SNP in Factor V Leiden (coagulation factor) increase ability to form clots

Question 17

Give 3 examples of how concomitant disease can causes variation in drug response.

Answer 17

1. Diseases affective the liver and kidneys can cause prolonged or intense drug effects
2. Diseases can cause gastric stasis e.g. migraine
3. Diseases that influence receptors e.g. familial hypercholesterolaemia

Question 18

What is familial hypercholesterolaemia?

How is it treated?

Answer 18

• FH is an inherited condition that leads to a lack of function of low-density lipoprotein receptors causing increased blood cholesterol and increase risk of MI
• Treated with PCSK9 inhibitors

Question 19

How can drug interactions with chemicals cause variation in drug responses?

Answer 19

Grapefruit juice and herbal remedies activate cytochrome P450 enzymes (drug metabolising enzymes)

Question 20

Give an example of how pharmacodynamic interactions can cause variation in drug responses.

Answer 20

• Sildenafil (vasodilator) used to treat pulmonary hypertension
• Mechanism of action potentiates organic nitrates (e.g. if patient is taking nitroglycerin) and combination can lead to severe hypotension