Lecture 1 Introduction to Personalised Medicine Flashcards
What is meant by mutlimorbitidy
The presence of two or more chronic medical conditions in an individual
What is meant by the term pharmacogenomics
The study of how a person’s genome influences their response to medications
Give examples of the benefits of personalised medicine in the clinic
Can reduce trial and error prescribing avoid adverse reactions increase patient compliance reveal additional uses control costs of health care
What development lead to major advances in the pharmacogenomic realm of medicine
Completion of the human genome project
Give an example of a pharmacogenomic drug that is targeted to patients with a particular disease in the right genomic background
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
What is meant by inter-individual variation
Variations in concentrations of the drug at the site of action or different responses to the same concentration of a drug
What is meant by pharmacokinetics
Where the drug concentration changes in the different compartments of the body
What are some of the main causes of variability in drug responses
Age ethnicity genomics immunological factors concomitant disease and other drug interactions
How does drug elimination change with age
Drug elimination is less efficient in new-borns and older people
What is significant about GFR in terms of the excretion of drugs
GFR in new-borns is 20% of the adult value
How can the half-life of digoxin vary across different ages
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
Give of example of a factor that can contribute to the altered activity of a drug in the elderly and in new-borns
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
How can ethnicity alter drug action
There are variations in genetics between ethnicities as well as differing environmental factors like diet
Some ethnicities can receive increased benefit to drugs over the normal responses T or F
T
Give an example of where a patient’s ethnicity impacts the metabolism of a drug
Ethanol metabolism is less efficient in Chinese patients
What is meant by a polymorphism
An alternative sequence at loci within the DNA strand
What is the most common form of an SNP
C-T base change
Inherited thrombophilia is a genetic condition associated with an SNP where is this found
The SNP is found in the coagulation factor V
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
Kidney and liver
Give an example of a concomitant disease that means that patients will be resistant to a particular drug
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
What kind of interactions need to be considered when administering a drug
Interactions with other drugs and with chemicals
Give an example of a drug whose interaction with another drug needs to be considered
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
What two genes does the warfarin genetic test look at
CYP29C - the enzyme that metabolises warfarin and VKORC – a gene that encodes the target of warfarin
Describe the warfarin genetic test
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
How many different genotypes of CYP2C are there
3
How many different genotypes of VKORC are there
3
