Intro lec Flashcards
What is the need for personalised medicine?
- Find additional use for drugs
- increase patient compliance
- avoid adverse side effects
- reduce trial and error prescriptions therefore control healthcare costs more
What does pharmacogenomics refer to? provide an example
the way genes influence our response to medicine –> genetic polymorphisms in drug metabolising enzymes WARFARIN
Give 3 examples of where personalised medicine has been applicable and or applied?
- Warfarin treatment
- Familial hypocholsterolaemia (abnormalities in LDLrs)
- ALLONAP test - predicts the longevity of a patients heart using genetic data
What is PLAVIX and how is does it relate to personalised medicine?
Inhibits platelet aggregation in arteries
Broken down better in some individuals than others –> due to polymorphisms in SIPCYP2C19 – enzyme that metabolises drugs to their active form
INTER INDIVIDUAL VARIATION - what 2 aspects makes up this? What are the most effective ways of monitoring this?
PHARMACODYNAMIC VARIATION - different responses to the same concentration of drug between individuals. Most effective way to monitor this is by using physiological end-points»_space; allow better monitoring of individual response
PHARMACOKINETICS - action of a particual drug within the body
What are the main causes of variability to drug response? Reasons
- Age - drug metabolism less efficient in elderly and newborns
- Ethnicity - drug metab better in some ethnicities than others due to genomic differences
- Concominant diseases - diseases already present that impact drug action
- Genomics
- Drug interactions
AGE - how does it impact drug interactions? DIgoxin as an example
- Drug metab less efficient in newborns –> half life of Digoxin 200h in neonates compared to adults
- GFR in newborns 20% slower than adults
- body composition changes with age
ETHNICITY - how does it impact drug interactions
- Environment - differences in diet
- Variations occur in genome between different ethnicities
- –> for this reason genomic testing more useful than just ethnicity
GENETICS - how does this impact drug interactions?
Mutations (heritable change in DNA sequence) or Polymorphisms (alternative sequence at allele in DNA strand) can mean that individuals respond to drugs differently
Polymorphisms - what is the most common?
Inherited Thrombophilia - how is this an example of how genes can impact response to medicine?
C»_space; T most common polymorphism
Inherited thrombophilia – polymorphism in coagulation factor in the blood – increases ability to form blood clots
DRUG INTERACTIONS - how do these impact drug effects?
Diuretics / Sildenafil as examples
Drugs interact with each other! This impacts the effects of a drug in the body
Diuretics - often given to lower blood pressure –> these lower plasma K+ but also predispose a patient to digoxin toxicity
Sildenafil (viagra) –> if patient is already taking organic nitrates, there is a large combination effect seen (sildenafil decreases blood vessel constriction) causing DANGEROUSLY LOW BLOOD PRESSURE
CONCOMINANT DISEASES - how do these impact drug effects – PCSK9 inhibitors
Diseases that impact the liver and kidneys can caused prologned drug effects
Diseases can also impact receptors eg FAMILIAL HYPERCHOLESTEROLAEMIA – impacts LDLrs – PCSK9 inhibitors now used to treat this
Gene testing - WARFARIN/CYP2C/VKORK genotyping –> what are each of these elements
Warfarin - drug used to thin blood after clotting event
CYP2C - enzyme which metabolises warfarin. Can have faster and slower metabolisers between individuals (faster metabolisers need higher dose)
VKORK - warfarin drug target where G»_space; A polymorphism most common. This makes a patient more sensitive to warfarin (so a lower dose is required)
Warfarin genotyping – genotypes needed for higher and lower doses?
GG = larger dose needed! A –> G = G less sensitive so higher dose needed, A very sensitive so low dose
1, 2 and 3* versions of CYP29C –> 1* fast and 3* slow metaboliser. Therefore an AA1* genotype = very low dose required!
