18 - Pharmacogenomics Flashcards
1
Q
Pharmacogenomics
A
- Study of how a person’s genetic make up affects their response to a drug
- Example of precision medicine
2
Q
Genetic Variation
A
Genetic variation in coding regions of genes determines drug response
3
Q
Examples of variability in drug response
A
- Genetics
- Gender
- Obesity
- Race
- Pregnancy
- Age
4
Q
Benefits of pharmacogenomics
A
- Predicting drug over dose
- Preventing adverse drug reactions
- Improving efficacy
- Predicting the activation of pro drugs
- Developing targeted drugs for cancer therapy
- Enabling drug discovery/development
5
Q
Four main processes involved in drug pharmacokinetics
A
- Absorption
- Distribution
- Metabolism
- Excretion
6
Q
Drug receptors
A
- DNA variants determines the type of receptors, how many, and efficiency
- As a results, a higher or lower amount of the drug is needed or a different drug
- Many receptors = strong response, no receptors = no response
7
Q
Breast cancer and T-DM1
A
- Some breast cancers make too many HER2 receptors, which helps the cancer develop and spread
- T-DM1 (antibody-drug conjugate) used to treat these cancers and works by attaching to HER2 receptors on cancerous cells and killing them
- Tumour tissue is tested to determine if T-DM1 is the right treatment
- If there is high number of HER2, T-DM1 can be used
- IF tumour is HER2 negative, T-DM1 will not work
8
Q
Drug uptake
A
- Some drugs need to be actively taken into cells
- DNA variants can affect uptake of certain drugs
- DNA variants can affect how quickly some drugs are removed from the cells. If drugs are removed too quickly, they might not have time to act.
9
Q
Statins and muscle problems
A
- Statins act in liver to lower cholesterol
- To work must first be taken into the liver cells.
- Statins are transported by a protein made by the SLCO1B1 gene.
- A DNA variant causes reduced simvastatin to be absorbed by cells.
- When taken at high doses, simvastatin can build up causing muscle weakness and pain.
- Genetic testing the SLCO1B1 gene can be done to determine if simvastatin is the best statin and what dose would work best.
10
Q
Drug breakdown
A
- DNA variants can affect the speed of drug breakdown
- If the drug is metabolised more quickly than most people, a higher dose may be required (or different drug)
- If drug is metabolised slower, smaller dose may be required
11
Q
Depression and amitriptyline
A
- The breakdown of the antidepressant drug amitriptyline is influenced by two genes CYP2D6 and CYP2C19.
- Genetic testing for these genes can help decide what dose of the drug is needed.
- Fast metabolisers will need a higher dose, or a different drug.
- Slow metabolizers will need a smaller dose or a different drug to avoid a bad
reaction.
12
Q
Cytochrome Oxidase P450 enzymes
A
- 57 different genes, 17 different families
- CYP1, CYP2, CYP3 are primarily involved in drug metabolism
- 6 metabolise 90% of drugs. Two most significant enzymes are CYP3A4 and CYP2D6
13
Q
Drug dose
A
- Determines both efficacy and safety of a drug
- Genetic factors play a role
- EG warfarin
14
Q
Warfarin drug dose
A
- SNPs in CYP2C9 (enzyme metabolizing warfarin) & VKORC1 (enzyme inhibited by warfarin) determine the dose requirement.
- Loss-of-function SNPs in either or both genes cause reduced enzyme activity and a lower warfarin doses is required, to avoid overexposure, and achieve therapeutic anticoagulation.
15
Q
Targeted Drug Development
A
- Some diseases are due to specific mutations in a gene
- The protein may not work correctly or may not be made at all
- Drugs can be created based on how the mutation affects the protein (drug only works for specific mutation)
