Week 6: Pharmacogenomics Flashcards
Personalised/stratified medicine
Personal/stratified medicine is the use of genetic information to refine diagnosis, individualise treatments, prevent adverse drug effects, manage epidemics and develop new therapies
Stratification
Patients are grouped by disease subtypes, demographics, clinical features and biomarkers
Personalisation
Patient individual: preferences, clinical features, medication history, environment, behaviours, habits and biomarkers
Factors affecting drug response
- Age
- Sex
- Health
- Genetics
- BMI
- Diet
- Lifestyle
- Psychological state
- Previous exposure to drug
- Other exposures
Pharmacogenetics/Pharmacogenomics
The study of variations in drug response due to genetic makeup
Pharmacokinetics
The study of the absorption, distribution, metabolism and excretion of drugs
Pharmacodynamics
The study of biochemical, psychologic and molecular effects of drugs on the body, primarily receptor binding, post-receptor effects and chemical interactions
Glucose-6-phospahte dehydrogenase (G6PD)
- G6PD is located on the X chromosome
- G6PD is important in protecting red blood cells against oxidative damage
- G6PD deficiency predisposes towards acute haemolytic anaemia
- In people with G6PD deficiency, haemolytic anaemia can occur after eating fava beans or certain legumes
G6PD and antimalarials
The deficiency provides some protection from malaria but can also cause haemolysis after administration of some antimalarial drugs (eg. primaquine)
Declaration of Helsinki
- All research including human subjects should be of high quality
- The potential benefits to the participant or general population should be greater than the potential harm from the research
- Researchers should obtain documented informed consent from the participant or guardian
- Researchers should respect the confidentiality of the participant and the research data
- Study participants are allowed to withdraw from the study at any time without this action adversely affecting their care
Heinz bodies and G6PD
Heinz bodies are structures that are formed from the breakdown of haemoglobin in red blood cells. They occur due to oxidative damage from toxins, medications, or as a result of underlying G6PD deficiency or thalassaemia. Heinz bodies can cause red blood cells to break down, a condition known as Heinz body anaemia
Cystic fibrosis transmembrane conductane transported (CFTR)
CFTR is a member of the ATP-binding cassette (ABC) transporter family that functions as a gated chloride channel located in the mucus membranes. Defects in this channel result in the mucus having less osmotic potential and so thicker
DeltaF508 CFTR
The most common mutation in the gene associated with cystic fibrosis causes deletion of phenylalanine at residue 508 (delta F508) of the gene product CFTR. As a result, the protein doesn’t fold properly and does not efficiently traffic to the plasma membrane. The small amount of deltaF508 that makes it to the cell membrane has defective channel function. The altered structure of the mRNA also leads to a reduction in translation efficiency, so deltaF508 can be assigned to at least 3 classes.
Traditional treatments for cystic fibrosis
- Medicines for lung problems
- Antibiotics to prevent and treat chest infections
- Mucus thinner
- Bronchodilators
- Steroid medicine - Exercise
- Airway clearance techniques
- Dietary and nutritional advice
- Lung transplants
Predicting adverse drug reactions
Hearing loss in cystic fibrosis
- Aminoglycosides antibiotics are commonly used in cystic fibrosis patients to treat Pseudomonas aeruginosa respiratory infections
- Aminoglycoside-induced hearing loss may occur in 1% - 15% of patients with cystic fibrosis ranging from mild to severe
- A mitochondrial DNA A1555G point mutation in the 12S ribosomal RNA gene is associated with non-syndromic deafness and increased susceptibility to aminoglycoside-induced hearing loss
