L43 + 44 Personalised Medicine DT

Question 1

What does the one size fits all model mean to patients

Answer 1

patient may not recieve the optimal drug or even the optimal dose for the disease

the prescribed drug may have adverse reactions which can be life threatening.

Patients may find the drugs may not work in them causing distress, particularly for cancer patients.

Question 2

What is the combination of pharmacogenetics, biomarkers and metabonomics used for?

Answer 2

• Predicting the risk of disease occurance to allow the best intervention
• To discover more safer therapeutic ranges
• Indicate the best therapy for individuals and the monitoring and the optimisation of drug therapy for indiviual patients or groups by maximising efficacy

Question 3

define pharmacogenetics

Answer 3

the study of clinical testing of genetic variations (SNPs) resulting in patients experiencing different responses to drugs. Usually through varying metabolism.

Pharmacogenetics can affect both efficacy and side effect profile.

Question 4

What are Biomarkers?

Answer 4

Biomarkers are natually occuring markers that are used to predict the risk of a disease, indicate preferred drug therapy and monitor the progress of disease treatment. The biomarkers themselves can range from physical measurement (size of tumor) to complex biochemical measurements.

Question 5

What is metabonomics:

Answer 5

• measurement of metabolic profiles in body tissues or body fluids.
• Can also be used to predict the risk of disease occuring, inform best treatment and reflect progress of treatment.

Question 6

What is personalised medicine?

Answer 6

Overarching term that incoporates:

• pharmacogenetics
• pharmacogenomics
• biomarkers
• metabonomics

Aimed at providing individualised diagnosis diagnosis and treatment for all patients (based on genome) proteome or metabolome. For maximum therapeutic relief and minimum side effects.

Question 7

Give an example of a biomarker associated with a thepeutic agent

Answer 7

The LDL receptor is a biomarker. It is associated with Atorvastatin. which a HMG-CoA reductase inhibitor.

Question 8

Whats the current issue with chemotherapy?

Answer 8

The one size fits all model and all those associated problems

Question 9

discuss imatinibs use in chemotherapy

Answer 9

Imiatinib is a low molecular weight inhibitor of tyrosine kinase activity of ABC1-BCR fusion gene. the Tyrosine Kinase is an enzyme associated with CML. Imatinib works by binding to the ATP binding site of the kinase. It has a high sucess rae and few side effects: nausea, diarrhoea and vomiting.

Question 10

Discuss cetuximab use and side effects

Answer 10

anticancer drug for cholorectal cancer. the EGFR receptor is part of a subfamily of 4 closely related receptors:

• EGFR
• HER2,3 and 4

The increase in EGFR mediated signalling can contribute into a cell moving into a state of continuous and uncontrolled cell division. Therefore expanding the population of the malignant cells and increasing the tumor mass.

Side effects: weight loss, sore throat, fingernails changing

Question 11

Dont forget Herceptin. How does it work? What other Drug have we come across in MDD earlier for personalised med? and ADRs?

Answer 11

Ok. Herceptin targets the&raquo_space; HER2+ &laquo_space;cancer cell, allowing the immune system to targert and destroy the cell. Also blocks downstream cellular processes. side effects: Loss of appetite. Taste change.

Brentuximab. Works by targetting the cell membrane protein CD30 which is expressed by cancer cells in systemic anaplastic large cell lymphoma. side effects: FNF: Fever, Nausea, Fatigue

Question 12

state the three ways by which a patients particular gene sequence can affect the drug action?

Answer 12

• The presence of a particular SNP or protein biomarker can predict whether a drug will work or not.
• The presence of mutations in metabolising genes can predict serious ADRs
• Mutations in metabolising enzymes can also predict dose requirements

Question 13

Give an example of a dysfuntional enzyme

Answer 13

CYP 2D6 is dysfuntional in 7% of white and black americans resulting in reduced metabolism of codeine.

Question 14

What does advances in DNA array and proteomics mean?

Answer 14

Advances in DNA array and proteomics
technologies mean that many thousands of
RNA transcripts and proteins can be detected
in very low concentrations in cells.

Question 15

Pattern recognition technologies can be used to…

Answer 15

Pattern recognition techniques can then be
used to detect expression differences between
cancer cells and normal cells.