Developments in Personalised Medicince Flashcards
Define personalised medicine
The concept that managing a pateint’s health should be based on the individual patient’s specific charcateristics, including age, gender, height/weight, diet, environment etc
Define stratified medicine
The process by which therapies are matched with specific patient population charcateristics using clinical biomarkers
Define predictive medicine
A rapidly emerging field that entails predicting disease and instituting preventive measures in order to either prevent the disease altogether or significantly decrease its impact upon the patient
Define theranostics
Term used to describe the proposed process of diagnostic therapy for individual patients
Define pharmacogenetics
The study of clinical testing of genetic variation that gives rise to differing response to drugs
What is the scope of personalised medicine?
Treatment efficacy in specific patients
Determine optimal drug dosages
ID of patients who may suffer severe adverse drug reactions
Assess the extent or progression of disease
Examine surrogate measures for clinical outcomes
Identify patients who can benefit from specific preventative measures
What are the characteristics of a poor responder?
Decreased absorption
Increased metabolism/reduced pro-drug activation
Increased clearance/competition for transport molecule
Impaired receptor response
Reduced intracellular effects
What are the characteristics of an ADR?
Increased absorption Accumulated toxic metabolites Reduced clearance Increased receptor response Enhanced intracelullar effects
What are the two categories of drug metabolising enzymes?
Catalytic-mainly oxidative
Conjugative
What sort of metabolisers are those homozygous for CYP2D6?
Poor metabolisers
What sort of metabolisers are those heterozygous for CYP2D6?
Intermediate metabolisers
What sort of metabolisers are those who have gene duplications for CYP2D6?
Ultrarapid metabolisers
What are the substrates for CYP2D6?
Anti-depressants Anti-psycotics Anti-arrhythmics Beta-blockers Anti-hypertensives
Why are immunsuppressants needed?
Untreated, the body will identify new tissues as ‘non-self’ this will lead to an immune response producing IL-2 and rejection of the organ
Describe chronic allograft dysfunction
Usually a gradual process, although both the time of onset and the rate of progression vary
May develop as early as within a few months of the transplant or it may emerge after several years
Course is generally unremitting and ultiately leads to total loss of graft function, necessitating re-transplantation or a return to dialysis
Describe acute rejection
Usually first few weeks after transplantation but can occur at any time if the level of immunosuppression becomes inadequate
Cell-mediated response leads to injury or destruction of the funtioning cellular structures of the transplant
Reversible
What is involved in triple therapy?
A calcineurin inhibitor
An antiproliferative agent
A corticosteroid
What does Thiopurine Methyl Transferase (TpMT) do?
Metabolises Azathioprine
What are the effects of TPMT deficiency?
Profound bone marrow suppression- opportunistic infections, sepsis, death
Gastrointestinal effects- Nausea, vomiting, abnormal liver function
What are the complications of long-term immunosuppression?
Infection Cancer CVD Recurrent disease Toxicity Hirsutism
In which patients are BCCs most common?
White and fair-skinned
What is the ratio of incidence of BCC:SCC in normal patients?
4:1 ratio of BCC;SCC
What is the ratio of incidence of BCC:SCC in transplant patients?
4:1 ratio of SCC:BCC
What is the behaviour of NMSC in a normal patient?
Usually 1-2 lesions per person
Grow slowly
Rarely metastasise
Low mortality
What is the behaviour of NMSC in a transplant patient?
More aggressive behaviour Present earlier More numerous Grow more reapidly Metastasise earlier
What are the clinical risk factors of NMSC associated with UV?
Latitude- incidence much higher in hot countries
Exposure- outdoor exposure, sunbathing habits, cumulative sun exposure, holidays abroad
Host response- gender, skin typ, eye colour, hair colour
Premalignant lesions
Burning in childhood
What are the clinical risk factors of NMSC associated with immunosuppression?
Degree
Regimen
Duration
What are the clinical risk factors of NMSC associated with chemical exposure?
Smoking- ever vs never, how may packs?
Arsenic exposure
What are the clinical risk factors of NMSC associated with genetic factors?
UV-induced oxidative stress Melanisation Immune modulation Detocification of smoking derived chemicals Cell-cycle control
How would you go about developing a screening strategy for newly transplanted patients?
Use tumour latency as an end point
Check individual parameters for significance
Applying a step-wise model to generate significant set of predictors
Dichotomisation
Generating the predictive index
Simplifying the index
Grouping PI scores to generate screening groups
Model validation
What are the screening groups for NMSC and their parameters?
PI7 - Frequent (6 months)