Pharmacogenomics Flashcards
Why do some patients have an effect from the anti-hypertensive debrisoquine more than others?
debrisoquine, like many other drugs, is metabolised by the P450 2D6 which has many polymorphisms so will result in different metabolism of the drug leading to enhanced or decreased effect
Why do some patients treated with thiopurine drugs for leukaemia have high levels of toxicity and bone marrow supression?
thiopurine is activated by HPRT and inactivated by TPMT. TMPT is commonly mutated leading to inactivation of the enzyme. This means that patients with this mutation will have too high a concentration of thiopurine
Why do some patients experience more myopathy as a side effect of a statin than others?
SLCO1B1 is the transporter used to uptake statins into the liver for metabolism - a SNP in this gene will result in decreased uptake which will result in more side effects (myopathy)
Why do some patients benefit more from the treatment of non small cell lung cancer with the kinase inhibitor gefitinib than others?
some non small cell lung cancers have an EGFR mutation which leads to spontaneous kinase activity which will be better treated with gefitinib
Why are some asthma patients better treated with a 5-lipoxygenase inhibitor than others?
some patients have an insertion or deletion mutation in the promoter region of 5-LOX - these patients will have asthma that is less dependent on the action of leukotrienes so will have less benefit from a treatment with a 5-LOX inhibitor
How is optimal therapy for breast cancer predicted?
a panel of genes is screened which will help predictor which patients will benefit from aggressive chemotherapy treatment and which patients will not
What does the term pharmacogenomics mean?
the study of genes and their effect on pharmacodynamics and pharmacokinetics
How would the study of pharmacogenomics lead to improvement in human health?
can predict adverse drug reactions, can predict lack of drug efficacy, can tailor the right drug for the right patient
How can SNPs lead to changes in protein expression and function?
can cause a direct change in protein structure, can cause alternative splicing, can increase or decrease transcription, or can lead to protein degradation
