CML Antineoplastics Flashcards
What are the two types of drugs that have been developed to block the action of specific tyrosine kinases?
signal transduction inhibitors
antibodies
What are the three drugs that target the BCR-ABL tyrosine kinase in CML?
imatinib
dasatanib
nilotinib
The drugs used in CML can also be used for GIST by targeting what other tyrosine kinase?
c-kit
What’s the mechanism of action for imatinim, dasatanib and nilotinib?
they are competitive antagonists at the ATP binding site of BCR-ABL
What additional mechanism of action does dasatinib have?
targest src - a tyrosine kinase that’s upregulated in several types of cancer
What are two drugs designed as competitive antagonists of the ATP-binding site of EGFR?
eroltinib and getitinib
How can resistance arise to these drugs?
changes in target proteins - usually from mutation of the ATP binding site that prevents their binding
How are these drugs given?
oral - good bioavailability
How are these drugs metabolized?
in liver with CYP3A4
What’s the scucess rate for imatinib?
complete hematlogical and cytological response in 85-95% of patients! in the chronic phase of CML that is..
WHat’s still the only curative therapy for cML?
bone marrow transpoant
Are erlotinib and gefitinib as successful as imatinib?
no - probably because we don’t know that actual genetic defect
What are the toxicities for the STIs?
relatively minor - nausea, vomiting, fatigue, myalgia, diarrhea, skin rashes, drug ineratctions, etc.
the specific one is congestive heart failure and or MI
What’s the specific side effect for imatinib?
edema, bone marrow suppression
What’s the specific side effect for erlotinib and gefitinib?
interstitial pneumonia (remember they attack EGFR)
