Exam 2- 3/4/5 Flashcards
(50 cards)
3 types of SMKI
tyrosine kinase, serine/threonine kinase, and lipid kinase inhibitors
tyrosine kinase inhibitors
acting on Bcr-Abl, EGFR,
imatinib and erlotinib
serine/threonine kinase inhibitors
acting on B-raf
vemurafenib and trametinib
lipid kinase inhibitor
acting on PI-3K
idelalisib
mechanisms of tyrosine kinase activation include
genetic alteration, gene amplification, point mutation, protein accumulation
irreversible inhibition
SMKI forms a covalent bond with the cysteine residues in the active site of a protein kinase
reversible inhibition
type inhibition I to IV
group 1: targeting Bcr-Abl oncoprotein in chronic myeloid leukemia
imatinib (1st generation), nilotinib (2nd generation)
major cause of CML
the philadelphia chromosome (fusion of 9 and 22)
- this one mutation leads to cancer
imatinib clinical indication
- PH+ CML in blast crisis, accelerated phase or chronic phase after IFN therapy
- pediatric patients with PH+ CML in chronic phase
- PH+ ALL
- Kit+ GI stromal tumors (GIST)
monitoring PH+ CML after treatment
- hematologic tests: normal range of blood cell counts
- cytogenic tests: numbers of cells with PH+ chromosome
- molecular tests: q-RT-PCR: existence of PH+ DNA/mRNA
nilotinib is cabable of
overcoming imatinib reisistance resulting from Brc-Abl kinase mutations
Nilotinib clinical indication
chronic phase and accelerated phase PH+ CML resistant or intolerate to imatinib
effectiveness of nilotinib is based on
hematologic and cytogenetic response rates
do not use nilotinib is patients with
hypokalemia, long QT syndrome or hypomagnesemia.
gemfitinib
EGFR
erlotinib
EGFR
Tarceva
NSCLC, metastatic pancreatic cancer
lapatinib
EGFR/Her2
Tykerb
breast cancer
Afatinib
EGFR/Her2
cigarette smoking decreases
erlotinib plasma concentrations
severe ADRs of erlotinib
GI bleeding or perforations, renal disorders, hepatic disorders, ocular disorders- abnormal eyelash growth
common ADRs of lapatinib
GI- diarrhea, dermatologic, fatigue
severe ADRs of lapatinib
cardiac toxicity, hepatic toxicity, interstitial lung disease/pneumonitis
multiple tyrosine kinases
sunitinib, sorafenib