University:
University of North Carolina at Chapel Hill
Course:
NURS 312 | Pharmacology
Academic year:

2020
Views:

187

Pages:

1
Author:

rezancuk2j

3.1 – “Rev “Revolutionary olutionary Ki Kinase nase inh inhibitors”: ibitors”: imatinib, erlotinib, sorafenib, sunitinib, vemurafenib • Many cancers arise from kinase mutations → constitutive activation of proliferation signals, making these mutated kinases desirable targets for cancer therapy. • Many of the small molecule kinase inhibitors end in -nib (broken pen nib). Used to treat a variety of hematologic & solid malignancies (cracked crab bell). Tyrosine kinase inhibitors (inh (inhibited ibited tire sw swing) ing) • End in -tinib • Imatinib (imitating portrait of King George III) o Indications ▪ CML, characterized by increased levels of mature granulocytes, including eosinophils, neutrophils, basophils (colorful granules). Inhibits BCR-ABL fusion protein (“breakable” label) • BCR-ABL fusion protein results from t(9;22) – aka Philadelphia chromosome (hence the setting). The protein stimulates granulocytic precursors →CML. ▪ Blocks c-kit, found in GI stroma tumors (Congress Kit held by guy with beer belly & crab buttons) o Adverse effects ▪ Fluid retention → ankle & periorbital edema (king impersonator with baggy pantaloons) • Erlotinib (Earl of Tinib) o Blocks EGFR (Earl Geoffrey) ▪ Activation of EGFR → uncontrolled cell growth, metastasis, proliferation, angiogenesis. overexpressed in several solid tumors including non-small cell lung CA, pancreatic CA (crab on lung shaped lapel) o Adverse events ▪ Cutaneous involvement common, d/t EGFR expression in the skin. Classically papulopustular acneiform rash (Earl’s spotty rash) ▪ Diarrhea (muddy pants). Not usually severe. • Sunitinib (rising sun), Sorafenib (soaring eagle) o Inhibit multiple Y-kinases, including VEGF receptors – angiogenic growth factor . Result in blocking vasculogenesis needed for primary & metastatic tumors (hoeing up vegetables) o Indications: ▪ Sorafenib: RCC (flank crab suspender buckles), HCC ▪ Sunitinib: RCC (flank crab suspender buckles), GIST o Adverse effects ▪ Cutaneous effects including hyperkeratosis & rashes (farmer’s hyperkeratotic callouses & sunburn) ▪ ↑risk of hemorrhage, d/t disruption of VEGF-R on the vascular endothelium (farmer bleeding) • Vemurafenib (venomous snake) o -rafinib for B-Raf inhibit (B. FRA signature inhibited by broken nib). ▪ BRAF is a protein kinase involved in activation of melanocyte proliferation. V600E (valine → glutamic acid) seen in 4060% of patients with melanoma – hence vemu- for V→E mutated BRAF inhibitor. o Treats V600E BRAF positive malignant melanoma (disseminated ink). Improved survival & long-term events