Drugs Flashcards
Goldie-Coldman hypothesis
The hypothesis states that probability that a cancer develops a resistant clone is dependent on the mutation rate (genetic instability of the cancer) and size of the tumor.
Curative therapy for cancer requires that the therapy
1- prevents development of resistance using combination therapy
2- that therapy is provided when the tumor burden is low
3- for cytotoxic chemotherapy, that there is dose intensity to provide the highest dose in the shortest interval.
For targeted therapy, the dose intensity relates to the drug’s ability to maintain target inhibition.
Azacytidine is a nucleoside analogue ( antimetabolite) of cytidine that incorporates into DNA and reversibly inhibits DNA methyltransferase, blocking DNA methylation.
Azacytidine
; it also incorporates into RNA and disrupts normal RNA function and impairs tRNA cytosine-5-methyltransferase activity.
inhibits dihydrofolate reductase.
Methotrexate
histone deacetylase inhibtors
vorinostat and entinostat
Sodium thiosulfate use
Sodium thiosulfate was FDA approved for cisplatin-related ototoxicity in patients with localized solid tumors.
e.g 8 months old with non met hepatoblastoma
Vincristine is a vesicant and can cause significant tissue damage after extravasation.
apply a warm compress to the IV site, and consider local administration of hyaluronidase.
The goals of treating an extravasation of a vinca alkaloid are to disperse and dilute by increasing blood flow with a warm compress.
Hyaluronidase, an enzyme that degrades hyaluronic acid and improves absorption of locally injected drugs, can reduce risk of skin necrosis.
antidotes for doxorubicin extravasation.
Dexrazoxane and DMFO (difluoromethylornithine)
Multitargeted kinase inhibitors that target vascular endothelial growth factor receptor inhibition (VEGFR) side effect
hypertension, poor wound healing, and proteinuria. Class effect toxicity of inhibition of VEGF include increased blood pressure, proteinuria, and poor wound healing due to their effects on capillaries. Other toxicities of VEGF and multityrosine kinase inhibitors can be widening of the growth plate, cardiac dysfunction, palmar-plantar erythrodysesthesia, and gastrointestinal side effects including diarrhea.
Combination immune checkpoint therapy with PD-1 inhibition and anti-CTLA-4 side effects. have a high frequency of serious immune-related adverse events compared with anti PD-1 therapy alone.
Combination immune checkpoint therapy with PD-1 inhibition and anti-CTLA-4 have a high frequency of serious immune-related adverse events compared with anti PD-1 therapy alone.
autoimmune symptoms such as cardiomyositis, gastrointestinal perforation, hypo- or hyperthyroidism, uvitis, and hypophysitis.pneumonitis
isotretinoin (13-cis-retinoic acid) side effects
Cheilitis, hypertriglyceridemia, hypercalcemia
Inotuzmab MOA
Inotuzumab is a CD22-directed monoclonal antibody that releases calicheamicin when it binds to CD22 cells.
Calicheamicin binds to the DNA in the cancer cell’s nucleus and causes double-strand breaks, leading to cell death.
Calicheamicin antibody–drug conjugates
The lower rate of meningeal relapse observed in children with ALL treated with dexamethasone compared with prednisolone is, in part, related to ?
Prednisone, prednisolone, and dexamethasone are all nearly completely absorbed (>80%) after oral administration.
Prednisone is a prodrug requiring hepatic activation to prednisolone but is not altered by hepatic dysfunction.
Prednisolone is highly bound to transcortin; dexamethasone is not bound to transcortin.
Lower protein binding may increase free fraction of drug to enter the central nervous system and may contribute to lower rate of meningeal relapse in children with ALL treated with dexamethasone.
nelarabine side effects
Neurotoxicity associated with nelarabine is ascending weakness that starts in lower extremities. It is frequently referred to as Guillain-Barre-like. It is the dose-limiting toxicity of nelarabine and is only very slowly reversible.
bevacizumab and surgery
vascular endothelial growth factor inhibitor.
Bevacizumab can cause major wound healing and surgical complications, so it should not be given until the wounds have fully healed from his G-tube and central venous line placement. These complications occurred for minor surgeries such as port placement. It is suggested to wait at least 28 days before bevacizumab treatment.
dinutuximab, IL-2, and GM-CSF for neuroblastoma . side effects?
hypersensitivity reactions, capillary leak syndrome, and pain, is correct. Answer A is not correct because dinutuximab, IL-2, and GM-CSF are associated with potentially life threatening side effects including hypersensitivity reactions, capillary leak syndrome, and pain requiring narcotics during infusion of dinutuximab because the target of dinutuximab (GD2) is present on peripheral nerves.
All-trans-retinoid acid (ATRA) & arsenic trioxide
All-trans-retinoid acid (ATRA) administered in combination with arsenic trioxide (ATO) can be administered in combination with chemotherapy with lower anthracycline exposure and equivalent event-free and overall survival compared with anthracycline-based chemotherapy alone.
Differentiation occurs in 20% with ATRA and ATO
arsenic trioxide is associated with prolonged QTC
