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What is the con to using Nanoparticle albumin-bound paclitaxel (Abraxane) over normal paclitaxel?
What is the MOA of Paclitaxel?
Causes the buildup of the microtubules rather than allowing free tubulin dimers to form
What are the side effects of paclitaxel?
- Myelosuppression (neutropenia, less with nano-particle form)
- Peripheral neuropathy
- Hypersensitivity (unless pretreated with corticosteroid and antihistamines or using nano-particle form)
- Radiation recall
- Cardiotoxic (bradychardia)
What are the side effects of docetaxel?
- Less peripheral neuropathy than paclitaxel
- Less severe hypersensitivity than paclitaxel
- More fluid retention than paclitaxel
Are taxanes used to treat Leukemia?
No, mostly solid tumors
Which can cause cardiac arrhythmias, paclitaxel or doxetaxel?
What are the Topioisomerse II inhibitors?
Epidophyllotoxins = Etoposide (Ve Pesid)
What is Etoposide (Ve Pesid) derived from?
Mandrake or May apple tree
What is the MOA for Etoposide?
Inhibits topoisomerase II DNA repair enzymes and thus the resealing of DNA strand breaks
What are the indications for etoposide?
What are the side effects for etoposide?
Bone marrow, GI, vesicants, secondary leukemias, radiation recall
What drugs might you give with Etoposide to lower the amount needed and reduce bone marrow effects?
Cisplatin or Bleomycin
What are the Topoisomerase I inhibitors?
What is the MOA of Topoisomerase I inhibitors?
- 1)Drugs bind to DNA-topoisomerase I complex ( which relieves torsional strain in DNA during DNA replication by creating reversible single-strand breaks)
- 2)Prevents repair of the strand breaks
- 3)Impairs DNA replication
topotecan (Hycamtin) is given by what route?
What are the indications for topotecan (Hycamtin)?
What are the side effects for topotecan (Hycamtin)?
Bone marrow suppression
Irinotecan (Camptosar) is given by what route?
Which Topoisomerase I is a prodrug?
What are the indications for Irinotecan?
- Very specific:
- Metastatic cancer of the colon or rectum
What are the side effects of Irinotecan?
Severe diarrhea and myelosuppression
What are the antibiotic groups that are used as antineoplastics?
What are the Anthracenes and Anthracyclines?
- Doxorubicin (Adriamycin or Hydroxydaunorubicin)
- Doxorubicin-liposomal (Doxil)
- Daunorubicin (Cerubidine)
- Idarubicin (Idamycin)
- Epirubicin (Ellence)
What stage of the cell cycle do Anthracenes and Anthracyclines inhibit?
What regimen does Doxorubicin fit into, CHOP or ABVD?
What is the ending for a Anthracycline?
Why would you give doxorubicin in a liposomal formulation?
Increases the surface area and increases absorption
What is the MOA of anthracyclines?
- Intercalates DNA
- Distorts the structure
- RNA polymerase cannot use DNA as a template.
- Also binds to topoisomerase II (inhibiting DNA repair)
How are anthracyclines administered?
Do anthracyclines have vesicant properties?
What effects do anthracylclines have on the urine?
Turns it red
Anthracyclines can cause a cardiotoxic reaction, what is this reaction dependant on?
What is the antidote for the cardiotoxic reaction caused by anthracyclines?
- Dexrazoxane is a maybe ( iron chelator)
- May inhibit Doxorubicin’s ability to operate
What are the side affects of Doxorubicin and other anthracyclines?
- Cardiac toxicity (irreversible): arrhythmias, congestive heart failure
- radiation recall
What is the mechanism for cardiac toxicity caused by doxorubine and other anthrocyclines?
- CYP P450 system forms a superoxide anion causing free radical reactions in the presence of iron.
- Heart has little peroxidase enzymes to remove toxic products
Doxorubicin and Anthrocyclines are used to treate what?
Solid tumors and Leukemias
What are the routes of administration for Bleomycins?
IM and IV
What type of molecule is bleomycin?
What is the MOA for Bleomycin?
Binds to DNA forming a bleomycin-iron-oxygen complex which breaks DNA
What are the side effects of Bleomycin?
- Pulmonary fibrosis and toxicity (potentially fatal)
- Anaphylactic reactions
- Hyperkeratosis – blistering
- (very little bone marrow toxicity) Important for combination therapy.
What are the indications for Bleomycin?
What is the route of administration for L-aspariginase?
IV or IM
What is the MOA of L-asparaginase (Elspar) and pegasparagase (Oncaspar)?
- Breaks down Asparagine to ammonia and aspartic acid
- Limits protein synthesis in cancer cells requiring large amount of Asparagine for growth (ALL/Leukemia)
What are the indications for L-asparaginase (Elspar) and pegasparagase (Oncaspar)?
Acute lymphocytic leukemia (require L-asparagine)
What are the side effects of L-aspariginase?
- Hypersensitivity (E. coli derived)
- CNS neurotoxicity
- Liver and kidney damage pancreatitis (excess NH3)
- Coagulation deficiencies (reduces synthesis of coagulation factors)
Is L-asparaginase cytotoxic?
No, does not cause toxicity to bone marrow, gastrointestinal tract, and hair follicles
Arsenic Trioxide (As2O3)—(Trisenox) is used for what type of cancer?
- Differentiating Agents for Acute Promyelocytic Leukemia (APL)
- APL in patients refractory to first line therapy of tretinoin or anthracycline based therapy
What is the route of administration for Arsenic Trioxide (As2O3)—(Trisenox)
What is the mechanism of Action for Arsenic Trioxide (As2O3)—(Trisenox)?
- Induces differentiation of promyelocytic leukemia cells and induces apoptosis:
- Translocation produces the fusion protein PMS-RARα
- Arsenic binds to PML-RARα in a region containing zinc fingers (arsenic binds instead of zinc)
- Stimulates SUMOylation , ubiquitination, and degradation of the PML-RARα protein
- Allows partial differentiation of leukemic promyelocytes and eliminates leukemia-initiating cells
What are the side effects of Arsenic Trioxide (As2O3)—(Trisenox)?
Rash, nausea, vomiting, tachycardia, QT prolongation (EKG) leading to ventricular
Would you expect bone marrow suppression with Arsenic Trioxide (As2O3)—(Trisenox)?
What is the route of trentoin administration?
What is the mechanism of action for Trentoin?
- Induces differentiation of acute promyelocytic cells to normal myelocytic cells
- It acts by binding to a nuclear receptor and affects transcription
What is the indication for Trentoin?
APL in patient’s refractory to first line anthracycline based therapy
What are the side effects of Trentoin?
Vit A toxicity, fever, skin dryness and rash, CNS toxicities, teratogenic
Should you be taking a multivitamin when using Trentoin?
Not if it has Vitamin A in it