Chemo drugs Flashcards
What are the folate antagonists?
methotrexate and pemetrexed
What is the MOA of methotrexate?
inhibits dihydrofolate reductase which results in blockage of thymidylate and purine synthesis
What is the MOA of pemetrexed?
multi-targeted antifolate
What are the ADRs of the folate antagonists?
- myelosuppression
- mucositis
- renal tubular necrosis with high dose MTX
- Hematologic toxicity - neutropenic sepsis
What other disease states are the folate antagonists used for?
rheumatoid arthritis
What should be supplemented with the folate antagonists?
folic acid and vitamin B12
What is the rescue medicine for MTX?
leucovorin
What are the pyrimidine antagonists?
fluorouracil, capecitabine, cytarabine, and gemcitabine
What is the MOA of 5-FU?
inhibits thymidylate synthase, which inhibits formation of thymidine (affects DNA and RNA)
What is the MOA of cytarabine?
pyrimidine analog incorporated into DNA, but primary action is inhibition of DNA polymerase resulting in decreased DNA synthesis and repair
What is the MOA of gemcitabine?
pyrimidine antimetabolite that inhibits DNA synthesis by inhibition of DNA polymerase and ribonucleotide reductase
What are the major ADRs of the pyrimidine antagonists?
- myelosuppression
- mucositis, stomatitis
- diarrhea
- hand-foot syndrome
- cytarabine cerebellar toxicity
- cytarabine rash and conjunctivitis
What is the only oral pyrimidine antagonist?
capecitabine
What is the reversal agent for 5-FU
uridine triacetate
How do you treat cytarabine conjunctivitis?
steroid eye drops
What is the major drug interaction with pyrimidine antagonists?
warfarin
What are the purine antagonists?
fludarabine, thioguanine, and mercaptopurine
What is the MOA of the purine antagonists?
analogues of purines which get incorporated into DNA to prevent functional DNA synthesis
What are the ADRs of purine antagonists?
myelosuppression and liver toxicity
What is the most immunosuppressive purine antagonist?
fludarabine
What prophylaxis is required with fludarabine?
antiviral and bactrim
What drug classes are the antimetabolites?
purine antagonists, pyrimidine antagonists, and folate antagonists
What drug classes are the alkylating agents?
nitrogen mustard derivatives, platinum analogs, alkyl sulfonates
What are the nitrogen mustard derivatives?
cyclophosphamide, ifosfamide, bendamustine, and mechlorethamine
What is the MOA of the nitrogen mustard derivatives?
form DNA cross-links resulting in inhibition of DNA synthesis and function
What are the ADRs of the nitrogen mustard derivatives?
- myelosuppression
- N/V
- alopecia
- infertility
- hemorrhagic cystitis (acrolein)
- infections (bendamustine)
What is the antidote for bladder toxicity associated with the cyclophosphamide or ifosfamide?
hydration or mesna
What other type of cancer can alkylating agents cause?
leukemia
What are the platinum analogs?
Cisplatin, carboplatin, and oxaliplatin
What is the MOA of the platinum analogs?
form intrastrand and interstrand DNA cross-links; binds to nuclear and cytoplasmic proteins
What are the ADRs of cisplatin?
nephrotoxicity, ototoxicity, severe N/V, neuropathy, and electrolyte depression
What are the ADRs of carboplatin?
myelosuppression, moderate-severe N/V, and hypersensitivity
What are the ADRs of oxaliplatin?
Neuropathy, moderate-severe N/V, myelosuppression, and hypersensitivity
What is the antidote for cisplatin nephrotoxicity?
amifostine
When should cisplatin be avoided?
CrCl < 50
What can be used to treat platinum analog induced neuropathy?
duloxetine
What can be done to reduce ADRs associated with platinum analogs?
reduce the dose
What is the one alkylsulfonate?
busulfan
What is the MOA of busulfan?
cleavage of alkyl-oxygen bond and formation of a butyl compound that forms crosslinks with DNA
What are the ADRs of busulfan?
myelosuppression, pulmonary toxicity, and skin pigmentation
What is the MOA of bleomycin and dacarbazine?
binds to DNA, breaks single strand and double stand, leads to free radical formation and inhibits DNA synthesis
What are the ADRs of bleomycin?
pulmonary toxicity, hyperpigmentation, and febrile reactions
What are the ADRs of dacarbazine?
myelosuppression and N/V
What baseline test must be performed before initiating bleomycin?
pulmonary function test
What drug classes are enzyme inhibitors?
anthracyclines, epipodophyllotoxins, and camptothecans
What are the anthracyclines?
daunorubicin, doxorubicin, idarubicin, and epirubicin
What is the MOA of the anthracyclines?
- topoisomerase II inhibition
- Intercalation of DNA
- Formation of free radicals
What is the MOA of cardiotoxicity in the anthracyclines?
generation of semiquinone free radicals and oxygen free radicals
What are the ADRs of the anthracyclines?
myelosuppression, cardiomyopathy, N/V, extravasation, red urine (daunorubicin and idarubicin)
What tests should be monitored with anthracyclines?
EKG, BNP, and EF
What is the antidote for doxorubicin for cardiotoxicity?
dexrazoxane
What type of cancer can the anthracyclines cause?
leukemia
What are the epipodophyllotoxins?
etoposide and tenoposide
What is the MOA of the epipdodphyllotoxins?
topoisomerase II inhibition
What are the ADRs of the epipodophyllotoxins?
myelosuppression, hypotension, and alopecia
What is the for oral etoposide?
2 x IV dose (poor bioavailability)
What other cancer can epipodophyllotoxins cause?
leukemia
What are the camptothecans?
ironotecan and topotecan
What is the MOA of camptothecans?
topoisomerase I inhibition which is responsible for cutting single DNA strands
What are the ADRs of camptothecans?
myelosuppression, alopecia, and diarrhea
What is the treatment for early onset diarrhea secondary to camptothecans?
atropine within 2-6 hours
What is the treatment for late onset diarrhea secondary to camptothecans?
high dose loperamide
What are the microtubule targeting drug classes?
taxanes and vinca alkaloids
What are the taxanes?
paclitaxel, docetaxel, and cabazitaxel
What are the vinca alkaloids?
vincristine, vinblastine, and vinorelbine
What is the MOA of the taxanes?
bind to tubulin and stabilize microtubules. This prevents depolymerization (freezes cell in anaphase/telophase)
What is the MOA of the vinca alkaloids?
binds to tubulin and interferes with microtubule assembly. Prevents spindle formation
What are the ADRs of the taxanes?
myelosuppression, hypersensitivity, alopecia, and peripheral neuropathy
What are the ADRs of the vinca alkaloids
myelosuppression, constipation, and extravasation
What are the ADRs associated with vincristine?
less myelosuppression but dose-dependent neurotoxicity
Which drug can not be given intrathecally?
vincristine