Oncology Drugs Flashcards
Methotrexate
MOA
SE
Folic acid analog
Blocks DHF which reduces dTMP, DNA and protein synthesis
SEs: Myelosuppression think cytopenias, infections; this is reversible with Leucovorin
Fatty liver change
Mucositis (mouth ulcers)
Teratogenic
How do you reverse myelosuppression due to MTX?
Leucovorin
What is 5-FU
MOA
SE?
Pyrimidine analog thats activated to 5F-dUMP–>complex with Folic Acid
Complex blocks THYMIDYLATE SYNTHASE, which decreases dTMP, DNA, and protein synthesis
SEs: Myelosuppression (but not reversible with Leucovorin)
Rescue with Uridine instead
Photosensitivity
Cytarabine (arabinofuranosyl cytidine)
MOA
SE
Pyrimidine analong that blocks DNA polymerase
SE: Pancytopenia incl throbocytopenia and megaloblastic anemia
What is Azathiprine, 6-MP, 6-TP (thioguanine)
Purine analogs that block de nove purine synthesis
Activated by HGPRT, turns them into active metabolites that are inactivated by XO.
Dont take these with Allopurinol bc it blocks XO and then these will build up to toxic levels (except for 6-TG)
SE: Bone marrow, GI, Liver
What are the anti-metabolites and where do they act?
Methotrexate, 5-FU, Cytarabine, Azathioprine, 6-MP, 6-TG
Work in the S phase
What are the anti-tumor antibiotics?
Dactinomycin (actinomycin-D)
Doxurubicin (Adriamycin)
Daunorubicin
Bleomycin
Dactinomycin
MOA
SE
Intercalates in DNA
Used for childhood tumors (Wilms, Ewing, Rhabdo)
SE: Myelosuppression
Doxorubicin/Daunorubicin
MOA
SE
Intercalate into DNA
Generate free radicals
Cause breaks in DNA, blocking replication
Dilated Cardiomyopathy (use Dexrazoxane to prevent this) Myelosuppression, alopecia
what can be used to prevent cardiotoxicity (dialated cardiomyopathy) from doxo/daunorubicin?
Dexrazoxane which is an Fe chelating agent
Prevents free radical formation
Bleomycin
MOA
SE
Induce free radical formation–>breaks in DNA strands
Use in Hodgkins/Testicular
SE: Pulmonary Fibrosis
Minimal myelosuppression
skin changes and mouth sores
Works in G2 phase
What are the alkylating agents?
Cyclophosphamide, Ifosfamide, the Nitrosureas (carmustine, lomustine, semustine, streptozosin) and Bisulfan
Cyclophosphamide
Ifosfamide
MOA
SE
Covalently link DNA at Guanine N-7
Has to be activated in the liver first
Myelosuppression esp myelodysplastic syndrome
But most importantly is HEMORRHAGIC CYSTITIS, prevent with MESNA bc it binds acrolein
SIADH
What can be used to treat hemorrhagic cystitis from cyclophosphamide/ifosfamide?
Mesna
What are the nitrosureas?
The mustines?
Carmustine, Lomustine, Semustine, Streptozocin
How do the Nitrosureas work?
SE?
Cross link DNA, and can X BBB, but requires bioactivation first
SE:
Obviously CNS toxicity ie convulsions, dizziness, ataxia
Busulfan
MOA
SE?
X-Links DNA
Used for CML
Severe myelosuppression
Pulmonary fibrosis
Hyperpigmentation
What are the microtubule inhibitors?
Vincristine, Vinblastine, Paclitaxel, other TAXOLS
Vincristine, Vinblastine
MOA
SE
Bind B tubulin, prevents spindle formation
blasts the spindle, M-phase arrest
Vincristine-neurotoxicity (areflexia, peripheral neuritis) and paralytic ileus, no myelosuppression
Vinblastine blasts bone so causes myelosuppression
Paclitaxel, taxols, Docetaxel
MOA
SE
Hyperstabilizes polymerized microtubules in M phase
Spindle CANT BREAK DOWN
Myelosuppression, alopecia, HSR
Cisplatin, Carboplatin
X-link DNA
SE Nephrotox, CN8 damage
Prevent nephrotox with Amifostine and Cl-diuresis
What is Amifostine needed for?
Fix nephrotox from Cisplatin or carboplatin. Use with Cl- diuresis
Its a free radical scavenger
Etoposide, Teniposide
MOA
SE
Etwoposide Topo two Inhibitor
SE: myelosuppresson, GI irritation, alopecia
Irinotecan, Topetecan
MOA
SE
Inhibit Topo I
Prevent DNA unwinding and replication
SE: SEVERE MYELOSUPPRESSION, diarrhea
Hydroxyurea
MOA
SE
Blocks ribonucleotide reductase which decreases DNA synthesis
S-phase specific
Melanoma, CML, sickle cell
Myelosuppression, GI Upset
Prednisone, Prednisolone
MOA
SE
Triggers apoptosis
These two glucocorticoids used in CA
Can cause cushings, cataracts, acne, peptic ulcers
Tamoxifen, Raloxifene
MOA
SE
SERMs
Estrogen Receptor antagonist in breast but agonist in bone (Raloxifene)
Tamoxifen causes endometrial CA, raloxifene prevents it
Trastuzumab (Herceptin)
MOA
SE
Mab against Her2Neu which is a tyrosine kinase receptor (EGFR)
Used for breast AND GASTRIC CA so it treats 2 cancers (tras2zumab)
SE Cardiotox…heartceptin ~herceptin
Imatinib
MOA
SE
Tyrosine kinase inhibitor of bcr-abl from CML and c-kit which is in GI stromal tumors
Causes fluid retention, myalgias, diarrhea
Rituximab
MOA
SE
Mab against CD20+ which are B cells
Non Hodkins, RA with MTX, ITP
SE: incr risk for PML (progressive mulifocal leukoencephalopathy) which is demyelination associated with JC virus. also incr risk with natalizumab
Vemurafenib
MOA
SE
Inhibits B-Raf kinase that has a V600E mutation
Use for metastatic melanoma
Bevacizumab
MOA
SE
Mab against VEGF–>inhibits angiogenesis
SE: Hemorrhage and impaired wound healing
