Pharm Oncology Flashcards
Describe the cell cycle. tumor suppressors modulate the G1 restriction point? What classes of drugs/drugs work during the S phase? G2 phase? M phase? G1/G0 phase?
MItosis occurs in which cell in split in two.
G0 is resting phase.
G1 is when the cellular content is duplicated (Rb, p53 modulate checkpoint before next step)
In S phase, DNA is duplicated
In G2, the DNA is checked again to make sure there were no mistakes
M phase again.
What is the mechanism of azathioprine (1), 6 mercaptopurine (2), and 6 thioguanine? How are they used clinically? Toxicity? How are they activated? How is 1 activated? What increases toxicity of 1 and 2?
Purine analogs which leads to decr. de novo purine synth
Activated by HGPRT
1 is metabolized into 6-MP
Preventing organ rejection RA IBD SLE Wean pts. off steroids Treat steroid refractory chronic disease
Myelosuppresion
GI
LIver
1/2 metabolized by XO, so allopurinol and febuxostat incr. toxicity
What is the mechanism of Cladribine (2CDA)? Clinical use? Toxicity?
Purine analog that has multiple mechanisms (strand breaks, inhibition of DNAP)
Hairy Cell Leukemia
Myelosuppression
Nephrotoxicity
Neurotoxicity
What is the mechanism of cytarabine? Use? Toxicity?
Pyrimidine analog leading to inhibition of DNAP
Leukemias (AML), lymphomas
Leukopenia
thrombocytopenia
megaloblastic anemia
What is the mechanism of 5-flourouracil? Uses? Toxicity? Reversal?
Pyrimidine analog that Inhibits thymidylate synthase leading to decr. dTMP leading to decr. DNA
Colon cancer, pancreatic cancer, basal cell CA (topical)
Myelosuppresion (not reversible with leucovorin)
What is the mechanism of methotrexate? Use? Toxicity?
Folic aid analog that competitively inhibits DHFR leading to decr. dTMP and decr. DNA synth
Cancers: Leukemias (ALL), lymphomas, chorioCA, Sarcomas
Ectopic pregnancy Medical abortion (with misoprostol) RA Psoriasis IBD Vasculitis
Myelosuppresion (reversible with leucovorin)
Hepatotoxicity
Mucositis
Pulm. fibrosis
What is the mechanism of bleomycin? Use? Toxicity?
Induces free radical formation lt breaks in DNA strands
Testicular cancer, Hodgkins lymphoma
Pulm. fibrosis, skin hyperpig, mucositis
Minimal myelosuppresion
What is the mechanism of dactinomycin? Use? Toxicity?
intercalates in DNA
Wilms tumor
EWING sarcoma
rhabdomyosarcoma
childhood tumors (children ACT out)
Myelosupprsion
What is the mechanism of doxorubicin and daunorubicin? Use? Toxicity? Prevention?
Generates free radicals
Intercalates in DNA lt breaks in DNA lt decr. replicaiton
Solid tumors, leukemias, lymphomas
Cardiotoxicity (dil cardiomyopathy)
myelosuppression
Alopecia
Dexrazoxane used to prevent CM
What is the mechanism of busulfan? Use? Toxicity?
cross links DNA
CML
ablate patients bone marrow prior to transplant
Severe myelosuppresion (in almost all cases)
pulm. fibrosis
hyperpigmentation
What is the mechanism of cyclophosphamide, ifofsamide? Use? Toxicity?
Cross link DNA at guanine N-7.
Bioactivation by liver
Solid tumors, leukemia, lymphomas
Myelosuppresion
Hemorrhagic cystitis
What is the mechanism of nitrosoureas (carmustine, lomustine, semustine, streptozocin)? Use? Toxicity?
Require bioactivation
Cross BBB
Cross link DNA
Brain tumors (including GBM)
CNS toxicity (convulsions, dizziness, ataxia)
What is the mechanism of paclitaxel (other taxols)? Use? Toxicity?
Hyperstabilizes microtubules in M phase so taht mitotic spindle cannot break down (anaphase cannot occur)
“It is taxing to stay polymerized”
Ovarian and breast CAs
Myelosuppresion
Alopecia
HSR
What is the mechanism of vincristine (1), vinblastine (2)? Use? Use of 1? 2? Toxicity 1? 2?
Vinca alkaloids that bind beta tubulin and inhibit its polymerization into microtubules lt preventing of mitotic spindle formation
Solid tumors, leuk, HL (2), NHL (1), lymphomas
1=neurotoxicity (areflexia, periph neuritis, paralytic ileus)
2=myelosuppression
What is the mechanism cisplatin/carboplatin? Clinical use? Toxicity?
Cross link DNA
Testicular, bladder, ovary, and lung CA
Nephrotoxicity, ototoxicity
What is the mechanism etoposide, teniposide? Clinical use? Toxicity?
Inhibits topoisomerase II lt incr. DNA degradation
Solid tumors (test and Small Cell lung cancer) leuk and lymph
myelosuppresion, GI upset, alopecia
What is the mechanism irinotecan (1), topotecan (2)? Clinical use 1? 2? Toxicity?
Inhibit topoisomerase I and prevent DNA unwinding and replication
Colon cancer-1
ovarian and small cell lung cancers-2
Severe myelosuppresion
Diarrhea
What is the mechanism hydroxyurea? Clinical use? Toxicity?
Inhibits ribonucleotide reductase leading to decr. DNA synth
Melanoma, CML, Sickle cell disease (incr. HbF)
Severe myelosuppression
GI upset
What is the mechanism prednisone, prednisolone? Clinical use? Toxicity?
Various; bind intracytoplasmic receptor; alter gene transcription
Most commonly used glucocorticoids in cancer chemo
CLL, NHL
Immunosuppressants (auto immune)
Cushing like symptoms: weight gain, central obesity, muscle breakdown, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis
What is the mechanism bevacizumab? Clinical use? Toxicity?
MAB against VEGF. Inhibits angiogenesis
Solid tumors (CRC, RCC)
Hemorrhage, blood clots, impaired wound healing
What is the mechanism erlotinib? Clinical use? Toxicity?
EGFR tyrosine kinase inhibitor
Non-small cell CA
Rash
What is the mechanism imatinib? Clinical use? Toxicity?
Tyrosine kinase inhibitor of BCR-ABL (CML; 9;22) and c-kit (GIST)
CML, GIST
Fluid retention
What is the mechanism rituximab? Clinical use? Toxicity?
MAB against CD20, found in most b cell neoplasms
NHL, CLL, IBD, RA
Incr. risk of progressive multifocal leukoencephalopathy (JC virus)
What is the mechanism tamoxifen (1), raloxifene (2)? Clinical use? Toxicity?
SERMs-receptor antag in breast and agonists in bone
Block binding of estrogen to ER + cells
1=Breast cancer treatment and prevention
2=prevent osteoporosis
1=partial agonist in endometrium, which incr. risk of endometrial cancer; hot flashes
2=no incr. in endometrial CA b/c it is an antag there
