Oncology Drugs Flashcards
Name the antimetabolites
Azathioprine, 6-mercaptopurine, 6-thioguanine, cladribine, cytarabine, 5-fluorouracil, methotrexate
Mechanism of azathioprine, 6-MP and 6-TG
purine (thiol) analogs –> decreased de novo purine synthesis
activated by HGPRT
azathioprine is prodrug to 6-MP
Use of azathioprine, 6-MP and 6-TG
preventing organ rejection RA IBD SLE to wean pts off steroids and to tx steroid-refractory chronic disease
Toxicity of azathioprine, 6-MP and 6-TG
MYELOSUPPRESSION
GI, liver
Metabolism of azathioprine and 6-MP
metabolized via xanthine oxidase
increased toxicity if used with allopurinol or febuxostat (used to treat gout)
Mechanism of cladribine
purine analog –> multiple mechanism (e.g. inhibition of DNA polymerase, DNA strand breaks)
Use of cladribine
hairy cell leukemia
Toxicity of cladribine
myelosuppression, nephrotoxicity, and neurotoxicity
Mechanism of cytarabine
pyrimidine analong –> inhibition of DNA polymerase
Use of cytarabine
leukemias (AML), lymphomas
Toxicity of cytarabine
leukopenia, thrombocytopenia, megaloblastic anemia
CYTarabine causes panCYTopenia
Mechanism of 5-fluorouracil
pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes with folic acid
complex inhibits thymidylate synthase –> decreased dTMP –> decreased DNA synthesis
Use of 5-FU
colon cancer, pancreatic cancer, basal cell carcinoma (topical)
Toxicity of 5-FU
myelosuppression, which is NOT reversible with leucovorin (folinic acid)
Mechanism of methotrexate
folic acid analog that competitively inhibits dihydrofolate reductase –> decreased dTMP –> decreased DNA synthesis
Use of methotrexate
cancers: leukemia (ALL), lymphoma, choriocarcinoma, sarcomas
Non-neoplastic: ectopic pregnancy, medical abortion (with misoprostol), RA, psoriasis, IBD, vasculitis
Toxicity of methotrexate
myelosuppression (reversible with leucovorin)
hepatotoxicity
mucostitis (e.g. mout ulcers)
pulmonary fibrosis
Name the antitumor antibiotics
bleomycin, dactinomycin, doxorubicin, daunorubicin
Mechanism of bleomycin
induces free radical formation –> breaks in DNA strands
Use of bleomycin
testicular cancer, Hodgkin lymphoma
Toxicity of bleomycin
pulmonary fibrosis
skin hyperpigmentation
mucositis
Mechanism of dactinomycin (actinomycin D)
intercalates in DNA
Use of dactinomycin
Wilms tumor
Ewing sarcoma
Rhabdomyosarcoma
CHILDHOOD TUMORS - Kids ACT out
Toxicity of dactinomycin
myelosuppression
Mechanism of doxorubicin/daunorubicin
generate free radicals
intercalate in DNA –> breaks in DNA –> decreased replication
Use of doxorubicin/daunorubicin
solid tumors
leukemias
lymphomas
Toxicity of doxorubicin/daunorubicin
CARDIOTOXICITY (dilated cardiomyopathy)
myelosuppression
alopecia
toxic to tissues following extravasation
Agent given with doxorubicin/daunorubicin to prevent cardiotoxicity
Dexrazoxane - iron chelating agent
Name the alkylating agents
busulfan, cyclophosphamide, ifosfamide, nitrosureas (carmustine, lomustine, semustine, streptozocin)
Mechanism of busulfan
cross-links DNA
Use of busulfan
CML
used to ablate bone marrow before transplant
Toxicity of busulfan
SEVERE MYELOSUPPRESSION
pulmonary fibrosis
hyperpigmentation
Mechanism of cyclophosphamide/ifosfamide
cross-link DNA at guanine N-7
require bioactivation by liver
Use of cyclophosphamide/ifosfamide
solid tumors
leukemia
lymphoma
Toxicity of cyclophosphamide/ifosfamide
myelosuppression HEMORRHAGIC CYSTITIS (partially prevented with MESNA and hydration)
Mechanism of nitrosureas
require bioactivation
cross BBB –> CNS
cross link DNA
Use of nitrosureas
brain tumors (including glioblastoma multiforme)
Toxicity of nitrosureas
CNS toxicirty (convulsions, dizziness, ataxia)
Name the microtubule inhibitors
paclitaxel (other taxols), vincristine, vinblastine
Mechanism of paclitaxel/taxols
hyperstabilize polymerized microtubules in M phase so that mitotic spindle cannot break down (anaphase cannot occur)
Use of paclitaxel/taxol
ovarian and breast carcinomas
Toxicity of paclitaxel/taxol
myelosuppression
alopecia
hypersensitivity
Mechanism of vincristine/vinblastine
vinea alkaloids that bind beta-tubulin and inhibit its polymerization into MTs –> prevent mitotic spindle formation (M-phase arrest)
Use of vincristine/vinblastine
solid tumors
leukemias
Hodgkin (vinblastine) lymphoma
Non-Hodgkin (vincristine) lymphoma
Toxicity of vincristine
neurotoxicity (areflexia, peripheral neuritis)
paralytic ileus
Toxicity of vinblastine
bone marrow supression
Mechanism of cisplatin/carboplatin
cross-link DNA
Use of cisplatin/carboplatin
testicular
bladder
ovary
lung carcinomas
Toxicity of cisplatin/carboplatin
nephrotoxicity, ototoxicity
How can prevent nephrotoxicity of cisplatin/carboplatin
use with amifostine (free radical scavenger) and chloride (saline) diuresis
Mechanism of etoposide/teniposide
etoposide inhibits topoisomerase II –> increased DNA degradation
Use of etoposide/teniposide
solid tumors (testicular and small cell lung)
leukemia
lmyphoma
Toxicity of etoposide/teniposide
myelosuppression, GI upset, alopecia
Mechanism of irinotecan, topotecan
inhibit topoisomerase I and prevent DNA unwinding and replication
Use of irinotecan, topotecan
colon cancer (irinotecan) ovarian and small cell lung (topotecan)
Toxicity of irinotecan, topotecan
severe myelosuppression
diarrhea
Mechanism of hydroxyurea
inhibits ribonucleotide reductase –> decreased DNA synthesis (S-phase specific)
Use of hydroxyurea
melanoma, CML, sickle cell disease (increase HbF)
Toxicity of hydroxyurea
severe myelosupression
GI upset
Mechanism of prednisone/prednisolone
various; bind intracytoplasmic receptor; alter gene transcription
Use of prednisone/prednisolone
CLL
non-Hodgkin lymphoma (part of combo)
immunosuppressants (autoimmune diseases)
Toxicity of prednisone/prednisolone
Cushing like symptoms
Mechanism of bevacizumab
monoclonal antibody against VEGF inhibiting angiogenesis
Use of bevacizumab
colon cancer and renal cell carcinoma
age related macular degeneration
Toxicity of bevacizumab
hemorrhage
blood clots
impaired wound healing
Mechanism of erlotinib
EGFR tyrosine kinase inhibitor
Use of erlotinib
non small cell lung carcinoma (adenocarcinoma if EGF positive)
Toxicity of erlotinib
rash
Mechanism of imatinib
tyrosine kinase inhibitor of BCR-ABL (philadelphia chromosome fusion gene) and c-kit (GI stromal tumors)
Use of imatinib
CML, GI stromal tumors
Toxicity of imatinib
fluid retention
Mechanism of rituximab
Ab against CD20 on B cells
Use of rituximab
Non-Hodgkin lymphoma
CLL
IBD
RA
Toxicity of rituximab
increased risk of progressive multifocal leukoencephalopathy (PML) from JC virus
Mechanism of tamoxifen/raloxifene
selective estrogen receptor modulators
- antagonists in breast and agonists in bone
- block binding of estrogen to ER + cells in breast
Use of tamoxifen/raloxifene
breast cancer treatment (tamoxifen only) and prevention
osteoporosis for raloxifene
Toxicity of tamoxifen
partial agonist in endometrium –> increased risk of endometrial hyperplasia and cancer
increased risk for hot flashes
Toxicity of raloxifene
no increase in endometrial cancer because antagonist in endometrial tissue
Mechanism of trastuzumab
Ab against Her-2, a tyrosine kinase receptor (through interrupted cellular signaling and antibody-dependent cytotoxicity)
Use of trastuzumab
HER2 + breast cancer and gastric cancer
Toxicity of trastuzumab
cardiotoxicity
Mechanism of vemurafenib
small molecule inhibitor of BRAF oncogene + melanoma
Use of vemurafenib
metastatic melanoma