Cell Cycle Specific Drug Tables - Fitz Flashcards
5-Fluorouracil…active metabolites and their actions
FdUMP - inhibits thymidylate synthase (no dTMP)
FdUTP - insert and damage DNA
FUTP - insert and damage RNA
Cytarabine (Ara-C)…conversion and action
Kinases convert to Ara-CTP, which inhibits DNA synthesis
Gemcitabine…conversion and action
Kinases convert it to nucleotide analogs, which inhibit DNA synthesis
5-FU uses
- Solid tumors (colorectal, breast, ovarian)
- Topical - basal cell carcinoma
Capecitabine uses
Colorectal, metastatic/resistant breast
Gemcitabine use
Pancreatic cancer
Cytarabine use
AML (w/ 6-thioguanine, daunorubicin)
5-FU toxicities
GI intolerance, mucositis, myelosuppression
Capecitabine toxicities
Same as 5-FU, + hand-foot syndrome
Gemcitabine toxicity
Neutropenia
Cytarabine toxicity
Granulocytopenia (severe)
MTX function
MTX(glu)n function
MTX = blocks DHFR, blocking thymidine, methionine and serine synthesis MTX(glu)n = blocks GAR and AICAR transformylase, blocking purine synthesis
Pemetrexed function
Specialty vs. MTX?
Thymidylate synthase and GAR transformylase inhibitor
Does NOT inhibit DHFR, circumvents MTX resistance
Pemetrexed uses
Mesothelioma (w/ cisplatin), refractory NSCLC
High dose MTX uses
Requires what?
CNS prophylaxis for leukemia and high-risk lymphoma
Leucovorin rescue
Intermediate dose MTX use
Gestational trophoblastic disease (choriocarcinoma)
Low dose MTX uses
CNS prophylaxis (intrathecal), bladder and desmoid (IV), ALL and APL (oral)
MTX toxicities
BM suppression, mucositis, renal failure (high dose)
Pemetrexed toxicities
BM suppression, renal failure
6-Mercaptopurine function
Inhibits purine ring biosynthesis and nucleotide interconversion, disrupting DNA and RNA
6-Thioguanine function
Same as 6-Mercaptopurine
Inhibits purine ring biosynthesis and nucleotide interconversion, disrupting DNA and RNA
Fludarabine conversion and function
Tumor kinases convert it to nucleotide triphosphates, which insert and disrupt DNA and RNA
Cladribine conversion and functions
Tumor kinases convert it to nucleotide analogs, which inhibit DNA synthesis; also inhibits ribonucleotide reductase
6-Mercaptopurine use
ALL remission maintenance
6-Thioguanine use
AML (w/ daunorubicin and cytarabine)
Fludarabine use
CLL (or hairy cell leukemia)
Cladribine use
Hairy cell leukemia (or CLL)
6-Mercaptopurine toxicities
Myelosuppression; toxicity w/ allopurinol or febuxostat; hepatotoxicity
6-Thioguanine toxicities
Myelosuppression, hepatotoxicity (long use)
Fludarabine toxicities
Why give IV?
Myelosuppression, opportunistic infections
IV = avoid GI bacteria generating toxic fluroradenine
Cladribine toxicities
Myelosuppression, drug fever
Vinca alkaloid function
Inhibit tubulin polymerization, causing microtubule shortening and M-phase disruption
Taxane function
Inhibit tubulin fraying, causing microtubule lengthening and M-phase disruption
Vinblastine uses
Testicular (w/ bleomycin and cisplatin), lymphomas, neuroblastoma
Vincristine uses
ALL, lymphoma, neuroblastoma, Wilms, Ewings
Vinorelbine use
Advanced non-small cell lung cancer (alone or w/ cisplatin)
Paclitaxel uses
Solid tumors - Advanced breast and ovarian (w/ cisplatin)
Docetaxel uses
Solid tumors - Advanced breast, ovarian recurrence
Vinblastine toxicities
BM suppression, blisters
Vincristine toxicities
Neurotoxicity, peripheral neuropathy, ileus, blisters
Vinorelbine toxicities
BM suppression, blisters
Paclitaxel toxicities
Requires what?
Neutropenia, thrombocytopenia, peripheral neuropathy, hypersensitivity during infusion
Needs anti-histamine and corticosteroid pretreatment
Docetaxel toxicities
Neutropenia, peripheral neuropathy
Etoposine and Teniposide - function
Topoisomerase 2 inhibitors, causing DNA double strand breaks
Irinotecan and Topotecan - function
Topoisomerase 1 inhibitors, causing DNA single strand breaks
Etoposide uses
Oat cell carcinoma of lung, testicular cancer (w/ cisplatin and bleomycin)
Teniposide uses
Glioma, neuroblastoma
Irinotecan use
Metastatic colorectal cancer
Topotecan use
2nd line treatments for various failed 1st treatments
Etoposide toxicities
Leukopenia, secondary leukemia (DNA repair error)
Teniposide toxicity
Leukopenia
Irinotecan toxicities
Requires what?
Severe diarrhea (life-threatening), myelosuppression
Loperamide co-treatment (for diarrhea)
Topotecan toxicities
Neutropenia, mucositis
Bleomycin function
Fe(3+)-mediated free radical damage to DNA
Dactinomycin function
DNA intercalating agents
Doxorubicin, Daunorubicin, Epirubicin - functions
- Inhibit topoisomerase 2
- DNA intercalating agents
- Free radical generation –> DNA strand breaks
Mitoxantrone function
Inhibit topoisomerase 2
Bleomycin use
Testicular (w/ Vinblastine, cisplatin/etoposide)
Doxorubicin and Epirubicin - uses
Breast, ovarian, lung, thyroid, lymphoma, sarcoma, etc.
Daunorubicin uses
AML, ALL
Idarubicin uses
AML, ALL, CML blast crisis
Mitoxantrone uses
Breast, prostate, NHL
Bleomycin toxicity
Pulmonary fibrosis
‘rubicins and Mitoxantrone - toxicities
Cardiotoxicity, dilated cardiomyopathy, CHF (cumulative)