Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
23 Cards in this Set
- Front
- Back
|
Mechlorethamine
(nitrogen mustard) |
alkylating agent - electrophiles that add alkyl groups to 7N guanine which causes GT pairing instead of GC
also causes cross-link DNA and linkage with proteins Least stable, rapidly metabolizing Clinical use: Hodgkin's disease, lymphoma, carcinoma of breast and ovary, melanoma, peripheral stem cell mobilization Toxicities: myelosuppression, sterility, secondary leukeumia (5-7 year latency, mutations of chromosome 5,7,8) |
|
|
Cyclophosphamide
(nitrogen mustard) |
alkylating agent - electrophiles that add alkyl groups to 7N guanine which causes GT pairing instead of GC
also causes cross-link DNA and linkage with proteins Must be activated by P450s --> hydroxyphosphamide --> acrophosphamide --> phospharamide mustard Clinical use: Hodgkin's disease, lymphoma, carcinoma of breast and ovary, melanoma, peripheral stem cell mobilization Toxicities: myelosuppression, hemorrhagic cystitis (cyclophosphamide, acrolein) sterility, secondary leukeumia (5-7 year latency, mutations of chromosome 5,7,8) |
|
|
Ifosfamide
(nitrogen mustard) |
alkylating agent - electrophiles that add alkyl groups to 7N guanine which causes GT pairing instead of GC
also causes cross-link DNA and linkage with proteins Clinical use: Hodgkin's disease, lymphoma, carcinoma of breast and ovary, melanoma, peripheral stem cell mobilization Toxicities: myelosuppression, sterility, secondary leukeumia (5-7 year latency, mutations of chromosome 5,7,8) |
|
|
Melphalan
(nitrogen mustard) |
alkylating agent - electrophiles that add alkyl groups to 7N guanine which causes GT pairing instead of GC
also causes cross-link DNA and linkage with proteins Clinical use: Hodgkin's disease, lymphoma, carcinoma of breast and ovary, melanoma, peripheral stem cell mobilization Toxicities: myelosuppression, sterility, secondary leukeumia (5-7 year latency, mutations of chromosome 5,7,8) |
|
|
Chlorambucil
(nitrogen mustard) |
alkylating agent - electrophiles that add alkyl groups to 7N guanine which causes GT pairing instead of GC
also causes cross-link DNA and linkage with proteins Clinical use: Hodgkin's disease, lymphoma, carcinoma of breast and ovary, melanoma, peripheral stem cell mobilization Toxicities: myelosuppression, sterility, secondary leukeumia (5-7 year latency, mutations of chromosome 5,7,8) |
|
|
Busulfan
(Alklyl sulfonates) |
alklylating agent - add alkyl group to 7N of guanine causing GT pairing instead of GC pairing. Cross links DNA and links proteins to DNA
Clinical uses: Hodgkin's disease, lymphoma, carcinoma of the breast and ovary, melanoma, peripheral stem cell mobilization Toxicities: myelosuppression, sterility, leukemia (5-7 year latency, chromosomal abnormalities on 5,7,8) |
|
|
Carmustine or BCNU
Semustine or MeCCNU Lomustine or CCNU (nitrosourea) |
alklylating agent - add alkyl group to 7N of guanine causing GT pairing instead of GC pairing. Cross links DNA and links proteins to DNA
Clinical uses: Hodgkin's disease, lymphoma, carcinoma of the breast and ovary, melanoma, peripheral stem cell mobilization Toxicities: myelosuppression, sterility, leukemia (5-7 year latency, chromosomal abnormalities on 5,7,8) |
|
|
Streptozocin
Chlorozotocin (nitrosourea) |
alkylating agents
Clinical uses: Hodgkin's disease, lymphoma, carcinoma of the breast and ovary, melanoma, peripheral stem cell mobilization Toxicities: myelosuppression, sterility, leukemia (5-7 year latency, chromosomal abnormalities on 5,7,8) |
|
|
Daunorubicin
Doxorubicin Idarubicin (anthracycline) |
antibiotics isolated from Streptomyces peucetius
intercalate into DNA preventing replication react with P450s to generate radicals in the presence of Fe induce DNA strand breaks (prevents topoisomerase II) Clinical uses: acute leukemia, lymphomas, breast cancer, sarcomas Toxicities: cardiotoxicity (cardiomyopathy), myelosuppresion, vesicants |
|
|
Mitoxantrone
(anthracycline) |
synthetic antiobiotic
intercalates into DNA preventing replication react with P450 to create radicals in the presence of Fre generates fewer radicals and lower toxicity especially to cardiac cells than natural anthracyclines induce DNA strand breaks (topoisomerase II inhibitors) Clinical uses: acute leukemia, lymphomas, breast cancer, sarcomas Toxicities: cardiotoxicity (cardiomyopathy), myelosuppresion, vesicants |
|
|
Bleomycin
|
antibiotic isolated from Streptomyces veicillus
binds to iron to cause free radical formation which breaks DNA strands Clinical use: testicuar cancer, lymphomas, Hodgkin's disease Toxicities: pulmonary fibrosis |
|
|
Dactinomycin
|
antibiotic isolated from Streptomyces
intercalates between GC pairs in DNA blocking transcription by RNA polymerase Clinical uses: Wilm's tumor, rhabdomyosarcoma, Kaposi's sarcoma, gestational choriocarcinoma, Hodkin's disease Toxicity: myelosuppression |
|
|
Mitomycin C
|
antibiotic isolated fro Streptomyces caespitosus
alklyates DNA by crosslinking DNA at the 6N position of adenine and the 7N position of guanine Clinical use: GI, head, neck canccer Toxicity: late myelosuppression |
|
|
Methotrexate
(folic acid analog) |
antimetabolite
requires polyglutamation by the folylpolyglutamate synthase for cytotoxic activity resulting in depletion of critical reduced folates inhibits dihydrofolate reductase (DHFR) which turns folate to THF inhibition of thymidylate and purine synthesis incorporates dUTP into DNA resulting in inhibition of DNA synthesis and function Used for acute lymphoblastic leukemia (ALL), osteosarcoma, lymphoma, carcinoma of the breast (not used), ovary, bladder, head and neck, psoriasis, and rheumatoid arthritis Toxicity: myelosuppression, hemorrhagic cystitis |
|
|
5-fluorouracil (5-FU)
(pyrimidine analog) |
antimetabolite related to uracil
inhibit conversion of orotic acid to UMP resulting in impaired nucleic acid synthesis can be incorporated in DNA/RNA and cause point mutations can act as a substrate for thymidylate synthase and cause inhibition of thyidine synthesis binding time of 5FU to TS can be prolonged by using leucovorin 5FU is converted to FUTP which impairs RNA processing and function 5FU is converted to FdUMP which inhibits thymidylate synthase and 5,10 methylene THF, which inhibits synthesis of pyrimidines and DNA synthesis Leucovorin stabilizes FdUMP-thymiidylate synthase-5,10methylene THF ternary compex increasing 5FU potency Used for breast/colon cancer, esophageal cancer, squamous cell carcinoma of the head and neck Toxicity: mucositis, diarrhea |
|
|
Cytosine arabinoside (ara C)
(pyrimidine analog) |
antimetabolite related to cytosine
interferes with DNA replication when incorporated into DNA Used for acute myeloid leukemia and lymphoma Toxicities: myelosuppression, cerebellar dysfunction |
|
|
2'2'-difluorodeoxycytidine (gemcitabine)
(pyrimidine analog) |
antimetabolite related to cytosine
following intracellular phosphorylation, inhibitions ribonucleotide reductase and inhibits de novo nucleotide production may also be incorporated into DNA to interfere with DNA replication Used for pancreatic cancer and non-small cell lung cancer Toxicities: myelosuppression, flu-like syndrome |
|
|
6 thioguanine (6TG)
6-mecaptopurine (6MP) (purine analog) |
antimetabolite that are substrates for hypoxanthine guanine phosphoribosyl transferase and are converted to thioinosine. Thioinosine inhibits synthesis of adenine and guanine, interfering with DNA synthesis.
Thioinosine inhibits the initial conversion of phosphoribosyl pyrophosphate + glutamine to ribosylamine-5-phosphate, the rate limiting step in purine synthesis Used for acute lymphoblastic leukemia (ALL) Toxicities: myelosuppression |
|
|
Fludarabine
(purine analog) |
antimetabolite that inhibits DNA polymerase, DNA primase, and ribonucleotide reductase.
Is incorporated into DNA and RNA Used for chronic lymphocytic leukemia (CLL) and low grade lymphomas Toxicity: myelosuppression, CD4 T cell depletion, peripheral neuropathy |
|
|
2' deoxycoformycin (pentostatin)
(purine analog) |
antimetabolite that inhibits adenosine deaminase leading to accumulation of intracellular adenosine and deoxyadenosine nucleotides which blocks DNA synthesis by inhibiting ribonucleotide reductase
Used for hairy cell leukemia and T- and B-cell lymphomas Toxicity: myelosuppression |
|
|
2' cholordeoxyadenosine
(purine analog) |
antimetabolite that is an adenosine deaminase resistant purine analog
induces DNA strand breaks Used for hairy cell leukemia, chronic lymphocytic leukemia, and low grade lymphoma Toxicity: myelosuppression especially thrombocytopenia |
|
|
Vincristine
(Vinca alkaloid) |
Inhibits tubulin polymerization disrupting the formation of microtubule assembly during mitosis. May also inhibit DNA, RNA, and protein synthesis.
Overexpression of P170 glycoprotein results in enhanced effllux of the drug. Cross-resistance is observed with taxanes, epipodophyllotoxins, anthracyclines, and actinomycin D. Mutatinos in a and b tubulin causes decreased affinity to vincristine. Administered only by IV route Rapidly distributed into body tissue within 30 min. Poor penetration of BBB and CSF. Metabolized by liver P450. Excreted in bile and feces (80%) and urine (15-20%) t1/2 = 80hrs Indicated for acute lymphoblastic leukemia, Hodgkin's and non-Hodgkin's lymphoma, MM, rhabdomyosarcoma, neuroblastoma, Ewing's sarcoma, Wilms' tumor, chronic leukemias, thyroid cancer, brain tumor |
|
|
Vinorelbine
(vinca alkaloid) |
Semisynthethic alkaloid derived from vinblastine
Inhibits tubulin polymerization and prevents microtubule formation during mitosis May inhibit DNA, RNA, and protein synthesis Vinorelbine has lower affinity for axonal microtubules than vincristine and vinblastine do. Overexpression of P170 glycoprotein results in efflux of the drug. Cross-resistance occurs with taxanes, epipodophyllotoxins, anthracyclines, and actinomycin D Mutations in a and b-tubulin proteins cause decreased binding to vinorelbine Oral availability is 27% to 43% with peak plasma conc. after 2 hrs. Widely distributed into most tissues. Extensive binding to plasma proteins (80%). Metabolized by P450. One metabolite, desacetyl vinorelbine, has antitumor activity like the parent drug. Most is excreted through enterophetaic biliary system (50%) with some through kidneys (15-20%). t1/2 = 27-43 hrs Indicated for non-small cell lung cancer, breast cancer, ovarian cancer, Hodgkin's lymphoma Should be infused as a rapid push in a free-flowing IV to avoid extravasation. Breast feeding should be avoided. Toxicity: myelosuppression (neutropenia nadir by Day 7 and recovery by Day 14), nausea/vomiting (w/in 24 hrs), GI toxicities (constipation, diarrhea, stomatitis, anorexia), vesicant, neurotoxicity |
