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S- S phase
MOA: Works in the S phase of the cell cycle.
Blocks the enzyme dihydrofolate reductase and thus prevents formation of Tetrahydrolfate
The binding to DHFR is competitive and reversible which is beneficial for the use of Leucovorin.
Leucovorin is an antidote that saves the host cells but have no effect on the cancer cells
Used for acute lymphoblastic leukemia, osteogenic sarcoma
AE include nephrotoxicity, neutoropenia, thrombocytopenia and pulmonary and hepatotoxicity.
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inhibits synthesis of pyrimidine (C, T, U)
inhibits Thymidate synthase thus decreased dTMP, decreased DNA and protein synthesis
When used with Leucovarin, it acts as an amplifying agent
Used for metastatic breast cancer,carcinoma of GI, ovary,bladder, pancreas, prostate. Also metastatic cancer of the colon
AE is nausea and alopecia. Also diarrhea. Also myelosuppression.
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It is incorporated into the DNA and blocks the elongation of DNA thus decreased DNA synthesis.
Used for AML
AE is neurotoxicity
Azthroprine and Mercaptopurine (Antimetabolites)
Used for cancer chemotherapy and immunosupresants.
Cyclophosphamide (Alkylating Agent)
Cell Cycle non specific---so goes and affects DNA directly
Converted in the liver to become active and nitrogen mustard. Transcription and Translation inhibited
Used for Chronic Lymphatic Leukemia, Non-Hodgkins, Ovarian carcinoma
Acrolein can cause cystitis in the bladder which can be treated with the antidote, MESNA since it binds to the acroelin in the urine
- AE is myelosuppression
- Can also cause SIADH and water intoxication causing hyponatremia. Antidote needed is DEMECLOCYCLINE by interfering with the insertion of water channels in the collecting ducts
Used for CML
AE is pulmonary fibrosis and hyperpigmentation
Nitrosureas (Alkylating Agent)
Crosses the BBB
brain tumors including astrocytomas.
AE is CNS toxicity
Breaking the cross link between DNA
Used for testicular, bladder, ovarian, urogenital
Don't use aluminum needles when injecting it since this inactivates the drug
AE is nephrotoxicity which can also cause elctrolyte imbalances. This can be prevented by the antidote AMIFOSTINE which wil scavenge free radicals.
Other adverse effects of ototoxicity and marked nausea and vomiting.
Doxorubicin (Cytotoxic Abx)
It is a Topoisomerase 2 poision thus preventing it from relieving stress and thus decreased DNA replication.Also causes free radical formation
Used for Hodgkins lymphoma, sarcomas, and brest, ovary and lung cancer.
The free radicals can cause excesive bleeding at the site of injection. Can be prevented by the antidote, DIMETHYL SULFOXIDE
AE is CARDIOTOXICITY and the antidote for this is DEXARZOXANE which is an iron chelator
Similar to Doxorubicin but its special use is Leukemia
Binds to DNA helix and thus prevents the transcription of DNA
Used for Wilm's Tumor, Ewing Sarcoma, rhabomyosarcoma
AE is hepatopoeitic supression, and pancytopenia
Causes DNA fragmentation due to free radical formation.
Used as a combination therapy for testicular cancers. Also used for lymphomas and squamous cell carcinomas
AE is pulmonary fibrosis and pulmonary toxicity
Vincristine and Vinblastine (Natural Products)
Both drugs affect the assembly of spindles and thus is affecting the M phase.
Vincristine is used for Hodgkins and AE is peripheral neuropathy,sensory and motor parethesias.
Vinblastine AE are myelotoxic and thus bone marrow suppression
Etoposide (Natural Product
Inhibits Topo 2 and thus increases DNA degradation. Specific for late S and early G2 phase
Used for testicular cancer in part of the combination therapy with Vinblastine and Bleomycin.
AE is dose limiting leukopenia.
Campotothecins and Topotecan
MOA is inhibiting Topo 1
Used for colorectal cancer, ovarian and small cell cancers.
Inhibits microtubules dissassembly so the microtubules become too big and are non functional. Thus affecting M phase
Used for breast and ovarian carcinomas
AE are CARDIAC. Also cause peripheral peripheral neuropathy
Clearance is reduced if this drug is given with Cisplatin so higher toxicitiy
Tamoxifen (anti hormonal)
Blocks binding of estrogen to estrogen receptor in estrogen receptor positive breast carcinoma.
It can be used as a treatment and as a prophylaxis for breast cancer.
There is an increased risk of endometrial cancer with long time use of this drug since it acts as an agonist at endometrial receptors.
Used in pt's who aren't responding to Tamoxifen for breast cancer. However only give to POSTMENOPAUSAL women