Alkylating agents
Sulfur mustard |
Nitrogen mustard/ 1)Meclorethamine |
Nitrosurea |
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Given IV. |
Streptoazocin |
is converted into episulfonuim ion attacked by nucleophile from cells and becomes alkylated biopolymer. |
Becomes the unstable aziridinuim ion and then gives alkylated biopolymer. |
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2) Chlorambucil |
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Relatively stable; given oral. |
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Least toxic, long-acting. |
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3) Cyclophosamide |
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Active orally and parenterally. |
Both sulfur and nitrogen mustard are converted into unstable 3-membered (onium) intermediates that they act by.
Plant products
Vinca alkaloids |
Ixabepilone |
Include vincristine, vinblastine, vinrosidine, vinleurosine |
semisynthetic amide analogue of the spindle poison, Epothilone B. |
1) Paclitaxel (taxol) |
Has lactam in its structure providing increased invivo stability. |
MOA: spindle poison inhibiting mitosis. |
Uses: Metastatic breast cancer |
Uses: ttt of breast, ovarian & aids-related kaposi sarcoma. |
Signal transduction (PK) inhibitors
Imatinib mesylate |
Sorafenib tosylate |
MOA: Competitive inhibition of TK--> inducing apoptosis or non-dividing cells. |
MOA: Broad spectrum kinase inhibitor |
Uses: CML, GIST, acute lymphoblastic leukemia (+ve philadelphia chromosomes) |
Uses: renal cell carcinoma and colon cancer |
SE: thrombocytopenis, skin rash, N/V, pulmonary edema. |
SE: Skin rash, HTN, fatigue, increased risk of bleeding & wound healing time. |
Advantage: Orally administered, better patient tolerability.
Disadvantage: Cardiotoxicity
Resistance to tyrosine kinase forms:
- Altering amino a' to stop binding
- Increasing kinase levels
- Drug is substrate to efflux transporter, BCRP.
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Anti-metabolites
Pyrimidine antimetabolites |
Purine antimetabolites |
Folic a' antimetabolites |
1) 5-FU |
1) 6-MP |
1) Methotrexate |
MOA: thymidylate synthase inhibitor or incorporated into RNA & DNA. |
Is invivo converted into 6-thionosinate. |
MOA: dihydrofolate reductase inhibitor |
2) Uracil mustard |
MOA: inhibits the rate-limiting step during purine synthesis. |
Uses: remission in leukaemia and breast cancer management. |
Alkylating agent. |
Uses: |
MOA: Damages DNA that in take in uracil. |
- with methotraxate for lymphocytic leukemia. |
Uses: Non-hodgkins lymphoma |
- Immunosuppressive for UC, psoriatic arthirits, systemic lopus erythromatosis. |
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Allopurinol potentiates its effect by inhibiting its metabolism. |
Miscellaneous compounds
Platinum complexes |
Synthetic retinoid analog |
1) Cisplatin |
1) Bexarotene |
MOA: Cross-links DNA causing DNA conformational changes. |
MOA: binds to activated retinoid X receptors in skin. |
Uses: with bleomycin & vinblastine for metastatic testicular tumors. |
Use: cutaneous T-cell lymphoma |
2) Carboplatin |
Immunotherapy/monoclonal antibodies
**Block |
**Flag |
**Deliver |
1) Trastuzumab |
1) Rituximab |
1) Brentuximab vedotin |
Blocks HER-2 receptors to stop growth. |
chimeric (hybrid) monoclonal antibody. |
Delivers chemotherapy drugs inside tumor cells. |
2) Bevacizumab |
Flag malignant B lymphocytes with CD20 receptor for the immune cells. |
Blocks VEGF--> no new blood vessels. |
Use: Non-Hodgkins B-cell lymphoma. |
MOA: targeted therapy by selective binding on receptor to--**
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Antibiotics
Anthracyclines |
Actinomycin |
1) Danorubicin HCl |
1) Bleomycin |
MOA: intercalates into DNA causing indirect inhibition of topoisomerase II--> decreased RNA & DNA synthesis. |
Has multiple heterocyclic rings and cytotoxic glycosides. |
SE: Cardiotoxicity, release of hydroxyl and superoxide radicals. |
MOA: Fragmentation of DNA. |
2) Doxorubicin HCl |
2) Mitomycin C |
Uses: Acute leukaemia, Hodgkins's disease |
3 anti-cancer functional gps: Quinone + Aziridine + Carbamate. |
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MOA: cross-links double helical DNA |
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Unreactive in natural state--reduction--> Indol-hydroquinone (bifunctional alkylating agent) |
Hormones
Testolactone |
Tamoxifen |
Letrozole |
MOA: Aromatase inhibitor stopping estrogen synthesis from testosterone. |
Non-steroidal agent with anti-estrogen properties. |
MOA: Aromatase inhibitor |
Uses: Breast cancer in post-menopausal women. |
MOA: binds to estorgen receptors resulting in decreased DNA transcription. |
Uses: locally advanced or metastatic breast cancer. |
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Uses: breast cancer in post-menopausal women. |
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