Exam one: antineoplastic agents MOA, AE, TU etc Flashcards
- Therapeutic Use: Hodgkin’s Disease
- MOA: Alkylating agent (Nitrogen Mustard)
- AE: bone marrow and GI mucosa
- Notes: most reactive alkylating agent.
Mechlorethamine
- Therapeutic Use: Broad spectrum
- MOA: Alkylating agent; prodrug; hydroxylated by CYP2B
- AE: bone marrow and GI mucosa; renal toxicity
- Notes: most widely used alkylating agent. Use with mesna.
Cyclophosphamide
- Carmelo penetrates the lane (BBB)
- Therapeutic Use: Highly lipophilic to treat malignant gliomas
- MOA: Alkylating agent (Nutrosoureas)
- AE: Severe cumulative myelosuppression. Long term Tx leads to renal failure.
- Notes:
Nitrosoureas
- Carmustine
- Lomustine
- Therapeutic Use: malignant myeloma, Hodgkin’s disease (ABVD)
- MOA: Triazene Alkylating agent. Methylating agent. Prodrug CYP demethylation in liver
- AE: myelosuppression, N/V and flu-like symptoms.
- Notes:
Dacarbazine
- Therapeutic Use: Hodgkin’s and non-hodgkin’s, brain tumors.
- MOA: Methylhydrazine; Prodrug; monofunctional – produces chromosomal damage.
- AE: bone marrow suppression; neurotoxicity
- Notes: Only the PROs can handle the brain tumors.
Procarbazine
- Therapeutic Use: testicular, ovarian, head/neck, bladder, esophageal, lung, colon cancers.
- MOA: Platinum Complex alkylating agent. React with nucleophilic sites on DNA and proteins to produce apoptosis. Monofunctional (produces chromosome damage)
- AE: nephrotoxicity and neurotoxicity. Myelosuppression
- Notes: Carboplatin is much less toxic.
Platinum Complexes
- Therapeutic Use: colorectal cancer combined with FOLFOX
- MOA: React with nucleiohilic sites on DNA and proteins to produce apoptosis.
- AE: peripheral neuropathy
- Notes: No cross resistance with other platinum agents.
Oxaliplatin
• Drugs: 6-thiopurine; 6-mercaptopurine; 6-thioguanine
• Therapeutic Use: inhibits purine synthesis.
o 6-MP: ALL; works with allopurinol (xanthine oxidase inhibitor)
o 6-TG: acute granulocytic leukemia
• MOA: Antimetabolites; inhibit purine synthesis
• AE: can become lethal if drug accumulates.
• Notes:
6-Mercaptopurine (6-MP)
- Therapeutic Use: non-hodgkin lymphoma, CLL, hairy cell leukemia (Cladribine).
- MOA: Antimetabolite; Adenosine analogs causing DNA problems => apoptosis.
- AE: Myelosuppression
- Notes:
6-Thioguanine (6-TG)
Fludarabine-5’- phosphate
• Therapeutic Use: hard tumors; RA, ALL, Burkitt’s lymphoma, non-Hodgkin’s, carcinomas, oseteogenic sarcomas, choriocarcinomas, breast cancer.
• MOA: Folic acid inhibitor; inhibits dihydrofolate reductase
• AE: toxicity prevented or reversed by leucovorin; bypasses blocked DHFR. Renal damage.
• Notes: Structurally very similar to tetrahydrofolate.
crystal METH is LEUCrative!!!
Methotrexate
• Therapeutic Use: colorectal cancer; Breast cancer (CMF; no estrogen receptor).
• MOA: Antimetabolite; Uracil analog (prodrug) causing a decrease in DNA synthesis => impaired RNA translation.
• AE: Myelosuppresion and GI
• Notes: Commonly given drug.
o 5-fluorouracil makes ur Colon FLUOw.
5-Fluorouracil (5-FU)
- Therapeutic Use: AML
- MOA: antimetabolite; cytosine deoxyriboside analog, prodrug (met to AraCTP)
- AE: myelosuppresion
- Notes:
Cytarabine (AraC)(Cytosine arabinoside)
- Therapeutic Use: metastatic pancreatic cancer; non small cell lung and bladder cancer.
- MOA: Antimetabolite; Cytosine deoxyriboside analog; prodrug
- AE: myelosuppresion is dose limiting.
- Notes:
Gemcitabine
o Treatment of choice with glucocorticoids for ALL (MOPP); Given with Actinomycin D.
o Curative therapy for metastatic testicular tumors, in combination w/ bleomycin and cisplatin.
o Note: Ball Blaster!
- MOA: Plant Alkaloids; anti-mitotic; M-phase specific; binds tubulin blocking polymerization activity
- AE: peripheral neuropathy and myelosuppresion.
Vinca Alkaloids (Vin-)
Vinblastine
Vincristine
- Therapeutic Use: metastatic cancers, abraxane is albumin-bounds taxol
- MOA: Plant alkaloid; Anti-mitotic M-phase specific; promotes MT polymerization and stabilization blocking mitosis.
- AE: Hypersensitivity & neutropenia.
- Notes: Mitosis is a TAXANE process!
Taxanes
- Paclitaxel
- Abraxane
- Therapeutic Use: FYI
- MOA: Plant alkaloids; S-phase specific; binds and stabilizes TOPO-1 DNA complex (allows breakage but not resealing)
- AE: Myelosuppression.
- Notes: Toco interacts with Topo!
Camptothecins
=Topotecan
- Therapeutic Use: FYI
- MOA: Plant alkaloids; Complexes with TOPO-II
- AE: Myelosuppression
- Notes: eTOPOside interacts with TOPO-II
Epipodophyllotoxins
Etoposide
- Therapeutic Use: anti-tumor antibiotic
- MOA: binds to DNA by intercalating (sandwiching) between GC base pairs.
- AE: Myelosuppression
- Notes: one of most potent anti-tumor agents known. Curative in regimen with Vincristine and Cyclophosphamide.
Actinomycin D (Dactinomycin)
• Therapeutic Use: FYI. Antitumor antibiotic
• MOA: Intercalate with DNA and binds to the backbone of DNA
• AE: FYI
• Notes: can be cardiotoxic, epirubin is less cardiotoxic.
o Adrian Peterson is the backbone of offense/DNA cause he can intercalate through the gaps… Ya buddy!
Anthracyclines
Adriamycin (Doxorubicin)
-Bleomycin
- Therapeutic Use: APL with high rate of complete remission
- MOA: Retinoids; stimulate transcription of genes that have retinoic acid receptors induces differentiation.
- AE: Vitamin A toxicity
- Notes: tRETINoin is a RETINoid which affects RETINol (vitamin A)
Tretinoin (ATRA)
- Therapeutic Use: CML
- MOA: inhibits BRC/ABL Tyr kinase and c-kit receptor protein kinase.
- AE: Non-severe
- Notes: concerned with drug interactions that use P450 isoforms.
Imatinib mesylate (Gleevac)
- Therapeutic Use: cancer (esp. lung)
- MOA: inhibits EGFR tyrosine kinase, blocks signal transduction pathways required for cell proliferation and survival
- AE: possible diarrhea and acne-like rash
- Notes: induces of P450 decrease plasma gefitinib.
Gefitinib
- Therapeutic Use: Refractory multiple myeloma
- MOA: acts as a reversible inhibitor of 26S proteasome silences NF-KB.!!!
- AE: FYI
- Notes: She stressed this in class! –Zomib is a proteasome inhibitor.
Bortezomib
• Therapeutic Use: breast cancer • MOA: blocks Her2/neu receptor • AE: FYI • Notes: Not for pt who expresses ER. Pt tumor must express HER2/neu marker o Be sure to treat HER boobs!
Trastuzumab (Herceptin)
- Therapeutic Use: B cell non-hodgkin lymphoma
- MOA: binds CD20 of normal and malignant B cells causing lysis
- AE: N/F/C on 1st infusion
- Notes:
Rituximab
- Therapeutic Use: colon cancer
- MOA: binds EGFR; inhibits cell growth apoptosis
- AE: acne-like rash
- Notes: Cetux sounds like cecum which is near the colon.
Cetuximab
- Therapeutic Use: metastatic colorectal cancer
- MOA: angiogenesis inhibitor binding VEGF
- AE: HTN
- Notes: Often used in combination therapy.
Bevacizumab
- Therapeutic Use: leukemias and cancers
- MOA: immunomodulatory, antiproliferative, and antiviral. Cytokines binding JAK-STAT.
- AE: F/C, myelosuppresion; neurotoxicity.
- Notes:
Interferon-alfa
- Therapeutic Use: melanoma and renal cell cancer
- MOA: induces a T-cell response that is cytolytic for tumor cells.
- AE: Flu-like symptoms
- Notes: two starts with a “T” so it stimulates Tc cells.
Interleukin-2 (IL-2)
- Therapeutic Use: prophylaxis of chemotherapy-induced neutropenia
- MOA: increases production of neutrophils and stimulates phagocytic and cytotoxic activity.
- AE: bone pain in lower back, sternum, and pelvis.
- Notes
Granulocyte Colony-Stimulating Factor (G-CSF)
- Therapeutic Use: good for bone marrow problems
- MOA: increases neutrophils and monocytes
- AE: fever and bone pain
- Notes:
Granulocyte/Macrophage Colony-Stimulating Factor (GM-CSF
