Pharm - Antineoplastics Flashcards
Antineoplastic drug classes
Cytotoxic, targeted antineoplastics, hormonal therapy, immunotherapy, other
Limitations of antineoplastic care
- Tumor cell resistance
- Host toxicity
- Inability to suppress metastasis
- Drug resistance
Induction chemotherapy
- given to induce remission
- treatment of acute leukemia
Consolidation chemotherapy
- given once remission is achieved to sustain it
- treatment of acute leukemia
Maintenance chemotherapy
- given in lower doses for prolonged time to prolong remission
- only acute leukemia, sometimes lung and colorectal
Myoablative chemotherapy
- high dose to obliterate bone marrow
- followed by bone marrow or stem cell transplant to rebuild bone marrow
Adjuvant chemotherapy
- to destroy any microscopic spread of cancer cells after primary tumor is removed
- given to prevent recurrence
Neoadjuvant chemotherapy
- given prior to surgery, often attempting to shrink tumor
Chemoradiosensitization
- small doses given during radiation therapy to increase effectiveness
Palliative chemotherapy
- given to address sxs without expecting significant reduction in cancer
Administration of cytotoxic agents
- intermittent combination regimes
- optimizes synergistic effect of drugs while minimizing toxicity
- occasionally single agents are used
Administration of targeted agents
- continuously or intermittently
- alone or in combination with cytotoxic agents
Classes of cytotoxic agents
- cell cycle specific - DNA synthesis inhibitors, topoisomerase inhibitors, mitotic inhibitors
- cell cycle non-specific - DNA alkylating agents, DNA intercalating agents
General cytotoxic drug toxicity
- bone marrow: leukopenia, thrombocytopenia, anemia
- GI epithelium: oral mucositis, gastroenteritis
- hair follicles: alopecia
DNA synthesis inhibitors classes
- folate antagonists, purine/ pyrimidine analogues
Folate antagonist exemplar
Methotrexate
Folate antagonist mechanism
- inhibits dihydrofolate activity –> prevents production of nucleotides
- S phase specific
Methotrexate indications
- acute leukemia, breast cancer, osteosarcoma, trophoblastic tumors
Purine/ pyrimidine analogue exemplar
Fluorouracil
Fluorouracil indications
- breast, colorectal, gastric cancer
Fluorouracil mechanism
- structural analogue of uracil –> prevents biosynthesis of nucleotides –> DNA strand breaks/ premature chain termination
- active metabolite interferes with RNA function
DNA synthesis inhibitors toxicity
- Myelosuppression (primary dose-limiting)
- oral mucositis
- diarrhea, hepatic and renal toxicity (methotrexate), alopecia (fluorouracil)
DNA alkylating agents classes
Nitrogen mustards, platinum compounds
Nitrogen mustard exemplar
cyclophosphamide
Platinum compounds exemplar
cisplatin
cyclophosphamide mechanism
- prodrug converted into phosphoramide mustard (alkylating) and acrolein (toxic metabolite)
DNA alkylating agents mechanism
- cross link DNA by binding alkyl groups into DNA bases –> interrupt synthesis, transcription, DNA repair, development of lethal mutations
Cisplatin mechanism
- no alkyl group, but crosslink DNA via guanine residues
Cisplatin indications
Lung and ovarian cancer
Cyclophosphamide toxicity
- Myelosuppression (dose limiting)
- severe N/V
- alopecia
- hemorrhagic cystitis
Cisplatin toxicity
- myelosuppression (milder)
- Severe N/V, emetogenic
- alopecia
- nephrotoxicity, ototoxicity, sensory peripheral neuropathy
DNA intercalating agent classes
- Anthracyclines, other