Pharm - Antineoplastics Flashcards
1
Q
Antineoplastic drug classes
A
Cytotoxic, targeted antineoplastics, hormonal therapy, immunotherapy, other
2
Q
Limitations of antineoplastic care
A
- Tumor cell resistance
- Host toxicity
- Inability to suppress metastasis
- Drug resistance
3
Q
Induction chemotherapy
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- given to induce remission
- treatment of acute leukemia
4
Q
Consolidation chemotherapy
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- given once remission is achieved to sustain it
- treatment of acute leukemia
5
Q
Maintenance chemotherapy
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- given in lower doses for prolonged time to prolong remission
- only acute leukemia, sometimes lung and colorectal
6
Q
Myoablative chemotherapy
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- high dose to obliterate bone marrow
- followed by bone marrow or stem cell transplant to rebuild bone marrow
7
Q
Adjuvant chemotherapy
A
- to destroy any microscopic spread of cancer cells after primary tumor is removed
- given to prevent recurrence
8
Q
Neoadjuvant chemotherapy
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- given prior to surgery, often attempting to shrink tumor
9
Q
Chemoradiosensitization
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- small doses given during radiation therapy to increase effectiveness
10
Q
Palliative chemotherapy
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- given to address sxs without expecting significant reduction in cancer
11
Q
Administration of cytotoxic agents
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- intermittent combination regimes
- optimizes synergistic effect of drugs while minimizing toxicity
- occasionally single agents are used
12
Q
Administration of targeted agents
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- continuously or intermittently
- alone or in combination with cytotoxic agents
13
Q
Classes of cytotoxic agents
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- cell cycle specific - DNA synthesis inhibitors, topoisomerase inhibitors, mitotic inhibitors
- cell cycle non-specific - DNA alkylating agents, DNA intercalating agents
14
Q
General cytotoxic drug toxicity
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- bone marrow: leukopenia, thrombocytopenia, anemia
- GI epithelium: oral mucositis, gastroenteritis
- hair follicles: alopecia
15
Q
DNA synthesis inhibitors classes
A
- folate antagonists, purine/ pyrimidine analogues
16
Q
Folate antagonist exemplar
A
Methotrexate
17
Q
Folate antagonist mechanism
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- inhibits dihydrofolate activity –> prevents production of nucleotides
- S phase specific
18
Q
Methotrexate indications
A
- acute leukemia, breast cancer, osteosarcoma, trophoblastic tumors
19
Q
Purine/ pyrimidine analogue exemplar
A
Fluorouracil
20
Q
Fluorouracil indications
A
- breast, colorectal, gastric cancer
21
Q
Fluorouracil mechanism
A
- structural analogue of uracil –> prevents biosynthesis of nucleotides –> DNA strand breaks/ premature chain termination
- active metabolite interferes with RNA function
22
Q
DNA synthesis inhibitors toxicity
A
- Myelosuppression (primary dose-limiting)
- oral mucositis
- diarrhea, hepatic and renal toxicity (methotrexate), alopecia (fluorouracil)
23
Q
DNA alkylating agents classes
A
Nitrogen mustards, platinum compounds
24
Q
Nitrogen mustard exemplar
A
cyclophosphamide
25
Platinum compounds exemplar
cisplatin
26
cyclophosphamide mechanism
- prodrug converted into phosphoramide mustard (alkylating) and acrolein (toxic metabolite)
27
DNA alkylating agents mechanism
- cross link DNA by binding alkyl groups into DNA bases --> interrupt synthesis, transcription, DNA repair, development of lethal mutations
28
Cisplatin mechanism
- no alkyl group, but crosslink DNA via guanine residues
29
Cisplatin indications
Lung and ovarian cancer
30
Cyclophosphamide toxicity
- Myelosuppression (dose limiting)
- severe N/V
- alopecia
- hemorrhagic cystitis
31
Cisplatin toxicity
- myelosuppression (milder)
- Severe N/V, emetogenic
- alopecia
- nephrotoxicity, ototoxicity, sensory peripheral neuropathy
32
DNA intercalating agent classes
- Anthracyclines, other
33
Anthracycline exemplar
- Doxorubicin
34
Doxorubicin mechanism
- bind to DNA --> deformation and uncoiling
- Inhibit topoisomerase II --> strand breaks
- generate free radicals --> cleave DNA
35
Other DNA intercalating exemplar
Bleomycin
36
Bleomycin info / indications
- greatest effect in G2 effect
| - Hodgkin's disease and testicular cancer
37
Doxorubicin toxicity
- Myelosuppression (dose limiting)
- N/V (moderate sever)
- oral mucositis, alopecia
- cardiotoxicity (dose limiting)
38
Bleomycin toxicity
- Myelosuppression (mild)
- N/V (mild)
- oral mucositis, alopecia
- pulmonary toxicity
39
Topoisomerase inhibitor classes
- podophylotoxins, camptothecin analogues
40
Podophylotoxin exemplar
Etoposide
41
Etoposide mechanism
- Interfere with topoisomerase II --> prevent recoiling of DNA
- S phase
42
Etoposide indications
Lung, gastric cancer
43
Camptothecin analogue exemplar
Irinotecan
44
Irinotecan mechanism
Inhibits topoisomerase I --> prevents relaxation of supercoiled DNA
45
Irinotecan indications
Colorectal, gastro-esophageal, lung cancer
46
Topoisomerase inhibitor toxicity
- Myelosuppression (dose limiting)
- N/V
- Alopecia (etoposide)
- Diarrhea (dose limiting in irinotecan)
47
Mitotic inhibitor classes
Taxanes, vinca alkaloids
48
Taxanes exemplar
Paclitaxel
49
Paclitaxel indications
Breast, ovarian, lung
50
Vinca alkaloids exemplar
Vincristine
51
Vincristine indications
Acute leukemia, lymphomas, neuroblastoma
52
Mitotic inhibitors mechanism
- Interfere with microtubule structure, rendering them nonfunctional
- M phase
53
Mitotic inhibitors toxicity
- Myelosuppression, esp neutropenia (dose limiting paclitaxel)
- Peripheral neuropathy (dose limiting)
- Alopecia, N/V
- Paralytic ileus (vincristine)
- Hypersensitivity rxns (paclitaxel)
54
Targeted antineoplastics targets
- Proteins more abundant in cancer cells
- proteins that drive cancer proliferation
- chromosome abnormalities present only in cancer cells
55
Targeted agent toxicity
- Most common: diarrhea, liver problems
- Skin: acneiform rash, dry skin, nail changes, hair depigmentation
- problems with blood clotting and wound healing
- high BP
- GI perforation (rare but serious)
56
Targeted antineoplastic classes
Protein kinase inhibitors, proteasome inhibitors, monoclonal antibodies
57
Protein kinase inhibitors exemplar
Imatinib
58
Protein kinase inhibitors mechanism
- impede pathways promoting malignant cell transformation
59
Imatinib mechanism/ indications
- Inhibits BCR-ABL tyrosine kinase
| - CML
60
Imatinib adverse effects
- nausea, edema, rash, and diarrhea
61
Proteasome inhibitors exemplar
Bortezomib
62
Bortezomib adverse effects
- fatigue
- peripheral neuropathy (dose limiting)
- N/V, diarrhea/ constipation
myelosupprression
63
Bortezomib indications
Multiple myeloma, mantle cell lymphoma
64
Monoclonal antibodies exemplar
Rituxamib
65
Rituxamib mechanism
- naked mAB - binds and blocks antigens in cancer cells
66
Rituxamib adverse effects
- hypersensitivity rxns
- fever, chills, nausea, HA
- myelosuppression
67
Immunotherapy agent classes
Cytokines, immune checkpoint inhibitors
68
Hormone antagonist classes
Estrogen antagonists, aromatase inhibitors, GnRH antagonist, androgen antagonists
69
Cytokines exemplar
Interferon alpha
70
Interferon alpha indications
Hairy cell leukemia, malignant melanoma, renal cell carcinoma
71
Immune checkpoint inhibitors exemplar
Ipilimumab
72
Ipilimumab mechanism
mAB against CTLA-4 antigen
73
Ipilimumab indications
metastatic malignant melanoma
74
Ipilimumab adverse effects
- rash, fatigue, nausea
| - diarrhea assoc w/ severe immune enterocolitis
75
Estrogen antagonist exemplar
Tamoxifen
76
Aromatase inhibitor exemplar
Letrozole
77
GnRH agonist exemplar
Leuprolide
78
Androgen antagonists exemplar
Flutamide
79
Tamoxifen mechanism/ indications
- selective estrogen receptor modulator
| - ER + breast cancer
80
Letrozole mechanism/ indications
- prevents androgens --> estrone/ estradiol
| - only post-menopausal ER+
81
Leuprolide mechanism
- after initial surge, complete inhibition of testicular/ ovarian function
82
Flutamide mechanism/ indications
- Prevents binding to/ downregulates T receptors --> inhibits tumor growth
- first 2 weeks of GnRH agonist therapy or for metastatic prostate cancer
