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Heme/Onc > Oncology Drugs > Flashcards

Oncology Drugs Flashcards

1
Q

What is the mechanism of action of Alkylating agents?

A

Cause intra- and inter-strand cross-links between DNA bases

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2
Q

What drugs are in the category of Alkylating agents?

A 
Cyclophosphamide
Dacarbazine (DTIC)
Ifosfamide
Mechlorethamine
Melphalan
Nitrosureas
Procarbazine
Temozolamide
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3
Q

The metabolites of which Alkylating agents are toxic to the bladder and how can you protect against this toxicity?

A

Cyclophosphamide
Ifosfamide

Use hydration + MESNA

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4
Q

Which Alkylating agents penetrate the CNS?

A

Nitrosoureas
Procarbazine
Temozolamide

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5
Q

What Alkylating agent is the parent drug of the class?

A

Mechlorethamine - nitrogen mustard gas

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6
Q

What is the mechanism of action of the Platinum derivative drugs?

A

Cross-link DNA

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7
Q

What drugs are in the category of Platinum derivative drugs?

A

Carboplatin
Cisplatin
Oxaliplatin

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8
Q

For each of the Platinum derivative drugs (Carboplatin, Cisplatin, Oxaliplatin), rank the following toxicities in order from greatest to least:
Renal
Neuro
Heme

A 
Carboplatin = Heme >>>> Renal/Neuro
Cisplatin = Renal > Neuro > Heme
Oxaliplatin = Neuro >> Heme >>>> Renal
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9
Q

What is the mechanism of action of Anti-tumor antibiotics?

A

Damage DNA physical structure by intercalating into DNA helix and alter DNA function by inhibiting RNA/protein synthesis

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10
Q

What drugs are in the category of Anti-tumor antibiotics?

A

Actinomycin D

Bleomycin

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11
Q

What cancer is Acitnomycin D a curative regimen for?

A

Pediatric cancers

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12
Q

What are toxicities of Acinomycin D?

A

Myelosuppression
Nausea/vomiting/diarrhea
Muscositis
Radiation recall

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13
Q

What are toxicities of Bleomycin?

A

Pulmonary and cutaneous toxicity, especially with decreased renal function
Can persist in lung and cause fatal recall of lung toxicity during surgery with high O2 inspired

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14
Q

Why does Bleomycin cause pulmonary and cutaneous toxicity, especially with decreased renal function?

A

Tissues clear it with bleomycin hydrolase - but lungs and skin lack this hydrolase
Therefore, if renal clearance of the drug is decreased, the drug can build up in lungs and skin, causing toxic effects

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15
Q

What is the mechanism of action of the Topoisomerase directed agents?

A

Forms a complex of the drug, enzyme, and DNA and the drug stabilizes the break, preventing repair and altering function

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16
Q

What are the Topoisomerase I directed agents?

A

Irinotecan

Topotecan

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17
Q

What are the Topoisomerase II directed agents?

A

Anthracyclines - Doxorubicin, Daunorubicin, Idarubicin
Mitoxantrone
Etoposide

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18
Q

What are toxicities of Irinotecan?

A 
2 types of diarrhea
- Early = atropine sensitive
- Late = reflecting enterohepatic clearance
Myelosuppression
Nausea/Vomiting/Fatigue/Alopecia
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19
Q

What are toxicities of Topotecan?

A

Nausea/Vomiting/Fatigue/Alopecia

Myelosuppression

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20
Q

What are toxicities of anthracyclines (Doxorubicin, Daunorubicin, Idarubicin)?

A

Myelosuppression
Mucositis
Alopecia
Cardiac toxicity due to free radical generation (but Idarubicin less cardiotoxic)

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21
Q

How are the anthracyclines (Doxorubicin, Daunorubicin, Idarubicin) cleared and when must you dose adjust?

A

Cleared by liver

Adjust in hepatic failure

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22
Q

What drugs are in the category of antimetabolites?

A 
Methotrexate
5-Fluorouracil
Cytaracine
Gemcitabine
Fludarabine
Mercaptopurine
Pentostatin
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23
Q

What is the mechanism of action of methotrexate?

A

Folate inhibitor

Inhibits dihydrofolate reductase, blocking DNA/RNA formation

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24
Q

What are the side effects of methotrexate?

A

At standard dose - myelosuppression, mucositis

At high doses - intentionally give lethal dose, but with leucovorin (to rescue normal cells)

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25
What is the mechanism of action of 5-Fluorouracil?
Pyrimidine analog | Inhibits thymidine synthesis by forming complex with folate and thymidylate synthase
26
What are the side effects of 5-Fluorouracil?
Myelosuppression GI Cerebellar/neurocognitive Rare coronary spasm
27
What can be used to enhance the toxicity of 5-FU to cancer cells?
Leucovorin | Enhances complex of thymidilate synthase + folate +5-FU
28
What is the mechanism of action of cytarabine (Ara-C) and Gemcitabine?
Cytosine analog | Inhibits DNA synthesis
29
What are the side effects of Cytarabine and Gemcitabine?
Myelosuppression Cerebellar effects Eye irritation Hand/foot syndrome - prominent with gemcitabine
30
What antimetabolite drugs are the purine analogs?
Fludarabine | Mercaptopurine
31
What is the mechanism of action of pentostatin?
Behaves like a purine analog | Not incorporated into DNA directly, inhibits adenosine deaminase and signals apoptosis in T cells
32
What is the mechanism of action of asparaginase?
Clears circulation of asparagine | Decreases protein synthesis in susceptible cells types and indirectly damages DNA
33
What are some side effects of asparaginase?
Hypersensitivity Hyperglycemia Pancreatitis Altered clotting functions
34
What is the mechanism of action of Hydroxyurea?
Reversible inhibition of ribonucleotide reductase by chelation of non-heme Fe --> decreased dNTP pools --> stalled replication --> apoptosis
35
What are some side effects of hydroxyurea?
Myelosuppression | Mucositis
36
What are the microtubule directed cytotoxic agents?
Vincristine Vinblastine Paclitaxel Dacitaxel
37
What is the mechanism of action of vincristine and vinblastine?
Mitotic inhibitor - blocks mitosis
38
What are the toxicities of vincristine and vinblastine?
Vincristine - neurotoxic > myelosuppression | Vinblastine - myelosuppression > neurotoxic
39
What is the mechanism of action of Paclitaxel and Docitaxel (taxanes)?
Microtubule polymerstabilizers | Promote microtubule formation but are abnormal and shortened; do not function normally
40
What are toxicities of Paclitaxel and Docitaxel?
Myelosuppression Neuropathy Fluid retention - vascular leak Hypersensitivity reactions
41
What is the mechanism of action of arsenical?
Generate free radicals
42
What are side effects of arsenic?
Heavy metal toxicity - kidney, cardiac conduction (QT prolongation)
43
What are the hormonal oncologics?
``` Goserelin Tamoxifen Letrozole Examestane Prednisone ```
44
What is the mechanism of action of Goserelin?
LHRH analog | Decrease LH release by pituitary and decrease testosterone production
45
What is the mechanism of action of Tamoxifen?
Estrogen receptor antagonist
46
What is the mechanism of action of Letrozole?
Type II aromatase inhibitor | Non steroidal - target P450 aromatase
47
What is the mechanism of action of Examestane?
Type I aromatase inhibitor | Steroidal - target substrate binding site
48
What is the mechanism of action of prednisone?
Glucocorticoid receptor action induces apoptosis in lymphoid tissue
49
What is the mechanism of action of tretinoin (all trans retinoic acid)?
Induces differentiations of leukemia cells bearing translocation t(15;17) that alters structure & function of retinoic acid
50
What are side effects of all trans retinoic acid?
Teratogenic Cutaneous (dry skin, ocular kaeratitis) Increased intracranial pressure Differentiation syndrome
51
What is differentiation syndrome?
Cytokine storm in APL after all trans retinoic acid | Presents with fever, peripheral edema, pulmonary opacities, hypoxemia, respiratory distress, hypotension, etc.
52
What drug should be given to control differentiation syndrome?
Dexamethasone (steroids)
53
What drugs are in the category of tyrosine kinase inhibitors and what is the target for each?
Imatinib - BCR-ABL Erlotinib - EGF receptor Sorafenib - multitarget (VEGF, raf, others) Sunitinib - multitarget (VEGF, raf, others)
54
What are side effects of Imatinib?
Cytopenias Liver abnormalities Fluid retention Rare cardiomyopathy
55
What are side effects of Erlotinib?
Diarrhea | Cutaneous
56
What are side effects of Sorafenib, Sunitinib?
Hypertension Proteinuria Clotting/bleeding
57
What are side effects of Interferon?
Fatigue Cytopenia Fever, chills
58
What is mechanism of action of Interleukin-2?
Induces T cell response, cytolytic for tumors
59
What are side effects of Interleukin-2?
Hypotension Vascular leak Altered mental status Cardiopulmonary effects
60
What drugs are antibodies and what is their target?
Cetuximab - anti-EGFR Trastuzumab - anti-Her2/neu Rituximab - anti-CD20
61
What are side effects of antibodies?
Infusion reaction = fever, chills, hypotension, bronchospasm
62
What drug is an antiangiogenic agent?
Bevacuzimab | Anti-VEGF monoclonal antibody that prevents angiogenesis
63
What are treatments of choice for AML?
High dose Cytarabine (Ara-C) and Danorubicin (anthrocycline)
64
What are major side effects of AML treatment with Cytarabine and Danorubicin?
Tumor lysis syndrome Cytarabine-induced cerebellar toxicity Cardiomyopathy due to anthracycline
65
What are treatments of choice for APL?
All trans retinoic acid, arsenic
66
What are major side effects of APL treatment with all trans retinoic acid or arsenic?
Differentiation syndrome due to all trans retinoic acid
67
What are treatments of choice for CML?
Imatinib
68
What are major side effects of CML treatment with Imatinib?
Resistance to imatinib
69
What are treatments of choice for ALL?
Asparaginase Intrathecal chemo PCP prophylaxis Cryoprecipitate
70
What are major side effects of ALL treatment with Asparaginase?
Allergic reaction, thrombosis, pancreatitis
71
What are treatments of choice for CLL?
Wait and see
72
What are treatments of choice for Hodgkin's lymphoma?
``` ABVD combination chemo +/- radiation A - Adriamycin (Doxorubicin) B - Bleomycin V - Vinblastine D - Dacarbazine ```
73
What are major side effects of Hodgkin's treatment with ABVD?
Doxorubicin - cardiac toxicity Bleomycin - pulmonary toxicity Myelosuppression Nausea/Fatigue/Vomiting
74
What are treatments of choice for DLBCL (diffuse large B-cell lymphoma)?
``` R-CHOP +/- radiation Rituximab (CD20 antibody) Cyclophosphamide Doxorubicin Vincristine Prednisone ```
75
What are major side effects of treatment with R-CHOP?
Rituximab - infusion reaction Cyclophosphamide - bladder toxicity, at high doses also cardiac toxicity and lung toxicity Doxorubicin - cardiac toxicity Vincristine - neurotoxicity, myelosuppression Prednisone
76
What are treatments of choice for follicular lymphoma?
Close surveillance Treat if symptomatic Drugs of choice are controversial
77
What are treatments of choice for MALT lymphoma?
Triple therapy for H. pylori
78
What are treatments of choice for T cell non-Hodgkin lymphoma?
``` CHOP Cyclophosphamide Doxorubicin Vincritine Prednisone ```
79
What are treatments of choice for multiple myeloma?
Multiagent therapy with Bisphosphate therapy

Heme/Onc (1 decks)

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