Chemotherapy Pharm Flashcards by nancy Gillcrist

class 1 agents
class 2 agents
class 3 agents

• Class 1: all cells killed
; ex: nonspecific alkylating agents, nitrogen mustard

• Class 2: cell cycle specific; plateaus
ex: vinblastine, methotrexate

•	Class 3 agents: non-cycle specific but slower rate of kill than class 1; 
example: daunorubicin

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survival curves are ____

what does that mean?

logarithmic

-a given dose kills a constant fraction of cells

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MDR

multidrug resistance

over production of glycoproteins that pump drugs out of cells

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nitrogen mustards def and mechanism (4 are?)

Mech: DNA is alkylated –> causes misreading and strand breaks

MICC - melphalan, ifosfamide, chlorambucil, cyclophasphamide

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melphalan and chlorambucil

nitrogen mustards; phenylalanine derivatives

orally; 1.5-2 hr half life

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clyclophosphamide

nitrogen mustard –>activated to aldophosphamide by hepatic cyt p450 –> hydrolized to active phosphoramide mustard in target cells

-inactivated by aldehyde dehydrogenase 

reduced hepatotoxicity BUT -->
o	Toxicities (different than the others) – immunosuppression, pulmonary fibrosis, cystitis, water retention, alopecia, carcinogenesis

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ifosfamide

Cyclophosphamide derivative for testicular cancer

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2 chloroethyl nitrosureas

carmustine

lomustine

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nitrosureas

carmustine and lomustine
Mech: Alkylation, DNA crosslinking, and carbamoylation of proteins
o lipid soluble –> disappear rapidly from plasma into lipids/CNS = long half-life

toxicities: delayed/severe hematopoietic depression;

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which nitrosurea can be implantable wafer for treatment of malignant glioma.

carmustine

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cisplatin

platinum coordinate; only the cis-dichloro form is active. Used for testicular/ovarian cancer, and head/neck cancers.
• Mechanism: alkylation by dissociation of Cl- ions leaving a + charged complex –> crosslinks are formed.

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3 platinum coordination complex drugs

cisplatin
oxaliplatin
carboplatin

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which form of cisplatin is active?

inactive?

cis-dichloro is active

plasma bound drug is inactive

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oxaliplatin

cisplatin analogue used to treat colorectal cancer.

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toxicity of platinum coordinator complexes

myelosuppression, nephrotoxicity, ototoxicity; nephrotoxicity can be attenuated by administration of the free radical scavenger amifostine.

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carboplatin

platinum coordinator complex with less renal toxicity; dose is limited by leukopenia and thrombocytopenia

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procarbazine

nonspecific alkylator (DNA, RNA, protein)
•	treat Hodgkin's lymphoma.

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classes of alkylating agents

nitrosureas
platinum coordinators
nitrogen mustards
procarbazine

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vinca alkaloids

Vincristine and vinblastine

potent plant-derived antitumor agents
• Mechanism: INHIBITS microtubule formation

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vincristine - class? toxicity?

vinca alkaloid

neurotoxicity and stimulates ADH release

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vinblastine - class? toxicity?

vinca alkaloid

myelosuppression and mucositis

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2 taxanes?

paclitaxel and docetaxel

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paclitaxel

taxane from yew tree Taxus; inhibits microtubule reorganization

which taxane is natural? which is semisynthetic?

docetaxel is semisynthetic

paclitaxel is natural

ixabepilone

binds directly to β-tubulin and, in contrast to the vinca alkaloids, promotes polymerization/stabilizes microtubules, arresting cells in G2/M. o Used for treatment of taxane- and anthracycline-resistant breast cancer.

2 Epipodophylotoxins

Etoposide and teniposide

etoposide and teniposide

from mandrake plant podophyllotoxin • Uses: Hodgkin's lymphoma, diffuse histiocytic lymphoma and lung small cell carcinoma • Mechanism: Inhibit topoisomerase II   • Toxicities: leukopenia, thrombocytopenia

2 derivatives from the plant alkaloid camptothecin their mechanism?

irinotecan and topotecan inhibit topoisomerase 1

irinotecan

derivative of plant alkaloid camptothecin inhibits topoisomerase 1 treatment of metastatic colorectal cancer.

topotecan

derivative of the plant alkaloid camptothecin inhibits topoisomerase 1 Effective for treatment of ovarian and small cell lung carcinoma.

2 anthracyclines

Daunorubicin and doxorubicin

anthracyclines o Free radical and strand breaks formation o Inhibition of DNA topoisomerase II • CARDIOTOXICITY

dexrazoxane

a protectant, iron chelator that inhibits free radical formation can reduce cardiac damage from anthracyclines

what drug do you pair with anthracyclines (daunorubicin and doxorubicin) to prevent ROS and reduce cardiac damage?

dexrazoxane

bleomycin

antibiotic • causes depurination and depyrimidation--> strand breaks • NOT a substrate for MDR • Toxicity: sub-acute or chronic pneumonitis, lesions of the skin

what is NOT a substrate for MDR?

bleomycin

an anti-metabolite? | its antidote if there is toxicity?

methotrexate | leucovorin

methotrexate

- folic acid analogue; inhibits dihydrofolate reductase | 

folic acid analogue that is a competitive inhibitor of the enzyme dihydrofolate reductase?

methotrexate

leucovorin

treats MTX toxicity | by supplying reduced folate to cells

pyrimidine analogues

analogues of uridine or cytidine --> synthesis of defective DNA and chain termination 5GACC --> 5 fluorouracil, gemcitabine, azacitidine, capecitabine, cytosine arabinoside

5GACC

the pyrimidine analogues --> synthesis of defective DNA and chain termination 5 fluorouracil, gemcitabine, azacitidine, capecitabine, cytosine arabinoside

capecitabine

a 5-FU prodrug whose final step of activation is catalyzed by thymidine phosphorylase; used in metastatic breast and colon cancer.

azacitidine

pyrimidine analogue | o Used to treat myelodysplastic syndrome.

purine analogues

6 mercaptopurine and 6 thioguanine converted by HPRT S phase of cell cycle is most sensitive

asparaginase

catalyzes conversion of asparagine to aspartate --> inhibition of protein synthesis. o Toxicities: Reduction in concentration of secreted proteins (clotting factors, insulin, albumin, etc.), hypersensitivity reactions, hepatotoxicity.

kinase inhibitors

``` GIVES gefitinib imatinib mesylate vemurafenib erlotinib sorafenib ```

Imatinib mesylate

treats CML | ---blocks the ATP-binding site of the c-abl tyrosine kinase

vorinostat

• Histone deacetylase inhibitor; Used to treat cutaneous T cell lymphoma

all trans retinoic acid

(vitamin A) - First line therapy for promyelocytic leukemia

cetuximab

directed against EGF receptor

trastuzumab

cell-mediated cytotoxicity; |  . 

bevacizumab

• Ab against VEGF; Designed to inhibit angiogenesis; | o risk of thromboembolic events;

rituximab

anti-CD20 monoclonal antibody | o Toxicity: can result in HBV reactivation.

ipilimumab? gemtuzumab ozogamicin? pembrolizumab?

TARGETs: - -CTLA-4  --myeloid surface antigen CD33. - -PD-1 receptor (programmed cell death 1)

intrathecal methotrexate

CNS prophylactic into CSF - dihydrofolate reductase inhibitor that targets CNS since chemo doesn't cross into there but cancer can toxicity: meningitis