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160 Cards in this Set
- Front
- Back
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what is the main goal of chemotherapy?
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to cause a lethal cytotoxic lesion that can arrest a tumor's progression
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what types of tumors are most susceptible to chemotherapy?
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undifferentiate and have high growth fractions
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what does log kill mean?
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that at a specific dose, a specific number of tumor cells are killed
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when is a diagnosis of leukemia made?
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when there are 10^9 leukemic cells
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what are the cell cycle specific agents?
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antimetabolites
bleomycins microtubule inhibitors epipodophyllotoxins camptothecins |
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what are the cell cycle nonspecific agents?
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alkylating agents
platinum corrdination complexes antitumor antibodies |
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when are cell cycle specific drugs most effective?
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in hematologic malignancies
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when are cycle non-specific drugs useful?
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in low growth fraction solid tumors
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how is multidrug resistance achieved?
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primarily by efflux pumps - P glycoprotein
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what adverse effects are common to almost all chemotherapies?
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severe vomiting
stomatitis alopecia |
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what does leucovorin due?
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rescues the bone marrow from methotrexate
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what does mesna do?
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reduces hemorrhagic cystitis caused by ifosamide and cyclophosphamide
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what does dexrazoxane do?
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reduces anthracycline-induce cardiotoxicity
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how can neutropenia associated w/ treatment of cancer be reversed?
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with filgrastim - human GCSF
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when are treatment induced neoplams more common?
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when alkylating agents are used
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what are the main classes of anticancer drugs?
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antimetabolites
antitumor antibiotics alkylating agents microtubule inhibitors epipodophyllotoxins camptothecins hormonal agents signal transduction inhibitors differentiating agents |
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what are the major antimetabolites?
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folate analogs
purine analogs pyrimidine analogs |
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what is the general MOA of the antimetabolites?
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target pathways related to nucleotide or nucleic acid synthesis
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when do antimetabolites exhibit maximal effects?
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during S-phase
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what are the folate analogs?
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methotrexate
pemetrexed |
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what does methotrexate do?
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inhibits dihydrofolate reductase
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how does methotrexate lead to cell death?
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decreases synthesis of dTMP and purine nucleotides --> decreased DNA synth --> cell death
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what are the common adverse effects of methotrexate?
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stomatitis
mucositis myelosuppression alopecia nausea vomiting |
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what is a complication of high dose methotrexate?
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renal damage
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what can long term use of methotrexate lead to?
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hepatic fibrosis and cirrhosis
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what other adverse effects of methotrexate are there?
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pneumonitis
neurologic toxicities defective oogenesis or spermatogenesis abortion teratogenesis |
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what is pemetrexed?
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folate analogue
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what does pemetexed do?
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potent inhibitor of thymidylate synthase
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what does pemetrexed do?
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induces thymineless death - decreased production of dTMP
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what is administered w/ pemetrexed?
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folic acid and B12
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what are the purine analogs?
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mercaptopurine
thioguanine flubarabine cladribine pentostatin |
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what is mercaptopurine?
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a thiol analogue of hypoxanthine
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what is the MOA of mercaptopurine?
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converted to thio-IMP by salvage pathway - HGPRT --> inhibits de novo purine ring synth
also blocks formation of AMP and GMP from IMP |
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how is mercaptopurine metabolized?
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to thiouric acid by xanthine oxidase
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what drug interaction is relevant w/ mercaptopurine use?
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allopurinol - dose of of MP must be lowered
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what are the adverse effects of mercaptopurine?
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nausea, vomiting, diarrhea
bone marrow suppression hepatotoxicity |
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what does 6-thioguanine do?
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inhibits purine synthesis and the phosphorylation of GMP to GDP
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what are the adverse effects of 6-thioguanine?
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nausea, vomiting, diarrhea
bone marrow suppression hepatotoxicity |
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what is the moa of fludarabine?
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incorporated into DNA + RNA --> alters fxn and decreases synth
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what is the moa of cladribine?
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incorporated into DNA --> strand breaks
depletes intracellular NAD and ATP |
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what is pentostatin?
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selective inhibitor of ADA
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what does inhibition of ADA lead to?
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causes an increase in intracellular adenosine 2'-deoxyadenosine --> inhibits S-adenosyl homocystein hydrolase --> toxic to lymphocytes
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what are the pyrimidine analogs?
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fluorouracil
capecitabine cytarabine gemcitabine 5-azacytidine |
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what is the moa of 5-fluoruracil?
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converted to 5-FdUMP --> inhibits DNA synth --> thymineless death
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what are the adverse effects of 5-fluoruracil?
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nausea, vomiting, alopecia, bone marrow depression
hand-foot syndrome - erythematous desquamation on palms and soles |
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what is capecitabine?
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oral pro-drug of 5-FU
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what is the moa of cytarabine?
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incorporated into DNA and inhibits DNA polymerase
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how do anti-tumor antibiotics work?
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bind to DNA through intercalation between bases and block synth of new RNA and DNA, cause DNA strand scission, and interfere w/ cell replication
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what are the anti-tumor antibiotics?
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anthracycline
mitoxantrone actinomycin bleomycin mitomycin plicamycin |
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what are the anthracyclines?
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doxorubicin
daunorubicin idarubicin epirubicin |
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what is the moa of gemcitabine?
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phosphorylated --> inhibit DNA synthesis from:
inhibition of ribonucleotide reductase incorporation into DNA |
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what is the moa of 5-azacytidine?
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incorporated into DNA and RNA --> interferes w/ cytosine methylation --> alter gene expression --> differentiation
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what is the moa of the antracyclines?
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inhibit topoisomerase II
intercalation in DNA --> strand breakage binds to cell membranes and alters ion transport generation of free radicals |
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what are the adverse effects of anthracyclines?
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myelosuppresion
cardiotoxicity - due to free radicals |
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how is cardiotoxicity reduced in anthracyclines?
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w/ dexrazoxane - Fe chelating agent
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when does radiation cell reaction occur?
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erythema at sites of prior radiation w/ anthracycline therapy
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what is mitoxantrone?
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an anthracene compound
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what are the adverese effects of dactinomycin?
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skin abnormalities assoc w/ inflammation at sites of prior radiation therapy
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what is bleomycin?
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mix of two peptides - A2 and B2
cell cycle specific - arrest cell in G2 |
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what is the moa of belomycin?
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complexes Fe and creates free radicals
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what are the adverse effects of bleomycin?
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pulmonary toxicity (pneumonitis, fibrosis)
very little myelosuppression |
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when is mitomycin used?
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targets hypoxic tumor cells
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what is the most severe adverse effect seen w/ mitomycin?
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hemolytic uremic syndrome
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what is the moa of plicamycin?
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decreases plasma Ca levels through action on osteoclasts that is independent of its action on tumor cells
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what is the moa of alkylating agents?
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exert cytotoxic effects via transfer of alkyl groups to cellular constituents
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what are the adverse effects of alkylating agents?
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nausea, vomiting
mutagenic, carcinogenic |
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how are the emetic effects caused by alkylating agents reduced?
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5-HT3 antagonists
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what are the alkylating agents?
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nitrogen mustards
ethylenimines and methylmelammines alkyl sulfonates nitrosoureas triazenes |
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what are the nitrogen mustarges?
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mechlorethamine
cyclophosphamide ifosfamide melphalan chlorambucil |
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what is unique about the handling of mechlorethamine?
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must be made just prior to admin - is unstable
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what are the adverse effects of mechlorethamines?
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severe nausea and vomiting
severe bone marrow suppression immunosuppressive vesicant |
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how is cyclophosphamide administered?
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oral or IV
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how is cyclophosphamide activated?
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by CYP2B
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what are the adverse effects of cyclophosphamide?
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nausea, vomiting, bone marrow suppression, hemorrhagic cystits, alopecia, sterility, inappropriate ADH secretion
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how does cyclophosphamide cause hemorrhagic cystitis?
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caused by acrolein - a metabolite
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how is hemorrhagic cystitis that occurs w/ cyclophosphamide prevented?
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by admin of mesna - reacts w/ acrolein in bladder
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how is ifosfamide acitvated?
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by hydroxylation by CYP3A4
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what are the adverse effects of ifosfamide?
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platelet suppresion, neurotoxicity, urinary tract toxicity
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what are the nitrosoureas?
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carmustine
lomustine semustine streptozocin |
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which nitrosoureas are lipophilic and cross the BBB?
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carmustine and lomustine
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what does steptozocin target?
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B cells of islet of langerhans
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what are the adverse effects of cisplatin?
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myelosuppression
nausea, vomiting nephrotoxicity ototoxicity peripheral neuropathy |
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how is renal toxicity caused by cisplatin reduced?
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amifostine
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what are the platinmum coordination complexes?
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cisplatin
carboplatin oxaliplatin |
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what are the adverse effects of carboplatin?
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nausea, neurotoxicity, ototoxicity, nephrotoxicity
dose limiting toxicity is myelosuppression |
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what are the adverse effects of oxaliplatin?
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neurotoxicity, exacerbated by cold
hematological toxicty |
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what are the adverse effects of procarbazine?
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nausea, vomiting, myelosuppression
hemolytic anemia, pulmonary reactions, disulfiram-like reactions MAOI |
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what is the MOA of platinum coordination complexes?
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inhibit DNA synthesis and binds DNA
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what are the major classes of microtubule inhibitors?
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Vinca Alkaloids
Taxanes Epothilones |
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what are the Vinca Alkaloids?
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Vincristine
Vinblastine Vinrelbine |
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what are the taxanes?
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paclitaxel
docetaxel |
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what are the epothilones?
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ixabepilone
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what is the moa of the vinca alkaloids?
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bind to B-tubulin and inhibit ability to polymerize into microtubules
stops cellular division --> apoptosis |
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what are the adverse effects of vincristine?
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peripheral neuropathy
bone marrow suppression, alopecia |
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what are the adverse effects of vinblastine?
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myelosuppression
alopecia, peripheral neuropathy |
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what are the adverse effects of vinorelbine?
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peripheral neuropathy
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what is the moa of taxanes?
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bind to B tubulin and promote microtubule polymerization --> stabilization --> inhibits cell division --> apoptosis
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what are the adverse effects of paclitaxel?
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hypersensitivity, myelosuppression, peripheral neuropathy
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how is paclitaxel administered?
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in 50% ethaol and 50% polyethoxylated castor oil
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what should patients receiving paclitaxel be pre-medicated w/?
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dexamethasone, diphenydramine, H2 blocker
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what are the adverse effects of docetaxel?
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myelosuppression, peripheral neuropathy, fluid retention, alopecia
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what should patients receiving docetaxel be pretreated w/?
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dexamehtasone
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what is the moa of ixabepilone?
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binds to B tubulin --> stabilization --> apoptosis
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which drugs comprise the epipodophyllotoxins?
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etoposide
teniposide |
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what is the moa of the epipodophyllotoxins?
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inhibit topoisomerase II --> DNA dmage
blocks cell in late S-G2 phase |
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which drugs comprise the camptothecins?
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topotecan
irinotecan |
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what is the moa of camptothecins?
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inhibit toposiomerase I
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what hormonal agents are used in chemotherapy of neoplasms?
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glucocorticoids
estrogens estrogen inhibitors progestins androgens androgen inhibitors |
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which drugs comprise the glucorcorticoids used in chemotherapy of neoplasms?
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dexamthasone
prednisone hydrocortisone |
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when are glucocorticoids used in anti-cancer?
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to suppress mitosis in lymphocytes
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what are the estrogen drugs?
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diethylstilbestrol
ethinylestradiol |
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what is the moa of the estrogens?
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inhibit testosterone production
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what is SERMs?
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selective estrogen receptor modulatoss
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what are SERDs?
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selective estrogen receptor downregulators
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what are AIs?
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aromatase inhibitors
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what are the classes of estrogen inhibitors?
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SERMs
SERDs AIs |
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what drugs comprise the SERMs?
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tamoxifen
toremifine |
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which drugs make up the SERDs?
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fulvestrant
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what is the moa of AIs?
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convert androstenedion to estrone
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which drugs comprise the AIs?
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aminoglutethimide
anastrozole and letrozole exemestan and formestane |
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which drugs are progestins?
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hydroxyprogesterone
megestrol |
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what effects fo the progestins have?
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stimulate appetite and restore sense of well being in cachectic patients
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when administering gonadotropin releasing hormone agonists, there is an initial surge - how can this be avoided?
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by giving an androgen receptor block such as flutamide
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what is abarelix?
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a gonadotropin releasing hormone antagonist
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what effects does abarelix have?
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reduces serum testosterone w/o transient initial increase observed w/ GnRH agonists
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what are the two groups of androgen receptor blockers?
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steroidal
nonsteroidal |
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what are the steroidal androgen receptor blockers?
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cyproterone amd megestrol
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what are the nonsteroidal androgen receptor blockers?
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flutamide
nilutamide bicalutamide |
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list the adrogens
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testosterone
fluoxymesterone |
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what is the mainstay treatment for prostate cancer?
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androgen deprivation therapy
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how is androgen deprivation therapy achieved?
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gonadotropin releasing hormone agonists
gonadotropin releasing hormone antagonists androgen receptor blockers |
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what are the gonadotropin releasing hormone agonists?
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goserelin
leuprolide nafarelin buserelin triptorelin |
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What does gefitinib do?
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inhibits EGFR tyrosine kinase
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what does erlotinib do?
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inhibits EGFR tyrosine kinase
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what does lapatinib do?
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inhibits EGFR tyrosine kinase and ErbB2 tyrosine kinase
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what does cetuximab do?
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monoclonal antibody against EGFR
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what does trastuzumab do?
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monoclonal antibody against ErbB2
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what do imatinib, dasatinib, and nilotinib do?
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inhibit tyrosine kinase of Bcr-Abl --> leads to death of leukemic cells
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what does sorafenib do?
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inhibi3ts serine/threonine kinase RAF
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what does sirolimus do?
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binds to FKBP12 --> inhibits mTOR --> inhibits cell cycle
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what does bortezomib do?
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inhibits proteasome
induces growth inhibition and apoptosis of tumor cells w/ few cytotoxic effects on normal cells |
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what does bevacizumab do?
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monoclonal IgG1 antibody against VEGF-A
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what does sunitinib do?
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inhibits VEGFR-1, VEGFR-2, and PDGFR
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what does thalidomide do?
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immunomodulatory drug; inhibits angiogenesis and co-stimulates T cells
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what does lenalidomide do?
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analogue of thalidomide
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what are the angiogenesis inhibitors?
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bevacizumab
sunitinib thalidomide lenalidomide |
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what drugs are anti-CD20 antibodies?
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Rituximab
Tositumomab Ibritumomab |
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what is alemtuzumab?
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an anti-CD52 antibody
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what is denileukin deftitox?
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fusion protein of diptheria toxin and IL-2
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what is gemtuzumab?
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conjugate of anti-CD33 antibody and calicheamicin
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what is the moa of denileukin deftitox?
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binds to IL-2 receptor ad enters cell through clathrin coated pits --> subunit of DT in cytosol --> inhibition of protein synthesis
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what are the differentiating agents?
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retinoids
arsenic trioxide |
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what are the adverse effects of retinoids?
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mucocutaneous, skeletal, liver, teratogenic effects
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what are the toxic effects of arsenic trioxide?
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fatigue, QT prolongation, arrhythmias
syndrome: fever, dyspnea, skin rash, fluid retention, weight gaint |
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what is the moa of asparaginase?
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hydrolyzes serum asparagine --> tumor cells need increased asparagine --> cell death
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what are the adverse effects of asparaginase?
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hypersensitivity
decrease in clotting factors liver abnormalities pancreatitis, seizures, coma due to ammonia toxicity |
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what is the moa of hydroxyurea?
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inhibits ribonucleotide reductase --> depletion of deoxynucleoside pools --> kills cells in S phase
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when would hydroxyurea be administered for something other than cancer?
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sickle cell disease - increases expression of fetal hemoglobin
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when is mitotane used?
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targets adrenocortical cells
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what stimulates red blood cell growth?
|
erythropoietin
darbopoetin alfa |
