Cancer Chemotherapy Flashcards
What is mechanism of alkylating agents?
Blocks DNA replication and transcription
What are the cytotoxic actions of alkylating agents?
Proliferative dependent (except nitrosoureas)
Mainly affect G1 and S phases
How do cells gain resistance to alkylating agents?
Decreased permeability or uptake; increased nucleophiles or repair
What is Na-2-Mercaptoethanesulfonate
Used to decrease hemorrhagic cystitis produced by acrolein
Reacts with acrolein in urine to detoxify and prevent binding to bladder wall
What are the four alkylating agents?
Mechlorethamine
Cyclophosphamide
Chlorambucil
Bendamustine
What is unique about mechlorethamine?
It is not excreted
What is mechlorethamine used for?
Hodgkins disease
How is cyclophosphamide activated?
Activated by cytochrome P450s to active metabolites
What are the unique toxicities of cyclophosphamide?
Hemorrhagic cystitis
SIADH
What is Chlorambucil used for?
Chronic lymphocytic leukemia
What is the unique toxicity for chlorambucil?
Hepatotoxicity
What is the MoA of drugs containing platinum?
Binds to guanine in DNA; forms intrastrand crosslinks
Binds extensively to protein
What are the dose-limiting toxicities of platinum drugs?
Nephrotoxicity
Peripheral neuropathy
Ototoxicity
What are the anthracyclines and their MoA?
Doxorubicin and Daunorubicin
Tight binding between DNA base pairs
Blocks topoisomerase II
What is the unique toxicity of anthracyclines?
Cardiotoxicity
Can be prevented by dexrazoxane
What are the uses for anthracyclines?
Breast cancer
Sarcoma
MOPP-resistance Hodgkin’s
Carcinomas
What is the MoA of mitoxantrone?
Binds to DNA to produce drug-DNA-topoisomerase II complexes
Lower incidence of cardiotoxicity
What are the epipodophyllotoxins and their MoA?
Etoposide and Tenopside
Forms a ternary complex with DNa-topoisomerase
Kills in S and G2 phases
What are the uses of epipodophyllotoxins?
Tisticular tumors
Small-cell lung cancer
What is the MoA of Captothecin analogs?
Inhibitors of topoisomerase I
CCS: Act in S phase
What are Bleomycins?
Combination of several structurally related antibiotics
Most active in G2 phase
What are the unique toxicities of Bleomycins?
Pulmonaryy gibrosis and pneumonitis
What are the uses of bleomycins?
Advanced testicular carcinoma
Lymphomas in combination therapy
What is the MoA of dactinomycin?
Interaction at purine-pyrimidne base pairs of DNA and intercalate between strands
Prevents DNA transcription
What are the unique toxicities of dactinomycin?
Oral and GI ulceration
Stomatitis
What are the uses for dactinomycin?
Methotrexate-resistant choriocarcinoma
Wilm’s tumor
Rhabdomyosarcoma
What are antimetabolites?
Compounds that mimic endogenous biochemicals required for DNA, RNA synthesis or function of enzymes
What is the function of methotrexate?
Inhibits dihydrofolate reductase
Decreases DNA synthesis
CCS- S phase
What is Leucovorin used for?
Minimizes the toxid effects of folate depletion in normal cells
