Cytotoxic Chemo Flashcards
Growth Fraction
Proportion of cells in a tumor that are actively dividing
2 common toxicities of Topotecan/Irinotecan
Myelosuppression and Diarrhea
2 Purine Antimetabolites
6-MP and 6-GT
4 Plant Alkyloids
(1) Vin-‘s; (2) -side’s; (3) -can’s; (4) -taxel’s
5 Alkylating Agents
Cyclophosphamide, Mechlorethamine, Platinum Analogs, Procarbazine, Busulfan
5 Antibiotics for Chemotherapy
(1) Doxorubicin/Daunorubicin; (2) Bleomycin; (3) Dactinomycin; (4) Mitomycin
6 Antimetabolites
Methotrexate, 6-MP and 6-TG, 5-FU, Cytarabine, Gemcitabine
Acrolein is breakdown product of what
Cyclosphosphamide
Administration of Vinca Alkyloids
Parenterally
Alkylating agents: CCNS or CCS?
CCNS
Anthracyclines
Doxorubicin, Daunorubicin
Anthracyclines (-rubicin): CCS or CCNS?
CCNS
Anticancer drugs kill a fixed proportion of tumor cell populatino
Log-Kill Hypothesis
Antimetabolites: CCNS or CCS?
CCS, primarily S phase
Binds to dsDNA and inhibits DNA-dependent RNA synthesis
MOA of Dactinomycin
Bleomycin toxicities
Pneumoitis, Pulmonary Fibrosis, Alopecia
Bleomycin: CCS or CCNS?
CCS: G2 phase
Block formation of mitotic spindle by preventing assembly of tubulin dimers into microtubules
MOA of Vinca Alkyloids
Cisplatin toxcitities
Nephrotoxicity, Ototoxicity, Myelosuppression
Class with Cardiotoxicity
Anthracyclines (-rubicins)
Clearance of Vinca Alkyloids
Bililary Excretion
Concurrent Agent for 5-FU
Leucovorin (Enhanced action)
Concurrent Agent for 6-MP
Allopurinol (increases toxicity!)
Concurrent Agent for Anthracyclines
Dexroxazone (Fe chelator, reduced cardiotoxicity)
Concurrent Agent for Cisplatin
Amifostine (Cytoprotection)
Concurrent Agent for Cyclophosphamide
Mesna (protect against Acrolein production)
Concurrent Agent for MTX
Luecovorin (Metabolic rescue)
Concurrent Agent for Tumor Lysis Syndrome
Allopurinol
Concurrent Agents for Bone Mets
Pamidronate, Zoledronate (reduced bone pain and fractures)
Dactinomycin: CCS or CCNS?
CCNS
Deoxycytidine analog that inhibits ribonucleotide reductase –> Diminishes pool of deoxyribonucleoside triphosphates for DNA synthesis
MOA of Gemcitabine
Distinctive adverse effect of Anthracyclines
Cardiotoxicity
Dose Limiting Toxicity of 6-MP and 6-GT
Bone Marrow Suppression
Drug that causes blisters on contact with tissues
Vesicant
Elimination of Etoposide
Renal
First-Order Kinetics
A given dose kills a constant proportion of a cell population rather than a constant number of cells
Forms H2O2, which generates free radicals and causes DNA strand scission
Procarbazine
General MOA of Cyclophosphamide
Alkylating Agent
General MOA of Mechlorethamine
Alkylating Agent
General MOA of Platinum Agents
Alkylating Agents
How can you reduce toxicity of Methotrexate
Folinic Acid (Leucovorin)
In what phase to Vinca Alkyloids work
M Phase
Increases degradation of DNA and inhibits mitochondrial ETC
MOA of Etoposide/Teniposide
Inhibit Topo 1
MOA of Topotecan/Irinotecan
Inhibits Thymidylate Synthase and leads to “thymineless death” of cells
5-FU
Kinetics of Cytotoxic drugs
First-Order Kinetics
Leucovorin Rescue
Reduce toxic effects of Methotrexate by administration of Folinic Acid (Leucovorin)
Log-Kill Hypothesis
Anticancer drugs kill a fixed proportion of tumor cell populatino
Main toxicity of Gemcitabine
Myelosuppression
Main use of Daunorubicin
Acute Leukemias
Methotrexate clearance is dependent on
Renal function
Mitomycin: CCS or CCNS?
CCNS
MOA of 5-FU
Inhibits Thymidylate Synthase and leads to “thymineless death” of cells
MOA of 6-GT
Purine Antimetabolite
MOA of 6-MP
Purine Antimetabolite
MOA of Bleomycin
Generates free radicals
MOA of Cytarabine (ARA-C)
Pyrimidine antimetabolite
MOA of Dactinomycin
Binds to dsDNA and inhibits DNA-dependent RNA synthesis
MOA of Doxorubicin/Daunorubicin
Intercalate b/t base pairs, Inhibit Topo 2, Generate free radicals
MOA of Etoposide/Teniposide
Increases degradation of DNA and inhibits mitochondrial ETC
MOA of Gemcitabine
Deoxycytidine analog that inhibits ribonucleotide reductase –> Diminishes pool of deoxyribonucleoside triphosphates for DNA synthesis
MOA of Mitomycin
Alkylating agent that cross-links DNA
MOA of Paclitaxel/Docetaxel (Taxanes)
Prevent microtubule disassembly in mitotic spindle
MOA of Procarbazine
Forms H2O2, which generates free radicals and causes DNA strand scission
MOA of Topotecan/Irinotecan
Inhibit Topo 1
MOA of Vinca Alkyloids
Block formation of mitotic spindle by preventing assembly of tubulin dimers into microtubules
Of all the antimetabolites, __ is most specific for S phase
Cytarabine
Prevent microtubule disassembly in mitotic spindle
MOA of Paclitaxel/Docetaxel
Primary use of Procarbazine
Hodgkin’s Lymphoma
Proportion of cells in a tumor that are actively dividing
Growth Fraction
Purine antimetabolites are used mainly in
Acute Leukemias and Chronic Myelocyte Leukemia
Pyrimidine antimetabolite
Cytarabine
Resistance to 5-FU
Decreased activation of 5-FU, Increased Thymidylate Synthase activity, Reduced drug sensitivity
Resistance to 6-MP and 6-GT
Decreased HGPRTase activity (activating enzyme) or increase production of Alkaline Phosphatases
Resistance to Alkylating agents
Increased DNA repair; Decreased drug permeability; Production of trapping agents (thiols)
Resistance to Vinca Alkyloids
Increased efflux
Special cyclophosphamide toxicity
Hemorrhage Cystitis
The metabolism of 6-MP by Xanthine Oxidase is inhibited by
Allopurinol
Use of Mechlorethamine
Hodgkin’s Lymphoma
Use of Taxanes
Advanced Breast and Ovarian cancers
Uses of Dactinomycin
Melanoma and Wilms tumor
Vesicant
Drug that causes blisters on contact with tissues
Vincristine toxicities
Peripheral neuropathy, Paralytic Ileus
What is needed for Cyclophosphamide antitumor activity
Hepatic CYP450 biotransformation
What may protect against cardiotoxicity from Anthracyclines
Dexrazoxane
When to give Allopurinol
Tumor Lysis Syndrome, 6-MP
When to give Amifostine
Cisplatin (cytoprotection)
When to give Leucovorin
MTX, 5-FU
When to give Mesna as concurrent agent
Cyclophasphamide (protect against Acrolein production)