Cancer Chemotherapy Drugs Flashcards
(97 cards)
What are CCS drugs?
Cell Cycle Specific Drugs that are particularly effective during a specific phase of the cell cycle (Go).
What are CCNS drugs?
Cell Cycle Non-Specific Drugs that kill tumor cells in both cycling and resting phases of the cell cycle.
Growth Fraction
The proportion of cells in a tumor population that are actively dividing.
Log-Kill Hypothesis
A hypothesis meaning that anticancer drugs kill a fixed proportion of a tumor cell population, not a fixed number of tumor cells. i.e. 3-log-kill will reduce a populationfrom 10^6 to 10^3.
Myelosurpressant
A drug that surpresses the formation of mature blood cells such as erythrocytes, leukocytes, and platelets. This is known as “bone marrow surpression”
Oncogene
A mutant form of a normal gene that is found in naturally occurring tumors and which, when expressed in noncancerous cells, causes them to behave like cancer cells.
Rescue Therapy
The administration of endogenous metabolites to counteract the effects of anticancer drugs on normal (nonneoplastic) cells.
Vesicant
A drug that causes blisters on contact with tissues. Can be particularly damaging to veins if administered in high concentrations into small vessels.
i.e. Mechlorethamine
What phase of the cell cycle do the Vinca Alkaloids act on?
M
What phase of the cell cycle do the antimetabolites act on?
S (DNA Synthesis)
What phase of the cell cycle do the podophyllotoxins act on?
S (DNA Synthesis) and G2 (Synthesis of components needed for DNA Synthesis)
What phase of the cell cycle does Bleomycin act on?
G2 (Synthesis of components needed for DNA Synthesis)
What are the 6 methods of resistance to anticancer drugs?
- Increased DNA Repair
- Formation of Trapping Agents
- Changes in Target Enzymes
- Decreased Activation of ProDrugs
- Inactivation of Anticancer Drugs
- Decreased Drug Accumulaiton
Explain resistance via increased DNA repair and give examples of drugs that use this method.
The rate of repair of DNA damage is increased.
i.e. Alkylating Agents and Cisplatin
Explain resistance via formation of trapping agents and give examples of drugs that use this method.
Some tumor cells increase the production of thiol trapping agents (ex. glutathione) which interact with anticancer drugs that form reactive electrophilic species.
i.e. Bleomycin, Cisplatin, Anthracyclines
Explain resistance via changes in target enzymes and give examples of drugs that use this method.
Changes in the drug sensitivity of a target enzyme (ex. dihydrofolate reductase), and increased synthesis of the enzyme.
i.e. Methotrexate
Explain resistance via decreased activation of prodrugs and give examples of drugs that use this method.
Decrease in the activity of tumor cell enzymes needed to convert these prodrugs to their cytotoxic metabolites.
i.e. Purine Antimetabolites (Mercaptopurine and Thioguanine) and Pyrimidine Antimetaboites (Cytarabine and Fluorouracil)
Explain resistance via inactivation of anticancer drugs and give examples of drugs that use this method.
Increased activity of enzymes capable of inactivating anticancer drugs.
i.e. Most purine and pyrimidine antimetabolites
Explain resistance via increased decreased drug accumulation and give examples of drugs that use this method.
Increased expression of MDR1 gene for a cell surface glycoprotein (p-glycoprotein), which is the transport molecule involved in the accelerated efflux of many anticancer drugs in resistant cells.
Alkylating Agents
CCNS Drugs that form reactive molecular species that alkylate nucleophillic groups on DNA bases, especially the N-7 position on guanine. This leads to crosslinking of bases, abnormal base pairs, DNA strand breakage.
- Nitrogen Mustards (chlorampbucil, cyclophosphamide, meclorethamine)
- Nitrosoureas (carmustine, lomustine)
- Alkylsulfonates (busulfan)
- Cisplatin, Dicarbazine, Procarbazine
Describe the pharmacokinetics of CYCLOPHOSPHAMIDE:
- CYP450 mediated biotransformation is needed for antitumor activity
- Acrolein is a breakdown product
Describe the clinical uses of CYCLOPHOSPHAMIDE:
- Non-Hodgkins Lymphoma
- Breast and Ovarian Cancers
- Neuroblastoma
Describe the toxicity of CYCLOPHOSPHAMIDE:
- GI Distress
- Myelosurpression
- Alopecia
- Hemorrhagic Cystitis (from formation of acrolein; reduced by vigorous hydration and mesna)
- Cardiac Dysfunction
- Pulmonary Toxicity
- Inappropriate ADH secretion
Describe the mechanism and pharmacokinetics of MECLORETHAMINE.
Spontaneously converts in the body to a reactive cytotoxic product.