Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key


Play button


Play button




Click to flip

45 Cards in this Set

  • Front
  • Back
When does the chromosome replication take place in the cell cycle?
S Phase
What are the 3 different classes of chemotherapeutic agents?
Class 1: Kills all cells regardless of their state of proliferation

Class 2: Cell cycle specific

Class 3: Not cell cycle specific, BUT better on proliferating cells
What are some of the mechanisms to chemo resistance?
Transport defects
Somatic mutations
Gene Amplification
Over-production of membrane glyco-protiens(MDRs) which actively pump drugs out of cells
What are the 5 major classes of chemotherapuetic agents?
Natural (some disrupt the biological process)
AntiMetabolites (mimic some natural substrate or cofactor)
Enzymes (usually degrade an amino acid)
Biological response modifiers (regulatory factors)
What are the 5 principle classes of alkylating agents in use?
Nitrogen Mustards
How do the nitrogen mustards work?
They alkylate DNA at the N-7 position of guanine thus introducing lethal errors in DNA. Alkylated DNA is also subject to DEPURINATION leading to the introduction of both single and double strand breaks.
What makes Cyclophosphamide so great?
BC it must be activated by CYP2C9 and hydrolyzed to the active phosphoramide mustard in target cells, hepatotoxicity and other side effects are reduced or eliminated.
Which mustard do we want to use for testicular cancer?
Which ethylenimine is useful for breast and ovarian cancer?
What are nitrosoureas good for?
BCNU (carmustine) and CCNU (lomustine) are good for alkylation, DNA crosslinking and carbamoylation of protiens. Since they are lipids they have good penetration into CNS.
What are the Nitrogen mustards? (4)
Melphalan (oral), chlorambucil, cyclophosphamide, ifosfamide
What makes Streptozocin special?
It preferentially acts on pancreatic islet cells
What are the triazenes?
Dacarbazine- inhibits RNA and protein synthesis more than DNA
Temoxolomide-good for anaplastic astrocytoma
What other alkylating agents do we talk about that are not in the 5 principle classes?
Cisplastin (platinol), Oxalaplatin, Carboplatin and finally Procarbazine
What is the advantage of Carboplatin over cisplastin?
Less renal toxicity. Side effects are attenuated by giving amifostine (a free radical scavenger)
Both work by dissociation of chloride ions to leave a positively charged complex which leads to cross linking
What are the natural products?
Vinca alkyloids, Taxanes, Epipodophyllotoxins, Camptothecin derivatives, & Antibiotics
What are the vinca alkyloids and how do they work?
Vincristine and Vinblastine.
They bind to tubulin causing depolymerization, thus disrupting microtubule structure. This inhibits spindle fiber formation and mitosis (**M phase of cell cycle) as well as dirupting cytoskeletal movement.
What are the toxicities of the Vinca alkyloids?
NEUROTOXICITY- vincristine
myelosupression, mucositis- vinblastine

Vinorelbine is a semisynthetic derivative of vinblastine w increased specificity for microtubules and less neurotoxicity.
How does Paclitaxel work?
What is docetaxel?
Paclitaxel (Taxol) is a diterpine antineoplastic agent from the yew tree.
It inhibits microtubule disassembly, freezing them in the polymerized state.

This is in contrast to the vinca alkyloids

Docetaxel is a semisynthetic analogue of paclitaxel
Which chemo drug inhibits Topoisomerase II and comes from the mandrake?

Etoposide- VP-16

Teniposide- VM-26

*remember* Topoisomerase II is ATP-dependent!
What are the camptothecin derivatives and what do they do?
The campothecin derivitive inhibit Topoisomerase I (NOT ATP-dependent)



These drugs are effective in the treatment of lung and colon cancer (metastatic)
What is Dactinomycin?
AKA Actinomycin D
An antibiotic wich interalates between G:C pairs.
What does Dactinomycin do?
At low levels it inhibits RNA synthesis and at high doses it will inhibit both RNA and DNA synthesis

Side effects are myelosupression and RADIATION SENSITIVITY
What are the anthracyclines?
Daunorubicin (daunomycin)
Doxorubicin (adriamycin)
What do the anthracyclines do?
Mechanism is likely: DNA intercalation and introduction of single stranded breaks
What is the major side effect of anthracyclines?
A severe side effect of the drug is CARDIOTOXICITY (digitalis unresponsive CHF)

DEXRAZOXANE (Zinecard) is an iro chelator which inhibits free radical formation and can be used to reduce cardiac damage.
How does Bleomycin work?
Bleomycin is a peptide antibiotic which binds to DNA and brings an Fe compex into a position in which oxidation leading to depyrimidation and depurination is facilitated.
Its liek a cross between an intercalating agent and an alkylating agent.
Side effects of Bleomycin?
Because bleomycin is accumulated in the skin, lung and tumor tissue and toxic side effect can be subacute/chronic pneumonitis and skin lesions
How does Methotrexate (MTX) work?
MTX is and ANTIMETABOLITE and a folic acid analogue that competitively inhibits the enzyme Dihydrofolate reductase which blocks the conversion of FH2 --> FH4
What specific rxns does MTX inhibit?
In the S phase of the cell cycle:
Pyrimidine biosynthesis converting dUMP-->DTMP is inhibited bc FH4 is the methyl DONOR in the rxn

2 purine biosynthesis rxns are also inhibited bc FH4 is a required COFACTOR
What are the current strategies of chemotherapy?
Based on a combination of empiric and theoretical factors:
1) Combinations of drugs
2)Induction and maintenence protocols
3)attempts at cell recruitment
4) attempts at cell syncronization
Is MTX bound to plasma proteins?
What are the toxicities of MTX?
Yes, MTX is bound to plasma proteins

Myelosuppression, renal-, hepato- & neurotoxicity. Leukencephalopathy after intrathecal administration, esp w cranial readiation.
What is Leucovorin used for?
MTX Rescue
It effectively aborts MTX toxicity by supplying reduced folate to cells, thus bypassing the inhibited reductase.
It can also potentiate the actions of 5-Flourouracil.
What is the principle mechanism for 5-FU?
5-FU is metabolized to 5-FdUMP which is a potent suicide inhibitor of THYMIDYLATE SYNTHETASE.
defective transcripts are synthesized due to incorporation of 5-FUTP into cellular RNA
How can we get additional effectiveness in 5-FU pharmacology?
Use in presence of allopurinol or AFTER MTX tx.
What is another flouropyrimidine?
Capecitabine: this is a 5-FU prodrug whose final step f activation is catalyzed by thymidine phosphorylase, an enzyme which is ELEVATED in metastatic breast and colon cancer.
What pyrimidine analogue has been found to be effective in tx of hematologic malignancies?
Cytosine Arabinoside
What is the mechanism of Cytosine Arabinoside?
CA is a potent inhibitor of DNA polymerase and when incorporated into DNA causes defective ligation and premature chain termination.

CA is S PHASE SPECIFIC and inhibits DNA synthesis.
What is another pyrimidine analogue?
effective in tx of MYELODYSPLASTIC syndrome.
What are the prototypic purine analogues?

What is thier mechanism of action?
6-mercaptopurine & 6-thioguanine

they are converted by hypoxanthine-guanine-phosphoribosyl transferase (HPRT) to nucleoside monophosphates.
Describe the metabolism of the purine analogues.
1)S-methylation by TPMT (6-MP and 6-TG)
(polymorphisms in TPMT may result in variable effectiveness/toxicity)
2) Oxidation by XO to 6-thiouric acid (6-MP only)
(XO metabolism is inhibited in the presence of allopurinol)
What are the toxicities of the 6-MP and 6-TG?
What other purine analogue is used to tx HAIRY CELL Luekemia?
Inhibits adenosine deaminase
Neutropenia is dose-limiting toxicity
Where does HYDROXYUREA block the cell cycle?
G1/S boundary
Inhibits ribonucleotide synthesis and DNA synthesis
Primary adverse effect is leukopenia
What is the prototypic ENZYME for cancer chemotherapy?
catalyzes the conversion of asparagine to aspartate.

In lymphoid cells, levels of asparagine synthetase are very low, deprivation of asparagine in these cells results in prtein synthesis inhibition