Walters just the shit he talked about Flashcards
What is the growth fraction?
% of cells actively proliferating
Which types of tumors do not respond well to drug therapy and why?
Large, bulky tumors because:
- Poor Rx penetration
- Large # of cells are in non-proliferative state
- Increased chance it has already metastasized
G-1 cell phase
Cell growth
S phase
DNA synthesis
G-2 cell phase
Pre-mitotic cell growth
M phase
Mitosis
G-0 phase
Resting
Which cell cycle phases are most sensitive to chemotherapy?
S phase and mitosis
Vinblastine
- Vinca Alkaloid
- MOA: makes cells accumulate in G-2 and S phase;
- Use w/ARA-C which blocks DNA synthesis in S phase
What are the consequences of alkylation?
- Ring opening
- Depurinization (guanine recognized as foreign and excised)
- Miscoding (G-C for A-T)
- Cross-linking (leads to inter & intra strand cross-linking)
Mechlorethamine
- Nitrogen mustard
- Powerful vesicant → severe tissue necrosis
- Tx for extravasation: Na Thiosulfate (donates e- and protects DNA)
- Used to treat Hodgkin’s as part of MOPP
Cyclophosphamide
• Nitrogen mustard
• Not a vesicant
• Aldophosphamide metabolized to phosphoramide mustard
• SE:
1. Leukopenia (tx: filgrastim & sargramostim)
2. Hemorrhagic cystitis (tx: hydration & MESNA)
3. SIADH
Nitrosoureas
- Preferred site of attack is Oxygen
- Not phase specific but effects seen in S phase
- Not vesicant
Pralaxatrate
- Folic acid analog
* IV only
Methotrexate
- Folic acid analog
- Polyglutamated thus trapping MTX in cell
- Followed by low Leucovorin rescue dose to selectively rescue healthy cells
How do pyrimidine analogs work?
- Steric hinderance causing improper stacking and fragmentation
- Inhibition of elongation and DNA polymerase
6-Mercaptopurine
- Purine analog (hypoxanthine analog to be exact)
- Incorporates into DNA & RNA
- Inhibits conversion of IMP → AMP
- Forms 6-THIO-GMP
- Used w/allopurinol (SE: hyperuricemia & hyperuricosuria) to lower dose needed
Vinca Alkaloids
- From periwinkle plant
* Bind tubuline → metaphase arrest and neurotoxicity
Vincristine
- Vinca Alkaloid
* SE: alopecia, SIADH, neurotoxicity & loss of Achilles reflex
Procarbazine
- MOA not clear
* Generation of free radicals → strand breakage & translocations
What is the MOA of Anthracyclines?
Intercalates between any 2 base pairs in opposite strands of DNA causing local uncoiling of the double helix which interferes with the ability of topoisomerase II to re-anneal the strands
Doxorubicin
- Anthracycline
- Severe local vesicant → adriamycin flare
- SE: turns urine red & cardiotoxicity (MOA: Quinones attached to the anthracycline ring form semiquinones that chelate iron forming an Rx-Fe-DNA complex)
- Tx cardiotoxicity w/Dexrazoxane (iron chelator)
What do biological response modifiers do?
Enhance the patient’s immune response to a neoplasm or they alter cell differentiation
Alemtuzumab
- Monoclonal Ab
* MOA: IgG variant that targets B Cells (CD25 Ag) → lysis through antibody- & complement-dependent cytotoxicity
90Y-Ibritumomab Tiuxetan
- Monoclonal Ab
* MOA: Binds selectively to CD20 B cell Ag; emits high energy β particles that destroy the cell from inside → apoptosis
Denileukin Diftitox
- Biological response modifier
- MOA: recomb of IL-2 and diphtheria toxin that binds to IL-2 receptors
- Cells w/low affinity receptors are less sensitive to this drug
What do BCR-ABL Protein Tyrosine Kinase Inhibitors target?
- Philadelphia chrom (9:22)
* BCR breaks at 22, ABL breaks at 9, chromosomes fuse and new fusion gene allows cells to proliferate unregulated
Thalidomide
- Inhibits angiogenesis
- Has immunomodulatory & anti-inflammatory activity
- Decreases TNF-α synthesis and inhibits leukocyte migration
- Pregnancy category X
Lenalidomide
Less teratogenic derivative of thalidomide
Pomalidomide
• Used only if lenalidomide and bortezomib
fail
• Pregnancy category X
What does MOPP stand for?
Mechlorethamine
Oncovin (aka Vincristine)
Procarbazine
Prednisone
