Walters just the shit he talked about

Question 1

What is the growth fraction?

Answer 1

% of cells actively proliferating

Question 2

Which types of tumors do not respond well to drug therapy and why?

Answer 2

Large, bulky tumors because:

1. Poor Rx penetration
2. Large # of cells are in non-proliferative state
3. Increased chance it has already metastasized

Question 3

G-1 cell phase

Answer 3

Cell growth

Question 4

S phase

Answer 4

DNA synthesis

Question 5

G-2 cell phase

Answer 5

Pre-mitotic cell growth

Question 6

M phase

Answer 6

Mitosis

Question 7

G-0 phase

Answer 7

Resting

Question 8

Which cell cycle phases are most sensitive to chemotherapy?

Answer 8

S phase and mitosis

Question 9

Vinblastine

Answer 9

• Vinca Alkaloid
• MOA: makes cells accumulate in G-2 and S phase;
• Use w/ARA-C which blocks DNA synthesis in S phase

Question 10

What are the consequences of alkylation?

Answer 10

1. Ring opening
2. Depurinization (guanine recognized as foreign and excised)
3. Miscoding (G-C for A-T)
4. Cross-linking (leads to inter & intra strand cross-linking)

Question 11

Mechlorethamine

Answer 11

• 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

Question 12

Cyclophosphamide

Answer 12

• Nitrogen mustard
• Not a vesicant
• Aldophosphamide metabolized to phosphoramide mustard
• SE:
1. Leukopenia (tx: filgrastim & sargramostim)
2. Hemorrhagic cystitis (tx: hydration & MESNA)
3. SIADH

Question 13

Nitrosoureas

Answer 13

• Preferred site of attack is Oxygen
• Not phase specific but effects seen in S phase
• Not vesicant

Question 14

Pralaxatrate

Answer 14

• Folic acid analog

* IV only

Question 15

Methotrexate

Answer 15

• Folic acid analog
• Polyglutamated thus trapping MTX in cell
• Followed by low Leucovorin rescue dose to selectively rescue healthy cells

Question 16

How do pyrimidine analogs work?

Answer 16

1. Steric hinderance causing improper stacking and fragmentation
2. Inhibition of elongation and DNA polymerase

Question 17

6-Mercaptopurine

Answer 17

• 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

Question 18

Vinca Alkaloids

Answer 18

• From periwinkle plant

* Bind tubuline → metaphase arrest and neurotoxicity

Question 19

Vincristine

Answer 19

• Vinca Alkaloid

* SE: alopecia, SIADH, neurotoxicity & loss of Achilles reflex

Question 20

Procarbazine

Answer 20

• MOA not clear

* Generation of free radicals → strand breakage & translocations

Question 21

What is the MOA of Anthracyclines?

Answer 21

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

Question 22

Doxorubicin

Answer 22

• 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)

Question 23

What do biological response modifiers do?

Answer 23

Enhance the patient’s immune response to a neoplasm or they alter cell differentiation

Question 24

Alemtuzumab

Answer 24

• Monoclonal Ab

* MOA: IgG variant that targets B Cells (CD25 Ag) → lysis through antibody- & complement-dependent cytotoxicity

Question 25

90Y-Ibritumomab Tiuxetan

Answer 25

* Monoclonal Ab | * MOA: Binds selectively to CD20 B cell Ag; emits high energy β particles that destroy the cell from inside → apoptosis

Question 26

Denileukin Diftitox

Answer 26

* 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

Question 27

What do BCR-ABL Protein Tyrosine Kinase Inhibitors target?

Answer 27

* Philadelphia chrom (9:22) | * BCR breaks at 22, ABL breaks at 9, chromosomes fuse and new fusion gene allows cells to proliferate unregulated

Question 28

Thalidomide

Answer 28

* Inhibits angiogenesis * Has immunomodulatory & anti-inflammatory activity * Decreases TNF-α synthesis and inhibits leukocyte migration * Pregnancy category X

Question 29

Lenalidomide

Answer 29

Less teratogenic derivative of thalidomide

Question 30

Pomalidomide

Answer 30

• Used only if lenalidomide and bortezomib fail • Pregnancy category X

Question 31

What does MOPP stand for?

Answer 31

Mechlorethamine Oncovin (aka Vincristine) Procarbazine Prednisone