Cancer Pharmacology

Question 1

Methotrexate is a ___ analog

Answer 1

Folic Acid

Question 2

MOA of Methotrexate

Answer 2

Inhibits dihydrofolate reductase

Blocks conversion of folic acid to tetrahydrofolic acid

Question 3

When treating with methotrexate, there with be decreased synthesis of ____ (4x)

Answer 3

1) Denovo synthesis of Thymidylate
2) Purine nucleotides
3) Serine
4) Methotrexate

Question 4

What is the rescue drug that is used with methotrexate

Answer 4

Leucovorin (Folinic Acid)

Question 5

Leucovorin bypasses the ___ and is converted to ___

Answer 5

1) Dihydrofolate reductase

2) N5N10 Methylene FH4

Question 6

With Leucovorin administration with Methotrexate, there will be less severe ____ and ____ toxicity

Answer 6

1) Gastrointestinal

2) Bone Marrow

Question 7

Adverse Effects of Leucovorin

Answer 7

Mucositis: Mucosal Ulceration and Myelosuppression

Question 8

Pt comes in with a glioblastoma. What is the MOA of the agent that you would use to treat this CNS tumor?
What is the name of the agent?

Answer 8

1) Forms covalent linkages with DNA via intra- and inter strand crosslinking
2) Carmustine

Question 9

How does DNA crosslinking prevent replication in cancer?

Answer 9

1) Prevents unwinding DNA for mRNA production or DNA replication

Question 10

List the microtubule drugs

Answer 10

1) Vinca Alkaloids

2) Taxanes

Question 11

Examples of Vinca Alkaloids - microtubule drug

Answer 11

1) Vinblastine

2) Vincristine

Question 12

Examples of Taxanes - Microtubule drugs

Answer 12

Paclitaxel

Docetaxel

Question 13

MOA of Vinca Alkaloids

Answer 13

Microtubule Destabilization: Binds B-tubulin and inhibits microtubule assembly

Question 14

MOA of Taxanes

Answer 14

B-tubulin and promote microtubule formation and stabilization

Question 15

Adverse Effects of Vinca Alkaloids

Answer 15

1) Hair loss and local Cellulitis

2) Numbness and Tingling of extremities and loss of deep tendon reflexes –> Motor weakness

Question 16

Adverse Effects of Taxanes

Answer 16

1) Peripheral Sensory Neuropathy (Paclitaxel)
2) Fluid retention
3) Neutropenia (Docetaxel)

Question 17

Vinca Alkaloids and Taxanes both halt cell in ___

Answer 17

M phase

Question 18

Use ___ for treatment of non-small cell lung cancer with high levels of cell surface P-glycoprotein

Answer 18

Cabazitaxol

Question 19

___ expression often confers resistance to natural product chemotherapies

Answer 19

P-glycoprotein

Question 20

Treat CLL with ___

Answer 20

Antracyclins (Doxorubicin)

Question 21

MOA of Doxorubicin (4x)

Answer 21

1) Topoisomerase II Inhibitor *******
2) Intercalates DNA and Blocks synthesis of DNA and RNA and blocks DNA strand scission
3) Generates semiquiones and Oxygen free radicals
4) Binds to cellular membrane to alter fluidity and ion transport

Question 22

Acute effects of Doxorubicin (5x)

Answer 22

1) Nausea
2) Red Urine
3) Alopecia
4) Myelosuppression
5) Stomatitis

Question 23

Bleomycin v. Doxorubicin Toxicity

Answer 23

1) Doxorubicin - Cardiac Toxicity

2) Bleomycin - Pulmonary Toxicity: Pneumonitis w/ cough, SOB, dry crackles, infiltrates on CXR

Question 24

A pt with constipation due to colon cancer can be treated with Ziv-aflibercept and Bevacizumab. What are the MOAs of both?

Answer 24

1) Growth Factor Inhibitor - prevents the ligand from interacting with the target
- Ziv-Aflibercepet binds VEGFA1, VEGFB1, and PIGF (Placental Growth factor)
- Bevacizumab binds ALL forms of VEGFA

Question 25

Imatinab treats ___

Answer 25

CML

Question 26

MOA of Imatinab (2x)

Answer 26

* ***1) Prevents phosphorylation of kinase substrate by ATP | 2) Inhibits PDGFR, Stem cell factor, and cKit (GI stromal Tumors)

Question 27

Adverse side effects of Imatinab

Answer 27

1) Fluid Retention of Ankle 2) Periorbital Edema 3) Diarrhea 4) Myalgias

Question 28

6-mercaptopurine is a ___ analog

Answer 28

purine

Question 29

6-MP is metabolized via ___ via the 1st pass metabolism

Answer 29

Xanthine Oxidase

Question 30

Allopurinol is often given with 6-MP in order to reduce the effects of hyperuricemia due to tumor lysis. If this occurs what must you do?

Answer 30

Reduce the dosage of Allopurinol (by 50-75%)

Question 31

List the drugs that are sus. to P-glycoprotein Resistance (5x)

Answer 31

1) Anthracyclines: Doxorubicin and Daunorubicin 2) Vinca Alkaloids: Vinblastine and Vincristine 3) Epipodophyllotoxins (Etoposide) 4) Taxanes: (Paclitaxel) 5) Dactinomycin - Antitumor Antibiotic

Question 32

MOA of Anthracyclines

Answer 32

Inhibits Topoisomerase II

Question 33

MOA of Vinca Alkaloids

Answer 33

antimitotic

Question 34

MOA of Epipodophyllotoxins

Answer 34

Inhibits Topoisomerase II via DNA strand breakage

Question 35

What is the DNA strand breakage induced by in Epipodophyllotoxins

Answer 35

Ternary Complex of Drug , DNa, and Enzyme

Question 36

List the Epipodophyllotoxins

Answer 36

1) Etoposide | 2) Teniposide

Question 37

Dactinomycin MOA

Answer 37

1) binds dsDNA and intercalates between adj. guanine -cytosine base pairs

Question 38

Dactinomycin will prevent ___ polymerase from transcribing RNA

Answer 38

DNA-dependent RNA polymerase