Pharmacology Cancer Drugs

Front 1

What is the MOA for cyclosporine and tacrolimus?

Back 1

They bind to and inhibit calcineurin. Calcineurin normally acts as a message amplifier to stimulate gene transcription of cytokine genes (IL-2,3,4, TNF, IFN, GM-CSF)

Front 2

What is the DLT for cyclosporine and tacrolimus?

Back 2

Renal toxicity (75% of patients). Must watch creatinine clearance.

Front 3

What is the use for cyclosporine and tacrolimus?

Back 3

prevention of transplant rejection

Front 4

What is the inactive prodrug for 6-mercaptopurine?

Back 4

Azathioprine

Front 5

What is the main target of azathioprine?

Back 5

inhibition of purine synthesis in lymphocytes (no HGPRT pathway, must make purines de novo)

Front 6

What is the function of Mycophenolate Mofetil?

Back 6

it is a potent inhibitor of IMP dehydrogenase (de novo synthesis of purines; hurts lymphocytes badly)

Front 7

What are the cell cycle specific agents?

Back 7

Antimetabolites (cytarabine, fluorouracil, azathioprine, mercaptopurine, methotrexate, thioguanine), Bleomycin, Vinca Alkaloids (vincristine and vinblastine), Topoisomerase inhibitors (-tecans and -posides)

Front 8

What are the cell cycle-nonspecific agents?

Back 8

Alkylating agents (busulfan, cyclophosphamide, mechlorethamine, melphalan), Antibiotics (dactinomycin, daunorubicin, doxorubicin, mitomycin), Cisplatin, Nitrosureas (CARLOS)

Front 9

What constitutes primary resistance?

Back 9

When there is little or no log kill on the first response.

Front 10

What constitutes acquired resistance?

Back 10

The occurrence 2-3 years after chemotherapy, where cancer cells are now resistant to the chemotherapeutic agent that you used.

Front 11

What does the ribonucleoside and ribonucleotide look like for thymine?

Back 11

There is no such thing.

Front 12

What are two cancer targets associated with nucleotide metabolism?

Back 12

Ribonucleotide reductase and folate's action in converting dUMP to dTMP

Front 13

How do lymphocytes attain purines?

Back 13

Through de novo synthesis (not able to produce them through HGPRT pathway)

Front 14

True or False: nucleotide bases are naturally in their enol form?

Back 14

FALSE, they are naturally in their keto form

Front 15

What is MOPP therapy, and what is it mainly used for?

Back 15

Mechlorethylamine, Oncovin (Vincristine), Procarbazine, and Prednisone. It is mainly used for Hodgkin's Lymphoma (MOPP up the Hodgkins).

Front 16

Name the three nitrosureas

Back 16

CARmustine, LOmustine, and Semustine (CARLOS); these gain access to the CNS

Front 17

What is the DLT for cisplatin? How about for oxaliplatin? How about for carboplatin?

Back 17

nephrotoxicity, nephrotoxicity, BM suppression

Front 18

What is PVB therapy, and what is it mainly used for?

Back 18

cisPlatin, Vinblastine, and Bleomycin

Front 19

What is the DLT for bleomysin?

Back 19

Pulmonary fibrosis

Front 20

What is the DLT for Vinblastine? How about for Vincristine?

Back 20

BM suppression, peripheral neuropathy

Front 21

What can limit the DLT of Cisplatin?

Back 21

saline infusion to alleviate the nephrotoxicity

Front 22

What is the MOA for Procarbazine, and what therapy is it part of?

Back 22

It is metabolized to a reactive compound that inhibits the synthesis of DNA, RNA, and protein. It is very toxic, and a potent carcinogen

Front 23

What is the MOA for Cisplatin/Oxaliplatin/Carboplatin?

Back 23

Alkylating agent (Cell cycle-Nonspecific)

Front 24

Is cyclophosphamide and ifosfamide active, or must it be activated? What can be taken to decrease the toxicity of the drug?

Back 24

They must be activated by the liver. It forms two cytotoxic compounds (acrolein and phosphoramide mustard) that can be alleviated by Mesna.

Front 25

What is a toxic side effect of cyclophosphamide?

Back 25

Hemorrhagic cystitis (alleviated with mesna, a sulfhydryl compound that inactivates the acrolein)

Front 26

What therapy is Cyclophosphamide part of, and for which type of cancer is it useful?

Back 26

CHOP; Cyclophosphamide, Hydroxy-daunorubicin (doxorubicin), Oncovin (Vincristine), and Prednisone). This is used for Non-Hodgkin's Lymphoma.

Front 27

Name some other uses for Cyclophosphamide, other than for CHOP therapy for Non-Hodgkin's Lymphoma.

Back 27

Solid tumors, breast cancer, immune suppression (transplants, RA, and SLE).

Front 28

What is the MOA for methotrexate?

Back 28

It inhibits dihydrofolate reductase, leading to decreased dTMP synthesis, leading to decreased DNA synthesis.

Front 29

Which antidote is given concurrently with methotrexate?

Back 29

Leucovorin. It acts as a methyl-transfering agent to thymidylate synthetase.

Front 30

What cellular compounds involve folate?

Back 30

DNA synthesis, RNA synthesis, and amino acid synthesis

Front 31

How do cancerous cells resist the function of methotrexate?

Back 31

Resistant cells increase the level of DHFR a thousandfold

Front 32

Name four clinical utilities of methotrexate.

Back 32

ALL, Choriocarcinoma, Osteosarcoma, and Immune suppression (RA, psoriasis)

Front 33

What is common between 5-FU and cytarabine/gemcitabine? Different?

Back 33

They are both pyramidine analogs. 5-FU inhibits Thymidylate Synthetase enzyme, whereas Cytarabine/gemcitabine inhibit DNA polymerase and RR.

Front 34

What three things must be present to irreversibly inhibit Thymidylate synthetase?

Back 34

N5N10 Methylene Tetrahydrofolate, Thymidylate Synthetase, and FdUMP.

Front 35

What makes cytarabine/gemcitabine able to chain-terminate?

Back 35

The 4'-OH is flipped in plane.

Front 36

How do cancer cells get around the action of cytarabine/gemcitabine?

Back 36

The cancer cells will decrease the deoxycytidine enzyme (the first enzyme to add a phosphate group to the cytarabine molecule)

Front 37

How do you increase the effectiveness of cytarabine/gemcitabine?

Back 37

Add vinca alkaloids (vincristine, vinblastine) to the mixture to disrupt the microtubules. This is a synchronization technique that is highly effective.

Front 38

What is the MOA for 6-mercaptopurine and 6-thioguanine?

Back 38

After being acted upon by HGPRT, the now ribose-phosphorylated molecule can inhibit amidophosphoribosyl transferase

Front 39

What must you do if you are taking 6-MP/6-TG concurrently with allopurinol?

Back 39

Decrease 6-MP/6-TG levels, because the xanthine oxidase enzyme being inhibited by the allopurinol is the enzyme that normally breaks down the 6-MP/6-TG

Front 40

What is the alternative to using allopurinol to decrease uric acid levels during tumor lysis? What is the MOA for this new enzyme?

Back 40

Rasburicase; It catalyses the conversion of uric acid to allantoin. Allantoin is an inactive metabolite of purine metabolism, and is five to ten times more soluble than uric acid, so renal excretion is more effective

Front 41

What is the MOA for Fludarabine, and what kind of drug is it?

Back 41

Inhibits DNA polymerase, DNA primase, RR, and is incorporated into DNA and RNA. It is a purine analog.

Front 42

What is the MOA for Cladribine?

Back 42

An ADA-resistant purine analog

Front 43

What is the MOA for Dactinomycin?

Back 43

intercalates with DNA (used with Wilm's tumor)

Front 44

What is the MOA of Doxorubicin (Adriamycin) and Daunorubicin?

Back 44

Intercalates DNA, inhibiting topoisomerase resealing, leading to DNA breaks

Front 45

What is the DLT for Doxorubicin (Adriamycin) and Daunorubicin?

Back 45

Cardiotoxicity (due to free radicals) and BM suppression

Front 46

What is so special about mitomycin?

Back 46

It becomes an alkylating agent AFTER intracellular reduction (from the hypoxic environment). Mitomycin is the best available drug for use against hypoxic tumor cells

Front 47

What is the MOA for Bleomycin?

Back 47

Intercalates DNA and chelates iron (binds oxygen like hemoglobin), leading to free radical formation to break DNA.

Front 48

What is the MOA of Vinca Alkaloids, and give two examples.

Back 48

Binding of the vinca alkaloids (vinblastine and vincristine) to tubulin inhibits the further addition of tubulin units.

Front 49

What distinguishes vinca alkaloids from many other chemotherapeutic drugs?

Back 49

They do not involve an interaction with DNA, therefore they do not lead to an increase chance of carcinogenesis.

Front 50

Name two chemotherapeutic regimes that utilize vinca alkaloids, and what they are used for.

Back 50

MOPP treatment for Hodgkin's Lymphoma (Mechlorethamine, Oncovin (Vincristine), Procarbazine, and Prednisone), and PVB treatment for testicular cancer (Cisplatin, Vinblastine, and Bleomycin)

Front 51

What is the function of Paclitaxel/Cocetaxel, and how does it differ from vinca alkaloids?

Back 51

They prevent breakdown of microtubules, versus prevention of microtubule formation with vinca alkaloids (vinblastine/vincristine).

Front 52

Name two topoisomerase I inhibitors.

Back 52

Irinotecan and topotecan (-tecan; think of a single straw sitting in a te(a) can!).

Front 53

Name two topoisomerase II inhibitors.

Back 53

Etoposide and Teniposide (-poside)

Front 54

Name two synthetic antibodies that bind the EDGF receptor.

Back 54

Cetuximab (anti-ErbB1) and Trastuzumab (anti-ErbB2)

Front 55

Name a synthetic antibody that binds the BCR-ABL tyrosine kinase.

Back 55

Imatinib (Gleevac)

Front 56

Name a synthetic antibody that binds the RAF molecule (within RAS signaling pathway)

Back 56

SoRAFenib

Front 57

Name a synthetic antibody that binds the ATP-binding spot of the tyrosine kinase of the EGFR receptor.

Back 57

Erlotinib

Front 58

Name a synthetic antibody that inhibits the proteosome, resulting in an accumulation of ubiquitinated proteins, and eventually cell death by apoptosis.

Back 58

Bortezomib (almost like zombie)

Front 59

What percentage of breast cancers are associated with amplification and overexpression of Her2/Neu?

Back 59

25%

Front 60

How is L-asparaginase selective to cancer cells?

Back 60

Since this enzyme depletes blood asparagine, the tumor cells are starved of asparagine (they cannot synthesis it intracellularly because they lack aspargine synthetase), whereas normal cells can synthesize their own asparagine.

Front 61

Name an alternative to SERMs (Selective Estrogen Receptor Modulators) like tamoxifen and raloxifene in treating breast cancer.

Back 61

The aromatase inhibitor letrozole (prevents the conversion of androgens to estradiol in women within the adrenal glands). Used mainly for post menopausal women.

Front 62

What is the function of Bevacizumab?

Back 62

It is a synthetic antibody that binds to, and inhibits VEGF, leading to decreased cancer angiogenesis.

Front 63

What is the function of the chemotherapeutic agent Rituximab?

Back 63

Monoclonal antibody that binds antigen CD-20 on B-lymphocytes, leading to maturation of those B-lymphocytes.

Front 64

Name two chemotherapeutic regimes used for Hodgkin's Lymphoma.

Back 64

MOPP (Mechlorethylamine, Oncovin (Vincristine), Procarbazine, and Prednisone), and ABVD (Adriamycin (Doxorubicin), Bleomycin (also in PVB), Vinblastine, and Dacarbazine).

Front 65

Name two chemotherapeutic regimes used for testicular cancer.

Back 65

PVB (Cisplatin, Vinblastine, Bleomycin) and BEP (Bleomycin, Etoposide, and Cisplastin)

Front 66

Cisplatin, notably a bad drug for causing nausea and vomiting, is often times treated with which two antiemetic drugs?

Back 66

Ondansetron and dexamethasone (maybe metoclopramide too).

Front 67

What is the recombinant DNA molecule used to stimulate the production of RBCs?

Back 67

Erythropoeitin

Front 68

What is the recombinant DNA molecule used to stimulate the production of G-CSF?

Back 68

FlIgrastim (GRA - STIM)

Front 69

What is the recombinant DNA molecule used to stimulate the production of GM-CSF?

Back 69

Sargramostim (Granulocyte-monocyte stimulator)

Front 70

How long after administration of chemotherapy should you give erythropoeitin/filgrastim/sargramostim?

Back 70

No sooner than 24 hours