Pharm Chemotherapy

Front 1

Cure of cancer requires 10^? to 10^ cells be killed?

Back 1

it requires 10^10 to 10^12 cells be killed

Front 2

In marrow transplantation, is a leukemia patient more likely to relapse if donor is an identical twin or matched sibling?

Back 2

identical twin

Front 3

Which type of tumors are antigenic?

Back 3

chemically and virally induced tumors

Front 4

What two disorders are associated with a high incidence of malignancy?

Back 4

inherited immuno deficiency and immunosuppression

Front 5

What are the 4 reasons that chemo therapy is curative of large tumors when used alone?

Back 5

1) Large tumors have a high proportion of non-proliferating cells. 2) first order kinetics (constant proportion) it would take the same amount of drugs to kill 10^10 to 10^7 cells as it would to kill 10^7 to 10^4 Cells. 3) between doses, while waiting for GI and bone marrow recovery, cells would rise to previous levels/or higher level. 4) resistance

Front 6

what are the 5 principles of chemotherapy?

Back 6

1. Use combination; 2. Use drugs that show effectiveness against the tumor in question; 3. Use drugs that use different mechanism to avoid resistance; 4 use drugs that have different toxicities; hit tumors early and hit them with the highest maximal doses

Front 7

Name 3 mechanisms of resistance

Back 7

1. MDR (pumps drugs out of the plasma); 2. Gene amplification (overprod of an enzyme that confers resistance of cells to drugs); 3. Resistance to alkylating agents

Front 8

Name the 2 types of alkylating related resistance

Back 8

1. Glutathione can combine with alkylating agents and diminish their activity (see the drug as a toxin); 2. Glutathione transferases - enzymes that mediates glutathione conjugation to alkylating agents

Hint 8

None

Front 9

In gene amplification, which is related to unstable resistance, homeneous staining regions or "double minutes"?

Back 9

Double minutes, which code proteins to confer drug resistance to tumor cells

Front 10

What drug combinations are used in Breast cancer?

Back 10

CAF, CMF, AT(cyclophosphamide, doxorubicin[adriamycin] or methotrexate, 5-FU

Front 11

Which drug combinations are used in colon cancer?

Back 11

5-FU with leucovorin

Front 12

Which two drug combinations are used in Hodgkin's disease?

Back 12

MOPP - mustard, oncovin (vincristine), procarbazine, prednisone. ABVD - Adriaycin (Doxorubicin), bleomycin, vinblastine, dacarbazine

Front 13

Which two drug combinations are used to treat testicular cancer?

Back 13

BEP - bleomycin, etoposie, cisplatin. VIC - Vinblastine, ifosfamide, cisplatin

Front 14

What is tumor lysis syndrome?

Back 14

tumor lysis --> b/d of nucleic acid products to cause uric acid production and renal damage

Front 15

What is the potential risk of using antimetabolites?

Back 15

Pregnancy: teratogens, and spontaneous abortions during the first trimester

Front 16

Name three drugs associated with heart toxicity

Back 16

Doxorubicin, cyclophosphamide, and anthracyclines (antibiotics)

Front 17

Which two drugs are associated with lung damage?

Back 17

Bleomycin and BCNU

Front 18

Which drug is associated with kidney damage?

Back 18

Cisplatin

Front 19

Which two drugs are associated with buring or bloody uring?

Back 19

cyclophosphamide and ifosfamide

Front 20

What can be used to avoid the burning or bloody urine seen with cyclophosphamide and ifosfamide

Back 20

Mesna (a sulfhydryl)

Front 21

Name three drugs that can lead to peripheral numbness.

Back 21

cyclophosphamide, cisplatin and vincristine

Hint 21

None

Front 22

What are the toxicities associated with cyclophosphamide.

Back 22

urine (burning & bloody), heart, neuro: numb/tinglining/hearing

Hint 22

None

Front 23

In terms of pharmacokinetics, what is special about cyclophosphamide?

Back 23

It is a prodrug

Front 24

What are the 3 mechanisms of nitrogen mustards?

Back 24

1. Covalent bonding, 2. Crosslinking DNA, and 3. 7-nitrogen guanine rxn (most cytotoxic)

Front 25

What can be used with ifosfamide to avoid bladder toxicity and psychosis?

Back 25

MESNA

Front 26

Name the 5 classes of Alkylating agents.

Back 26

Nitrogen mustards, alkyl sulfonates, nitrosourease, triazenes, platinum based compounds

Front 27

Name the 4 classes of antimetabolites

Back 27

folic acid analogs, pyrimidine analogs, purine analogs, substitute urea

Front 28

Name 5 classes of Natural products. (HINT: VETAC)

Back 28

Vinca alkaloids, taxanes, epipophylotoxins, camptothecins, antibiotics

Hint 28

None

Front 29

Name 3 of biological hormone chemo drugs

Back 29

Tamoxifen, leuprolide, flutamide

Hint 29

None

Front 30

What are the 2 platinum based drugs?

Back 30

Cisplatin and carboplatin

Front 31

Which drug can enter the CSF and cause psychosis?

Back 31

Procarbazine

Hint 31

None

Front 32

What is dacarbazine use in?

Back 32

melanoma, Hodgkin's (AVBD), and sarcomas

Front 33

What is procarbazine used to treat?

Back 33

Hodgkins MOPP

Front 34

What class of drug is used in brain tumors and why?

Back 34

Nitrosoureas, becaues they are lipid soluble

Front 35

What are the mechanisms of action for cisplatin?

Back 35

covalently binds DNA bases, can cross link N-7 or -6 of guanine

Front 36

In terms of toxicity what is the difference and similiarity between cisplatin and carboplatin?

Back 36

Cisplatin: less myelosuppression, but more nephrotoxic, and nausea causing than Carboplatin.

Hint 36

None

Front 37

Cisplatin is highly toxic: name 4 precautions for its use

Back 37

1. Don't use with other nephrotoxic drugs, 2. Monitor Mg, K and Ca (renal toxicity), 3. maintain high urine flow (vigorous hydration), 4. Aggressive use of antimimetics,

Hint 37

None

Front 38

What are the two major concerns with carboplatin use?

Back 38

nephrotoxicity (but less than cisplatin) and myelosuppression (MAJOR) especially WBC suppression

Front 39

What is methotrexate an analog of?

Back 39

folic acid

Front 40

what is 5-FU an analog of

Back 40

dUMP

Front 41

What is methotrexate's mechanism of action?

Back 41

inhibition of DHFR enzyme --> depletion of folates

Front 42

How do methotrexate and aspirin interact?

Back 42

Aspirin displaces methotrexate from plasma proteins

Hint 42

None

Front 43

What can reverse the actions of methotrexate?

Back 43

Leucovorin

Front 44

What are 3 unique toxicities associated with methotrexate?

Back 44

renal tubule obstruction, pneumonitis, neurotox after intrathecal admin... liver?

Hint 44

None

Front 45

What are 4 precautions used with methotrexate?

Back 45

1. Lower dose with reduced GFR, 2. Hyrdrate pt, 3. Continuous plasma concentration monitoring, 4. Can cause ascites, so monitor liver

Hint 45

None

Front 46

give the pharmacokinetics of 5-FU

Back 46

(5-FU is a pyrimidine analog) first it undergoes conversion to F-dUMP --> which then competes for thymidylate synthase with dUMP (to dTMP) and reduce DNA synth

Front 47

What should 5FU be used with to potentiate treatment of colon cancer

Back 47

Leucovorin

Front 48

What is an uncommon toxicity related to 5FU?

Back 48

reversible cerebral toxicity

Front 49

How is 5-FU metabolized?

Back 49

liver

Front 50

What do 5FU, methotrexate, and gemcitibine have in common?

Back 50

they are all antimetabolite cancer drugs

Front 51

What is 2,2-difluorodeoxycytidine?

Back 51

the active metabolite of gemcitibine

Front 52

Which type of cancer is Gemcitibine use to treat?

Back 52

non-small cell lung cancer, bladder cancer, and pancreatic cancer

Front 53

What are the3 mechanisms of gemcitibine (dfdCTP)?

Back 53

(1) competes with dCTP as DNA pol inhibitor... (2) inhibition of ribonucleotide reductase... and (3) it's incorportated into DNA leading to strand termination --> apoptosis

Hint 53

None

Front 54

How would you describe the toxicities of Gemcitibine?

Back 54

mild

Front 55

What mechanism do vincristine and vinblastine share in common?

Back 55

The both bind tubulin of the mitotic spindle and induce metaphase arrest

Front 56

of vincristine and vinblastine, which causes myelosuppression?

Back 56

vinblastine causes myelosuppression

Front 57

of vincristine and vinblastine, which causes peripheral neuropathy?

Back 57

vincristine

Front 58

What are the 2 vinca alkaloids?

Back 58

vincristine and vinblastine

Front 59

What are the 2 taxanes?

Back 59

Taxol and taxotere

Front 60

Between taxol and taxotere, which is retained longer?

Back 60

Taxotere

Hint 60

None

Front 61

What is the mechanism of action of taxanes, and which other cancer drug is similar?

Back 61

Taxanes bind tubulin like the vinca alkaloids, but it's not at the same site… taxanes renders the microtubules less suseptible to depolymerization (increasing microtubule level in cell)... also they may effect p53 dependent and independent apoptosis

Hint 61

None

Front 62

What is the mechanism of resistance for taxanes?

Back 62

related to p-glycoproteins --> and mutations in ∂ and ß subunits of tubulin

Front 63

What are taxanes dissolved in to increase solubility?

Back 63

cremophor E1 + EtOH

Front 64

How is the anaphylactic rxn dealt with when using taxanes?

Back 64

premedicate with antihistamines

Front 65

Which are taxanes use to treat?

Back 65

ovarian (with carboplatin), non-small cell lung cancer, breast cancer, prostate cancer

Front 66

Compare the toxicities of taxol and taxotere.

Back 66

taxol neuro toxicity >> taxotere… Taxotere cap leak syndrome>>> taxol… both can cause sensory neuropathy

Front 67

what type of myelosuppression is seen in taxol and taxotere?

Back 67

neutropenia and thrombocytopenia

Front 68

What type of toxicity is seen in antibiotics (anthracyclines)?

Back 68

cardiotoxicity

Front 69

What is used to treat Wilm's tumor (a kidney tumor in children)

Back 69

Actinomycin D (an antibiotic)

Front 70

What is the mechanism of action for daunomycin and Doxorubican (both antibiotics)?

Back 70

inhibits function of topoisomerase II (which serves to unwind DNA) causing DNA damage… but to a lesser degree it superoxide --> hydrogen peroxide

Front 71

How is Daunomycina dn doxorubican eliminated?

Back 71

liver

Front 72

What type of toxicity is seen in daunomycin and doxorubicin?

Back 72

cardiac toxicity due to a lack of catalase

Front 73

How is at risk for toxicity in theuse of daunomycin and doxorubicin?

Back 73

people w/ 1) HTN, 2) heart disease, 3) people receiving > 2,000 rads, 4) people that receive extravasation across a joint

Front 74

What do actinomycin D, doxorubicin, bleomycin, etopiside (VP-16), and camptothecins, have in common?

Back 74

they're all antibiotics used in treating cancer

Front 75

What diseases are combinations are bleomycin used to treat?

Back 75

AVBD (Hodgkin's) and BEP (testicular cancer)

Front 76

what is the mechanism of action for bleomycin?

Back 76

nicks DNA, inhibits DNA ligase, leading to the progresive DNA fragmentation

Front 77

How can you tell if pulmonary toxicity is being caused by bleomycin?

Back 77

drop in DL-CO2

Front 78

How does Etopiside work?

Back 78

in cancer, it acts by targeting topoisomerase II: relaxes DNA by generating transient single strand nicks

Hint 78

None

Front 79

Which drugs inhibit topoisomerase I and II?

Back 79

I: Camptothecins (irinotecan) … II: Daunomycin & doxorubicin… etopiside

Hint 79

None

Front 80

What do toptecans and irinotecans have in common?

Back 80

they are both camptothecins

Front 81

Which prodrug must be converted to the active metabolite SN38?

Back 81

Irinotecans

Front 82

What is topotecan use to treat?

Back 82

ovarian and lung cancer

Front 83

What is irinotecans use to treat?

Back 83

GI/colon cancer

Front 84

Which patients respond well to tamoxifen?

Back 84

Postmenopausal female responders had progesterone and estrogen receptors

Front 85

What is the indication when a patient has bone pain and hypercalcemia in response to tamoxifen?

Back 85

this indicates metastasis improvement

Front 86

What are the SE of tamoxifen use?

Back 86

hotflashes, increased endometrial cancer, venous thrombosis, anovulation, and problems with EYES!!! CATARACTS

Hint 86

None

Front 87

What is the mechanism of action for tamoxifen?

Back 87

blocks estrogen stimulation, and progesterone receptor synthesis and stimulates TGFß production

Front 88

What is flutamide used to treat?

Back 88

Flutamide is a antiandrogen used to treat prostate cancer

Front 89

How does flutamide work?

Back 89

it blocks cytoplasmic receptors of dihydrotestosterone

Front 90

What is the toxicity associated with flutamide?

Back 90

liver

Front 91

What is leuprolide used to treat?

Back 91

prostate cancer

Front 92

How does leuprolide work?

Back 92

leuprolide is an analog of GnRH, thus prevent its release--> producing surges in LH and FSH --> followed by their reduction --> followed by a fall in testosterone and dihydrotestosterone

Front 93

What is the mechanism behind giving enzymes such as arginase?

Back 93

some tumors cannot produce arginase, thus by reducing circulating levels of arginase the tumor cells are denied a necessary amino acid

Front 94

What do isotretinoin and all trans retinoic acid do?

Back 94

induce differentiation

Front 95

name the Hematopoietic growth factors used in cancer treatment

Back 95

erythropoietin, GM-CSF, and G-CSF

Front 96

what toxicity is associated with the use of GnRH and LHRH analogs, such as leuprolide?

Back 96

hot flashes, loss of libido, impotence