Drugs Of Cancer

Front 1

What is cancer

Back 1

Disease characterized by a shift in control mechanisms that control proliferation and differentiation

Front 2

What are factors influencing cancer

Back 2

1. Gender

2. Age

3. Race

4. Genetic environmental carcinogens

Front 3

What are some chemical toxins that are mutagenic

Back 3

1. Azo dyes

2. Asbestos

3. Benzene

Front 4

What are some infection agents that cause cancer

Back 4

1. HHV-8

2. Human papilloma virus

Front 5

What is a sarcoma and give examples

Back 5

Cancer in connective tissue

Fat, bone, muscle

Front 6

What is a carcinoma and give examples

Back 6

Cancer in epithelial cell

Lung, breast, colon, prostate

Front 7

What are the stages of Tumor Progression

Back 7

1. Hyperplasia

2. Dysplasia

3. Carcinoma in situ (not cross basal lamina)

4. Cancer (Malignant tumors) - metastasis

Front 8

When treating the tumor what do you look at

Back 8

1. Type of tumor

2. Location and amount of disease

3. Health of patient

Front 9

What are the objectives of cancer treatment

Back 9

1. Kill cancer cell

2. Lead them to apoptosis

3. Contain/limit cell growth

Front 10

What are some types of cancer treatments

Back 10

1. Surgery

2. Radiation

3. Chemotherapy

Front 11

Is mono therapy or combination therapy better for chemotherapy treatment

Back 11

Combination therapy

Front 12

What is the timing of chemotherapy

Back 12

Cycles = intense tx periods followed by days of no tx

Front 13

What is the MOA of Genotoxic Agents

Back 13

Alkylate DNA (non cell cycle dependent)

Front 14

What are some cell cycle dependent agents

Back 14

1. Anti-metabolites

2. Cytoskeletal inhibitors

3. Topoisomerase inhibitors

Front 15

When did the first drugs come out that cured cancer (which cancers)

Back 15

1960's and 1970's

Leukemias and lymphomas

Front 16

What are the genotoxic agents

Back 16

1. Cisplatin

2. Doxorubicin

3. Cyclophosphamide

Front 17

What happens when you alklyate DNA

Back 17

1. Fragments DNA

2. Create inter/intra strand DNA cross link (affects DNA separation)

3. Induces mispairing of nucleotides (leads to mutation)

4. Forms DNA adducts (DNA polymerase can't work)

Front 18

Which genotoxic agents need to be given by IV

Back 18

1. Platinum based chemotherpeutics agents (i.e. Cisplatin)

2. Doxorubicin

Front 19

Which genotoxic agent can be given orally every day

Back 19

Cyclophosphamide

Front 20

What are the general adverse effects of genotoxic agents

Back 20

These agents affect cells that are rapidly dividing:

1. Hematopoietic effects

2. GI effects

3. Hair loss

4. Increase risk of developing cancer

Front 21

What are the specific adverse effects of Cisplatin, Doxorubicin, and Cyclophosphamide

Back 21

Cisplastin = renal and ototoxicity

Doxorubicin = Heart effects (Heart failure)

Cyclophosphamide = Bladder irration (hemorrhagic cystitis)

Front 22

Which of the genotoxic agents has the least adverse effects

Back 22

Cyclophosphamide

Front 23

Draw out the Cell Cycle

Back 23

Draw Out the Cell Cycle

Front 24

Where on the cell cycle do the drug work

Back 24

G1, S, G2, Mitosis (Prophase, Metaphase, Anaphase, Telophase)

Front 25

Which drug class works on the S phase

Back 25

Antimetabolites

Front 26

How do Antimetabolites work

Back 26

Similar to natural metabolites

Prevent cells from carrying out vital function and unable to grow and survive

Interfere with production of Nucleic acids, RNA, DNA

Front 27

What are the 3 types of Antimetabolites

Back 27

1. Folate Antagonist

2. Purine Antagonist

3. Pyrimidine Antagonist

Front 28

What is the Folate Antagonist

Back 28

Methotextrate

Front 29

What is the MOA of Methotextrate

Back 29

Inhibit dihyrdrofolate reductase (enzyme involved in forming purine and pyrimidines by allowing Carbon donation; thus no DNA replication and growth blocked)

Front 30

Which cancers are methotexrate used

Back 30

1. Acute lymphocytic leukemia (most common)

2. Large cell lymphoma

3. High grade lymphoma

4. Head and neck cancers

5. Breast and Bladder cancer

6. Rheumatoid arthritis

Front 31

What are the next generation of Antifolate

Back 31

Pemetrexed

Front 32

What is the MOA of Pemetrexed

Back 32

Inhibits Dihyrdofolate

Inhibits thymidylate synthase

Inhibits glycinamide ribonucelotide formyl transferase

Front 33

Where is Premetrexed used

Back 33

Second line therapy for non small cell lung cancer

Front 34

What is a problem with Antifolates

Back 34

Problems with Hematopoeitic effects

Front 35

What is Folinic Acid Rescue Therapy

Back 35

Give Folinic Acid with methotrexate and antifolates to decrease myelosuppression

Front 36

What is the MOA of Folinic Acid

Back 36

THF analog can be used as methyl donor

DHFR insensitive

Therefore some DNA/RNA base synthesis can be carried out in normal blood and GI cells

Front 37

What is the function of Purine Antagonists

Back 37

Prevent continued replication of DNA and cell division

Front 38

What are 2 examples of Purine Antagonists

Back 38

6-Mercaptopurine

6- Thioguanine

Front 39

When do you used Purine Antagonists

Back 39

1. Acute lymphocytic or myelocytic leukemia

2. Lymphoblastic leukemia (kids)

3. Acute myelogenous and myelomonocytic leukemias

4. Inflammatory bowel disease

5. Organ transplant

Front 40

What are some ways cells can metabolize MP and TG and inactivate them

Back 40

Xanthine oxidase

TPMT (Thiopurine S-Methyltransferase)

Front 41

What is the TPMTP Polymorphisms of Extensive, intermediate, and poor metabolizers

Back 41

wt/wt (90%) = extensive metabolizer

wt/mut (10%) = intermediate metabolizer

mut/mut (1/300) = poor metabolizer

Front 42

How do you determine TPMT Phenotype

Back 42

Metabolism of MP in blood samples then look at the metabolism/drug ratio

Front 43

Do poor metabolizers need more or less drugs

Back 43

Less drugs

Front 44

What is the MOA of Pyrimidine Antagonists

Back 44

Block synthesis of pyrimidine containing nucleotide

Front 45

What are the 2 Pyrimidine Antagonists

Back 45

5-Fluorouracil (5-FU)

Cytarabine

Front 46

What is the MOA of 5-Fluorouracil

Back 46

Inhibits Thymidylate Synthase

Front 47

When would you use 5-FU

Back 47

Colorectal Cancer

Front 48

What is the drug class used in Mitosis

Back 48

Cytoskeletal inhibitors (inhibit microtubule function)

Front 49

What are the 2 groups of cytoskeleton and the drugs in each class

Back 49

Taxanes:

1. Paclitaxel

2. Docetaxel (anaphase)

Vinca Alkaloids

1. Vincristine

2. Vimblastin

3. Vindesine (metaphase)

Front 50

When do you use Cytoskeletal Chemotherapies

Back 50

1. Breast

2. Testicular

3. Hodgkin

4. Kid leukemia

5. Rhabdomyosarcoma

6. Lung cancer

7. Neuroblastoma

Front 51

Which phase of the cycle do Topoisomerase I inhibitors work

Back 51

G2 Phase

Front 52

What is the function of Topoisomerase

Back 52

nicks DNA strands and allows the tension to relax and also reseals the DNA so replication can occur

Front 53

What are the 2 Topoisomerase I inhibitors

Back 53

1. Topotecan

2. Irinotecan

Front 54

What are the Topoisomerase II inhibitors

Back 54

1. Etoposide

2. Teniposide

Front 55

Which phase does Hormonal therapy work

Back 55

G1

Front 56

What is the MOA of Hormonal therapy

Back 56

Starve cancer cells from hormonal signals needed for growth

Block hormones on target cell and prevent hormone production

Front 57

Where would you use hormonal therapy

Back 57

1. Breast

2. Ovarian

3. Prostate

4. Endometrial

Front 58

What are the 3 types of hormonal antagonists

Back 58

1. Selective estrogen receptor modulator (SERM)

2. Selective androgen receptor modulator (SARM)

3. Aramatase inhbitor

Front 59

What are the 2 types of Estrogen Receptors

Back 59

ER alpha

ER beta

Front 60

Compare and Contrast ER alpha to ER beta

Back 60

Look at chart

Front 61

Which cancer does SERM target

Back 61

Breast cancer cells

Front 62

What is the MOA of SERM

Back 62

Changes gene expression preventing cell division

Front 63

What are the 3 SERM drugs

Back 63

1. Tamoxifen

2. Raloxifene

3. Toremifene

Front 64

How do SERMs work

Back 64

Drug goes in blocks estrogen receptor and inhibits estrogens growth stimulation effect

Front 65

What are the issues with Tomaxifen and its Drug Interactions

Back 65

1. Tamoxifen is a pro drug and it needs CYP2D6 to turn it into the active metabolite Endoxifen

2. CYP2D6 has variable metabolism activity (i.e. poor, moderate, extensive metabolizers)

3. Problems with Serotonin Uptake Inhibitors (Paroxetine, Fluxoetine, Bupropion)

Front 66

What type of metabolizer works best with Tamoxifen

Back 66

Extensive metabolizer

Front 67

What do Aromatase inhibitors do

Back 67

Inhibit the production of estrogen and estrodiol

Front 68

What are the 3 Aromatase Inhibitors

Back 68

1. Exemestane

2. Anastrozole

3. Letozole

Front 69

What are the SERM an Aromatase Inhibitors indications

Back 69

1. Advanced or Metastatic breast cancer

2. High risk population for invasive breast cancer

Front 70

What do Specific Androgen Receptor Modulators (SARM) work

Back 70

Block androgen receptors

Front 71

What are the 2 SARMs

Back 71

1. Flutamide

2. Bicalutamide

Front 72

Why does Chemotherapy Fail

Back 72

A lot of side effects

Front 73

Which drug causes bone marrow depression

Back 73

Procarbazine

Front 74

Which drugs cause nephrotoxicity

Back 74

Platinum analog (Cisplatin, Carboplatin)

Purine Antagonists (6-Mercaptopurine)

Front 75

Which drugs cause hepatotoxicity

Back 75

Vinca Alkaloids (Vincristine, Vinlastine)

Etoposide

Front 76

Which drugs cause Nausea and vomiting

Back 76

Topotecan cpds

Front 77

Which drugs cause Alopecia

Back 77

Etoposide

Vinca Alkaloids

Front 78

Which drugs cause Cardiotoxicity

Back 78

Anthracyclines (Doxorubicin, Daunorubicin)

Herceptin

Front 79

Which drugs cause Hemorrhagic cystitis

Back 79

Cyclophosphamide

Front 80

Which Drugs cause Neuropathy

Back 80

Platinum Analogs (Cisplastin, Carboplatin)

Vinca Alkaloids (Vincristine, Vinblastine)

Taxol Based Chemotherapeutics

Front 81

What are 4 mechanisms related with Resistance and Chemotherapy

Back 81

1. Increased expression of target proteins therefore need higher amount of cancer drug, but that amount will kill all cells

2. Failure of drugs to enter cancer cell or increased rate of removal of drug from cancer

cell

3. Drugs fail to reach target cell/target molecule no longer present

4. Target Molecule is Altered

Front 82

What causes a failure of drugs to enter cancer cells (increases efflux)

Back 82

P-Glycoprotein

Front 83

1. What are the Biological Response Modifiers (2)

2. What are its MOA

3. Where are they primarily used for

4. What is the route of administration

5. What are the side effects

Back 83

1.a. Interferons

b. Interleukin 2

2. Modify immune system response

3. Hematopoietic neoplasias (blood cancer)

4. Parenteral routes

5. Flu-like symptoms (mild) to fever and capillary leak syndrome (Sever)

Front 84

What is the Monoclonal Antibody Therapy Drugs

Back 84

Rituximab

Trastuzumab (herceptin)

Front 85

1. What is the MOA of Rituximab

2. Function

3. Side effects

Back 85

1. Binds to CD20 antigen (receptor) on the surface of B lymphocytes which activates phagocytosis and antibody dependent apoptosis

2. Inhibits proliferation of lymphocytes and lymphoma cells

3. Hypersensitivity reaction and anaphylactic shock

Front 86

1. What is the MOA of Trastuzumab

2. What are the side effects

3. Which patients does it work really well for

Back 86

1. Binds to epidermal growth factor receptor protein (HER2) (over expressed in some cancers like breast)

2. Allergic rxn, heart muscle damage, pulmonary toxicity

3. HER2+ metastatic breast cancer and early stage HER2+ breast cancer

Front 87

1. What is the Angiogenesis inhibitor

2. Which cancers is it used for

3. What is its MOA

4. What are its advantages

5. What are its disadvantages

Back 87

1. Bevacizumab (Avastin)

2. Metastatic colorectal and NSCL

3. Endothelial cell growth into the tumor

4. Fewer side effect, less chance of resistance

5. Angiogenesis is important in wound healing and normal development, long term effect no yet known

Front 88

1. What are the 3 Protein Kinase Inhibitors

Back 88

1. Imatinib

2. Erlotinib

3. Ruxolitinib

Front 89

1.What is the function of Imatinib

2. Which cancer is it used for

Back 89

1. Prevents phosphorylation of specific proteins involved in cell growth and differentiation

2. Chronic Myelogenous Leukemia

Front 90

1. What is the function of Erlotinib

2. Which cancer is it used for

Back 90

1. EGFR tyrosine kinase inhibitor

2. Lung and pancreatic cancer

Front 91

1. What is the function of Ruxolitinib

2. What cancer is it used for

Back 91

1. JAK-1 and JAK-2 inhibitor

2. Myelofibrosis

Front 92

What are the benefits of the New Generation of Chemotherapeutics

Back 92

less side effects

oral medication