Pharmacology- Heme/onc (Neoplastic)

Front 1

Methotrexate
-Mechanism of action

Back 1

S-phase-specific antimetabolite. Folic acid analog that inhibits dihydrofolate reductase, resulting in decrease dTMP and therefore decrease DNA and protein synthesis

Front 2

Methotrexate
-Clinical use (NI)

Back 2

Leukemias, Lymphoma, Choriocarcinoma, Sarcoma, Abortion, Ectopic Pregnancy, Rheumatoid Arthrithis, Psoriasis

Front 3

Methotrexate
-Toxicity

Back 3

Myelosuppresion, which is reversible with leucovorin (folinic acid) "rescue"
Macrovesicular fatty chage in liver
Mucositis

Front 4

What reverses side effect of Methotrexate?

Back 4

Leucovorin (folinic acid)

Front 5

Carmasutine
-Mechanism

Back 5

Alkylating agent causes prolonged myelosuppresion

Front 6

5- fluorouracil
-Mechanism

Back 6

S-phase-specific antimetabolite. Pyrimidine analog bioactivated to 5F-dUMP which covalently complexes folic acid. The complex inhibits Thymidylate synthase resulting in decrease dTMP and same effects as MTX

Front 7

5-Fluorouracil
-Clinical use (NI)

Back 7

Colon cancer and other solid tumors, basal cell carcinoma (topical). Synergy with MTX

Front 8

5-Flurorouracil
-Toxicity

Back 8

Myelosuppression, which is not reversible with leucovorin; photosensitivty. Can "rescue" with Thymidine

Front 9

What is used to rescue 5-Fluroruracil?

Back 9

Thymidine

Front 10

6-Mercaptopurine (6-MP)
-Mechanism

Back 10

Blocks de novo purine synthesis. *Activated by HGPRTase
S-phase specific

Front 11

6- Mercaptopurine
-Clinical use

Back 11

Leukemias, Lymphomas (not CLL or Hodgkins)

Front 12

6-Mercaptopurine
-Toxicity

Back 12

Bone Marrow, GI, Liver
Metabolized by xanthine oxidase thus increase toxicity with allopurinol

Front 13

Cytarabine
-Mechanism

Back 13

*Inhibits DNA polymerase

Front 14

Cytarabine
-Clinical use

Back 14

AML, ALL, High-grade Non-hodgkin's lymphoma

Front 15

Cytarabine
-Toxicity

Back 15

Leukopenia, thrombocytopenia, Megaloblastic anemia

Front 16

Cyclophosphamide, ifosfamide
-Mechanism

Back 16

*Alkylating agents, covalently x-link (inter strand) DNA at Guanine N-7. Require bioactivation by liver

Front 17

Cyclophosphamide
-Clinical use

Back 17

Non-hodkin's lymphoma, Breast cancer and ovarian carcinomas

Front 18

Cyclophosphamide
-Toxicity

Back 18

Myelosuppresion
*Hemorrhagic cystitis, which can be partially prevented with Mesna

Front 19

What is used to treat side effect of Cyclophosphamide

Back 19

Mesna (Hemorrhagic cystitis)

Front 20

Nitrosoureas
-Mechanism

Back 20

Alkylate DNA. require Bioactivation. Cross Blood- Brain barrier--> CNS

Front 21

Nitrosoureas
-Clinical use

Back 21

Brain tumors (including glioblastoma multiforme)

Front 22

Nitrosureas
-Toxicity

Back 22

CNS toxicity (dizziness, ataxia)

Front 23

Carnustine
-type of drug

Back 23

Nitrosoureas

Front 24

Cisplantin, carboplatin
-Mechanism

Back 24

Cross-link DNA

Front 25

Cisplantin
-Clinical use (NI)

Back 25

testicular, bladder, ovary, and lung carcinoma

Front 26

Cisplantin
-Toxicity

Back 26

Nephrotoxicity and acoustic nerve damage

Front 27

Busulfan
-Mechanism

Back 27

Alkylates DNA

Front 28

Busulfan
-Clinical use

Back 28

CML. also used for ablating bone marrow in hematopoetic stem cell transplant

Front 29

Busulfan
-Toxicity

Back 29

Pulmonary fibrosis, hyperpigmentation

Front 30

Doxorubicin
-Mechanism

Back 30

Generate free radicals and noncovalently intercalate in DNA (creating breaks in DNA strand to decrease replication)

Front 31

Doxorubicin
Clinical use

Back 31

Part of the ABVD combination regimen for Hodgkin's Lymphomas; also for Myelomas, sarcomas, and solid tumors (Breast,ovary, lungs)

Front 32

Doxorubicin
-Toxicity

Back 32

**Cardiotoxicity (dilated cardiomyopathy); also myelosuppresion and marked alopecia. Toxic extravasation

Front 33

Dactinomycin
-Mechanism

Back 33

Intercalates in DNA

Front 34

Dactinomycin
-Clinical use

Back 34

Childhood tumors (children act out)
Wilm's tumor, Ewing's sarcoma, Rhabdomyosarcoma

Front 35

Dactinomycin
-Toxicity

Back 35

Myelosuppression

Front 36

Bleomycin
-Mechanism

Back 36

Induces formation of free radicals, which can cause breaks in DNA strands

Front 37

Bleomycin
-Clinical use

Back 37

Testicular cancer, Hodgkin's lymphoma (part of ABVD regiment for Hodgkin's)

Front 38

Bleomycin
-Toxicity

Back 38

*Pulmonary fibrosis, skin changes, but minimal myelosuppression

Front 39

Hydroxyurea
-Mechanism

Back 39

Inhibits Ribonucleotide Reductase--> Decrease DNA synthesis (S-phase specific)

Front 40

Hydroxyurea
-Clinical use

Back 40

Melanoma, CML, sickle-cell disease (Increase HbF)

Front 41

Hydroxyurea
-Toxicity

Back 41

Bone marrow suppression, GI upset

Front 42

Etoposide
-Mechanism

Back 42

G2-phase-specific agent that inhibits topoisomerase II and increase DNA degradation

Front 43

Etoposide
-Clinical use

Back 43

Small cell carcinoma of the lung and prostate, testicular cancer, leukotriene

Front 44

Etoposide
-Toxicity

Back 44

Myelosuppression, GI irritation, Alopecia

Front 45

Prednisone
-Mechanism

Back 45

May trigger apoptosis. May even work on nondividing cells

Front 46

Prednisone
-Clinical use

Back 46

Most commonly used glucocorticioid in cancer chemotherapy. Used in CLL, Hodgkins' lymphomas (part of the MOPP regimen). Also an immunosuppresant used in autoimmune diseases

Front 47

Prednisone
-Toxicity

Back 47

Cushing-like symptoms, immunosuppresion, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis

Front 48

Tamoxifen, raloxifene
-Mechanism

Back 48

SERMs- receptor antagonists in breast, agonists in bone (prevents osteoporosis) blocks the binding of estrogen to estrogen receptor-positive cells

Front 49

Tamoxifen
-Clinical use

Back 49

Breast cancer. also useful to prevent osteoporosis

Front 50

Tamoxifen
-Toxicity

Back 50

Increase risk of endometrial carcinoma via partial agonists effects "hot flashes"
Raloxifene does not cause endometrial carcinoma because its an endometrial antagonist

Front 51

Trastuzumab
-Mechanism

Back 51

Herceptin
Monoclonal antibody against HER-2 (erb-B2) Helps kils breast cancer cells that overexpress HER-2 possibly through antibody-dependent cytotoxicity

Front 52

Trastuzumab
-Clinical use

Back 52

Metastatic breast cancer

Front 53

Trastuzmab
-Toxicity

Back 53

Cardiotoxicity

Front 54

Imatinib
-Mechanism

Back 54

Gleevec; Philadelphia chromosome bcr-abl tyrosine kinase inhibitor

Front 55

Imatinib
-clinical use

Back 55

CML, GI stromal tumors

Front 56

Imatinib
-Toxicity

Back 56

Fluid retention

Front 57

Vincristine, vinbastine
-Mechanism

Back 57

M-phase-specific alkaloids that bind to tubulin and *block polymerization of microtubules so that mitotic spindle cannot form. Microtubules are the vines of your cells

Front 58

Vincristine
-Clinical use

Back 58

part of the MOPP regiment for Hodgkina's lymphoma. Wilm's tumor, choriocarcinoam

Front 59

Vincristine
-Toxicity

Back 59

Neurotoxicity (areflexia, peripheral neuritis), paralytic ileus (vincristine)
Vinblastine- blasts bone marrow (suppression)

Front 60

Paclitaxel
-Mechanism

Back 60

M-phase specific agents that bind to tubilin and hyperstabilize polymerized microtubules so that mitotic spindles can't break down (anaphase cannot occur)

Front 61

Paclitaxel
-Clinical use

Back 61

Ovarian and breast carcinomas

Front 62

Paclitaxel
-Toxicity

Back 62

Myelosuppresion and hypersensitivity

Front 63

Chlorambucil
-Mechanism

Back 63

Alkylating agent substitutes Alkyl group for H+ ion in a # of organic compounds DNA-DNA interstrand and DNA-protein cross-linking occurs leading to interference in DNA rep , transcription of RNA and nucleic acid function

Front 64

Aprepitant
-Mechanism

Back 64

High affinity antagonist of Neurokinin-1 (NK-1) receptor which has control over emetic reflex. Approved for chemotherapy induced vomiting

Front 65

Megestrol acetate
-Clinical use

Back 65

used to stimulate appetite

Front 66

Sorafenib
-Mechanism of action

Back 66

Multikinase inhibitor targeting serine/threonine and tyrosine kinase in tumor cells and vasculature. Used for renal cell carcinoma