Heme/onc Drugs

Front 1

Warfarin
- Mechanism?
- Metabolism?
- Clinical Use?
- What is used to monitor it?
- Toxicity?
- Effect on Pregnancy?

Back 1

M: inhibits gamma-carboxylation of Vitamin K dependent Factors II, VII, IX, X, Protein C, Protein S
* Metabolized by p450
C: Chronic anticoagulant
* Monitor with INR/PT
T: bleeding, skin/tissue necrosis
* Causes bleeding, early termination, and bone malformation in fetus

Front 2

Heparin
- Mechanism?
- Clinical Use?
- Is it safe in pregnancy?
- What do you treat overdose with?
- Toxicity?

Back 2

M: potentiates ATIII causes degradation of Clotting Factors (especially Thrombin)
C: Immediate anticoagulation (IV), Can be used during pregnancy (doesn't cross placenta)
* Monitored with PTT
T: bleeding, HIT, osteoporesis
* Treat overdose with Protamine Sulfate (positively charged - binds negatively charged Heparin)

Front 3

- What is HIT?
- What are the advantages of Low Molecular Weight Heparin?

Back 3

HIT - Heparin-Induced Thrombocytopenia - PF4, Heparin, Platelets form complexes that use up platelets inducing thrombocytopenia and bleeding
LMWH: longer half life, doesn't have to be monitored

Front 4

Leupirudin, Bivalirudin
- Mechanism?
- Clinical Use?

Back 4

M: derivatives of Hirudin (leech saliva) - directly inhibit Thrombin
C: used in patients with HIT that can't use Heparin for anticoagulation

Front 5

Streptokinase, Urokinase, tPA, APSAC (Anistreplase)
- Mechanism?
- Effect on PT? PTT? Bleeding Time?
- Clinical Use?
- Toxicity?
- Contraindications?
- Treatment of Overdose?

Back 5

M: converts plasminogen to plasmin, which aids in fibrinolysis
* increases PT, PTT, no effect on bleeding time
C: Early treatment of MI or Ischemic Stroke
T: Bleeding so contraindicated in patients with active bleeding, history of bleeding or clotting factor deficiencies, recent surgery, etc.
* Treat toxicity with Aminocaproic Acid (inhibits fibrinolysis)

Front 6

Aspirin
- Mechanism?
- Clinical Use?
- Toxicity?
- Toxicity in Children?

Back 6

M: irreversibly inhibits COX-1 & COX-2 - inhibits TXA2 inhibiting platelet aggregation
* normal PT, PTT, increased bleeding time
C: Antipyretic, Analgesic, Anti-inflammatory, Anti-platelet
T: Liver & Renal toxicity, Gastric Ulceration, Hyperventilation (Respiratory Alkalosis), Tinnitus (CN VIII toxicity)

Front 7

Clopidogrel, Ticlopidine
- Mechanism?
- Clinical Use?
- Toxicity?

Back 7

M: Irreversibly inhibits ADP receptors (which inhibits the IIaIIIb receptor from surfacing, inhibiting fibrinogen linking)
C: ACS, Coronary Stenting, can help in thrombotic stroke
T: neutropenia (Ticlopidine)

Front 8

Abiciximab
- Mechanism?
- Clinical Use?
- Toxicity?

Back 8

M: Monoclonal Ab against IIbIIIa receptors for fibrinogen (inhibits aggregation of platelets)
C: Acute Coronary Syndrome, Percutaneous Transluminal Coronary Angioplasty
T: Bleeding, Thrombocytopenia

Front 9

- What cancer drugs act in the S phase?
- What cancer drugs act in the G2 phase?
- What cancer drugs act in the M phase?

Back 9

S - Antimetabolites, Etoposides
G2 - Bleomycin
M - Vinca Alkaloids & Taxols

Front 10

Methotrexate
- Mechanism?
- Clinical Use?
- Toxicity? Rescue?
- What effect does it have in pregnancy?

Back 10

M: inhibits dihydrofolate reductase
C: leukemias, lymphomas, choriocarcinoma, sarcomas, miscarriage & ectopic, RA, Psoriasis
T: Myelosuppression (treat with Leucovrin), microsteatotic fatty change, mucositis
* decreased folate causes neural tube defects in fetus

Front 11

5-Florouracil
- Mechanism?
- Clinical Use?
- Toxicity?
- Treatment of Overdose?

Back 11

M: pyrimidine analog which is bioactivated and covalently bonded to Folic Acid - this complex inhibits thymidylate synthetase (decreases pyrmidine synthesis)
C: colon cancer, solid tumors, basal cell carcinoma
* Synergy with MTX
T: Myelosuppression (NOT reversible by Leucovorin), Photosensitivity
* Use thymidine to rescue

Front 12

6-Mercaptopurine
- Mechanism?
- Metabolized by what?
- Clinical Use?
- Toxicity? Increased with what?

Back 12

M: purine analogue - gets incorporated into chain and inhibits purine synthesis
* Activated by HGPRTase
C: leukemias, lymphomas (not Hodgkins or CLL)
T: Myelosuppression, hepatotoxicity, GI upset
* Increased toxicity with Xanthine Oxidase inhibitors (Allopurinol)

Front 13

6-Thioguanine
- Mechanism?
- Clinical Use?
- Toxicity?

Back 13

M: purine analogue, incorporated into DNA inhibiting purine synthesis
C: ALL
T: myelosuppression, hepatotoxicity
* Allopurinol does NOT affect it

Front 14

Cytrabine
- Mechanism?
- Clinical Use?
- Toxicity?

Back 14

M: Pyrimidine antagonist
C: AML, ALL, non-Hodgkin's Lymphoma
T: myelosuppression (leukopenia, neutropenia, megaloblastic anemia)

Front 15

Dactinomycin
- Mechanism?
- Clinical Use?
- Toxicity?

Back 15

M: intercalates into DNA
C: childhood tumors (Wilms, rhabdomyosarcoma, Ewing's)
T: Myelosuppression

* Children dACTinomycin out

Front 16

Doxorubicin (Adriamycin), Daunorubicin
- Mechanism?
- Clinical Use?
- Toxicity?

Back 16

M: noncovalently intercalates DNA through free radical production
C: Hodgkin's (AVBD therapy), myeloma, sarcoma, solid tumors
T: Cardiotoxicity, Myelosuppression, Alopecia

Front 17

Bleomycin
- Mechanism?
- What phase of the Cell Cycle?
- Clinical Use?
- Toxicity?

Back 17

M: G2 specific, noncovalently intercalates DNA through free radical production
C: testicular cancer, Hodgkin's (ABVD therapy)
T: Pulmonary Fibrosis, Skin Changes, Myelosuppression (minimal)

Front 18

Etoposide, Teniposide
- Mechanism?
- What phase of the cell cycle?

Back 18

M: inhibits DNA topoisomerase II in late S to G2 phase
C: small cell carcinoma (lung & prostate), testicular carcinoma
T: Myelosuppression, Alopecia, GI upset

Front 19

Cyclophosphamide, Ifosfamide
- Mechanism?
- Clinical Use?
- Toxicity?

Back 19

M: covalently X-lins DNA at guanine N-7
* Requires bioactivation by liver
C: Non-Hodgkin's lymphoma, Breat & ovarian cancer
T: myelosuppression, hemorrhagic cystitis (prevent with mesna)

Front 20

Carmustine, Lomustine, Semustine, Streptozocin
- Mechanism?
- Clinical Use?
- Toxicity?

Back 20

M: activated be liver and travels across BBB
C: brain tumors
T: CNS toxicity (dizziness, ataxia)

Front 21

Bulsufan
- Mechanism?
- Clinical Use?
- Toxicity?

Back 21

M: alkylates DNA
C: CML, bone marrow ablation in stem cell transplants
T: pulomonary fibrosis, hyperpigmentation

Front 22

Vincristine, Vinblastine
- Mechanism?
- Clinical Use?
- Toxicity?

Back 22

M: M phase specific - binds microtubules and inhibits formation of mitotic spindle by blocking polymerization
C: Hodkgin's (part of MOPP regimen), Wilm's, Choriocarcinoma
T: Vincristine has neurotoxicity, paralytic ileus, Vinblastine has myelosuppresion (BLAST the BONE marrow)

Front 23

Paclitaxel
- Mechanism?
- Clinical Use?
- Toxicity?

Back 23

M: hyperstabilizes tubules in M phase so that microtubules cannot break down
C: Breast & Ovarian Cancer
T: myelosuppression, hypersensitivity

Front 24

Cisplatin, Carboplantin
- Mechanism?
- Clinical Use?
- Toxicity?

Back 24

M: cross-links DNA
C: testicular, bladder, ovarian, lung cancer
T: nephrotoxic, acoustic nerve damage (CN VIII)

Front 25

Hydroxyurea
- Mechanism?
- Clinical Use?
- Toxicity?

Back 25

M: inhibits Ribonucleotide Reductase, S-phase specific
C: melanoma, CML, Sickle Cell (increases HbF)
T: myelosuppression & GI Upset

Front 26

Prednisone
- Mechanism?
- Clinical Use?
- Toxicity?

Back 26

M: glucocorticoid, triggers apoptosis (though can affect non-dividing cells also)
C: CLL, Hodgkin's (MOPP)
T: Iatrogenic Cushings - acne, osteoporesis, hypertension, truncal obesity, hyperglycemia, peptic ulcers, psychosis

Front 27

Tamoxifen, Raloxifene
- Mechanism?
- Clinical Use?
- Toxicity?

Back 27

M: Selective E2 Receptor Modulators - agonist in bone, anatagonist in breat
C: Breast Cancer, Osteoporosis
T: Tamoxifen increases risk of endometrial hyperplasia (agonist in endometrium) while Raloxifene has no such effect (anatogonist in endometrium)

Front 28

Trastuzumab
- Mechanism?
- Clinical Use?
- Toxicity?

Back 28

M: monoclonal Ab against HER-2 (erb-B2)
C: metastatic breast cancer
T: cardiotoxicity

Front 29

Imantinib
- Mechanism?
- Clinical Use?
- Toxicity?

Back 29

M: inhibitor of 9:22 translocated chromosome - tyrosine kinase activity inhibited (Philadelphia Chromosome)
C: CML, GI Stromal tumors
T: fluid retention