Hematology / Oncology Pharm

Front 1

Decreases thrombin and Xa, short half-life -- used for immediate anticoagulation for pulmonary embolism, stokre, acute coronary syndrome, MI, DVT.
1. major mechanism
2. follow what lab?

Back 1

Heparin
1. catalyzes the activation of antithrombin III
2. PTT

Front 2

Protamine sulfate is used for the rapid reversal of the effects of what drug?
1. mechanism

Back 2

Heparin
1. positively charged molecule that acts by binding negatively charged heparin

Front 3

act more on Xa, and can be administered without lab monitoring of PTT
1. problem

Back 3

low-molecular weight heparins (i.e. ENOXAPARIN)
1. not easily reversible

Front 4

binds platelets causing autoantibody production that destroys platelets and overactivates the remaining ones, resulting in a thrombocytopenic, hypercoagulable state

Back 4

Heparin causing Heparin-induced thrombocytopenia (HIT)

Front 5

Pathogenesis of HIT

Back 5

1. Heparin binds PLT factor 4 to form heparin:PF4 complex
2. Igs form against that complex -- autoantibody production leads to destruction of PLTs and activation of platelets --> thrombocytopenia AND hypercoagulable state

Front 6

Hirudin derivatives; directly inhibit thrombin
1. used for

Back 6

Lepirudin, bivalirudin
1. alternative to heparin for anticoagulating patients with HIT

Front 7

Alternative to anticoagulating patients with HIT
1. mechanism

Back 7

Lepirudin, bivalrudin
1. directly inhibits thrombin

Front 8

Has a long half-life. Requires monitoring of PT.
1. mechanism
2. how metabolized?

Back 8

Warfarin
1. interferes with normal synthesis of gamma-carboxylation of vitamin K-dependent clotting factors II, VII, IX, X, PC, and PS.
2. cytochrome P450

Front 9

Affects the extrinsic pathway
1. clinical use
2. huge contraindication

Back 9

Warfarin
1. Chronic anticoagulation
2. pregnancy -- because it crosses the placenta

Front 10

Toxicities include bleeding, teratogenesis, skin/tissue necrosis, and drug-drug interactions.

Back 10

Warfarin

Front 11

Acetylates and irreversibly inhibits COX 1 and 2 preventing what process which promotes platelet aggregation:
1. has what effect on PT, PTT, bleeding time?

Back 11

Aspirin (ASA)
inhibition of COX prevents conversion of arachidonic acid to TXA2 which promotes PLT aggregation
1. No effect on PT, PTT, but increases bleeding time

Front 12

Toxicities include gastric ulceration, bleeding, hyperventilation, Reye's syndrome, and tinnitus (CN VIII)
1. clinical use

Back 12

Aspirin (ASA)
1. antipyretic, analgesic, anti-inflammatory, antiplatelet

Front 13

Inhibit PLT aggregation by irreversibly blocking ADP receptors.
1. inhibit PLT binding to fibrinogen how?

Back 13

Clopidogrel, ticlopidine
1. prevent glycoprotein G2b/3a from being expressed

Front 14

Monoclonal antibody that binds to glycoprotein receptor 2b/3a on activated platelets, preventing aggregation
1. toxicities

Back 14

Abciximab
1. bleeding, thrombocytopenia

Front 15

Used for acute coronary syndrome; coronary stenting. decreases the incidenece or recurrence of thrombotic stroke
1. toxicity

Back 15

Clopidogrel, ticlopidine
1. Neutropenia (tocloopidine)

Front 16

used for acute coronary syndromes, percutaneous transluminal coronary angioplasty, monoclonal antibody
1.mechanism

Back 16

Abciximab
1. antibody to Gp2b/3a mimicking Glanzmann's disease

Front 17

Pyrimidine analog bioactivated to a form that covalently complexes folic acid. This complex inhibits thymidylate synthease resulting in a decrease in dTMP
1. Toxicity

Back 17

5-fluorouracil bioactivated to 5F-dUMP
1. myelosuppresion which is not reversible with leucovorin, photosensitivity

Front 18

Thymidine is administered to "rescue" the patient from this treatment
1. mechanism

Back 18

5-fluorouracil
1. bioactivated to 5F-dUMP which complexes with folic acid, this complex inhibits thymidylate synthase

Front 19

Blocks de novo purine synthesis. activated by HGPRTase.
1. toxicity
2. metabolized by:

Back 19

6-MP (mercaptopurine)
1. bone marrow, GI, liver.
2. xanthine oxidase

Front 20

Toxicity increased with allopurinol, why?

Back 20

6-MP
b/c allopurinol inhibits xanthine oxidase which metabolizes 6-MP

Front 21

what is histiocytosis X?

Back 21

proliferative disorder of dendritic langerhan cells from the monocyte lineage

Front 22

What is the site of action for Warfarin & Heparin?

Back 22

Warfarin acts in the liver

Heparin acts in the blood

Front 23

Describe the onset of action of Heparin vs. Warfarin

Back 23

heparin is raid in seconds

Warfarin is slow, limiedt by half lives of normal clotting factors

Front 24

what is the limit of Warfarin's onset of effectiveness?

Back 24

the half lives of normal clotting factors

Front 25

What is the duration of action for Heparin & warfarin?

Back 25

Hep has acute hours
Warfar has chronic (days)

Front 26

Which inhibits coagulation in vitro Heparin or warfarin?

Back 26

Heparin

Front 27

What is the treatment of acute overdose of warfarin?

Back 27

IV vitamin K & Fresh frozen plasma
Remember that Vit K will give you protein C & S faster so dont give Vit K first if their INR is real high

Front 28

Which crosses the palcenta Warfarin or heparain?

Back 28

Warfarin is teratogenic

Front 29

how do thrombolytics affect PT & PTT?

Back 29

they increase both because they are acting on the process which converts plasminogen to plasmin which breaks down the clot formed by either the intrinsic or extrinsic pathway

Front 30

What is the clinical use for thrombolytics?

when are the contraindicated?

Back 30

1. Early Mi
2. ischemic stroke

they are contraindicated in people with bleeding issues or sever HTN

Front 31

What is urokinase and what endogenous compound is it similar to in its action?

Back 31

urokinase is a thrombolytic and does the same thing as tPA

Front 32

What is aminocaproic acid?

Back 32

This is an antithrombolytic that inhibits the conversion of plasminogen to plasmin

Front 33

How does streptokinase affect clotting?

Back 33

Streptokinase combines with a proactivator and converts plasminogen to plasmin which breaks down the clot

Front 34

How does anistreplase (APSAC) affect clotting?

Back 34

Anestreplase converts plasminogen to plasmin

Front 35

Synergy with MTX, why?

Back 35

5-FU -- b/c it inhibits thymidylate synthase, which also prevents the synthesis of dTMP

MTX works by inhibiting dihydrofolate reductase so that it can't regenerate the THF that is needed to make dTMP from dUMP

Front 36

converted to a nucleotide analog that inhibits DNA polymerase
1. toxicities

Back 36

Cytarabine (ara-C)
converted to cytosine arabimoside triphosphate
1. megaloblastic anemia, luekopenia, thrombocytopenia

Front 37

toxicities include leukopenia, thrombocytopenia, megaloblastic anemia

Back 37

Cytarabine (C-ara)
1. inhibits DNA polymerase -- converted to cytosine arabinoside triphosphate

Front 38

Alkylating agents that covalently cross-link DNA at guanine N-7
1. require bioactivation by:

Back 38

Cyclophosphamide, ifosfamide
1. liver

Front 39

Methotrexate is an antimetabolite and inhibits what phase of the cell cycle?

Back 39

s phase

Front 40

What drug inhibits dyhydrofolate reductase?

Back 40

Methotrexate (it's a folate analog)

Front 41

what drug is a folic acid analogue?

Back 41

methotrexate

Front 42

What is leucovorin (folinic acid)?

Back 42

this is used with methotrexate to reverse its myelosuppressive effects.

It works by replacing folic acid. It is a metabolite that does not need to be acted on by dihydrofolate reductase so it can still be used and some DNA synth can occur?

Front 43

What thrombolytic comes from beta-hemolytic strep?

Back 43

streptokinase

Front 44

What is the toxicity of methotrexate?

Back 44

myelosuppression

Front 45

What is the mechanism of action of Busulfan?
1. toxicity

Back 45

it alkylates DNA
1. pulmonary fibrosis and hyperpigmentation

Front 46

What 2 drugs can cause pulmonary fibrosis?

Back 46

1. Busulfan
2. Bleomycin

Front 47

What drug causes Hyper pigmentation?

Back 47

Busulfan

Front 48

what drugs have a red color?

Back 48

Doxorubicin (adriamycin, daunorubicin

think RUBY red

Front 49

Mechanism of Doxorubicin (adriamycin)?

Back 49

generates free radicals & noncovalently intercalates in to DNA (this creates breaks in DNA strand to decrease replication)

Front 50

What drug non-covalently intercalates into DNA?

Back 50

Doxyrubicin/adriamycin
(also generates free radicals)

Front 51

What drug is cardiotoxic and causes toxic extravasation?

what other toxicities?

Back 51

Doxorubicin/adriamycin

alopeicia + myelosupression

Front 52

What is the mechanism for Dactinomycin (actinomycin)D?

toxicitiy? (its pretty standard)

Back 52

intercaltes into DNA

myelosuppression

Front 53

What is the mechanism for bleomycin?

Back 53

induces formation of free radicals, which cause breaks in DNA strands

Front 54

What is the mechanism for hydroxyurea? & what phase of cell cylce is affected?

Back 54

inhibts ribonucleotide reductase t/f DNA synthesis decreases

affects S phase

Front 55

What is the mechanism for Etoposide (VP-16)? what phase of cell cylce?

Back 55

G2 phase and S phase specific agent that inhibits topoisomerase 2 & increases DNA degredatoin

Front 56

What is the mechanism for Prednisone?

Back 56

may trigger apoptosis (but may work on undividing cells)

Front 57

What is the mechanism for Tamoxifen / raloxifene? how does it help women (2 different ways)?

Back 57

this is a SERM which is an estrogen receptor modulator

It acts as an estrogen antagonist in breast & agonist in the bone

Front 58

what drug inhibits topoisomerase 2?

Back 58

Etoposide (VP-16)

Front 59

What is the toxicity of tamoxifen? how is it different from raloxifene?

Back 59

increase risk of endometrial carcinoma due to its agonist effects

also causes hot flashes

Raloxifene does not increase risk for endometrial carcinoma because its an endometrial agonist

Front 60

What drug can cause Cushing's like symptoms, acen, immunosuppression, cataracts, acne?

Back 60

prednisone

Front 61

what drug can cause hyperglycemia?

Back 61

prednisone

Front 62

what drug can cause GI ulcers & psychosis?

Back 62

prednisone

Front 63

Hydroxyurea is used in CML and what other non-cancer disease?

Back 63

sickle cell b/c it increases fetal Hb

Front 64

Does bleomycin cause myelosuppresion?

Back 64

No daddy, it doesnt

Front 65

Bleomycin inhibits what phase of the cell cycle?

Back 65

G2 phase

Front 66

cause hemorrhagic cystitis
1. which can partially be prevented with:

Back 66

Cyclophosphamide, ifosfamide
1. mesna (sulfhydryl groups of mesna bind the intermediate metabolite acrolein which is toxic to the bladder)

Front 67

Cause myelosuppresion, which is why they are sometimes used as immunosuppressants

Back 67

Cyclophophamide, ifosfamide

Front 68

Alkylate DNA, but require bioactivation. cross the blood-brain barrier which is why they are used for brain tumors (including glioblastoma multiforme)

Back 68

Nitrosoureas
Carmustine, lomustine, semustine, streptozocin

Front 69

cause CNS toxicity (dizziness, ataxia) used for brain tumors
1. mechanism

Back 69

Nitrosoureas -- Carmustine, lomustine, semustine, streptozocin
1. alkylating agents that require bioactivation, cross blood-brain barrier

Front 70

Carmustine, lomusstine, semustine, streptozocin
1. mechanism

Back 70

Nitrosoureas
1. alkylate DNA, cross blood-brain barrier

Front 71

Cross-link DNA -- cause nephrotoxicity and acoustic nerve damage

Back 71

Cisplatin, carboplatin

Front 72

used for testicular, bladder, ovary, and lung carcinomas
1. cross-link DNA

Back 72

Cisplatin, carboplatin
1. mechanism

Front 73

Monoclonal antibody against HER-2 (erb-B2)
1. helps kill breast cancer cells that:

Back 73

Trastuzumab
1. overexpress HER-2, possibly through antibody-dependent cytotoxicity

Front 74

causes cardiotoxicity, used for metastatic breast cancer
1. mechanism

Back 74

Trastuzumab (Herceptin)
1. monoclonal antibody against HER-2 (erb-B2) which is expressed on breast cancer cells

Front 75

Philadelphia chromosome bcr-abl tyrosine kinase inhibitor
1. toxicity

Back 75

Imatinib (Gleevec)
1. fluid retention

Front 76

used for CML, GI stromal tumors
1. mechanism

Back 76

Imatinib (Gleevec)
1. Philadelphia chrosome bcr-abl tyrosine kinase inhibitor

Front 77

M-phase specific alkaloids that bind tubulin and block polymerization of microtubules so that mitotic spindle cannot form
1. toxicities

Back 77

Vincristine, vinblastine
1. vincristine --> neurotoxicity (areflexia, peripheral neuritis, paralytic ileus
2. vinblastine --> bone marrow suppression (Blast = Bone marrow

Front 78

causes neurotoxicity (areflexia, peripheral neuritis), paralytic ileus
1. mechanism

Back 78

Vincristine
1. M-phase specific alkaloid that binds tubulin and blocks polymerization of microtubules so that mitotic spindle cannot form

Front 79

bone marrow suppression, M-phase-specific alkaloid

Back 79

vinBLASTine BLASTS the bone marrow

Front 80

M-phase-specific agents that bind to tubulin and hyperstabilize polymerized microtubules so that mitotic spindle cannot break down (anaphase cannot occur)
1. toxicities

Back 80

Paclitaxel, other taxols
1. myelosuppresion and hypersensitivity

Front 81

causes myelosuppression and hypersensitivity

Back 81

Paclitaxel, other taxols

Front 82

prevents anaphase from occuring

Back 82

Paclitaxel, other taxols

Front 83

Cladribine is used for:
1. Mechanism

Back 83

Hairy cell leukemia
1. cytotoxic purine resistant to degradation by Adenosine deaminase

Front 84

What drug limits the nephrotoxicity caused by Cisplatin?
What is the mechanism?

Back 84

Amifostine
Scavenges free radicals

Front 85

What limits the cardiotoxicity of Doxo/Daunorubicin?
What is the mechanism?

Back 85

Dexrazoxane
Iron-chelating agent

Front 86

Leucovorin can be used to potentiate the toxicity of which drug?

Back 86

Leucovorin strengthens the association of 5-FU with thymidylate synthase