Hematology and Oncology Flashcards Preview

USMLE Step 1 > Hematology and Oncology > Flashcards

Flashcards in Hematology and Oncology Deck (34):


MoA: cofactor for activation of antithrombin, decreases thrombin, and decreases factor Xa. Short half-life

Use: immediate anticoagulation for PE, acute coronary syndrome, MI, DVT. Used during pregnancy (does NOT cross placenta). Track pt's PTTs.

Toxicity: bleeding, thrombocytopenia (HIT), osteoporosis, drug-drug interactions. For rapid reversal (antidote), use protamine sulfate (positively charged molecule that binds negatively charged heparin).

Notes: Low- molec-weight heparin (e.g.,, enoxaparin, dalteparin) act more on factor Xa, have better bioavailability and 2-4 times longer half-life. Can be administered subcutaneously and without laboratory monitoring. NOT easily reversible

Heparin-induced thrombocytopenia (HIT)- development of IgGs against heparin bound to platelet factor 4 (PF4). Antibody- heparin-PF4 complex activates plts-> thrombosis and thrombocytopenia.


Lepirudin, bivalirudin

Derivatives of hirudin (anticoagulant used by leeches); inhibit thrombin: Used as an alternative to heparin for anti coagulating pts w/ HIT


Warfarin (Coumadin)

MoA: interferes w/ normal synthesis & gamma-carboxylation of vit K- dependent clotting factors II, VII, IX, and X and proteins C & S. Metabolized by the cytochrome P-450 pathway. In lab assay, has effect on extrinsic pathway and increases PT. Long half-life.

Use: chronic anticoagulation (after STEMI, venous thromboembolism prophylaxis, and prevention of stroke in A fib). Not used in pregnant women (b/c warfarin, unlike heparin, CAN CROSS PLACENTA). Track pt's PT/ INR values.

Toxicity: bleeding, teratogenic, skin/ tissue necrosis, drug-drug interaxns. For reversal of warfarin overdose, give vit K. For rapid reversal of severe warfarin overdose, give fresh frozen plasma.



Drugs: alteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA)

MoA: directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots. Increased PT, increased PTT, no change in plt count.

Use: early MI, early ischemic stroke, direct thrombolysis of severe PE

Toxicity: bleeding. Contraindicated in pts w/ active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe HTN. Tx toxicity w/ aminocaproic acid (an inhibitor of fibrinolysis).


Aspirin (ASA)

MoA: irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) enzyme by covalent acetylation. Plts cannot synthesize new enzyme, so effect lasts until new plts are produced: increases bleeding time, decreases TXA2 and PGEs. No effect on PT or PTT.

Use: antipyretic, analgesic, anti-inflammatory, antiplatelet (decreases aggregation).

Toxicity: gastric ulceration, tinnitus (CN VIII). Chronic use can lead to acute renal failure, interstitial nephritis, and upper GI bleeding. Reye's syndrome in children w/ viral infection. Overdose causes respiratory alkalosis and metabolic acidosis.


ADP receptor inhibitors

Drugs: clopidogrel, ticlopidine, prasugrel, ticagrelor

MoA: inhibit plt aggregation by irreversibly blocking ADP receptors. Inhibit fibrinogen binding by preventing glycoprotein IIb/ IIIa from binding to fibrinogen

Use: acute coronary syndrome; coronary stenting. Decreases incidence or recurrence of thrombotic stroke.

Toxicity: neutropenia (ticlopidine)


Heparin vs. Warfarin

Structure: large anionic, acidic polymer (H). small lipid-soluble (W)

RoA: Parenteral IV or SubQ (H). Oral (W)

Site of axn: blood (H). Liver (W)

Onset of axn: rapid in sec (H). Slow, limited by half-lives of normal clotting factors.

MoA: activates antithrombin, which decreases the action of IIa (thrombin) and factor Xa (H). Impairs the synthesis of vit-K dependent clotting factors II, VII, IX, and X (vit-K antagonist) (W).

Duration of axn: acute-hours (H). chronic- days (W)

Inhbitis coagulation in vitro? yes (H) No (W)

Treatment of acute overdose: protamine sulfate (H). IV vit K & fresh-frozen plasma

Monitoring: PTT/ intrinsic pathway (H). PT/ INR/ extrinsic pathway (W)

Crosses placenta? yes (H). No- teratogenic (W)


Cilostazol, dipyridamole

MoA: phosphodiesterase III inhibitor; increases cAMP in plots, thus inhibiting pot aggregation; vasodilators.

Use: intermittent claudication, coronary vasodiln, prevention of stroke or TIAs (combined w/ aspirin), angina prophylaxis

Toxicity: nausea, headache, facial flushing, hypotension, abdominal pain


GP IIb/ IIIa inhibitors

Drugs: abciximab, eptifibatide, tirofiban

MoA: bind to glycoprotein receptor IIb/ IIIa on actiated plts, preventing aggregation. Abciximab is made from monoclonal antibody Fab fragments.

Use: acute coronary syndromes, percutaneous transluminal coronary angioplasty

Toxicity: bleeding, thrombocytopenia


Cancer drugs- cell cycle
(good diagram pg 369FA)

M phase: vinca alkaloids and taxols

G1 (synth of components needed for DNA synth): none

S (DNA synth): antimetabolites, etoposide

G2 (synth of components needed for mitosis): bleomycin, etoposide


(good diagram pg 370 FA)

Nucleotide synth:
- methotrexate, 5FU->decreases thymidine synth
- 6-MP: decreases purine synth

- Alkylating agents & cisplatin: cross-link DNA
- Dactinomycin & doxorubicin= DNA intercalators
- Etoposide: inhbitis topoisomerase II

Cellular division:
- Vinca alkaloids: inhibit microtubule formn
- Paclitaxel: inhibits microtubule disasembly


Methotrexate (MTX)
(antimetabolite, so S phase specific)
diagram pg 371 FA

MoA: folic acid analog that inhibits dihydrofolate reductase-> decreased dTMP-> decreased DNA synth & protein synth

- Cancers: leukemias, lymphomas, choriocarcinoma, sarcomas
- Non-neoplastic: abortion, ectopic pregnancy, RA, psoriasis

- myelosupression (reversible w leucovorin (folic acid) "rescue")
- macrovesicular fatty change in liver
- Mucositis
- Teratogenic


5- fluorouracil (5-FU)
(antimetabolite, so S phase specific)
diagram pg 371 FA

MoA: pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid. This complex inhibits thymidylate synthase-> decreased dTMP-> decreased DNA & protein synth

Use: colon cancer, basal cell carcinoma (topical)

- myelosuppression (which is NOT reversible w/ leucovorin)
- Overdose: "rescue" w/ thymidine
- Photosensitivity


Cytarabine (arabinofuranosyl cytidine)
(antimetabolite, so S phase specific)

MoA: pyrimidine analog-> inhibition of DNA polym

Use: leukemias, lymphomas

Toxicity: leukopenia, thrombocytopenia, megaloblastic anemia


Azathiprine 6- mercaptopurine (6-MP)
6-thioguanine (6-TG)

(antimetabolite, so S phase specific)

MoA: Purine (thiol) analogs -> decreased de novo purine synth. Activated by HGPRT

Use: leukemia

Toxicity: bone marrow, GI, liver. Metabolized by xanthine oxidase; thus increased toxicity w/ allopurinol


Dactinomycin (actinomycin D)

(antitumor antibiotic)

MoA: intercalates in DNA

Use: Wilms' tumor, Ewing's sarcoma, rhabdomyocarcoma. Used for childhood tumors. Mnemonic: used for children who ACT out

Toxicity: myelosuppression


Doxorubicin (Adriamycin), daunorubicin

(antitumor antibiotic)

MoA: generates free radicals. Noncovalently intercalate in DNA-> breaks in DNA-> decreased DNA replication

Use: solid tumors, leukemias, lymphomas

Toxicity: cardiotoxicity (dilated cardiomyopathy). myelosuppression, alopecia. Toxic to tissues following extravasation. Dexrazoxane (iron chelating agent), used to prevent cardiotoxicity.



(antitumor antibiotic)

MoA: induces free radical formn->causes breaks in DNA strands

Use: testicular cancer, Hodgkin's lymphoma

Toxicity: pulmonary fibrosis, skin changes. Minimal myelosuppression


Cyclophosphamide, ifosfamide

(alkylating agent)

MoA: covalently X-link (inter strand) DNA at guanine N-7. Require bioactivation by liver.

Use: solid tumors, lekemia, lymphomas, and some brain cancers.

Toxicity: myelosuppression; hemorrhagic cystitis, partially prevented w/ mesna (thiol group of mesna binds toxic metabolite


Nitrosoureas (carmustine, lomustine, semustine, streptozocin)

(alkylating agent)

MoA: require bioactivation. Cross BBB-> CNS

Use: brain tumors (including glioblastoma multiforme).

Toxicity: CNS toxicity (dizziness, ataxia).



(alkylating agent)

MoA: alkylates DNA

Use: CML. Also used to ablate pt's bone marrow before bone marrow transplantation.

Toxicity: pulmonary fibrosis, hyperpigmentation


Vincristine, vinblastine

(microtubule inhibitors)

MoA: alkaloids that bind to tubulin in M phase & block polymerization of microtubules so that mitotic spindle cannot form. Mnemonic: "microtubules are the vines of your cells"

Use: solid tumors, leukemias, and lymphomas

- vincristine: neurotoxicity (areflexia, peripheral neuritis), paralytic ileus
Mnemonic: vinBLASTine blasts bone marrow (suppression)


Paclitaxel, other taxols

(microtubule inhibitors)

MoA: hyperstabilize polymerized microtubules in M phase so mitotic spindle cannot break down (anaphase cannot occur).
Mnemonic: "it is TAXing to stay polymerized"

Use: ovarian and breast carcinomas

Toxicity: myelosuppression and hypersensitivity


Cisplatin, carboplatin

MoA: cross-link DNA

Use: testicular, bladder, ovary, and lung carcinomas

Toxicity: nephrotoxicity and acoustic nerve damage. Prevent nephrotoxicity w/ amifostine (free radical scavenger) and chloride diuresis


Etoposide, teniposide

MoA: inhibit topoisomerase II-> increased DNA degradation

Use: solid tumors, leukemias, lymphomas

Toxicity: myelosuppression, GI irritation, alopecia



MoA: inhibits ribonucleotide reductase-> decreased DNA synth (S- phase specific)

Use: melanoma, CML, SCD (increases HbF).

Toxicity: bone marrow suppression, GI upset


Prednisone, prednisolone

MoA: may trigger apoptosis. May even work on non dividing cells

Use: most commonly used glucocorticoid in chemo. Used in CLL, non-Hodgkin's lymphomas (part of combo chemo regimen). Also used as an immunosuppressant (e.g., autoimmune diseases).

Toxicity: Cushing-like Sx; immunosuppression, cataracts, acne, osteoporosis, HTN, peptic ulcers, hyperglycemia, psychosis


Tamoxifen, raloxifene

MoA: SERMs-receptor antagonists in breast and agonist in bone. Block the binding of estrogen to estrogen receptor- positive cells.

Use: breast cancer Tx and prevention. Also useful to prevent osteoporosis.

-tamoxifen: partial agonist endometrium, which increases the risk of endometrial cancer; "hot flashes"

- Raloxifene: no increase in endometrial carcinoma b/c it's an endometrial antagonist


Trastuzumab (Herceptin)

MoA: MAB against HER-2 (c-erbB2), a tyrosine kinase. Helps kill breast cancer cellist that over express HER-2, possibly thru antibody- dependent cytotoxicity.

Use: HER-2 positive breast cancer

Toxicity: cardiotoxicity


Imatinib (Gleevec)

MoA: Philadelphia chromosome bcr-abl tyrosine kinase inhibitor

Use: CML. GI stromal tumors

Toxicity: fluid retention



MoA: MAB against CD20, which is found on most B-cell neoplasms

Use: Non-Hodgkin's lymphoma, RA (w/ methotrexate)



MoA: small molecule inhibitor of forms of B-Raf kinase w/ the V600E mutation

Use: metastatic melanoma



MoA: MAB against VEGF. Inhibits angiogenesis.

Clinical Use: solid tumors.


Common chemotoxicities
good diagram (head to toes) pg 375

- Cisplatin/ Carboplatin-> acoustic nerve damage (and nephrotoxicity)
- Vincristine-> peripheral neuropathy
- Bleomycin, Busulfan-> pulmonary fibrosis
- Doxorubicin-> cardiotoxicity
- Trastuzumab-> cardiotoxicity
- Cisplatin/ Carboplatin-> nephrotoxicity (and acoustin nerve damage)
- Cyclophosphamide-> hemorrhagic cystitis
- 5-FU-> myelosuppression
- 6-MP-> myelosuppression
- Methotrexate -> myelosuppression