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Pharmacology > Hem-Onc > Flashcards

Hem-Onc Flashcards

1
Q

Heparin

A

Large anionic acidic polymer that activates antithrombin (decreases action of thrombin and factor Xa)

Parenteral administration, rapid onset of action, acute duration of action, does NOT cross the placenta

Monitor with PTT

Antidote: protamine sulfate

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2
Q

Enoxparin, dalteparin

A

Low molecular weight heparins.

Act more on factor Xa, have better bioavailability, and longter half-life than regular heparin.

Monitoring not required. Not easily reversible

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3
Q

Heparin-induced thrombocytopenia (HIT)

A

Development of IgG antibodies against heparin bound to platelet factor 4 (PF4). Antibody-heparin-PF4 complex activates platelets, leading to thrombosis and thrombocytopenia.

Argatroban, Bivalirudin - derived from anticoagulant used by leeches, inhibit thrombin directly, used to anticoagulate patients with HIT

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4
Q

Warfarin

A

Small lipid-soluble molecule that impairs synthesis of Vit K-dependent clotting factors (II, VII, IX, and X; as well as proteins C and S)

Oral administration, slow onset, chronic duration of action, crosses the placenta (teratogen)

Monitor with PT/INR

Antidote: IV Vit K and FFP

Decreased efficacy with concurrent use of P-450 enhancers (rifampicin, phenobarbital, phenytoin)

Increased efficacy with cimetidine, amiodarone, and TMP-SMX, which inhibit warfarin metabolism.

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5
Q

Apixaban, rivaroxaban

A

Direct factor Xa inhibitors

Used for Tx and PPx of DVT and PE (rivaroxaban), and stroke PPx in patients with A-fib

Oral agents do not require coag monitoring

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6
Q

Alteplase (tPA), retplase (rPA), tenecteplase (TNK-tPA)

A

Thrombolytics that convert plasminogen to plasmin, which cleaves thrombin and fibrin clots

Increase PT and PTT. No change in PC

Used in early MI, early ischemic stroke, and direct thrombolysis of severe PE

Antidote: aminocaproic acid (inhibitor of fibrinolysis)

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7
Q

Aspirin

A

Irreversible inhibition of COX-1 and COX-2 by covalent acetylation

Increased BT, decreased TXA2 and prostaglandins. No effect on PT or PTT

Antipyretic, analgesic, anti-inflammatory, antiplatelet aggregation

Toxicity: gastric ulcers, tinnitus, interstitial nephritis with chronic use. Reye syndrome in children with viral infection.

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8
Q

Clopidogrel, ticlopidine, prasugrel, ticagrelor

A

Irreversible ADP inhibitors. Inhibit platelet aggregation by preventing glycoprotein IIb/IIIa from binding fibrinogen

Used in ACS, coronary stenting, and to reduce recurrence of thrombotic stroke.

Toxicity: neutropenia with **ticlodipine **(presents as fever and mouth ulcers. TTP/HUS may occur

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9
Q

Cilostazole, dipyridamole

A

Phosphodiesterase III inhibitors that increase cAMP in platelets, thus inhibiting platelet aggregation. Increased cAMP in vessels cause vasodilation.

Used in intermittent claudication, coronary vasodilation, stroke PPx, angina PPx

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10
Q

Abciximab, eptifibatide, tirofiban

A

GP IIb/IIIa inhibitors that prevent platelet aggregation.

Used in unstable angina and percutaneous transluminal coronary angioplasty.

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11
Q

Methotrexate

A

Antimetabolite. Folate analog that inhibits dihydrofolate reductase, leading to decreased production of dTMP, dAMP, dGMP

Treats leukemias, lymphoma, choriocarcinomas, sarcomas

Also used for abortion, ectopic pregnancy, RA, psoriasis, and IBD

Toxicity: myelosuppression (reversible with leucovorin aka N-formyl-THF), macrovesicular change in liver, mucositis, teratogen

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12
Q

5-fluorouracil (5-FU)

A

Antimetabolite. Pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folate and inhibits thymidylate synthase (decreases dTMP)

Treats colon cancer, pancreatic cancer, and basal cell carcinoma

Toxicity: myelosuppression (not reversible with leucovorin, aka N-formyl-THF), photosensitivity

Treat overdose with uridine

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13
Q

Cytarabine

A

Antimetabolite. Pyrimidine analog that inhibits DNA polymerase

Treats leukemias and lymphomas

Toxicity: leukemia, thrombocytopenia, megaloblastic anemia

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14
Q

Azathioprine, 6-mercaptopurine, 6-thioguanine

A

Antimetabolites. Purine (thiol) analogs that are activated by HGPRT and decrease de novo purine synthesis.

Prevent organ rejection.

Treat RA, SLE (azathioprine), leukemia, IBD (6-MP, 6-TG)

Toxicity: bone marrow, GI, liver

Azathioprine and 6-MP are metabolized by xanathine oxidase so their toxicities increase with allopurinol administration

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15
Q

Dactinomycin (actinomycin D)

A

Antitumor antibody that intercalates in DNA

Used for Wilms tumor, Ewing sarcoma, rhabdomyosarcoma (childhood tumors)

Toxicity: myelosuppression

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16
Q

Doxorubicin (Adriamycin), daunorubicin

A

Antitumor antibiotics that generate free radicals and intercalate in DNA

Used for solid tumors, leukemias, and lymphomas

Toxicity: dilated cardiomyopathy (prevented with dexrazoxane, an iron chelating agent), myelosuppresion, alopecia

17
Q

Bleomycin

A

Antitumor antibiotic that induces free radical formation, causing breaks in DNA strands

Treats testicular cancer and Hodgkin lymphoma

Toxicity: pulmonary fibrosis, skin changes, mucositis

18
Q

Cyclophosphamide, ifosfamide

A

Alkylating agents that covalently cross-link DNA at guanine N-7 following bioactivation by the liver

Treat solid tumors, leukemia, lymphomas, and some brain cancers

Toxicity: myelosuppresion, hemorrhagic cysitis (mesna partially binds toxic metabolites)

19
Q

Nitrosoureas (carmustine, lomustine, semustine, streptozocin)

A

Alkylating agents that cross the BBB and cross-link DNA following bioactivation.

Treat brain tumors (glioblastoma multiforme)

CNS toxicity (convulsions, dizziness, ataxia)

20
Q

Busulfan

A

Alkylating agent that cross-links DNA

Treats CML. Also ablates patient’s bone marrow before bone marrow transplantation

Toxicity: severe myelosuppresion, pulmonary fibrosis, hyperpigmentation

21
Q

Vincristine, vinblastine

A

Vinca alkaloids that bind beta-tubulin and inhibit its polymerization into microtubules (prevents mitotic spindle formation)

Treats solid tumors, leukemia, and lymphomas

Vincristine toxicity: neurotoxicity (areflexia, peripheral neuritis), paralytic ileus

Vinblastine toxicity (myelosuppression; “blasts bone marrow”)

22
Q

Paclitaxel, other taxols

A

Hyperstabilize polymerized microtubules in M phase so that mitotis spindle cannot break down and anaphase cannot occur

Treats ovarian and breast carcinomas

Toxicity: myelosuppresion, alopecia, hypersensitivity

23
Q

Cisplatin, carboplatin

A

Cross-link DNA

Treat testicular, bladder, ovary, and lung carcinomas

Toxicity: acoustic nerve damage and nephrotoxicity (prevent with amifostine, a free radical scavenger, and chloride diuresis)

24
Q

Etoposide, teniposide

A

Inhibits topoisomerase II, increases DNA degredation

Treats solid tumors (especially testicular and small cell lung cancer), leukemias, lymphomas

Toxicity: myelosuppresion, GI irritation, alopecia

25
Q

Irinotecan, topotecan

A

Inhibit topoisomerase I and prevent DNA unwinding and replication

Irinotecan treats colon cancer

Topotecan treats ovarian and small cell lung cancer

Toxicity: severe myelosuppresion, diarrhea

26
Q

Hydroxyurea

A

Inhibits ribonucleotide reductase, decreasing DNA synthesis

Treats melanoma, CML, sickle cell disease (increases HbF)

Toxicity: myelosuppresion, GI upset

27
Q

Prednisone, prednisolone

A

Most commonly used glucocorticoids in cancer chemotherapy. May trigger apoptosis.

Used in CLL, non-Hodgkin lymphomas

Toxicity: Cushing-like symptoms

28
Q

Trastuzumab (Herceptin)

A

Monoclonal antibody against HER-2 (c-erbB2), a tyrosine kinase receptor

Treats HER-2 positive breast cancer and gastric cancer (“tras2zumab”)

Toxicity: cardiotoxicity (“heartceptin”)

29
Q

Tamoxifen, raloxifene

A

SERMs - receptor antagonists in breast and agonists in bone

Tamoxifen treats breast cancer. Raloxifene prevents osteoporosis.

Toxicity: tamoxifen is a partial agonist in the endometrium (increases risk of endometrial cancer); raloxifene has no effect in the endometrium

30
Q

Imatinib (Gleevec)

A

Tyrosine kinase inhibitor of bcr-abl (Philadelpha chromosome fusion gene in CML) and c-Kit (GI stromal tumors)

Treats CML and GI stromal tumors

Toxicity: fluid retention

31
Q

Rituximab

A

Monoclonal antibody against CD20 (found on most B-cell neoplasms)

Treats non-Hodgkin lymphoma, RA (with MTX), ITP

Toxicity: increases risk of progressive multifocal leukoencephalopathy

32
Q

Vemurafenib

A

Small molecule inhibitor of the B-Raf kinase with the V600E mutation

Treats metastatic melanoma

33
Q

Bevacizumab

A

Monoclonal antibody against VEGF. Inhibits angiogenesis

Treats solid tumors (colorectal cancer, RCC)

Toxicity: hemorrhage, impaired wound healing

Pharmacology (24 decks)

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