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133 Cards in this Set
- Front
- Back
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What is the mechanism of Heparin?
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Cofactor for the activation of antithrombin, ↓ thrombin, and ↓ factor Xa
Short t1/2 |
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What are the uses of Heparin?
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- Immediate anticoagulation for Pulmonary Embolism, Acute Coronary Syndrome, MI, and Deep Venous Thrombosis
- Used during pregnancy (doesn't cross placenta) |
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What do you need to monitor in patients taking Heparin?
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Follow PTT
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What are the toxic side effects of Heparin?
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- Bleeding
- Thrombocytopenia (HIT) - Osteoporosis - Drug-drug interactions |
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What is HIT?
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Heparin Induced Thrombocytopenia (HIT)
- Development of IgG antibodies against heparin bound to platelet factor 4 (PF4) - Antibody-heparin-PF4 complex activates platelets → thrombosis and thrombocytopenia |
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How do you rapidly reverse an overdose of Heparin? Mechanism?
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Protamine Sulfate (positively charged molecule that binds negatively charged heparin)
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What are the types of low molecular weight heparins (LMWH)? Mechanism? How are they different?
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Enoxaparin and Dalteparin
- Act more on Factor Xa - Better bioavailability and 2-4 times longer half-life - Can be administered subcutaneously and without lab monitoring - Not as easily reversible |
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What drugs can you use in a patient who requires anticoagulation but was taking heparin and got heparin-induced thrombocytopenia (HIT)? Source?
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Argatroban or Bivalirudin
- Derivatives of hirudin, the anticoagulant used by leeches |
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What is the mechanism and use of Argatroban?
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- Inhibits thrombin directly
- Used instead of heparin for anticoagulating patients with Heparin-induced thrombocytopenia (HIT) |
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What is the mechanism and use of Bivalirudin?
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- Inhibits thrombin directly
- Used instead of heparin for anticoagulating patients with Heparin-induced thrombocytopenia (HIT) |
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What is the mechanism of Warfarin?
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Interferes with normal synthesis and γ-carboxylation of vitamin K-dependent clotting factors II, VII, IX, and X and proteins C and S
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What clotting factors and proteins are affected by Warfarin?
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- Factor II
- Factor VII - Factor IX - Factor X - Protein C - Protein S |
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What is the effect of warfarin on blood tests?
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Increases PT (extrinsic pathway) / INR
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What are the clinical uses of Warfarin?
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- Chronic anti-coagulation (after STEMI, venous thromboembolism prophylaxis, and prevention of stroke in atrial fibrillation)
*NOT used in pregnant women (can cross placenta = teratogen) |
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What are the toxic side effects of Warfarin?
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- Bleeding
- Teratogen - Skin / tissue necrosis - Drug-drug interactions |
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How can you reverse a warfarin overdose?
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- Give Vitamin K
- For severe overdose, give fresh frozen plasma |
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What drugs are direct factor Xa inhibitors?
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- Apixaban
- Rivaroxaban |
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What is the mechanism of Apixaban and Rivaroxaban?
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Binds and directly inhibits activity of factor Xa
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What are the clinical uses of Apixaban and Rivaroxaban?
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- Treatment and prophylaxis of DVT and PE (rivaroxaban)
- Stroke prophylaxis in patients with atrial fibrillation - Oral agents do not require coagulation monitoring! |
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What are the side effects of Apixaban and Rivaroxaban?
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Bleeding (no specific reversal agent available)
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What is the structure of heparin and warfarin?
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- Heparin: large, anionic, acidic polymer
- Warfarin: small lipid-soluble molecule |
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What is the route of administration of heparin and warfarin?
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- Heparin: parenteral (IV, SC)
- Warfarin: oral |
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What is the site of action of heparin and warfarin?
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- Heparin: blood
- Warfarin: liver |
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What is the relative onset of action of heparin and warfarin?
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- Heparin: rapid (seconds)
- Warfarin: slow, limited by half-lives of normal clotting factors |
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What is the mechanism of action of heparin and warfarin?
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- Heparin: activates antithrombin, which ↓ the action of IIa (thrombin) and factor Xa
- Warfarin: impairs the synthesis of vitamin K-dependent clotting factors II, VII, IX, and X (vitamin K antagonist) |
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What is the duration of action of heparin and warfarin?
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- Heparin: acute (hours)
- Warfarin: chronic (days) |
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Do heparin and warfarin inhibit coagulation in vitro?
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- Heparin: yes
- Warfarin: no |
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How do you treat an acute overdose of heparin and warfarin?
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- Heparin: protamine sulfate
- Warfarin: IV vitamin K and fresh frozen plasma |
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What should you monitor in patients taking heparin and warfarin?
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- Heparin: PTT (intrinsic pathway)
- Warfarin: PT / INR (extrinsic pathway) |
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Do heparin and warfarin cross the placenta?
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- Heparin: no
- Warfarin: yes (teratogenic) |
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What are the types of thrombolytics?
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- Alteplase (tPA)
- Reteplase (rPA) - Tenecteplase (TNK-tPA) |
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What is the mechanism of Alteplase (tPA), Reteplase (rPA), and Tenecteplase (TNK-tPA)?
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Thrombolytics
- Directly or indirectly aids conversion of plasminogen to plasmin - Plasmin cleaves thrombin and fibrin clots - ↑ PT, ↑ PTT, and no change in platelet count |
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What are the clinical uses of Alteplase (tPA), Reteplase (rPA), and Tenecteplase (TNK-tPA)?
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- Early MI
- Early ischemic stroke - Direct thrombolysis of severe PE |
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What are the side effects and contraindications of Alteplase (tPA), Reteplase (rPA), and Tenecteplase (TNK-tPA)?
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- Bleeding
- Contraindicated in patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension |
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How do you treat toxicity of Alteplase (tPA), Reteplase (rPA), and Tenecteplase (TNK-tPA)? Mechanism?
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- Aminocaproic Acid - inhibits fibrinolysis
- Fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies |
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What is the mechanism of aspirin (ASA)?
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- Irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) enzyme by covalent acetylation
- Platelets cannot synthesize new enzyme so effect lasts until new platelets are produced |
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What lab values change in patients taking aspirin (ASA)?
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- ↑ Bleeding time, ↓ TXA2 and prostaglandins
- No effect on PT or PTT |
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What are the clinical uses of aspirin (ASA)?
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- Antipyretic
- Analgesic - Anti-inflammatory - Antiplatelet (↓ aggregation) |
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What are the toxic side effects of aspirin (ASA)?
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- Gastric ulceration
- Tinnitus (CN VIII) - Chronic use can lead to acute renal failure, interstitial nephritis, and upper GI bleeding - Reye syndrome in children with viral infection |
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What can an overdose of aspirin (ASA) cause?
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Respiratory alkalosis initially, which is then superimposed by metabolic acidosis
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What is the cause of Reye syndrome?
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Children with a viral infection who take aspirin
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What are the types of ADP receptor inhibitors?
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- Clopidogrel
- Ticlopidine - Prasugrel - Ticagrelor |
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What is the mechanism of Clopidogrel, Ticlopidine, Prasugrel, and Ticagrelor?
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- Inhibit platelet aggregation by irreversibly blocking ADP receptors
- Inhibits fibrinogen binding by preventing glycoprotein IIb/IIIa from binding to fibrinogen |
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What are the clinical uses of Clopidogrel, Ticlopidine, Prasugrel, and Ticagrelor?
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- Acute coronary syndrome
- Coronary stenting - ↓ Incidence or recurrence of thrombotic stroke |
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What are the side effects of Clopidogrel, Ticlopidine, Prasugrel, and Ticagrelor?
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- Neutropenia (ticlopidine)
- TTP / HUS may be seen |
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What drugs inhibit platelet aggregation via inhibition of phosphodiesterase III?
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Cilostazol and Dipyridamole
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What is the mechanism of Cilostazol and Dipyridamole?
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- Phosphodiesterase III inhibitor
- ↑ cAMP in platelets, thus inhibiting platelet aggregation - Vasodilates |
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What are the uses of Cilostazol and Dipyridamole?
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- Intermittent claudication
- Coronary vasodilation - Prevention of stroke or TIAs (combined with aspirin) - Angina pectoris |
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What are the side effects of Cilostazol and Dipyridamole?
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- Nausea
- Headache - Facial flushing - Hypotension - Abdominal pain |
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What are the types of GpIIb/IIIa inhibitors?
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- Abciximab
- Eptifibatide - Tirofiban |
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What is the mechanism of Abciximab, Eptifibatide, and Tirofiban?
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- Binds to the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation
- Abciximab is made from monoclonal antibody Fab fragments |
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What are the uses of Abciximab, Eptifibatide, and Tirofiban (GpIIb/IIIa inhibitors)?
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- Unstable angina
- Percutaneous transluminal coronary angioplasty |
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What are the side effects of Abciximab, Eptifibatide, and Tirofiban (GpIIb/IIIa inhibitors)?
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- Bleeding
- Thrombocytopenia |
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What are the drugs that interact with the cell cycle? Which part?
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- Antimetabolites (affect S)
- Etoposide (affects S and G2) - Bleomycin (affects G2) - Vinca alkaloids and taxols (affects M) |
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What anti-neoplastic drugs affect nucleotide synthesis? How?
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- Methotrexate and 5-Fluorouracil: ↓ thymidine synthesis
- 6-Mercaptopurine: ↓ purine synthesis |
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What anti-neoplastic drugs inhibit DNA synthesis? How?
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- Alkylating agents, Cisplatin: cross-link DNA
- Dactinomycin, Doxorubicin: intercalates into DNA - Etoposide: inhibits topoisomerase II |
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What anti-neoplastic drugs inhibit cellular division? How?
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- Vinca alkaloids: inhibit microtubule formation
- Paclitaxel: inhibits microtubule disassembly |
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What are the anti-metabolite drugs?
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- Methotrexate (MTX)
- 5-Fluorouracil (5-FU) - Cytarabine (Arabinofuranosyl Cytidine) - Azathioprine, 6-Mercaptopurine (6-MP), 6-Thioguanine (6-TG) |
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What is the mechanism of Methotrexate (MTX)?
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Folic acid analog that inhibits Dihydrofolate Reductase → ↓ dTMP → ↓ DNA and ↓ protein synthesis
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What are the clinical uses of Methotrexate (MTX)?
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- Cancers: leukemias, lymphomas, choriocarcinoma, sarcomas
- Non-neoplastic: abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis, IBD |
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What are the toxic side effects of Methotrexate (MTX)?
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- Myelosuppression
- Macrovesicular fatty change in liver - Mucositis - Teratogenic |
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How can you reverse the myelosuppression induced by Methotrexate (MTX)?
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Reversible with leucovorin (folinic acid) "rescue"
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What is the mechanism of 5-Flurouracil (5-FU)?
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- Pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid
- This complex inhibits thymidylate synthase → ↓ dTMP → ↓ DNA and ↓ protein synthesis |
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What is 5-fluorouracil (5-FU) used for?
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- Colon cancer
- Pancreatic cancer - Basal cell carcinoma (topical) |
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What are the toxic side effects of 5-fluorouracil (5-FU)?
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- Myelosuppression
- Photosensitivity |
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How can you reverse the myelosuppression induced by 5-Fluorouracil (5-FU)?
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Reversible with uridine "rescue"
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What is the mechanism of Cytarabine (Arabinofuranosyl Cytidine)?
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Pyrimidine analog → inhibition of DNA polymerase
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What is Cytarabine (Arabinofuranosyl Cytidine) used for?
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- Leukemias
- Lymphomas |
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What are the toxic side effects of Cytarabine (Arabinofuranosyl Cytidine)?
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- Leukopenia
- Thrombocytopenia - Megaloblastic anemia - CYTarabine causes panCYTopenia |
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What is the mechanism of Azathioprine, 6-Mercaptopurine (6-MP), and 6-Thioguanine (6-TG)?
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- Purine (thiol) analogs → ↓ de novo purine synthesis
- Activated by HGPRT |
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What are the clinical uses of Azathioprine, 6-Mercaptopurine (6-MP), and 6-Thioguanine (6-TG)?
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- Preventing organ rejection
- Rheumatoid Arthritis - Azathioprine: Systemic Lupus Erythematosus (SLE) - 6-MP and 6-TG: Leukemia and Inflammatory Bowel Disease |
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What are the toxic side effects of Azathioprine, 6-Mercaptopurine (6-MP), and 6-Thioguanine (6-TG)?
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- Bone marrow, GI, and liver toxicity
- Azathioprine and 6-MP are metabolized by xanthine oxidase; thus both have ↑ toxicity with allopurinol, which inhibits their metabolism |
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What are the anti-tumor antibiotics?
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- Dactinomycin (Actinomycin D)
- Doxorubicin (Adriamycin), Danorubicin - Bleomycin |
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What is the mechanism of Dactinomycin (Actinomycin D)?
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Intercalates in DNA
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What are the clinical uses of Dactinomycin (Actinomycin D)?
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- Wilms tumor
- Ewing sarcoma - Rhabdomyosarcoma - Used for childhood tumors ("children act out") |
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What are the toxic side effects of Dactinomycin (Actinomycin D)?
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Myelosuppression
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What is the mechanism of Doxorubicin (Adriamycin) and Daunorubicin?
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- Generates free radicals
- Intercalates in DNA → breaks in DNA → ↓ replication |
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What are the clinical uses of Doxorubicin (Adriamycin) and Daunorubicin?
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- Solid tumors
- Leukemias - Lymphomas |
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What are the toxic side effects of Doxorubicin (Adriamycin) and Daunorubicin?
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- Cardiotoxicity (dilated cardiomyopathy)
- Myelosuppression - Alopecia - Toxic to tissues following extravasation - Dexrazoxane (iron chelating agent), used to prevent cardiotoxicity |
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What is the mechanism of Bleomycin?
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Induces free radical formation, which causes breaks in DNA strands
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What are the clinical uses of Bleomycin?
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- Testicular cancer
- Hodgkin lymphoma |
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What are the toxic side effects of Bleomycin?
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- Pulmonary fibrosis
- Skin changes - Mucositis - Minimal myelosuppression |
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What are the alkylating agent drugs?
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- Cyclophosphamide, Ifosfamide
- Nitrosoureas (Carmustine, Lomustine, Semustine, Streptozocin) - Busulfan |
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What is the mechanism of Cyclophosphamide and Ifosfamide?
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- Covalently X-link (interstrand)
- DNA at guanine N-7 - Requires bioactivation by liver |
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What are the clinical uses of Cyclophosphamide and Ifosfamide?
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- Solid tumors
- Leukemia - Lymphomas - Some brain cancers |
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What are the toxic side effects of Cyclophosphamide and Ifosfamide?
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- Myelosuppression
- Hemorrhagic cystitis |
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How can you limit the hemorrhagic cystitis caused by Cyclophosphamide and Ifosfamide? Mechanism?
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Mesna - thiol group of mesna binds toxic metabolites
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What is the mechanism of Nitrosoureas (Carmustine, Lomustine, Semustine, and Streptozocin)?
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- Requires bioactivation
- Crosses blood-brain-barrier → CNS - Cross-links DNA |
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What are the clinical uses of Nitrosoureas (Carmustine, Lomustine, Semustine, and Streptozocin)?
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Brain tumors (including glioblastoma multiforme)
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What are the toxic side effects of Nitrosoureas (Carmustine, Lomustine, Semustine, and Streptozocin)?
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CNS toxicity (convulsions, dizziness, ataxia)
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What is the mechanism of Busulfan?
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Cross-links DNA
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What are the clinical uses of Busulfan?
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- CML
- Also used to ablate patient's bone marrow before bone marrow transplantation |
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What are the toxic side effects of Nitrosoureas (Carmustine, Lomustine, Semustine, and Streptozocin)?
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- Severe myelosuppression (in almost all cases)
- Pulmonary fibrosis - Hyperpigmentation |
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What are the types of microtubule inhibitors?
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- Vincristine and Vinblastine
- Paclitaxel and other Taxols |
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What is the mechanism of Vincristine and Vinblastine?
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- Vinca alkaloids that bind β-tubulin
- Inhibits its polymerization into microtubules - Prevents mitotic spindle formation (M-phase arrest) |
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What are the clinical uses of Vincristine and Vinblastine?
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- Solid tumors
- Leukemias - Lymphomas |
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What are the toxic side effects of Vincristine and Vinblastine?
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- Vincristine: neurotoxicity (areflexia, peripheral neuritis), paralytic ileus
- Vinblastine: blasts bone marrow (myelosuppression) |
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What is the mechanism of Paclitaxel and other Taxols?
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- Hyperstabilize polymerized microtubules in M phase so that mitotic spindle cannot break down (anaphase cannot occur)
- It is taxing to stay polymerized |
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What are the clinical uses of Paclitaxel and other Taxols?
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Ovarian and breast carcinomas
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What are the toxic side effects of Paclitaxel and other Taxols?
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- Myelosuppression
- Alopecia - Hypersensitivity |
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What is the mechanism and clinical uses of Cisplatin and Carboplatin?
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- Cross-links DNA
- Used for testicular, bladder, ovary, and lung carcinomas |
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What are the toxic side effects of Cisplatin and Carboplatin?
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- Nephrotoxicity
- Acoustic nerve damage - Prevents nephrotoxicity with amifostine (free radical scavenger) and chloride diuresis |
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What is the mechanism and clinical uses of Etoposide and Teniposide?
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- Inhibits topoisomerase II → ↑ DNA degradation
- Used for solid tumors (particularly testicular and small cell lung cancer), leukemias, and lymphomas |
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What are the toxic side effects of Etoposide and Teniposide?
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- Myelosuppression
- GI irritation - Alopecia |
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What is the mechanism and clinical uses of Irinotecan and Topotecan?
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- Inhibits topoisomerase I and prevents DNA unwinding and replication
- Used for colon cancer (irinotecan) - Used for ovarian and small cell lung cancers (topotecan) |
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What are the toxic side effects of Irinotecan and Topotecan?
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- Severe myelosuppression
- Diarrhea |
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What is the mechanism and clinical uses of Hydroxyurea?
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- Inhibits ribonucleotide reductase → ↓ DNA synthesis (S-phase specific)
- Used for melanoma, CML, sickle cell disease (↑ HbF) |
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What are the toxic side effects of Hydroxyurea?
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- Bone marrow suppression
- GI upset |
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What is the mechanism of Prednisone and Prednisolone?
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- May trigger apoptosis
- May even work on non-dividing cells |
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What are the clinical uses of Prednisone and Prednisolone?
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- Most commonly used glucocorticoids in cancer chemotherapy
- Used in CLL, non-Hodgkin lymphomas (part of combination chemotherapy regimen) - Also used as immunosuppressants (eg, autoimmune disease) |
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What are the toxic side effects of Prednisone and Prednisolone?
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Cushing like symptoms:
- Weight gain - Central obesity - Muscle breakdown - Cataracts - Acne - Osteoporosis - Hypertension - Peptic ulcers - Hyperglycemia - Psychosis |
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What is the mechanism of Tamoxifen and Raloxifene?
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- Selective estrogen receptor modulator (SERMs)
- Receptor antagonists in breast and agonists in bone - Blocks the binding of estrogen to ER (+) cells |
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What are the clinical uses of Tamoxifen and Raloxifene?
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- Breast cancer treatment (tamoxifen only) and prevention
- Raloxifene also useful to prevents osteoporosis |
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What are the toxic side effects of Tamoxifen and Raloxifene?
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- Tamoxifen: partial agonist in endometrium, which ↑ the risk of endometrial cancer, "hot flashes"
- Raloxifene: no ↑ in endometrial carcinoma because it is an endometrial antagonist |
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What is the mechanism of Trastuzumab (Herceptin)?
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- Monoclonal antibody against HER-2 (c-erbB2), a tyrosine kinase receptor
- Helps kill breast cancer cells that overexpress HER-2, through inhibition of HER2-initiated cellular signaling and antibody-dependent cytotoxicity |
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What are the clinical uses of Trastuzumab (Herceptin)?
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HER-2 positive breast cancer and gastric cancer (Tras2zumab)
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What are the toxic side effects of Trastuzumab (Herceptin)?
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- Cardiotoxicity ("HEART"ceptin damages the heart)
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What is the mechanism of Imatinib (Gleevec)?
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Tyrosine kinase inhibitor of bcr-abl (Philadelphia chromosome fusion gene in CML) and c-Kit (common in GI stromal tumors)
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What are the clinical uses of Imatinib (Gleevec)?
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- CML
- GI stromal tumors |
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What are the toxic side effects of Imatinib (Gleevec)?
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Fluid retention
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What is the mechanism of Rituximab?
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Monoclonal Ab against CD20, which is found on most B-cell neoplasms
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What are the clinical uses of Rituximab?
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- Non-Hodgkin Lymphoma (CD20 positive cells)
- Rheumatoid arthritis (with MTX) - Idiopathic Thrombocytopenic Purpura (ITP) |
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What are the toxic side effects of Rituximab?
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Increased risk of progressive multifocal leukoencephalopathy
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What is the mechanism and use of Vemurafenib?
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- Small molecule inhibitor of forms of the B-Raf kinase with the V600E mutation
- Used for metastatic melanoma |
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What is the mechanism and clinical uses of Bevacizumab?
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- Monoclonal antibody against VEGF, inhibits angiogenesis
- Used for solid tumors (colorectal cancer, renal cell carcinoma) |
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What are the toxic side effects of Bevacizumab?
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Hemorrhage and impaired wound healing
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Which chemo drug(s) cause(s) acoustic nerve damage?
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Cisplatin / Carboplatin
(and nephrotoxicity) |
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Which chemo drug(s) cause(s) peripheral neuropathy?
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Vincristine
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Which chemo drug(s) cause(s) pulmonary fibrosis?
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- Bleomycin
- Busulfan |
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Which chemo drug(s) cause(s) cardiotoxicity?
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- Doxorubicin
- Trastuzumab |
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Which chemo drug(s) cause(s) nephrotoxicity?
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Cisplatin and Carbolatin (and acoustic nerve damage)
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Which chemo drug(s) cause(s) hemorrhagic cystitis?
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Cyclophosphamide
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Which chemo drug(s) cause(s) myelosuppression?
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- 5-FU
- 6-MP - Methotrexate |
