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NR 566 Week 5 Study Outline_2020 | NR566 Week 5 Study Outline_LATEST

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NR 566 Week 5 Study Outline Many questions are written to assess your clinical application of the material from the textbook, in real-world scenarios. Chapter 18: Drugs Affecting the Hematopoietic ... System • Know the pharmacodynamics, pharmacotherapeutics clinical use, drug interactions and adverse drug reactions for: • 
o Anticoagulants 
 • Pharmacodynamics Oral anticoagulants such as warfarin (Coumadin) inhibit the hepatic synthesis of several clotting factors, including factor X. The decline in clotting factors is a function of the half-life of each factor, which varies from 5 hours for factor VII to 72 hours for factor II. • Heparin inhibits the activity of several activated clotting factors by accelerating the activity of antithrombin III. LMWH enoxaparin (Lovenox) potentiates the activity of antithrombin III and inactivates factors Xa and IIa (thrombin). Dabigatran (Pradaxa) is a direct thrombin inhibitor. Thrombin is required for the conversion of fibrinogen to fibrin in the clotting cascade, thus dabigatran's inhibition of thrombin prevents thrombi from forming. Fondaparinux (Arixtra) is a selective inhibitor of antithrombin III and a factor Xa inhibitor. An anticoagulant, rivaroxaban (Xarelto), is a highly selective factor Xa inhibitor that inhibits thrombin formation and the development of thrombi. Apixaban (Eliquis) is a selective inhibitor of factor Xa. • Aspirin antagonizes the cyclooxygenase pathway and interferes with platelet aggregation. NSAIDs have this same action. NSAIDs are not used as antiplatelet drugs, but this explains why concurrent use with anticoagulants is contraindicated • Ticlopidine (Ticlid) and clopidogrel (Plavix) reduce platelet aggregation by inhibiting the ADP pathway of platelets. Unlike aspirin, they have no effect on prostaglandin metabolism. Ticagrelor (Brilinta) reversibly interacts with the platelet P2Y12 ADP-receptor to prevent platelet activation. Vorapaxar (Zontivity) is a protease-activated receptor-1 (PAR-1) antagonist, inhibiting thrombin-induced and thrombin receptor agonist peptide-induced platelet aggregation • Precautions and Contraindications All anticoagulants are contraindicated for patients who are hypersensitive to the drug or actively bleeding or who have hemophilia, thrombocytopenia, severe hypertension (HTN), intracranial hemorrhage, infective endocarditis, active tuberculosis, or ulcerative lesions of the GI tract. Heparins are contraindicated in advanced hepatic or renal disease. They may be used in patients who are actively bleeding to treat disseminated intravascular coagulation (DIC). Heparin is Pregnancy Category C. • LMWHs are contraindicated for patients with allergies to pork, sulfites, or benzyl alcohol; uncontrolled bleeding; and in patients who have antiplatelet antibodies. Use caution in hepatic dysfunction and use of warfarin and increased risk of bleeding with adults Warfarin crosses the placenta and can cause hemorrhagic disorders in the fetus and serious birth defects. It is Pregnancy Category X and should not be administered during pregnancy. Rivaroxaban (Xarelto) was given a Black-Box Warning in August 2013 indicating the premature discontinuation of anticoagulants including rivaroxaban may lead to thrombotic events. An increased risk of stroke is seen in patients with atrial fibrillation when transitioning to warfarin. Rivaroxaban is Pregnancy Category C and is not recommended for use in pregnant women. Apixaban (Eliquis) was given a similar Black Box warning regarding premature discontinuation leading to thrombotic events when it was approved. Although there are no well-controlled studies, apixaban is Pregnancy Category B. Hypersensitivity to aspirin and cross-sensitivity with NSAIDs may occur, contraindicating the drug. Aspirin hypersensitivity is more prevalent in patients with asthma, nasal polyps, or chronic urticaria. Reye syndrome has been associated with its use in children and teenagers who have influenza or chickenpox. Reversible hepatotoxicity has occurred. Ticagrelor has a Black-Box Warning to not use in a patient with active pathological bleeding or history of intracranial hemorrhage. Ticagrelor should be discontinued 5 days prior to any surgery. Dabigatran has a Black-Box Warning concerning discontinuation increasing risk of thrombotic events. There is no reversal agent available for dabigatron if excessive bleeding occurs. Vorapaxar has a Black-Box Warning to not use in patients with a history of stroke, transient ischemic attack (TIA), intracranial hemorrhage, or active pathological bleeding. Vorapaxar is Pregnancy Category B, with no congenital malformations found in animal studies, • Also know: 
 o Use of anticoagulants in pregnancy
:Enoxaparin is Pregnancy Category B. Teratogenicity and fetal death have been reported as well for tinzaparin, although a clear cause-and-effect relationship was not established. Fondaparinux is also listed as Pregnancy Category B but without adequate or well-controlled studies in pregnancy. LMWHs do not cross the placenta and do not cause teratogenicity or fetal bleeding (Bates et al, 2012). The American College of Chest Physicians recommends LMWH as the first-line drug for women who require antithrombotic therapy during pregnancy (Guyatt et al, 2012). The pharmacokinetics of LMWHs are altered during pregnancy. LMWH passes in small amounts into breast milk but has low oral bioavailability and may be safely used during breastfeeding Aspirin is Pregnancy Category C and Pregnancy Category D in the third trimester. Aspirin should be avoided during lactation, especially in young infants (LactMed, 2010). If a woman is on chronic high-dose aspirin therapy, salicylates levels should be monitored in the infant ADRS: all anticoags can cause excessive bleeding, heparins: anemia and thrombocytopenia, Bleeding is the major adverse effect of ribaroxaban, pain (3.7%), upper abdominal pain (1.7%), osteoarthritis (1.7%), dyspepsia (1.3%), and fatigue (1.0%). The major adverse effect seen with apixaban is bleeding with major bleeding occurring in 2.13% of patients who used it for a year. Aspirin can produce gastric erosions that increase the risk of serious upper GI bleeding. This adverse effect is more likely when it is used in combination with other anticoagulants such as warfarin. Salicylism (tinnitus) associated with the use of aspirin occurs at serum levels above 200 mcg/mL. In addition to tinnitus, indications of aspirin toxicity are headache, hyperventilation, agitation, mental confusion, lethargy, diarrhea, and sweating Dyspnea is the major nonbleeding-related adverse effect seen with ticagrelor, with 13.8% of patients reporting symptoms. The dyspnea was mild to moderate in intensity and usually resolved with continued use but occasionally required discontinuation of therapy (0.9% of patients). Headache (6.5%), cough (4.9%), dizziness (4.5%), and nausea (4.3%) were other common adverse effects of ticagrelor. Ticlopidine-reversible neutropenia, Plavix similar to aspirin side effects, dabigatran –bleeding, GI , angioedema, thrombocytopenia Vorapaxar: bleeding, GI bleeding, rashes eruptions Drug interactions: cephalosporins and pencillins given parentally: coagulopathies and increased risk of bleeding when given with heparin: also given any route combined with warfarin increase risk of bleeding Heparin and LMWHs have similar drug interactions but also interact with antiplatelets (including NSAIDs) and dextran Warfarin has many drug interactions and increased INR monitoring (within 4 to 7 days) is recommended when other drugs are started or stopped, even short-term drugs such as antibiotics. Vitamin K has an antagonistic interaction with warfarin, decreasing warfarin's effectiveness. Warfarin interacts with any other drug that increases bleeding, including anticoagulants, antiplatelets, NSAIDs, and SSRIs. Antibiotics and antifungals may affect INR levels in patients taking warfarin. Herbal products that may increase bleeding include ginkgo biloba, and garlic. Herbal therapies that may decrease effectiveness of warfarin include St. John's wort, ginseng, and coenzyme Q10. Herbal therapies and foods that may influence the metabolism of warfarin include St. John's wort, echinacea, ginkgo, goldenseal, and grapefruit juice. Rifampin interacts with dabigatran, leading to decreased levels of dabigatran (66% of expected). DRUG of choice: warfarin: venous thrombosis, systemic thrombosis, PE, o Patient instructions for administration of clopidogrel (Plavix) and warfarin (Coumadin) Warfarin tablets are color coded by dose, and patients should learn the color code for the brand used. 
o Thromboprophylaxis
 The ACCP recommends the use of LMWH, low-dose heparin, or fondaparinux as thromboprophylaxis in the following surgical procedures: moderate-risk major general surgery, higher-risk patients who are having a major procedure for cancer, major vascular surgery, major gynecological surgery, major urological procedures, bariatric surgery, thoracic surgery, and many orthopedic surgeries LMWH should not be used for thromboprophylaxis in patients with mechanical prosthetic heart valves, especially pregnant women, as prosthetic heart valve thrombosis may occur. o Population needed warfarin starting dose adjustment: Further dosing is based on INR ICSI recommends lower initiation doses be considered for patients with any of the following (Maddali et al, 2013): • Older than 75 years • Multiple comorbid conditions • Poor nutrition (low albumin) • Elevated INR when off warfarin • Elevated liver function tests • Changing thyroid status If the INR is greater than 2 after the first three doses, consider decreasing the dose by one-half. If INR rises rapidly, search for reasons, such as drug interactions, poor nutritional status, infection, or systemic disease process. Monitoring is discussed later. 
o INR target goals warfarin should be given in a dose sufficient to maintain an INR between 2 and 3 In patients with acute PE, initial treatment is heparin, LMWH, or fondaparinux for at least 5 days and until INR is greater than or equal to 2.0 for at least 24 hours: DVT is the same treatment. All pts tilting disk valves and bileafletwith heart valves caged ball or caged diskprosthetic and mechanical INR 2.5-3.5 
o Anticoagulant preferred for patients at high risk for stroke with atrial fibrillation: Patients at high risk of stroke (CHADS2 score of 2 or greater) require oral anticoagulation therapy. The 2012 ACCP guidelines recommend 150 mg of dabigatran twice daily as the anticoagulant therapy of choice rather than warfarin (You et al, 2012). For patients with persistent or paroxysmal AF at high risk for stroke, the recommendation is warfarin with a target INR between 2 and 3 
o Drugs which decrease anticoagulant medication effectiveness: Clopidogrel should not be taken with proton pump inhibitors (PPI), such as OTC omeprazole (Prilosec OTC), because the PPI decreases the effectiveness of the clopidogrel. - - - - - - Continued [Show More]

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