NR 566 final study guide

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Know the pharmacodynamics, pharmacotherapeutics clinical use, drug interactions and adverse drug reactions for: Anticoagulants • Pharmacodynamics • Oral anticoagulants such as warfarin (Coumad... in) inhibit the hepatic synthesis of several clotting factors, including factor X. • 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.  Rivaroxaban (Xarelto) an anticoagulant, 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 • Pharmacotherapeutics: • They may be used in patients who are actively bleeding to treat DIC • Heparin is Pregnancy Category C: stillbirth, prematurity • Some heparin preparations contain benzyl alcohol: known to cause “gasping syndrome”: • fatal toxicity in neonates • Hyperkalemia may develop • Use for patient with DM or renal insufficiency requires care and frequent monitoring of aPTT • Has been associated with fatal medication errors r/t different strengths of preparations • JCo: anticoagulant therapy is a National patient Safety Goal: plan in place at each facility to reduce patient harm • LMWHs are contraindicated for patients with allergies to pork, sulfites, or benzyl alcohol; uncontrolled bleeding; and in patients who have antiplatelet antibodies • Renal impairment: cautious use • Body weight less than 50 kg associated with increased r/f bleeding: • enoxaparin dose adjustment • Cautious use: untreated HTN, retinopathy (HTN or DM caused), severe liver disease, recent Hx of ulcer, or malignancy • Not used for thromboprophylaxis in patients with mechanical heart values: especially pregnant (r/f heart value thrombosis) • Enoxaparin: Preg Cat B, tinzaparin: teratogenicity and fetal death, fondaparinux: Preg B • First line drug for women who require antithrombotic therapy during pregnancy: LMWH • Pharmacokinetics of LMWH is altered during pregnancy • Warfarin • Hepatic dysfunction potentiates response through impaired synthesis of coagulation factors • Use with caution: Hypermetabolic states produced by fever or hyperthyroidism increase responsiveness to warfarin: • r/t increased catabolism of vit K dependent coagulation factors • Increased r/f bleeding in older adults • Caution use based on balance between potential for decreased r/f thromboembolism and the risk for bleeding especially in those with dementia or severe cognitive impairment: Hx of three falls in the previous year or recurrent injurious falls, uncontrolled HTN, or non-adherent or unreliable • Warfarin is Pregnancy Category X: Crosses placenta and can cause hemorrhagic disorders in the fetus and serious birth defects • Safe during lactation • Rivaroxaban (Xarelto): Black-Box Warning: 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): Black Box warning premature discontinuation leading to thrombotic events • Although there are no well-controlled studies: 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 • Use with caution in liver damage, preexisting hypoprothrombinemia, or vit K deficiency • Preg Cat C and Cat D in third trimester • Avoid during lactation • Clopidogrel and ticlopidine: severe hepatic disease (r/f bleeding d/o), do not use in these patients • Not recommended for patients with GI d/o • Preg Category B • Ticlopidine: clearance increased with age, older adults increased sensitivity to this drug (closely monitor or ADRs) • Older adults: increased levels of clopidogrel: no dosage adjustments • In older adults clopidogrel is a safer drug • Ticlopidine: elevations in cholesterol and TC within 1 month of therapy: factor in HLD • Ticagrelor: 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: Black-Box Warning concerning discontinuation increasing risk of thrombotic events. • There is no reversal agent available for dabigatran • Vorapaxar: Black-Box Warning to not use in patients with a history of stroke, TIA, intracranial hemorrhage, or active pathological bleeding. • Vorapaxar is Pregnancy Category B, with no congenital malformations found in animal studies • ADRs • All anticoagulants: excessive bleeding • Risk is higher early in therapy, with wide fluctuations in aPTT or INR, and older adults (especially women over 60) • Heparins: cause thrombocytopenia and anemia • More likely with bovine than with porcine • Early thrombocytopenia 2 to 3 days after starting therapy and delayed forms 7 to 12 days • Platelet below 100,000: d/c heparin • Enoxaparin antidote: protamine sulfate 1 mg for each mg of enoxaparin dalteparin and tinzaparin: 1 mg for each 100 anti-Xa IUs of dalteparin • Slow IV injection • Fondaparinux: no known antidote • Heparin has a short half-life: Tx is usually d/c of the drug • Protamine sulfate antidote for heparin OD • Warfarin: toxicity and OD Tx withholding one or more doses • Or 1 to 10 mg of vitamin K is the antidote for minor bleeding • 5 to 50 may be used for frank bleeding • Hemorrhagic skin necrosis in women and cyanotic toes in men have been reported • r/t transient inhibition in proteins S and C • Allergic reactions: symmetrical, maculopapular, erythematous lesions • Some are isolated and some confluent: face, neck, and torso • May not appear until 8 to 10 days • Ribaroxaban: bleeding is major ADR • No reversal agent • Back pain, upper ABD pain, osteoarthritis, dyspepsia, and fatigue • Apixaban: bleeding • No reversal agent • ASA: gastric erosions: increased r/f serious upper GI bleeding • More likely when used in combo with other anticoags such as warfarin • Salicylism (tinnitus) : serum levels above 200 mcg/mL • Toxicity: tinnitus, HA, hyperventilation, agitation, confusion, lethargy, diarrhea, and sweating • Ticagrelor: bleeding • Dyspnea: sometimes improves with use or must be d/c • HA, cough, dizziness, and nausea • Ticlopidine: reversible neutropenia at 3 weeks to 3 months after initiation of therapy • Severe [Show More]

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