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NR566 Week 5 Study Outline Chapter 18: Drugs Affecting the Hematopoietic System_ LATEST,100% CORRECT

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NR566 Week 5 Study Outline Chapter 18: Drugs Affecting the
Hematopoietic System_ lATEST
• Know the pharmacodynamics, pharmacotherapeutics clinical use, drug interactions
and adverse drug reactions for:

Anticoagulants

• Pharmacodynamics
• Oral anticoagulants such as warfarin (Coumadin) 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:

• Precautions and Contraindications
• All anticoagulants are contraindicated for patients who are hypersensitive to the drug
or actively bleeding or who have hemophilia, thrombocytopenia, severe 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 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

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