NR566 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.
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.
