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Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
Chapter 32
Drugs Affecting Coagulation
Chapter 32
Drugs Affecting Coagulation
Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
Physiology of Coagulation Physiology of Coagulation • Normal circulation requires blood to circulate freely
through large and small blood vessels.
• However, blood must also be able to form clots to prevent excessive blood loss from injuries.
• Blood is composed of various cells and substances, each with a specific purpose that assists in maintaining a balance of coagulation and anticoagulation.
• The cascade is initiated by the tissue damage and platelet activation, which mobilize the clotting factors circulating in the blood.
• The clotting cascade occurs over two pathways, intrinsic and extrinsic.
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Pathophysiology Pathophysiology
• When blood flow is impeded and slowed in an area, coagulation occurs, leading to formation of a thrombus.
• Any excessive action from the coagulating factors may also produce a thrombus that obstructs blood flow.
• Arterial thrombosis is the most common cause of MI, stroke, and limb gangrene.
• Venous thrombosis leads to pulmonary embolism (PE) and postphlebitic syndrome.
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Pathophysiology (cont.)Pathophysiology (cont.)
• When clotting factors are deficient, blood clotting does not occur in a timely manner.
• A minor injury or trauma can cause prolonged bleeding.
• Inherited deficiencies of specific clotting factors produce three major hemophilic conditions.
• Fibrinolysis normally occurs in balance with blood coagulation.
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Drug Therapy for Hypercoagulation Drug Therapy for Hypercoagulation
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Anticoagulant Drugs Anticoagulant Drugs • Heparin, a naturally occurring anticoagulant, is produced
by mast cells located in connective tissue throughout the body.
• All anticoagulants interfere with the clotting cascade and prolong blood clotting time.
• They vary by their route and their method of action.
• There are two types of anticoagulants: parenteral and oral.
• The parenteral anticoagulants work by preventing the conversion of fibrinogen to fibrin.
• The oral anticoagulants work by preventing the synthesis of factors dependent on vitamin K for synthesis.
• Prototype drug: heparin and warfarin (Coumadin)
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Heparin: Core Drug Knowledge Heparin: Core Drug Knowledge
• Pharmacotherapeutics
– Parenteral anticoagulant. It interferes with the final steps of the clotting cascade.
• Pharmacokinetics
– Route: IV or SC. Onset depends on route of administration. Metabolism: liver. Excreted: kidneys.
• Pharmacodynamics
– Rapidly promotes the inactivation of factor X, which, in turn, prevents the conversion of prothrombin to thrombin.
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Heparin: Core Drug Knowledge (cont.)Heparin: Core Drug Knowledge (cont.)
• Contraindications and precautions
– Hypersensitive
• Adverse effects
– Bleeding and thrombocytopenia
• Drug interactions
– Several different drugs affect the action of heparin
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Heparin: Core Patient Variables Heparin: Core Patient Variables
• Health status
– Review history for allergies or prolonged bleeding times.
• Life span and gender
– Heparin is safe for pregnant women.
• Lifestyle, diet, and habits
– Assess activity level.
• Environment
– Assess environment where drug will be given.
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Heparin: Nursing Diagnoses and Outcomes Heparin: Nursing Diagnoses and Outcomes
• Risk for Injury, Hemorrhage, related to heparin therapy
– Desired outcome: hemorrhage will not occur.
• Risk for Injury, Heparin-induced thrombocytopenia, related to heparin therapy
– Desired outcome: heparin-induced thrombocytopenia will not occur.
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Heparin: Planning and InterventionsHeparin: Planning and Interventions
• Maximizing therapeutic effects
– Monitor laboratory values.
– Heparin levels should be allowed to reach steady state before aPTT is measured.
• Minimizing adverse effects
– If the aPTT during treatment exceeds the desired range, the dosage should be decreased.
– Use an IV controller or pump for continuous IV drip heparin.
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Heparin: Teaching, Assessment, and EvaluationsHeparin: Teaching, Assessment, and Evaluations
• Patient and family education
– Inform patients why the drug is needed and what it is expected to accomplish.
– Instruct patients to report any bleeding.
• Ongoing assessment and evaluation
– Monitor for signs of bleeding and review aPTT values to maintain heparin levels in the therapeutic range.
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QuestionQuestion
• What is the antidote for heparin?
– A. Vitamin K
– B. Clotting factor XII
– C. Sodium sulfate
– D. Protamine sulfate
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AnswerAnswer
• D. Protamine sulfate
• Rationale: Protamine sulfate is the antidote for heparin.
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Warfarin: Core Drug Knowledge Warfarin: Core Drug Knowledge
• Pharmacotherapeutics
– Used prophylactically for patients with a long-term risk for thrombus formation
• Pharmacokinetics
– Administered: oral. Highly protein bound. Metabolism: liver. Excreted: bile
• Pharmacodynamics
– Competitively blocks vitamin K at its sites of action
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Warfarin: Core Drug Knowledge (cont.)Warfarin: Core Drug Knowledge (cont.)
• Contraindications and precautions
– Active bleeding or bleeding disorders
• Adverse effects
– Bleeding and hemorrhage
• Drug interactions
– Several drug–drug and drug–food interactions
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Warfarin: Core Patient Variables Warfarin: Core Patient Variables
• Health status
– Assess the availability of vitamin K.
• Life span and gender
– Consider the patient’s age before therapy begins.
• Lifestyle, diet, and habits
– Obtain information about the patient’s dietary habits.
• Environment
– Assess environment where drug will be given.
• Culture and inherited traits
– Inherited variations of P-450 may alter drug response
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Warfarin: Nursing Diagnoses and Outcomes Warfarin: Nursing Diagnoses and Outcomes
• Risk for Injury, Bleeding, related to adverse effects of warfarin
– Desired outcome: The patient will not experience bleeding.
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Warfarin: Planning and InterventionsWarfarin: Planning and Interventions
• Maximizing therapeutic effects
– Warfarin dosage should be individualized until PT or the INR is in therapeutic range.
• Minimizing adverse effects
– Assess the patient’s response to warfarin therapy.
– Antidote is vitamin K (phytonadione)
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Warfarin: Teaching, Assessment, and EvaluationsWarfarin: Teaching, Assessment, and Evaluations
• Patient and family education
– Teach patients the signs of bleeding and methods to prevent bleeding.
– Take the drug at the same time every day.
• Ongoing assessment and evaluation
– Monitor the patient’s PT or INR to determine the therapeutic effects of warfarin.
– Therapy is effective when a thrombus is prevented and bleeding does not occur.
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QuestionQuestion
• Warfarin dose is titrated based on what lab value?
– A. aPTT
– B. PT and INR
– C. Platelet count
– D. CBC
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AnswerAnswer
• B. PT and INR
• Rationale: Dosage is based on achieving a therapeutic level as measured by changes in the prothrombin time (PT) and International Normalized Ratio (INR).
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Antiplatelet Drugs Antiplatelet Drugs
• They are used when overactive platelets pose long-term risks for hypercoagulability.
• Platelet aggregation is important in hemostasis.
• Antiplatelet drugs reduce platelet aggregation.
• Antiplatelet drugs differ in their modes of action and adverse effects.
• Prototype drug: clopidogrel (Plavix)
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Clopidogrel: Core Drug Knowledge Clopidogrel: Core Drug Knowledge
• Pharmacotherapeutics
– Used to reduce atherosclerotic events
• Pharmacokinetics
– Administered: oral. Metabolism: liver. Protein bound
• Pharmacodynamics
– Inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP-mediated activation of the glycoprotein IIb/IIIa complex and thus inhibits platelet aggregation
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Clopidogrel: Core Drug Knowledge (cont.)Clopidogrel: Core Drug Knowledge (cont.)
• Contraindications and precautions
– Hypersensitivity and active bleeding disorders
• Adverse effects
– Bleeding, GI distress, and neutropenia
• Drug interactions
– Tamoxifen, tolbutamide, warfarin, torsemide, fluvastatin, and many NSAIDs
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Clopidogrel: Core Patient Variables Clopidogrel: Core Patient Variables • Health status
– Assess for any contraindications to therapy.
• Life span and gender
– Use caution in children younger than 18 years.
• Lifestyle, diet, and habits
– Assess for behaviors that would increased bleeding.
• Environment
– Be aware of the environment in which the drug will be administered.
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Clopidogrel: Nursing Diagnoses and Outcomes Clopidogrel: Nursing Diagnoses and Outcomes
• Risk for Injury: Increased Risk for Bleeding related to decreased platelet aggregation from drug therapy
– Desired outcome: The patient will suffer no injury related to bleeding while on clopidogrel.
• Risk for Nausea related to adverse effects of clopidogrel
– Desired outcome: Nausea and GI distress will not be extreme enough to warrant stopping clopidogrel therapy.
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Clopidogrel: Planning and InterventionsClopidogrel: Planning and Interventions
• Maximizing therapeutic effects
– Ensure that clopidogrel is administered routinely to achieve its maximum therapeutic effects.
• Minimizing adverse effects
– Take clopidogrel with food to decrease GI problems.
– Remember that severe neutropenia is a potential risk.
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Clopidogrel: Teaching, Assessment, and EvaluationsClopidogrel: Teaching, Assessment, and Evaluations
• Patient and family education
– Inform patients and families about laboratory tests that are needed on a regular basis.
– Emphasize to patients that behaviors that may lead to injury should be avoided.
• Ongoing assessment and evaluation
– Periodic measurement of bleeding time and platelet function is needed throughout clopidogrel therapy.
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QuestionQuestion
• What is the most serious adverse effect of clopidogrel?
– A. Bleeding
– B. Neutropenia
– C. Arrhythmia
– D. Seizure
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AnswerAnswer
• B. Neutropenia
• Rationale: Neutropenia is a potential risk of therapy.
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Hemorheologic Drugs Hemorheologic Drugs
• The hemorheologic drugs act on RBCs to reduce blood viscosity and increase the flexibility of RBCs.
• This effect helps prevent thrombus formation and allows the RBCs to enter the microcirculation.
• These effects are helpful in treating peripheral vascular disease.
• Prototype drug: pentoxifylline (Trental)
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Pentoxifylline: Core Drug Knowledge Pentoxifylline: Core Drug Knowledge
• Pharmacotherapeutics
– Manage symptoms of intermittent claudication.
• Pharmacokinetics
– Administered: oral. Distribution: wide. Metabolism: liver. Excreted: kidneys. Onset: 2 to 4 weeks
• Pharmacodynamics
– Increases cAMP levels and increases cellular adenosine triphosphate levels
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Pentoxifylline: Core Drug Knowledge (cont.)Pentoxifylline: Core Drug Knowledge (cont.)
• Contraindications and precautions
– Intolerance to methylxanthines
• Adverse effects
– Effects occur in central nervous, CV, and GI systems
• Drug interactions
– Interact with a few drugs
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Pentoxifylline: Core Patient Variables Pentoxifylline: Core Patient Variables
• Health status
– Hypersensitive to the drug or to methylxanthines
• Life span and gender
– Determine if pregnant or breast-feeding.
• Lifestyle, diet, and habits
– Document occupation and daily activities.
• Environment
– Assess environment where drug will be given.
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Pentoxifylline: Nursing Diagnoses and Outcomes Pentoxifylline: Nursing Diagnoses and Outcomes
• Risk for Injury related to adverse pentoxifylline effects (dizziness, drowsiness, and blurred vision)
– Desired outcome: The patient will remain injury free while on pentoxifylline.
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Pentoxifylline: Planning and InterventionsPentoxifylline: Planning and Interventions
• Maximizing therapeutic effects
– Pentoxifylline must be taken for several weeks before the full therapeutic effects are evident.
• Minimizing adverse effects
– Give pentoxifylline with food to minimize GI upset.
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Pentoxifylline: Teaching, Assessment, and EvaluationsPentoxifylline: Teaching, Assessment, and Evaluations
• Patient and family education
– Inform patients that pentoxifylline does not have an immediate effect.
– Instruct patients to keep all follow-up visits with the prescriber.
• Ongoing assessment and evaluation
– Peripheral circulation should be reassessed periodically to measure improvement.
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QuestionQuestion
• The full therapeutic effects of pentoxifylline are usually evident after
– A. One hour
– B. One day
– C. One week
– D. Several weeks
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AnswerAnswer
• D. Several weeks
• Rationale: Patients must be instructed to continue pentoxifylline as prescribed because it must be taken for several weeks before the full therapeutic effects are evident.
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Thrombolytic Drugs Thrombolytic Drugs • Thrombolytic drugs assist in breaking down formed blood
clots.
• These drugs are used for patients who are diagnosed with an evolving, acute MI; a PE; or acute ischemic stroke.
• They may also be given to unclog central venous catheters.
• These drugs may be given systemically or directly at the site of the blood clot.
• Although these drugs are given during emergency situations and can save lives, their adverse effects can be life threatening.
• Prototype drug: alteplase, recombinant (Activase; Cathflo Activase)
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Alteplase, Recombinant: Core Drug Knowledge Alteplase, Recombinant: Core Drug Knowledge
• Pharmacotherapeutics
– Thromboembolic conditions
• Pharmacokinetics
– Administered: IV. Rapidly cleared from the plasma
• Pharmacodynamics
– Acts in the same way as endogenous tPA
– Converts plasminogen to plasmin
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Alteplase, Recombinant: Core Drug Knowledge (cont.)Alteplase, Recombinant: Core Drug Knowledge (cont.)
• Contraindications and precautions
– Hypersensitivity and active internal bleeding
• Adverse effects
– Internal or superficial bleeding
• Drug interactions
– Interacts with anticoagulants and antiplatelet drugs
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Alteplase, Recombinant: Core Patient Variables Alteplase, Recombinant: Core Patient Variables
• Health status
– Assess conditions that contraindicate administering.
• Life span and gender
– Determine the patient’s age and pregnancy status.
• Environment
– Assess environment where drug will be given.
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Alteplase, Recombinant: Nursing Diagnoses and Outcomes Alteplase, Recombinant: Nursing Diagnoses and Outcomes
• Risk for Injury related to drug-induced bleeding from alteplase
– Desired outcome: The patient will not suffer injury from alteplase.
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Alteplase, Recombinant: Planning and InterventionsAlteplase, Recombinant: Planning and Interventions
• Maximizing therapeutic effects
– Reconstitute alteplase recombinant in sterile water for injection without preservatives.
• Minimizing adverse effects
– Closely and continually monitor vital signs and observe for signs of active bleeding
– The patient should be connected to a cardiac monitor, both during the treatment and afterward.
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Alteplase, Recombinant: Teaching, Assessment, and EvaluationsAlteplase, Recombinant: Teaching, Assessment, and Evaluations
• Patient and family education
– Emphasize to patients and families the need for frequent assessment, pressure dressings, and activity limitations.
– Instruct patients to notify their nurse if they experience signs of adverse reactions.
• Ongoing assessment and evaluation
– Vital signs, evidence of bleeding, and laboratory test results should be assessed throughout therapy with alteplase recombinant as described previously.
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QuestionQuestion
• Alteplase, recombinant is a pregnancy category ____ drug.
– A. A
– B. B
– C. C
– D. D
– E. X
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AnswerAnswer
• C. C
• Rationale: Alteplase, recombinant is a pregnancy category C drug.
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Clotting Factors Clotting Factors
• Deficiencies of normal blood clotting factors are associated with prolonged bleeding and clot formation times.
• These deficiencies result from an inherited absence of the factor.
• Replacement of these factors with clotting factors is the treatment of choice.
• Prototype drug: antihemophilic factor
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Antihemophilic Factor: Core Drug Knowledge Antihemophilic Factor: Core Drug Knowledge
• Pharmacotherapeutics
– Deficiency of clotting factor VIII, hemophilia A
• Pharmacokinetics
– Administered: IV. T½: 4 to 24 hours
• Pharmacodynamics
– Factor VIII is an essential component of blood clotting. It is required for the conversion of prothrombin to thrombin.
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Antihemophilic Factor: Core Drug Knowledge (cont.)Antihemophilic Factor: Core Drug Knowledge (cont.)
• Contraindications and precautions
– Hypersensitivity to mouse protein
• Adverse effects
– Anaphylaxis, urticaria, nausea, and chills
• Drug interactions
– No important interactions are associated with AHF.
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Antihemophilic Factor: Core Patient Variables Antihemophilic Factor: Core Patient Variables • Health status
– Assess labs prior to administration.
• Life span and gender
– Assess pregnancy status.
• Lifestyle, diet, and habits
– Assess for behaviors that might result in injury.
• Environment
– Generally self-administered at home
• Culture and inherited traits
– Religious views forbidding receiving blood products
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Antihemophilic Factor: Nursing Diagnoses and Outcomes Antihemophilic Factor: Nursing Diagnoses and Outcomes
• Risk for Injury, Hemorrhage, related to deficiency of clotting factor VIII
– Desired outcome: the patient will receive enough factor VIII to prevent injury.
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Antihemophilic Factor: Planning and InterventionsAntihemophilic Factor: Planning and Interventions
• Maximizing therapeutic effects
– Refrigeration is required for AHF until it is used.
– Before reconstitution, warm the concentrate and the diluent to room temperature.
• Minimizing adverse effects
– After dilution, administer AHF within 3 hours to prevent bacterial growth.
– Administer IV route only.
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Antihemophilic Factor: Teaching, Assessment, and EvaluationsAntihemophilic Factor: Teaching, Assessment, and Evaluations
• Patient and family education
– Instruct patients and families to observe for bleeding from gums, skin, urine, stools, or emesis.
– Caution patients to avoid products containing aspirin or ibuprofen.
• Ongoing assessment and evaluation
– Blood studies are monitored as previously described when AHF is administered.
– Therapy is effective when prolonged bleeding is prevented or stopped.
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QuestionQuestion
• Antihemophilic factor is prescribed for patients who demonstrate a deficiency of clotting factor
– A. IV
– B. VII
– C. VIII
– D. XII
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AnswerAnswer
• C. VIII
• Rationale: Patient’s with a demonstrated deficiency of clotting factor VIII can be given AHF to prevent and control excessive bleeding.
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Hemostatic Drugs Hemostatic Drugs
• Hemostatics stop blood loss by enhancing blood coagulation.
• There are two types of hemostatic agents: systemic and topical.
• Systemic agents interfere with the breakdown of clots.
• Topical agents are used to control small amounts of bleeding or oozing, usually following surgery.
• Prototype drug: aminocaproic acid (Amicar)
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Aminocaproic Acid: Core Drug Knowledge Aminocaproic Acid: Core Drug Knowledge
• Pharmacotherapeutics
– Life-threatening hemorrhage
• Pharmacokinetics
– Administered: oral or IV. Most of the drug is excreted unchanged in the urine
• Pharmacodynamics
– Blocks the action of plasminogen activators
– Interferes with the binding of active plasmin to fibrin
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Aminocaproic Acid: Core Drug Knowledge (cont.)Aminocaproic Acid: Core Drug Knowledge (cont.)
• Contraindications and precautions
– Active intravascular clotting disorders
• Adverse effects
– GI distress, headache, dizziness, seizures, hypotension, arrhythmias, tinnitus, nasal congestion, vomiting, abdominal cramps, diarrhea, and diuresis
• Drug interactions
– Oral contraceptives or estrogen
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Aminocaproic Acid: Core Patient Variables Aminocaproic Acid: Core Patient Variables
• Health status
– Identify contraindications to the drug. • Life span and gender
– Assess pregnancy and breast-feeding status.• Environment
– Administered in an acute care setting, such as a hospital
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Aminocaproic Acid: Nursing Diagnoses and Outcomes Aminocaproic Acid: Nursing Diagnoses and Outcomes
• Risk for Altered Cardiovascular Perfusion related to volume loss secondary to uncontrolled bleeding or thrombophlebitis secondary to adverse effects of aminocaproic acid
– Desired outcome: adequate perfusion will be maintained as evidenced by presence of pulses, normal skin color and warmth, and capillary refill.
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Aminocaproic Acid: Planning and InterventionsAminocaproic Acid: Planning and Interventions
• Minimizing adverse effects
– Monitor vital signs at start of therapy and throughout therapy.
– Administer drug via IV infusion pump.
– Monitor intake and output and monitoring neurologic status.
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Aminocaproic Acid: Teaching, Assessment, and EvaluationsAminocaproic Acid: Teaching, Assessment, and Evaluations
• Patient and family education
– Teach patients and families about the role of aminocaproic acid in controlling bleeding.
– Instruct to change position slowly.
• Ongoing assessment and evaluation
– Monitor the patient throughout treatment and recovery for signs and symptoms of bleeding or embolism or any other untoward event.
– Drug therapy is effective if bleeding is controlled.
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QuestionQuestion
• Which of the following class of drugs should be avoided when giving a patient aminocaproic acid?
– A. Oral contraceptives
– B. Antifungals
– C. Antiarrhythmics
– D. Proton pump blockers
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AnswerAnswer
• A. Oral contraceptives
• Rationale: An increase in clotting factors leading to hypercoagulation may occur if aminocaproic acid is administered concurrently with oral contraceptives or estrogen.