Medical Treatment For Heart Dysrhythmias PDF

1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… Introduction All drugs used to combat dysrhythmias alter the electrical conduction system of the heart. The drugs used for the treatment of tachydysrhythmias ar...

1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… Introduction All drugs used to combat dysrhythmias alter the electrical conduction system of the heart. The drugs used for the treatment of tachydysrhythmias are the focus of this section. They reduce automaticity, which is the spontaneous depolarization of myocardial cells, including ectopic pacemakers. They also slow conduction of electrical impulses through the heart and prolong the refractory period of myocardial cells so they are less likely to be prematurely activated by adjacent cells. Antidysrhythmic drug therapy is commonly indicated in the following conditions: conversion of atrial fibrillation or atrial flutter to normal sinus rhythm (NSR); maintaining NSR after conversion from atrial fibrillation or atrial flutter; suppression of a fast or irregular ventricular rate, which alters the cardiac output; altered cardiac output leads to symptoms of decreased coronary, cerebral, and/or systemic circulation; and presence of dangerous dysrhythmias that may be fatal if not quickly terminated. For example, ventricular tachycardia may cause cardiac arrest. The clinical use of antidysrhythmic drugs for tachydysrhythmias has changed over the years. Clinicians use drugs not just to suppress dysrhythmias but to prevent or relieve symptoms or prolong survival. Many of the agents used to treat dysrhythmias do, in fact, produce prodysrhythmic effects. Thus, rational drug therapy for cardiac dysrhythmia requires accurate identification of the dysrhythmia, understanding of the basic mechanisms causing the dysrhythmia, observation of the hemodynamic and electrocardiogram (ECG) effects of the dysrhythmia, knowledge of the pharmacologic actions of specific antidysrhythmic drugs, and the expectation that therapeutic effects will outweigh potential adverse effects. Even when these criteria are met, antidysrhythmic drug therapy is somewhat empiric. Several different groups of drugs function as antidysrhythmics. They are classified according to their mechanisms of action and effects on the conduction system, even though they differ in other respects. Some drugs have characteristics of more than one group. There are various types of antidysrhythmics: class I sodium channel blockers, class II beta-adrenergic blockers, class III potassium channel blockers, and class IV calcium channel blockers. This section will build on previous knowledge of dysrhythmias by incorporating pharmacological treatments. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9aojXmGqF3… 1/36 1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9aojXmGqF3… 2/36 1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… Medical Management Management depends on the cause and symptoms. Resolving the causative factors may be the only treatment needed. If the bradycardia produces signs and symptoms of clinical instability (e.g., acute alteration in mental status, chest discomfort, or hypotension), 0.5 mg of atropine may be given rapidly as an intravenous (IV) bolus and repeated every 3 to 5 minutes until a maximum dosage of 3 mg is given. Administration of adenosine should be considered to interrupt the tachycardia. If the tachycardia is persistent and causing hemodynamic instability (e.g., acute alteration in mental status, chest discomfort, hypotension), synchronized cardioversion (i.e., electrical current given in synchrony with the patient’s own QRS complex to stop an arrhythmia) is the treatment of choice, if vagal maneuvers and adenosine are unsuccessful or not feasible. IV beta-blockers (Class II antiarrhythmic) and calcium channel blockers (Class IV antiarrhythmic) may also be considered in treating hemodynamically stable sinus tachycardia, although synchronized cardioversion may be used if medications are ineffective or contradicted (Page, Joglar, Caldwell, et al., 2016). Catheter ablation (see later discussion) of the SA node may be used in cases of persistent inappropriate sinus tachycardia unresponsive to other treatments. Treatment for POTS often involves a combination of approaches, with treatment targeted at the underlying problem. For example, patients with hypovolemia may be advised to increase their fluid and sodium intake, or use salt tablets if necessary. Sinus arrhythmia does not cause any significant hemodynamic effect and therefore is not typically treated. If PACs are infrequent; no treatment is necessary. If they are frequent (more than six per minute), this may herald a worsening disease state or the onset of more serious arrhythmias, such as atrial fibrillation. Medical management is directed toward treating the underlying cause (e.g., reduction of caffeine intake, correction of hypokalemia). Antithrombotic Medications. Antithrombotic drugs may include anticoagulants and antiplatelet drugs. Oral antithrombotic therapy is indicated for most patients with nonvalvular atrial fibrillation (e.g., absence of mechanical heart valve) because it reduces the risk of stroke https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9aojXmGqF3… 3/36 1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… (January et al., 2014, 2019). Atrial fibrillation guidelines recommend use of a scoring system to assist in assessment of stroke risk. Antithrombotic therapy is then selected based on risk factors outlined in the mnemonic CHA2DS2-VASC (see Chart 22-4) with each risk factor assigned points tallied for a total score that indicates an overall risk of stroke (January et al., 2014, 2019). According to pharmacologic treatment guidelines (January et al., 2014, 2019): •Patients with nonvalvular atrial fibrillation with a CHA2DS2-VASC score of zero may choose the option of no antithrombotic therapy. •Patients with nonvalvular atrial fibrillation with a CHA2DS2-VASC score of one may choose no antithrombotic therapy, treatment with an oral anticoagulant, or aspirin. •Patients with nonvalvular atrial fibrillation with a CHA2DS2-VASC score of 2 or higher for men and 3 or higher for women may choose warfarin, or a direct thrombin inhibitor (e.g., dabigatran), or a Factor Xa inhibitor (e.g., rivaroxaban, apixaban, edoxaban). Patients with atrial fibrillation with valvular heart disease or bioprosthetic heart valves may be prescribed warfarin, or a direct-acting oral anticoagulant, or a Factor Xa inhibitor (Malik, Yandrapalli, Aronow, et al., 2019). For patients with mechanical heart valves, warfarin is recommended (January et al., 2014, 2019). If immediate or short-term anticoagulation is necessary, the patient may be placed on IV or low– molecular-weight heparin until warfarin therapy can be started and the international normalized ratio (INR) level reaches a therapeutic range consistent with antithrombosis, usually defined as an INR between 2.0 and 3.0. Medication selection for all patients with atrial fibrillation depends upon stroke and bleeding risks as well as patient preferences and values (January et al., 2014, 2019). For instance, treatment with warfarin will require weekly INR testing during initiation of therapy, as well as ongoing monitoring. Home monitoring of therapy is an option for some patients. Direct-acting oral anticoagulants and Factor Xa inhibitors require baseline assessment of hemoglobin and hematocrit, as well as liver and renal function, along with INR. Advantages of these medications include fewer drug–drug interactions and dietary limitations, as well as the elimination of frequent INR testing. Medications that Control the Heart Rate. A strategy to control the ventricular rate of response so that the resting heart rate is less than 80 bpm is recommended in order to manage symptoms of atrial fibrillation (January et al., 2014, 2019). To decrease the ventricular rate in patients with paroxysmal, persistent, or permanent atrial fibrillation, a beta-blocker or non-dihydropyridine calcium channel blocker is generally recommended (January et al., 2014, 2019). Medications that Convert the Heart Rhythm or Prevent Atrial Fibrillation. For patients with atrial fibrillation lasting 48 hours or longer, anticoagulation is recommended prior to attempts to restore sinus rhythm, which may be achieved through pharmacologic or electrical cardioversion (January et al., 2014, 2019). In the absence of therapeutic anticoagulation, TEE may be performed prior to cardioversion to identify left atrial thrombus formation, including in the LAA (January et al., 2014, 2019). If no thrombus is identified, cardioversion can proceed. Medications that may be given to achieve pharmacologic cardioversion to sinus rhythm include flecainide, dofetilide, propafenone, amiodarone, and IV ibutilide (January et al., 2014, 2019). These medications are most effective if given within 7 days of the onset of atrial fibrillation. It is recommended that patients who were prescribed dofetilide be hospitalized so that the QT interval and renal function both may be monitored. Despite a degree of risk, dofetilide is a preferred medication because it is highly effective at converting atrial fibrillation to sinus rhythm, has fewer drug-to-drug interactions, and is better tolerated by patients than other medications. Some patients with recurrent atrial fibrillation may be prescribed flecainide to self-administer at home, an approach referred to as “pill in the pocket” (January et al., 2014, 2019). Preoperative administration of beta-blockers has resulted in a significant reduction in atrial fibrillation after cardiac surgery (Burrage, Low, Campbell, et al., 2019). Cholesterol-lowering drugs such as the HMG-CoA reductase inhibitors may also be prescribed to prevent newonset atrial fibrillation following cardiac surgery (Burrage et al., 2019). https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9aojXmGqF3… 4/36 1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… If symptomatic, paroxysmal atrial fibrillation is refractory to at least one Class I or Class III antiarrhythmic medication (see Table 22-1), and rhythm control is desired, catheter ablation may be indicated (January et al., 2014, 2019 Atrial flutter is treated with antithrombotic therapy, rate control, and rhythm control in the same manner as atrial fibrillation (January et al., 2014, 2019). Overview of Anti-arrhythmic Drugs Drug Therapy Atropine is the anticholinergic drug most often used for its cardiovascular effects. According to the Advanced Cardiac Life Support (ACLS) protocol, atropine is the drug of choice to treat symptomatic sinus bradycardia. Low doses (less than 0.5 mg) may produce a slight and temporary decrease in heart rate; however, moderate to large doses (0.5–1 mg) increase heart rate by blocking parasympathetic vagal stimulation. Although the increase in heart rate may be therapeutic in bradycardia, it can be an adverse effect in patients with other types of heart disease because atropine increases the myocardial oxygen demand. Atropine usually has little or no effect on blood pressure. Large doses cause facial flushing because of the dilation of blood vessels in the neck. Belladonna Alkaloid and Derivatives Atropine sulfate, the prototype of the anticholinergic drugs, is a naturally occurring belladonna alkaloid that can be extracted from the belladonna plant or prepared synthetically. It is usually prepared as atropine sulfate, a salt that is very soluble in water. Atropine sulfate is also classified as a muscarinic antagonist. Pharmacokinetics Atropine is well absorbed after all forms of administration. The peak effect occurs in 0.7 to 4 minutes with intravenous (IV) preparations, 30 minutes with intramuscular (IM) preparations, 1 to 2 hours with subcutaneous preparations, and 1.5 to 4 hours with inhalation preparation. The pharmacologic effects last for about 4 hours, except for ocular effects, which last for up to 2 weeks in normal eyes. The drug is absorbed systemically when applied locally to mucous membranes. Atropine crosses the blood–brain barrier and enters the CNS, where large doses produce stimulant effects and toxic doses produce depressant effects. It is metabolized in the liver and rapidly excreted in the urine. Atropine crosses the placenta and enters the breast milk. Action Atropine competitively blocks the effects of acetylcholine at muscarinic cholinergic receptors that mediate the effects of parasympathetic postganglionic impulses. It also prevents the action of acetylcholine in the CNS. Atropine depresses the salivary and bronchial secretions, dilates the bronchi, and increases cardiac output; large doses can decrease the motility of the GI and GU tracts. In addition, it relaxes the pupil of the eye and prevents the accommodation for near vision. Use In the past, atropine was used to control the symptoms of Parkinson’s disease—to relieve tremors and decrease rigidity. The development of the centrally acting anticholinergic agents has replaced the use of atropine for Parkinson’s disease. Impaired renal or hepatic function is a contraindication to the use of atropine. The most common use of atropine is the restoration of cardiac rate and arterial pressure during anesthesia when vagal stimulation produced by intra-abdominal traction causes a decrease in pulse rate, lessening the degree of atrioventricular block when increased vagal tone is a factor. Atropine also relieves bradycardia and syncope due to hyperactive carotid sinus reflex. It also serves as an antidote for cardiac collapse with an overdose of parasympathomimetic drugs also known as cholinergic agents and cholinesterase inhibitors such as physostigmine. Also, practitioners administer atropine in the preanesthesia stage to reduce respiratory tract secretions. In addition, atropine is an antidote for mushroom poisoning (Amanita muscaria). Symptoms of muscarinic poisoning include salivation, lacrimation, visual disturbances, bronchospasm, diarrhea, bradycardia, and hypotension. Atropine prevents the poison from interacting with muscarinic receptors, thus reversing the toxic effects. Muscarinic poisoning can also occur from cholinergic agonist drugs, cholinesterase inhibitor drugs, and insecticides that contain organophosphates. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9aojXmGqF3… 5/36 1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… Use in Children Systemic anticholinergics, including atropine, have essentially the same indications in children of all ages as in adults. Anticholinergic drugs cause the same adverse effects in children as in adults. However, the effects may be more severe in children, who are especially sensitive to these drugs. Facial flushing is common, and skin rashes may occur. In addition, the administration of atropine sulfate to children can cause hyperpyrexia or atropine fever. Use in Older Adults It is necessary to administer atropine cautiously in the geriatric population. In older adults, CNS reactions are more likely to occur. Use in Patients With Critical Illness When atropine is administered for cardiovascular symptoms, it is necessary to monitor the patient's cardiac status with an electrocardiogram. Adverse Effects Atropine sulfate may adversely affect several body systems. Cardiovascular adverse effects include bradycardia (low doses) and tachycardia (high doses). CNS adverse effects include blurred vision, mydriasis, cycloplegia, photophobia, and increased intraocular pressure. In the geriatric population, nervousness, weakness, confusion, and excitement are common. The most severe GI adverse effect is paralytic ileus. Genitourinary effects are urinary hesitancy and retention. The patient may also complain of decreased sweating, which leads to heat prostration. Overdose of atropine or other anticholinergic drugs produces the usual pharmacologic effect such as decreased secretions, increased heart rate, relaxation of the bronchial smooth muscle, and decreased GI and genitourinary tone in severe and exaggerated forms. The anticholinergic overdose syndrome is characterized by hyperthermia; hot, dry, flushed skin; dry mouth; mydriasis; delirium; tachycardia; paralytic ileus; and urinary retention. Myoclonic movements and choreoathetosis may be evident. Seizures, coma, and respiratory arrest may also occur. Treatment involves the use of activated charcoal to absorb the ingested drug. Hemodialysis, hemoperfusion, peritoneal dialysis, and repeated doses of charcoal are not effective. Physostigmine salicylate (Antilirium), an acetylcholinesterase inhibitor, is a specific antidote for overdose of anticholinergics. It is usually given intravenously at a slow rate of 1 mg/min because rapid administration may cause bradycardia, hypersalivation (with subsequent respiratory distress), and seizures. The IM/IV adult dose is 0.5 to 2 mg, IM or IV, and may be repeated every 10 to 30 minutes until a response is achieved. Additional doses may be required for life-threatening anticholinergic effects. For infants, children, and adolescents, give IM or IV at an initial dose of 0.02 mg/kg, with a maximum dose of 2 mg. The drug should be administered IV no faster than 0.5 mg/min to prevent bradycardia, respiratory distress, and seizures. The pediatric dose is warranted only for life-threatening cases. For infants, children, and adolescents, give IM or IV at an initial dose of 0.02 mg/kg, with a maximum dose of 2 mg. Administer IV no faster than 0.5 mg/min to prevent bradycardia, respiratory distress, and seizures. Repeated doses may be given every 5 to 10 minutes if life-threatening dysrhythmias, convulsions, or coma occurs with anticholinergic overdose. However, the benefit of repeat dosing must be balanced against the risk of physostigmine overdose. Excessive administration of physostigmine can precipitate a cholinergic crisis, leading to seizures and dysrhythmias. Atropine is the antidote for physostigmine overdose. Diazepam or a similar drug may be given for excessive CNS stimulation (e.g., delirium, excitement) that accompanies anticholinergic toxicity. Ice bags, cooling blankets, and tepid sponge baths may help reduce fever. Artificial ventilation and cardiopulmonary resuscitative measures are used if excessive depression of the CNS causes coma and respiratory failure. Infants, children, and the elderly are especially susceptible to the toxic effects of anticholinergic drugs. Contraindications Contraindications to the use of atropine include a known hypersensitivity to anticholinergic agents. Other contraindications include glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, bronchial asthma, bladder neck obstruction, and hepatic or renal disease. Nursing Implications Preventing Interactions Drugs that increase the anticholinergic effects of atropine include amantadine, antihistamines, tricyclic antidepressants, quinidine, disopyramide, and procainamide. Some herbs also increase the effectiveness of atropine. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9aojXmGqF3… 6/36 1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… Herb and Dietary Interactions: Atropine Sulfate Herbs and Foods That Increase the Effects of Atropine Sulfate Aloe Cascara Senna Administering the Medication Before administering atropine, the nurse assesses for hypersensitivity to anticholinergic agents, glaucoma, stenosing peptic ulcer, paralytic ileus, bronchial asthma, bladder neck obstruction, and cardiac dysrhythmias. The patient should be well hydrated, and the environment should be cool to protect from hyperpyrexia. If the patient has a history of urinary retention, the patient should void before administering the drug. Assessing for Therapeutic Effects The nurse assesses the heart rate if atropine is administered for bradycardia. In preoperative patients, the nurse assesses for diminished secretions, particularly when the drug is administered for head and neck surgery. Patients with Parkinson’s disease or Parkinson-like syndromes require assessment for decreased spasticity and tremors. Assessing for Adverse Effects The nurse assesses for the following conditions, which may indicate a severe anticholinergic reaction: Changes in rate, quality, and rhythm of the heart that indicates ventricular tachycardia Urinary retention Bowel sounds for signs of paralytic ileus Photophobia, mydriasis, blurred vision, and increased intraocular pressure Dry mouth Increased temperature. Elderly people and children are prone to hyperpyrexia due to suppression of perspiration and heat loss. Patient Teaching Patient Teaching Guidelines for Atropine Sulfate Avoid excessive high temperatures. Drink water frequently. Rinse the mouth frequently. Maintain good dental hygiene. Use hard candy to decrease dry mouth. Void before taking the medication. Visit the ophthalmologist regularly. Notify your prescriber if fluid intake is greater or less than urine output. Notify your prescriber if you develop a fever. Notify your prescriber if weakness becomes severe. Avoid the use of machinery if visual acuity or alertness is impaired. Unclassified Antidysrhythmic Drugs Adenosine (Adenocard), a naturally occurring component of all body cells, differs chemically from other antidysrhythmic drugs but acts like the calcium channel blockers. It depresses conduction at the AV node and is used to restore NSR in patients with paroxysmal supraventricular tachycardia; it is ineffective in other dysrhythmias. The drug has a very short duration of action (serum half-life of less than 10 seconds) and a high degree of effectiveness. It must be given by a rapid bolus injection, preferably through a central venous line. If given slowly, it is eliminated before it can reach cardiac tissues and exert its action. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9aojXmGqF3… 7/36 1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… Magnesium sulfate is another of the unclassified drugs given intravenously in the management of severe tachydysrhythmias, including treatment of torsades de pointes and management of digitalis-induced dysrhythmias. Its antidysrhythmic effects may derive from imbalances of magnesium, potassium, and calcium. Hypomagnesemia increases myocardial irritability and is a risk factor for both atrial and ventricular dysrhythmias. Thus, serum magnesium levels should be monitored in patients at risk and replacement therapy instituted when indicated. However, magnesium sulfate seems to have antidysrhythmic effects in some instances, even when serum magnesium levels are normal. Review Content Heparin is a pharmaceutical preparation of the natural anticoagulant produced primarily by mast cells in pericapillary connective tissue, and it is the prototype anticoagulant. Endogenous heparin is found in various body tissues, most abundantly in the liver and lungs. Exogenous heparin is obtained from bovine lung or porcine intestinal mucosa and standardized in units of biologic activity. Pharmacokinetics It is necessary to give heparin intravenously or subcutaneously, because the gastrointestinal (GI) tract does not absorb the drug. After IV injection, the drug acts immediately. After subcutaneous injection, heparin acts within 20 to 30 minutes. Metabolism takes place in the liver and the reticuloendothelial system. Excretion, primarily in the form of inactive metabolites, occurs in the urine. Hemodialysis does not remove it. Action Heparin combines with antithrombin III (a natural anticoagulant in the blood) to inactivate clotting factors IX, X, XI, and XII; inhibit the conversion of prothrombin to thrombin; and prevent thrombus formation. After thrombosis has developed, heparin can inhibit additional coagulation by inactivating thrombin, preventing the conversion of fibrinogen to fibrin, and inhibiting factor XIII (fibrin-stabilizing factor). Other effects include inhibition of factors V and VIII and platelet aggregation. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9aojXmGqF3… 8/36 1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… Figure 9.1. Details of the intrinsic and extrinsic clotting pathways. The sites of action of some of the drugs that can influence these processes are shown in red. Use Prophylactically, patients at risk for certain disorders take low doses of heparin prophylactically to prevent DVT and pulmonary embolism. These disorders include the following: Major illnesses (e.g., acute myocardial infarction, heart failure, serious pulmonary infections, stroke) Major abdominal or thoracic surgery A history of thrombophlebitis or pulmonary embolism, including in pregnant women Gynecologic surgery, especially in patients who have been taking estrogens or oral contraceptives or have other risk factors for DVT Restrictions such as bed rest or limited activity expected to last longer than 5 days Therapeutically, patients receive heparin to manage acute thromboembolic disorders (e.g., DVT, thrombophlebitis, pulmonary embolism). In these conditions, therapy aims to prevent further thrombus formation and embolization. Another use is in disseminated intravascular coagulation (DIC), a life-threatening condition characterized by widespread clotting, which depletes the blood of coagulation factors. The depletion of coagulation factors then produces widespread bleeding. The goal of heparin therapy in DIC is to prevent blood coagulation long enough for clotting factors to be replenished and thus control hemorrhage. In addition, clinicians use heparin to prevent clotting during cardiac and vascular surgery, extracorporeal circulation, hemodialysis, blood transfusions, and blood samples used in laboratory tests. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9aojXmGqF3… 9/36 1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… Heparin does not cross the placental barrier and is not secreted in breast milk, making it the anticoagulant of choice for use during pregnancy and lactation. Use in Children Little information about the use of anticoagulants in children is available. When children take heparin for systemic anticoagulation, weight is the basis for determining dosage (~50 units/kg). It is essential to use extreme caution to ensure that the vial concentration of heparin is correct. Fatalities in infants involving heparin overdoses have occurred. In addition, premature infants should not take heparin solutions containing benzyl alcohol as a preservative; fatal reactions have resulted. QSEN Alert: Technology Several major adverse events have resulted from the use of heparin, and it is classified as a high-alert drug. Nurses demonstrate consistent practic heightened individual awareness of the risks and by advocating for systems to account for human error, such as bar coding and “smart” pumps. Eff safety and quality include special safeguards to reduce the risk of errors that may harm the patient. Use in Older Adults Older adults often have atherosclerosis and thrombotic disorders, including myocardial infarction, thrombotic stroke, and peripheral arterial insufficiency, for which they receive an anticoagulant drug. They are more likely than younger adults to experience bleeding and other complications associated with this therapy. With standard heparin, general principles for safe and effective use apply. With LMWHs (Low Molecular Weight Heparin), elimination may be delayed in older adults with renal impairment. The drugs should be used cautiously. Use in Patients With Renal Impairment People with renal impairment may take heparin in usual dosages. However, the half-life of the drug may increase. Use in Patients With Hepatic Impairment Likewise, people with hepatic impairment may take heparin in usual dosages. However, the half-life of the drug may increase or decrease. Use in Patients With Critical Illness Heparin is often used in patients who are critically ill. However, the risk of bleeding is increased in the presence of other coexisting conditions. People who are critically ill have a high risk of DVT and pulmonary embolism as well as a higher morbidity and mortality, including an increase in length of hospital stay, the need and duration of mechanical ventilation, and death. Effective prevention and treatment of thrombosis are necessary and typically include LMWHs. In addition, it is essential to consider intermittent pneumatic compression devices and other measures to prevent DVT or pulmonary embolism. Use in Patients Receiving Home Care Patients may take standard heparin at home using the subcutaneous route. The use of LMWHs for home management of venous thrombosis has become standard practice. Daily visits by a home care nurse may be necessary if the patient or a family member is unable or unwilling to inject the medication. It is essential to take platelet counts before therapy begins and every 2 to 3 days during heparin therapy. If the platelet count falls below 100,000 platelets per microliter of blood or to less than half the baseline value, it is necessary to discontinue the heparin. Adverse Effects Hemorrhage is the major side effect of heparin therapy. Hypersensitivity to the drug has occurred, and local irritation with subcutaneous injections of heparin can cause erythema and mild pain. Heparin-induced thrombocytopenia (HIT) (type II) is a potentially life-threatening complication of heparin administration, leading to a decrease in platelet count and detectable HIT antibodies. This condition occurs in 1% to 3% of people receiving heparin at therapeutic levels for 4 to 14 days, sometimes sooner in those who have previously received heparin. HIT is one of the most common immune-mediated adverse drug reactions. All patients exposed to any heparin at therapeutic or prophylactic doses, even minute amounts in heparin flushes or on heparin-coated catheters as well as those receiving LMWH, are at risk. If HIT occurs, it is necessary to discontinue all heparin and manage anticoagulation with a DTI such as argatroban. Contraindications Contraindications include GI ulcerations (e.g., peptic ulcer disease, ulcerative colitis), intracranial bleeding, dissecting aortic aneurysm, blood dyscrasias, severe kidney or liver disease, severe hypertension, polycythemia vera, and recent surgery of the eye, spinal cord, or brain. Caution is necessary in patients with hypertension, renal or hepatic disease, alcoholism, history of GI ulcerations, drainage tubes https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9aojXmGqF… 10/36 1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… (e.g., nasogastric tubes, indwelling urinary catheters), threatened abortion, endocarditis, and any occupation with high risks of traumatic injury. Nursing Implications Preventing Interactions Many medications interact with heparin, increasing or decreasing its effect (Box 9.2). Some herbs and foods increase the effects of the drug. No herbs or foods that decrease the effects of heparin have been identified. BOX 9.2 Drug Interactions: Heparin Drugs That Increase the Effects of Heparin Alteplase, direct thrombin inhibitors, platelet inhibitors Increase the risk of bleeding Antithrombin Increases pharmacologic effects Cephalosporins Lead to potential coagulopathies and risk of bleeding Penicillins (parenteral) Lead to altered platelet aggregation and increased risk of bleeding Warfarin May prolong and possibly invalidate the PT; if receiving both heparin and warfarin, draw blood for the PT at least 5 hours after the last IV heparin d Drugs That Decrease the Effects of Heparin Antihistamines, digoxin, nicotine, nitroglycerin (IV), tetracycline Decrease the anticoagulant effect BOX 9.3 Herb and Dietary Interactions: Heparin Herbs and Foods That Increase the Effects of Heparin Chamomile, garlic, ginger, ginkgo, ginseng, high-dose vitamin E Administering the Medication Traditional anticoagulants have two significant limitations: a narrow therapeutic window of adequate anticoagulation without bleeding and a highly variable individual dose–response that requires monitoring by laboratory testing. Prescribers use the activated partial thromboplastin time (aPTT), which is sensitive to changes in blood clotting factors, except factor VII, to regulate heparin dosage. Thus, normal or control values of aPTT indicate normal blood coagulation, and therapeutic values of adequate anticoagulation indicate low levels of clotting factors and delayed blood coagulation. The aPTT should be maintained at approximately 1.5 to 2.5 times the control or baseline value during heparin therapy. The normal control value is 25 to 35 seconds; therefore, the therapeutic values of adequate anticoagulation are approximately 45 to 70 seconds. With continuous IV infusion, blood for the aPTT may be drawn at any time; with intermittent administration, blood for the aPTT should be drawn approximately 1 hour before a dose of heparin is scheduled. It is unnecessary to monitor aPTT with low-dose standard heparin given subcutaneously for prophylaxis of thromboembolism or with the LMWHs (e.g., enoxaparin). The nurse should be aware that heparin has disadvantages; parenteral injection is necessary, and the drug has a short duration of action, which means there is a need for frequent administration. Assessing for Therapeutic Effects The nurse assesses for the absence or reduction of signs and symptoms of thrombotic disorders (e.g., less edema and pain with DVT, less chest pain and respiratory difficulty with pulmonary embolism, absence of uncontrolled bleeding). It is also necessary to ensure that aPTT values are within the therapeutic range. Assessing for Adverse Effects The nurse assesses the patient for signs of overt bleeding or HIT. Protamine sulfate is an antidote for standard heparin and LMWHs. Protamine is typically given when hemorrhaging is present or for bleeding that may not respond to merely withdrawing the heparin. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9aojXmGqF… 11/36 1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… Patient Teaching Education related to bleeding risk is essential for patients receiving heparin. The nurse reinforces instructions for safe use of the drug and related anticoagulants, reminding patients to obtain laboratory tests. Additionally, the nurse teaches the patient how to observe for signs and symptoms of bleeding. General Considerations Anticoagulant drugs are given to people who have had or are at risk of having a heart attack, stroke, or other problems from blood clots. For home management of deep vein thrombosis, which usually occurs in the legs, heparin injections are likely to be given for a few days, followed by warfarin for long-term therapy. These medications help prevent the blood clot from getting larger, traveling to the lungs, or recurring later. All anticoagulants can increase the risk of bleeding, so safety precautions need to be taken to prevent injury. To help prevent blood clots from forming and decreasing blood flow through the arteries, risk factors contributing to cardiovascular disease need to be reduced. This can be done by a low-fat, low-cholesterol diet (and medication if needed) to lower total cholesterol to below 200 mg/dL and low-density lipoprotein cholesterol to below 130 mg/dL; weight reduction if overweight; control of blood pressure if hypertensive; avoidance of smoking; stress-reduction techniques; and regular exercise. To help maintain a steady level of anticoagulation with warfarin, do not change the intake of foods high in vitamin K, which decreases the effects of warfarin. These foods include broccoli, brussels sprouts, cabbage, cauliflower, chives, collard greens, kale, lettuce, mustard greens, peppers, spinach, tomatoes, turnips, and watercress. To help prevent blood clots from forming in the leg veins, avoid or minimize situations that slow blood circulation, such as wearing tight clothing, crossing the legs at the knees, prolonged sitting or standing, and bed rest. For example, on automobile trips, stop and walk around every 1 to 2 hours; on long plane trips, exercise the feet and legs in the seat and walk around when possible. Following instructions regarding these medications is critical. Too little medication increases the risk of problems from blood clot formation; too much medication can cause bleeding. While taking any of these medications, regular medical supervision and periodic blood tests are needed. The blood tests can help the health care provider regulate drug dosage and maintain safety. Notify the health care provider if there is a sudden stop in tobacco smoking because this may result in a reduced clearance of warfarin. A dosage change may be necessary. With enoxaparin, an injection is needed, usually every 12 hours. The patient or someone close to the patient may be instructed in injecting the medication, or a visiting nurse may do the injections, if necessary. Take the drugs as directed. Avoid taking other drugs without the health care provider's knowledge and consent, inform any health care provider (including dentists) that you are taking an anticoagulant drug before any invasive diagnostic tests or treatments are begun, and keep all appointments for continuing care. With warfarin therapy, the patient needs to avoid walking barefoot; avoid contact sports; use an electric razor; avoid injections when possible; and carry an identification card, necklace, or bracelet (e.g., MedicAlert) stating the name of the drug and the health care provider's name and telephone number. A routine blood test is necessary to ensure that the warfarin dose is appropriate. The results of this test determine the daily dose of warfarin. Once the warfarin dose stabilizes, the blood tests are done less often (e.g., every 2 weeks). Report any sign of bleeding (e.g., excessive bruising of the skin, blood in urine or stool). If superficial bleeding occurs, apply direct pressure to the site for 3 to 5 minutes or longer if necessary. Self-Administration With enoxaparin, wash hands and cleanse the skin to prevent infection; inject deep under the skin, around the navel, upper thigh, or buttocks; and change the injection site daily. If excessive bruising occurs at the injection site, rubbing an ice cube over an area before the injection may be helpful. With warfarin, as with all medications, take as prescribed. Because the prescriber may set a dosing schedule that could vary from one day to the next, do not rely on memory but keep a written record of the date and the amount of medication taken. Other Drugs in the Class LMWHs (Low Molecular Weight Heparin) are synthetic heparins, have smaller molecular structures, and efficiently inactivate factor Xa via antithrombin. The drugs are as effective as IV heparin in treating thrombotic disorders and provide a more predictable anticoagulant response at recommended doses. The drugs do not cross the placenta. Indications for their use include prevention or management of thromboembolic complications associated with surgery or ischemic complications of unstable angina and myocardial infarction. The currently available LMWHs, dalteparin (Fragmin) and enoxaparin (Lovenox), differ from standard heparin and each other; therefore, they are not interchangeable. LMWHs are typically given subcutaneously in fixed or weight-based dosing without monitoring of blood coagulation. These characteristics simplify outpatient anticoagulant therapy and safety. Enoxaparin may be administered intravenously in specific situations but should not be given intramuscularly. The drugs are also associated with less thrombocytopenia than is standard heparin. However, monitoring platelet counts during therapy is necessary. With significant bleeding, protamine sulfate may be considered. Although it does not completely neutralize LMWHs, clinical bleeding may be reduced. The Institute for Safe Medication Practices (ISMP) classifies the LMWHs as high-alert drugs because there is a possible risk of significant harm when the drugs are used in error. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9aojXmGqF… 12/36 1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… Vitamin K Antagonists Warfarin (Coumadin) is the most commonly used oral anticoagulant and is the prototype vitamin K antagonist. Pharmacokinetics Warfarin is well absorbed after oral administration. Administration with food may delay the rate but not the extent of absorption. The drug is highly bound to plasma proteins (98%), mainly albumin. Metabolism takes place in the liver. Excretion, primarily as inactive metabolites, occurs in the kidneys. Renal impairment does not affect drug metabolism but may decrease the excretion of the drug. Action Warfarin acts in the liver to prevent the synthesis of vitamin K–dependent clotting factors (i.e., factors II, VII, IX, and X). Like vitamin K in structure, warfarin acts as a competitive antagonist to hepatic use of vitamin K. Conversely, vitamin K serves as the antidote for warfarin. Warfarin does not affect circulating clotting factors or on platelet function, so the anticoagulant effects do not occur for 3 to 5 days after warfarin is started because clotting factors already in the blood follow their normal elimination pathway. Use Warfarin is most useful in the long-term prevention or management of venous thromboembolic disorders, including DVT, pulmonary embolism, and embolization associated with atrial fibrillation and prosthetic heart valves. In addition, warfarin therapy after myocardial infarction may decrease reinfarction, stroke, venous thromboembolism, and death. The smaller doses used now are equally effective as those used formerly, with similar antithrombotic effects and decreased bleeding risks. Use in Children After cardiac surgery, children receive warfarin to prevent thromboembolism, but there are no established doses and guidelines for safe, effective use. Accurate drug administration, close monitoring of blood coagulation tests, safety measures to prevent trauma and bleeding, avoiding interacting drugs, and informing others in the child's environment (e.g., teachers, babysitters, health care providers) are necessary. Use in Older Adults Warfarin metabolism may be altered in older adults. As patient age increases, a lower dose of warfarin is usually required to produce a therapeutic effect. Use in Patients With Hepatic Impairment Warfarin is more likely to cause bleeding in patients with hepatic disease because of decreased synthesis of vitamin K and decreased plasma proteins. In addition, only the liver eliminates warfarin; thus, it may accumulate in people with hepatic impairment, and dosage adjustment may be necessary. Use in Patients With Critical Illness Because the anticoagulant and antithrombotic effects of warfarin take several days to occur, critically ill patients require concurrent treatment with other anticoagulants, such as heparin or LMWHs. Heparin is usually continued until the international normalized ratio (INR) is the therapeutic range. Use in Patients Receiving Home Care For prevention of DVT, warfarin is usually self-administered at home, with periodic office or clinic visits for blood tests and other follow-up care. For home management of DVT, warfarin may be self-administered. However, a nurse usually visits, performs a fingerstick INR, and notifies the prescriber, who then prescribes the appropriate dose of warfarin. Precautions to decrease the risks of bleeding are necessary. However, the risk of bleeding has decreased in recent years because lower doses of warfarin are now used. In addition, medical conditions other than anticoagulation may cause bleeding during warfarin therapy. Adverse Effects The primary adverse effect associated with warfarin therapy is hemorrhage. Additionally, nausea, vomiting, abdominal pain, alopecia, urticaria, dizziness, and joint or muscle pain may occur. Contraindications Contraindications to warfarin include GI ulcerations, blood disorders associated with bleeding, severe kidney or liver disease, severe hypertension, and recent surgery of the eye, spinal cord, or brain. Caution is warranted in patients with mild hypertension, renal or hepatic disease, alcoholism, history of GI ulcerations, drainage tubes (e.g., nasogastric tubes, indwelling urinary catheters), or occupations with high risks of traumatic injury. Warfarin, a pregnancy category X medication, is contraindicated during pregnancy because it crosses the placenta https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9aojXmGqF… 13/36 1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… and may produce fatal fetal hemorrhage. The US Food and Drug Administration (FDA) has issued a BLACK BOX WARNING ♦ for warfarin because of the risk of its causing major or fatal bleeding. Nursing Implications Preventing Interactions Many medications and herbs interact with warfarin, increasing or decreasing its effect (Boxes 9.5 and 9.6). BOX 9.5 Drug Interactions: Warfarin Drugs That Increase the Effects of Warfarin Acetaminophen (high dose), allopurinol, amiodarone Increase the anticoagulant effect Alteplase, androgens, aspirin and other nonsteroidal anti-inflammatory drugs, azithromycin, bismuth subsalicylate, carbamazepine, chloral hydra ciprofloxacin and other quinolone antibiotics, cisapride, clarithromycin, clofibrate, cotrimoxazole, direct thrombin inhibitors, heparin, macrolide an propranolol, quinidine, ranitidine, ritonavir, sertraline, simvastatin, sulfinpyrazone, sulfonamide, tamoxifen, tetracyclines, thyroid hormones, tricyc Increase the risk of bleeding Antithrombin Increases the pharmacologic effect Cephalosporins Result in potential coagulopathies and risk of bleeding Drugs That Decrease the Effects of Warfarin Chlordiazepoxide, haloperidol, intravenous lipid emulsions (contains soybean oil), isotretinoin, meprobamate, spironolactone Cause effects by various mechanisms Chlorthalidone May diminish warfarin's ability to cause blood clots to form Ethchlorvynol, trazodone Cause effects by unknown mechanism Etretinate May induce anticoagulant's hepatic microsomal enzyme BOX 9.6 Herb and Dietary Interactions: Warfarin Herbs and Foods That Increase the Effects of Warfarin Angelica, cat's claw, chamomile, chondroitin, cranberry juice, feverfew, garlic, ginkgo, goldenseal, grape seed extract, green tea, psyllium, turme Herbs and Foods That Decrease the Effects of Warfarin Ginseng, St. John's wort, vitamin K, foods high in vitamin K (broccoli, brussels sprouts, cabbage, cauliflower, chives, collard greens, kale, lettuce tomatoes, turnips, and watercress) Administering the Medication Vitamin K antagonists such as warfarin have a narrow therapeutic window of adequate anticoagulation without bleeding and a highly variable individual dose–response that requires monitoring by laboratory testing. QSEN Alert: Safety When warfarin therapy begins, daily evaluation of INR is necessary until a stable daily dose is reached (the dose that maintains the prothrombin tim and does not cause bleeding). A therapeutic PT value is approximately 1.5 times control, or 18 seconds. After that, a patient's INR values require ch duration of oral anticoagulant drug therapy. If a prescriber changes the warfarin dose, more frequent INR measurements are necessary until a stable should administer warfarin after ensuring that laboratory values are within therapeutic parameters. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9aojXmGqF… 14/36 1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… QSEN Alert: Safety Institutions often have protocol for the therapeutic range of INR. In the absence of a protocol, the nurse holds the dose if the INR is above 3.0 and n Assessing for Therapeutic Effects As with heparin, the nurse assesses for the absence or reduction of signs and symptoms of thrombotic disorders (e.g., less edema and pain with DVT, less chest pain and respiratory difficulty with pulmonary embolism, absence of uncontrolled bleeding, hematuria or blood in the stools). It is also necessary to ensure that PT and INR values are within the therapeutic range. Assessing for Adverse Effects The nurse assesses for signs of bleeding, including excessive bruising of the skin, bleeding from IV sites or the gum line, and blood in urine or stool. As previously stated, vitamin K is the antidote for warfarin and may be administered if the INR level is 5 or more and signs of bleeding are present. Additionally, prothrombin complex concentrate (PCC), human (Kcentra), is used for urgent warfarin reversal with major or life-threatening hemorrhage. Patient Teaching The nurse reinforces instructions for safe use of warfarin, assists patients to obtain required laboratory tests, and teaches how to observe for signs and symptoms of bleeding. Direct Thrombin Inhibitors DTIs have benefits compared with agents such as heparin and warfarin, including the inhibition of both circulating and clot-bound thrombin. Other advantages of DTIs include a more predictable dose–response anticoagulant effect, inhibition of thrombin-induced platelet aggregation, and the lack of production of immune-mediated thrombocytopenia. Heparin and warfarin are indirect inhibitors of thrombin. The DTIs exert their effect by interacting directly with the thrombin molecule without needing a cofactor, such as heparin cofactor II or antithrombin. They inhibit thrombin's ability to convert soluble fibrinogen to fibrin and activate the fibrin-generating factors V, VIII, and IX. Because thrombin also stimulates platelets, DTIs also have antiplatelet activity. Both parenteral and oral DTIs are available. The original prototype of the bivalent type, hirudin, is not commercially available; however, its discovery led to the development through recombinant technology of parenteral derivatives, bivalirudin, desirudin, argatroban, and one oral DTI, dabigatran. Lepirudin, another derivative, was discontinued and is no longer on the market. The only oral DTI, dabigatran etexilate (Pradaxa) serves as the prototype in this discussion. Pharmacokinetics Dabigatran etexilate is an inactive prodrug that is rapidly hydrolyzed to dabigatran, its active form, in the body by plasma and hepatic esterases. The drug is excreted in the urine, and the systemic elimination is proportional to the glomerular filtration rate. Typically, the elimination half-life is 12 to 17 hours, extending in the elderly and those with renal failure. Action As an inactive prodrug, dabigatran etexilate lacks anticoagulant activity. With the conversion to the active form in the body, dabigatran has been shown to specifically and reversibly inhibit both free and fibrin-bound thrombin, the key enzyme in the coagulation cascade, thereby inhibiting coagulation. DTIs have no known antagonists. Given orally, the drug peaks in 1 hour. Use Dabigatran etexilate is used to prevent strokes and systemic embolization in individuals with nonvalvular atrial fibrillation. In addition, it is given for the treatment and prevention of deep venous thrombosis and pulmonary embolism. Therapeutic drug monitoring is not necessary. Use in Older Adults Dabigatran etexilate is identified in the Beers Criteria as a potentially inappropriate medication; it should be used with caution in older adults who have a creatinine clearance less than 30 mL/min or those 75 years and older. However, no dosage adjustment of dabigatran etexilate is needed in elderly patients with normal renal function. However, the risk of bleeding, a common side effect, increases with age. Use in Patients With Renal Impairment https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9aojXmGqF… 15/36 1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… Because dabigatran etexilate is cleared by the kidneys, it accumulates in patients with renal insufficiency, and dosage adjustments may be required based on creatinine clearance calculations. The use of the drug is not recommended in patients receiving hemodialysis. Adverse Effects The most common adverse effects associated with the administration of dabigatran etexilate are bleeding, dyspepsia, abdominal pain, gastritis, and anemia. Contraindications Contraindications include a known hypersensitivity to any of the components of dabigatran etexilate and in patients with active pathologic bleeding or with a mechanical prosthetic heart valve. Use in pregnancy and lactation requires caution. Nursing Implications The ISMP classifies dabigatran etexilate as a high-alert drug because of the possible risk of significant harm that results when it is used in error. Preventing Interactions Many medications interact with dabigatran etexilate, altering its effect (Boxes 9.7 and 9.8). No foods decrease the drug's bioavailability, although the drug's peak plasma concentration is delayed 2 hours if taken with food. BOX 9.7 Drug Interactions: Dabigatran Etexilate Drugs That Increase the Effects of Dabigatran Etexilate Anticoagulants, apixaban, aspirin, antiplatelet agents (especially clopidogrel), collagenase, dasatinib, defarasirox, deoxycholic acid, edoxaban, h inflammatory agents, pentosanpolysulfate sodium, prostacyclin analogues, salicylates, sugammadex, sulfinpyrazone, thrombolytics, tibolone, tic Increase the risk of bleeding Amiodarone, clarithromycin, dronedarone, ketoconazole P-glycoprotein/ABCB1 inhibitors, quinidine, verapamil May increase serum concentration Drugs That Decrease the Effects of Dabigatran Etexilate Antacids, atorvastatin, lumacaftor, P-glycoprotein/ABCB1 inducers, proton pump inhibitors May decrease serum concentration Estrogen derivatives, progestins May decrease the anticoagulant effects BOX 9.8 Herb and Dietary Interactions: Dabigatran Etexilate Herbs and Foods That Increase the Effects of Dabigatran Etexilate Alfalfa, anise, bilberry, omega-3 fatty acids, vitamin E Administering the Medication The drug capsules should be administered intact with a full glass of water without regard to meals. If the capsules are open or chewed, absorption is increased, and the risk of adverse drug effects is enhanced. Assessing for Therapeutic Effects The nurse assesses for the absence of signs and symptoms of thrombotic disorders, including HIT, and for laboratory values within normal range. A therapeutic range has not been established for tests of anticoagulant activity. Assessing for Adverse Effects The most common adverse effect associated with the administration of dabigatran etexilate is bleeding; therefore, assessing for signs of bleeding is a priority. Additionally, the nurse assesses for other adverse effects, including GI and hematologic effects. The anticoagulant effects of dabigatran can be reversed by idarucizumab (Praxbind). https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9aojXmGqF… 16/36 1/9/24, 1:57 AM herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbusjeLUzRyumZIEGwikvZDA89aMIS3TVE3sojJO9a… Patient Teaching Patients need to understand that stopping the drug without provider instruction could increase the risk of blood clots. Patients should notify other health care providers about taking dabigatran etexilate, particularly with spinal or epidural procedures that increase the risk of bleeding around the spine because paralysis may occur. Other Drugs in the Class In comparison to heparin, which binds only circulating thrombin, DTIs such as bivalirudin and desirudin block circulating thrombin and clotbound thrombin. Bivalirudin is given intravenously as a specific and reversible DTI approved for the treatment of patients with unstable angina undergoing percutaneous transluminal coronary angioplasty (PTCA), as an anticoagulant in patients undergoing PTCA, and as an alternative to heparin in patients with or at risk of developing HIT. Desirudin has been shown to be more effective than enoxaparin in preventing DVT following total hip replacement. Desirudin is administered subcutaneously, and highly protein bound drugs do not modify its effects. Argatroban is indicated for HIT, is eliminated in the liver, and can be used in people with end-stage renal disease. Administered intravenously, argatroban is very short acting due to its reversible binding to thrombin. Direct Factor Xa Inhibitors Direct factor Xa inhibitors inactivate circulating and clot-bound factor Xa. Unlike fondaparinux, which acts indirectly, this class of drugs binds directly and, by doing so, inhibits the production of thrombin. These direct oral anticoagulants, along with dabigatran, are at least as effective as the vitamin K antagonists but are associated with less life-threatening bleeding. Currently, three orally acting direct factor Xa inhibitors are approved, rivaroxaban, apixaban, and edoxaban; no direct factor Xa inhibitors are available for intravenous infusion. Rivaroxaban serves as the prototype. Pharmacokinetics Rivaroxaban is rapidly absorbed and is highly bound to protein. The drug undergoes partial metabolism by CYP3A4 (an isozyme of the cytochrome P-450 system) and is excreted in the urine (36% as unchanged drug) and feces (7% as unchanged drug). Peak plasma levels are reached in 2 to 4 hours, and the half-life is 5 to 9 hours. Actions Rivaroxaban inhibits platelet activation and fibrin clotting formation by inhibiting actor Xa in both intrinsic and extrinsic coagulation pathways. Use Rivaroxaban is used in the tr