Cardiac glycosides, digoxin toxicity, and the antidote.
Heart Failure, Atrial Arrythmias, and Cardiac Glycosides' Effects on the Diseased Heart
Heart failure is a clinical condition wherein the myocardium (heart muscle) is weakened and enlarged (cardiomegaly), decreasing the effectiveness of its contractions and blood circulation into the heart and the periphery (Kee et al., 2012; Moser, Riegel, Paul, Lennie, & Kirkwood, 2009). Due to the increased elasticity of ventricular walls in the weakened myocardium, increased preload (volume overload within ventricles) occurs, wherein more blood enters into the ventricle at the end of diastole. Cardiac after-load (pressure overload within ventricular walls) also increases due to the increased resistance in the aorta that must be overcome in order for blood to enter the circulation (Kee et al., 2012; Kusumoto, 2010). When compensatory mechanisms of the heart fail to overcome the increased workload of the heart, congestion occurs. Congestion may manifest in the systemic circulation as peripheral edema when the right ventricle fails; lung congestion marked by shortness of breath and dyspnea occurs when the left ventricle fails (Moser et al., 2009).
Cardiac glycosides help improve symptoms of congestive heart failure, but do not necessarily lower the rate of patient mortality (Adams & Holland, 2011). The mechanism of action of digoxin lies in its ability to inhibit the sodium-potassium ATPase pump and promote sodium-calcium exchange within the myocardial cells (Ehle et al., 2011). Intracellular calcium influx causes the myocardium to contract more forcefully (positive inotropic effect) (Kee et al., 2012). With stronger cardiac contractions, output increases to the heart and systemic circulation, and the patient's exercise tolerance improves. Increased cardiac output is evidenced by increased urine production, and relief of pulmonary and peripheral edema (Adams & Holland, 2011).
Cardiac glycosides also can be prescribed as anti-arrhythmics for certain common atrial dysrhythmias, such as atrial flutter and atrial fibrillation; its parasympathomimetic actions increase the vagal tone to the sinoatrial and AV node. This leads to a decreased heart rate (negative chronotropic effect) and slowed AV-node conduction (negative dromotropic effect) (Ehle et al., 2011). Atrial flutter can be identified by electrocardiogram (ECG) waves that are "recurring, regular, saw-tooth-shaped," originating from a "single ectopic in the right atrium, or less commonly, the left atrium" (Bucher, 2011, p. 826). Atrial flutter is associated commonly in older patients with cardiac and pulmonary conditions, including coronary artery disease, hypertension, mitral valve disorders, cot pulmonale, and pulmonary embolus (Bucher, 2011). Atrial flutter increases heart rate to 150 beats per minute and rarely to 300 beats per minute (CVA Cardiovascular Associates, 2013). Atrial fibrillation is associated commonly with underlying heart disease, including rheumatic heart disease, cardiomyopathy, and heart failure. In atrial fibrillation, chaotic atrial electric conduction from multiple ectopic foci causes ineffective atrial contraction (Bucher, 2011). Atrial quiver causes heart rates to increase up to 400 beats per minute despite lack of heart muscle contraction (CVA Cardiovascular Associates, 2013). Atrial fibrillation appears on ECGs as "chaotic, fibrillatory waves that replace P waves ... PR interval that is not measureable, and QRS complex with a normal shape and duration" (Bucher, 2011, p. 827). Both atrial flutter and atrial fibrillation are linked to formation of clots, increasing the risk of stroke in affected individuals (CVA Cardiovascular Associates, 2013).
Digoxin is available in capsules (0.05 mg, 0.1 mg, 0.2 mg), tablets (0.125 mg, 0.25 mg, 0.5 mg), elixir (0.05 mg/mL), and injection (0.25 mg/mL and 0.1 mg/mL) (Wilson et al., 2012). Digoxin falls under pregnancy category C (Kee et al., 2012). Several animal and human studies have shown digoxin crosses the placenta readily, but no teratogenic effects on the fetus have been found when mothers were injected with digoxin. However, the fetus also experiences adverse effects if the mother is experiencing digitalis toxicity (Frishman, Elkayam, & Aronow, 2012). Digoxin also is known to enter the breast milk (Vallerand, Sanoski, & Deglin, 2011).
Absorption rates for every medication route are different due to digoxin's low serum protein binding power (Kee et al., 2012). Tablets have a 70% absorption rate; capsules and elixirs have a 90% absorption rate; intramuscular injection has a 70%-85% absorption rate; and intravenous injection absorption rates are 100% (Ehle et al., 2011; Vallerand et al., 2011). The half-life of digoxin is 36 hours, increasing the risk of drug accumulation and toxicity (Kee et al., 2012). Only 30% of digoxin is metabolized in the liver. Thus 70% of the drug is excreted by the kidneys in its original chemical form (Vallerand et al., 2011).
Health care providers determine patient dosage requirements for digitalization, which is a procedure wherein patients take gradually increasing dosages of digoxin until tissues are saturated with the medication (Adams & Holland, 2011). Recommended dosage for an adult patient taking digoxin orally is "0.75-1.5 mg given as 50% of the dose initially and one quarter of the initial dose in each of two subsequent doses at 6-12 hours" for digitalization (Vallerand et al., 2011, p. 432). Maintenance dose for adults is 0.125 mg/day, depending on individual patient dosing factors (Wilson et al., 2012).
Individualized patient dosing is based on various factors, including body weight, age, renal function, and other medications taken (Ehle et al., 2011). Patients with lower lean body weight will need decreased dosage because the medication is distributed to lean body tissue (Ehle et al., 2011). Because the medication is excreted via the kidneys in its pure form, patients' renal function must be adequate to prevent accumulation (Wilson et al., 2012). Elderly patients and children have lower lean body weight and thus need decreased dosing (Ehle et al., 2011). Patients with impaired renal function should have their loading and maintenance doses decreased to prevent digitalis toxicity (Kee et al., 2012). Older adults need to be screened for renal impairment (Jelinek & Warner, 2011). Patients with known ischemic cardiac conditions should start with a lower dose of 25%-50% of the recommended dose. Ischemic conditions of the heart also inhibit the sodium-potassium pump, thus enhancing semitivity to the therapeutic effects of digoxin (Ehle et al., 2011). Lastly, patients with known thyroid dysfunction may experience altered metabolism of digoxin. Patients with slow metabolism due to hypothyroidism would need the digoxin dosage decreased, while patients with hyperthyroidism will need an increased dose (Kee et al., 2012).
Patients with ventricular dysrhythmias unrelated to heart failure and AV block should not be prescribed digoxin. Digoxin may worsen the AV block (Adams & Holland, 2011). Nurses should obtain a thorough medication history for all patients taking digoxin because it interacts with many other cardiac medications. Diuretics may cause hypokalemia, and thus increase patients' risk for dysrhythmia (Wilson et al., 2012). Intravenous calcium administered with digoxin also will increase the risk for dysrhythmias. Medications that prevent potassium excretion from the kidneys or increase serum potassium levels, such as spironolactone (Aldactone[R]), potassium supplements, and ACE inhibitors, may cause hyperkalemia, which reduces the therapeutic effects of digoxin (Adams & Holland, 2011). Double bradycardic effect will occur when digoxin is taken with beta-blockers (Vallerand et al., 2011). Alprazolam (Xanax[R]), quinidine (Quin-G[R], Quinora[R]), verapamil (Calan[R]), and amiodarone (Cordarone[R]) interact with digoxin by decreasing the medication's ability to distribute systemically and slowing the excretion rate of digoxin, resulting in higher risk for digoxin toxicity (Adams & Holland, 2011). Lastly, antacids and anti-cholesterol medications such as statins decrease the absorption of digoxin into tissues (Wilson et al., 2012).
Digoxin also interacts with herbal remedies, affirming the importance of assessing patients regarding their herbal supplement use. St. John's wort and psyllium (Metamucil[R]) decrease the absorption of digoxin into tissues (Vallerand et al., 2011). Aloe causes potassium excretion and increases patients' risk for digoxin toxicity. Ma-huang and ephedra also increase patients' risk for digoxin toxicity (Kee et al., 2012).
Digoxin toxicity refers to a group of symptoms experienced by patients due to the accumulation of digitalis within the body. Three pharmacokinetic scenarios that could result in digoxin toxicity include accidental intake of digoxin; drug accumulation caused by metabolic (liver) and excretion (renal) impairment; and drug accumulation due to drug-drug or drug-herb interactions (Kanji & MacLean, 2012). The serum therapeutic level of digoxin is narrow at 0.5-2.0 ng/dL. To prevent adverse effects, the optimal therapeutic level of digoxin should be maintained close to 1.8 ng/mL (Adams & Holland, 2011; Gair, Kent, Purssell, & Copland, 2011; Kee et al., 2012). The most serious toxic effects are dysrhythmias. They occur when digoxin causes sodium influx into the heart, which increases phase IV depolarization, limits resting threshold, and activates automacity of the heart's electrical conduction system. The most common dysrhythmias that occur during digoxin toxicity are AV block and extrasystoles, although any type of dysrhythmia may occur. AV block and extrasystoles also may occur even within therapeutic level (Kanji & MacLean, 2012).
Systemic signs and symptoms of digoxin toxicity result from sodium-potassium pump exchanges in parts of the body other than the heart: the gastrointestinal, ocular, and neurological systems (Kanji & MacLean, 2012). Systemic signs and symptoms of digoxin toxicity include anorexia, diarrhea, nausea and vomiting, headache, malaise, blurred vision, greenish (or white and yellow) halos seen around objects, and confusion (Kee et al., 2012).
Nursing Care for Patients Taking Digoxin
Prior to administration. Nurses should record a complete health history for patients, especially to determine if any co-morbidities or therapies might affect drug clearance (e.g., other cardiac disorders; hepatic and renal impairment). Baseline assessment to determine severity of heart failure should be done. This involves assessing patients' weight, baseline vital signs, breath sounds, and ECG results. Lastly, laboratory results pertinent to medication therapy, such as renal function and serum potassium, should be evaluated (Adams & Holland, 2011). When preparing the digoxin dosage, nurses should be especially vigilant regarding calculations and preparations, especially with digoxin elixir, as any additional dosage administered to patients could lead to digoxin toxicity. Because digoxin is a high-risk medication, drug dosages should be verified by another nurse (Kee et al., 2012).
During administration. Oral medication should be given consistently with meals. If patients have dysphagia, tablets can be crushed and mixed with food or fluids (Wilson et al., 2012). Intramuscular digoxin should be administered in large, deep muscle areas, such as the gluteal muscles, to reduce pain. Intravenous digoxin may be administered with diluents, such as 4 mL of sterile water for injection, D5W, or normal saline for every 1 mg of digoxin (Vallerand et al., 2011).
Before administering the medication, nurses should assess patients' apical pulse for at least 1 minute. If the heart rate is less than 60 or greater than 100 beats per minute, the medication should not be administered and the health care provider should be notified immediately. Also, any changes in the quality of heart rate, rhythm, and pulse should be reported to the health care provider (Vallerand et al., 2011). ECG, electrolyte values (e.g., potassium), renal function, and serum digoxin levels (compared to therapeutic digoxin levels) should be monitored frequently during therapy (Wilson et al., 2012). An increased risk for dysrhythmias exists during the digitalization period (Adams & Holland, 2011).
Nurses should evaluate the therapeutic effects of digoxin. Measuring patient urine output and weighing patients daily are good indicators of any progress with therapy. Daily weighing should follow the rule of "same time everyday using the same type of clothing" (Adams & Holland, 2011, p. 333). Any weight gain or weight loss of more than 1 kg per 24-hour period should be reported to the health care provider (Kee et al., 2012).
Patient and family teaching. Patients with a heart condition should be reminded to limit sodium intake. To prevent hypokalemia that may induce dysrhythmias in patients taking digoxin, patients are encouraged to eat potassium-rich foods, such as fresh and dried fruits, potatoes, and fruit and vegetable juice (Adams & Holland, 2011; Kee et al., 2012). When patients are discharged from acute care settings, patients and family members should be taught how to take the apical pulse for a full minute to determine the correct heart rate. If heart rate is less than 60 or greater than 100 beats per minute, they should withhold the medication and contact the health care provider immediately (Kee et al., 2012). Patients and family members should be taught to perform daily weights (Adams & Holland, 2011). They also should be able to identify signs and symptoms of digoxin toxicity and be reminded to seek health care immediately if this occurs (Wilson et al., 2012). Lastly, if there are small children in the family, the medication must be kept locked out of their reach (Kee et al., 2012).
Antidote: Digoxin immune Fab (Digibind, DigiFab)
The incidence of digoxin toxicity is 1%-30% (Schaeffer et al., 2012). Ensuring providers' correct dosage determination by careful consideration of patient factors, calculating correct dosages, dispensing and administering correctly, and providing essential patient and family teaching can prevent development of digoxin toxicity. However, in cases of severe digitalis toxicity, immediate reversal is needed to control potentially fatal signs and symptoms. This is done through antibody treatment with digoxin immune Fab (Digibind, DigiFab) (Kee et al., 2012).
Digoxin immune Fab reverses signs and symptoms of digoxin toxicity by binding to circulating digoxin, developing a complex molecule that cannot be absorbed by body tissue. This complex molecule will be excreted through the urine (Kee et al., 2012). A recent retrospective study found cardiac toxicity was stabilized in more than 80% of evaluated patients within 24 hours of digoxin immune Fab treatment (Schaeffer et al., 2012). Digoxin is administered intravenously for faster absorption and onset of therapeutic effects (Wilson et al., 2012). Prior to administration, serum digoxin levels should be monitored to determine dosage of digoxin immune Fab. Dosage to be administered will be calculated according to the amount of digoxin that must be neutralized; 38 mg of digoxin immune Fab can neutralize 0.5 mg of digoxin (dose of digoxin ingested (mg)/0.5 x 38) (Vallerand et al., 2011). Some patients may need a second dose for full neutralization (Wilson et al., 2012).
Digoxin immune Fab has no known contraindications. It currently is labeled under pregnancy category C. Because the product comes from a sheep antibody, this medication should be administered cautiously to patients with known hypersensitivity to sheep products (Vallerand et al., 2011). Some adverse effects include rebound heart failure symptoms, atrial fibrillation, and hypokalemia (Wilson et al., 2012). Due to the possibility of development of withdrawal symptoms, continuous monitoring of ECG, heart rate, blood pressure, and serum potassium should be done before and during the treatment. Nurses should expect rapid decrease of serum potassium with treatment. Patients should be evaluated for return of signs and symptoms of heart failure (Vallerand et al., 2011; Wilson et al., 2012). In case of emergency, cardiopulmonary resuscitation equipment should be kept at the patient's bedside. Repeat digitalization should not be started until all digoxin immune Fab has been excreted (Wilson et al., 2012).
Digoxin has been an acceptable adjunct treatment to improve signs and symptoms of heart failure for almost 2,000 years. Underdosage of digoxin will cause continuation of heart failure symptoms, while over-dosage may result in toxicity. In cases of severe digitalis toxicity, digoxin immune Fab can be given intravenously to patients. Thus, nurses should be vigilant in their care of patients undergoing digoxin therapy.
Adams, M.P., & Holland, L.N. (2011). Pharmacology for nurses: A pathophysiologic approach (3rd ed.). Upper Saddle River, NJ : Pearson.
Bucher, L.D. (2011). Nursing management: Heart failure. In S.L. Lewis, S.R. Dirksen, M.M. Heitkemper, L. Bucher, & I.M. Camera (Eds). Medical-surgical nursing: Assessment and management of clinical problems (8th ed.) (pp. 797-836). St. Louis, MO: Mosby Elsevier.
CVA Cardiovascular Associates. (2013). Atrial arrhythmias. Retrieved from http://www. cvapc.com/handler.cfm?event=practice, template&cpid=1196
Ehle, M., Patel, C., & Giugliano, R.P. (2011). Digoxin: Clinical highlights. A review of digoxin and its use in contemporary medicine. Critical Pathways in Cardiology, 10(2), 93-98.
Frishman, W.H., Elkayam, E., & Aronow, W.S. (2012). Cardiovascular drugs in pregnancy. Cardiology Clinics, 30, 463-491.
Gair, R., Kent, D., Purssell, R., & Copland, M. (2011). Chronic digoxin toxicity in elderly British Columbians. British Columbia Medical Journal, 53(9), 490-491.
Jelinek, H.E, & Warner, P. (2011). Digoxin therapy in the elderly: Pharmacokinetic considerations in nursing. Geriatric Nursing, 32(4), 263-269.
Kanji, S., & MacLean, R.D. (2012). Cardiac glycoside toxicity: More than 200 years and counting. Critical Care Clinics, 28, 527-535.
Kee, J.L., Hayes, E.R., & McCuistion, L.E. (2012). Pharmacology: A nursing process approach (7th ed.). St. Louis, MO: Saunders Elsevier.
Kusumoto, F.M. (2010). Cardiovascular disorders: Heart disease. In S.J. McPhee & G.D. Hammer (Eds.), Pathophysiology of disease: An introduction to clinical medicine (6th ed.) (pp. 256-265). Columbus, OH: McGraw-Hill.
Moser, D.K., Riegel, B., Paul, S., Lennie, T.A., & Kirkwood, P.L. (2009). Heart failure. In K.K. Carlson (Ed.), Advanced critical care nursing (pp. 237-275). St. Louis, MO: Saunders Elsevier.
Schaeffer, T.H., Mlynarchek, S.L., Stanford, C.F., Delgado, J., Holstege, C.P., Olsen, D., ... Bogdan, G.M. (2012). Treatment of chronically digoxin-poisoned patients with a newer digoxin immune fab-A retrospective study. Journal of the American Osteopathic Association, 110(10), 587-592.
Vallerand, A.H., Sanoski, C.A., & Deglin, J.H. (2011). Davis' drug guide for nurses (13th ed.). Philadelphia, PA: F.A. Davis.
Wilson, B.A., Shannon, M.T., & Shields, K.M (2012). Pearson nurse's drug guide 2012. Upper Saddle River, NJ: Pearson.
Rhea Faye Felicilda-Reynaldo, EdD, RN, is Assistant Professor, Department of Nursing, Missouri State University, Springfield, MO. She may be contacted at FayeFelicilda@missouri state.edu.
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|Title Annotation:||CNE SERIES: Nursing Pharmacology|
|Author:||Felicilda-Reynaldo, Rhea Faye|
|Date:||Jul 1, 2013|
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