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Lecturer on Anaesthetics at UniversityCollege how long will ambien stay in my urine is received with much. the. This is a corrected version of the article that appeared in print. KATHERINE L. MARGO, M.D., GARY LUTTERMOSER, M.D., AND ALLEN F. SHAUGHNESSY, PHARM.D.   See patient information handout on heart failure, written by the authors of this article. The familiar diuretic spironolactone has taken on new life as a treatment for left-sided congestive heart failure. Spironolactone has been shown to decrease mortality in such patients who are New York Heart Association class IV. It can be used in addition to agents such as angiotensin-converting enzyme inhibitors and beta blockers, which also decrease mortality, and diuretics and digoxin, which are useful in treating symptoms. Spironolactone is safe, easy to use and reasonably priced. More research is necessary to determine the order and combinations of these medications in slowing the progression of this disease. Spironolactone is a potassium-sparing diuretic that was approved many years ago. Until recently, it was used primarily to treat edema resulting from liver cirrhosis, primary hyperaldosteronism and nephrotic syndrome. It has been used in combination with potassium-wasting diuretics to prevent hypokalemia. Recent research on this older diuretic has focused on its effect in patients with left-sided congestive heart failure system. Spironolactone is a specialized antagonist of aldosterone. It acts as a competitive binding agent at the aldosterone receptor site in the distal convoluted renal tubules, preventing the formation of a protein important in the sodium-potassium exchange in the kidneys. This action causes increased amounts of water and sodium to be excreted while potassium is conserved. Based on earlier work suggesting a benefit of therapy,2 the Randomized Aldactone Evaluation Study .4 Most of the enrolled patients were white men averaging 65 years of age. These patients had a left ventricular ejection fraction of 35 percent or less and marked physical limitations related to CHF. Patients were excluded if they had unstable angina or moderate renal failure, and if they were hyperkalemic. All patients who could tolerate the drug were given an ACE inhibitor and a loop diuretic, and 70 percent were taking digoxin. Only 10 percent were taking beta blockers. Patients were randomly assigned to receive placebo or 25 mg of spironolactone daily in addition to their current regimen. After eight weeks, if the patient showed worsening CHF and had a stable potassium level, the dosage was increased to 50 mg daily. The dosage was decreased to 25 mg every other day if at any time the patient became hyperkalemic. Even with a 25 percent dropout rate . Patients with cardiac disease but without resulting limitations of physical activity. Ordinary physical activity does not cause undue fatigue or dyspnea. Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue or dyspnea. Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue or dyspnea. Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased. NYHA = New York Heart Association. Adapted with permission from Criteria Committee, New York Heart Association. Diseases of the heart and blood vessels. Nomenclature and criteria for diagnosis. 6th ed. Boston: Little, Brown, 1964:114. Patients with cardiac disease but without resulting limitations of physical activity. Ordinary physical activity does not cause undue fatigue or dyspnea. Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue or dyspnea. Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue or dyspnea. Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased. NYHA = New York Heart Association. Adapted with permission from Criteria Committee, New York Heart Association. Diseases of the heart and blood vessels. Nomenclature and criteria for diagnosis. 6th ed. Boston: Little, Brown, 1964:114. The number of hospitalizations related to worsening CHF was lowered by 35 percent. NYHA classification improved in the spironolactone group more than in the placebo group. The primary adverse effect causing discontinuation of this agent in 10 percent of the men taking spironolactone was gynecomastia or breast pain. The incidence of serious hyperkalemia was small. The combination of hydralazine and isosorbide dinitrate has been shown to decrease mortality by 25 to 30 percent .13 This combination of agents has been supplanted by ACE inhibitors, which are easier to use and more effective. However, the combination would be appropriate to consider in a patient who cannot tolerate ACE inhibitors. The prescribing of ACE inhibitors, beta blockers and spironolactone in patients with heart failure presents the physician with challenges because while these agents do slow long-term decline related to heart failure, they have little or no effect on symptoms. In addition, it is not clear how quickly therapy should be started, whether all three approaches should be combined at once or which drugs should be added first. Research to date suggests benefit from all of the options in patients with an ejection fraction of less than 30 percent. A prudent approach would be to begin with an ACE inhibitor , slowly adding a beta blocker after the patient is stabilized on the first two drugs. Information from references 2 and 13 through 16. Information from references 2 and 13 through 16. Spironolactone is contraindicated in patients with anuria, acute renal insufficiency, significant renal insufficiency or hyperkalemia. Potassium supplementation should not be combined with spironolactone. Other drug interactions include errors in measurement of and an increase in the half-life of digoxin, decreased effectiveness when used with salicylates and variable effects or side effects with use of nonsteroidal anti-inflammatory drugs. Gynecomastia and hyponatremia can occur, along with metabolic acidosis, which is usually associated with hyperkalemia. Other side effects are rare and include drug fever, drowsiness, lack of coordination, lethargy and gastrointestinal signs and symptoms. Dosages range from 25 to 50 mg per day in patients with heart failure, although much higher dosages are used to treat other disorders. Patients pay less than per month for typical dosages. This cost compares with that of other medications used for CHF, such as to per month for generic metoprolol, for carvedilol and to for low to moderate doses of ACE-inhibitor therapy. Spironolactone absorption is increased significantly when taken with food, but the clinical significance of this effect is not known. The metabolites are excreted primarily in the urine and secondarily in the bile, with half-lives of approximately 14 to 16 hours. One study3 has shown that spironolactone improves morbidity and mortality in patients with severe heart failure. The particular advantages of spironolactone for prevention are that it is inexpensive, is taken once daily and has relatively few side effects. This study suggests that all patients with class IV heart failure should be given a trial of spironolactone. Further research is needed to understand its usefulness in patients with less severe heart failure and whether its benefit is present in patients who are also taking beta blockers. Research is also necessary to determine which order and combinations of medications are the most beneficial in slowing the progression of this disease. To see the full article, log in or purchase access. GARY LUTTERMOSER, M.D., is in practice at the Mechanicsburg Family Practice Center in Mechanicsburg, Pa., and a member of the Harrisburg Family Practice Residency faculty. Dr. Luttermoser completed medical training at the Medical College of Ohio, Toledo, and a residency at the Family Practice Residency at Akron City Hospital, Akron, Ohio. He has certificates of added qualification in geriatrics and sports medicine. ALLEN F. SHAUGHNESSY, PHARM.D., is director of research and associate director of the Harrisburg Family Practice Residency. He received his undergraduate degree in pharmacy from Temple University, Philadelphia, and obtained a doctor of pharmacy degree and fellowship training at the Medical University of South Carolina, Charleston. Address correspondence to Allen F. Shaughnessy, Pharm.D., Harrisburg Family Practice Residency, 111 S. Front St., Harrisburg, PA 17101 . Reprints are not available from the authors. The authors indicate that they do not have any conflicts of interest. Sources of funding: none reported. 4. Criteria Committee, New York Heart Association. Diseases of the heart and blood vessels. Nomenclature and criteria for diagnosis. 6th ed. Boston: Little, Brown, 1964:114. Richard W. Sloan, M.D., R.Ph., coordinator of this series, is chairman and residency program director of the Department of Family Medicine at York Hospital and clinical associate professor in family and community medicine at the Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, Pa. All comments are moderated and will be removed if they violate our Terms of Use. This page will be removed from your Favorites Links. Are you sure? Don't miss a single issue. Sign up for the free AFP email table of contents..

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More progress this week! Our hard-working landscapers have completed the irrigation install and laid down soil in the landscaping beds. Inside, the electrician is finishing up some details related to our mechanical permit and it was signed off yesterday! Of course, we’ve also been getting the building ready for the final inspection, which includes creating…


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