diuretics

Potassium supplements during hot weather may lower mortality risk for patients taking diuretics

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A study from researchers at the Perelman School of Medicine at the University of Pennsylvania found the risk of mortality is lower for patients on the diuretic furosemide when they receive potassium supplements during hot temperature days.

Patients who received the additional potassium saw a near 10% drop in mortality, researchers said in a Perelman press release.

Individuals with hypokalemia have an increased risk of death from cardiac arrhythmias or other causes. While some patients are prescribed combination diuretics that contain both a thiazide and potassium-sparing diuretic, clinical staff may not be aware that sweating can increase the risk of potassium loss in warmer weather.

“We already know that hot outdoor temperatures are associated with increased risk of heat stroke, dehydration, heart disease, respiratory diseases and higher risk of death overall, but people who take furosemide and have insufficient intake of potassium are at increased risk,” Sean Hennessy, PharmD, PhD, a professor of epidemiology and systems pharmacology and translational therapeutics at Perelman and senior author, said in the release. “As outside temperatures increase, the apparent survival benefit of potassium also increases.”

Furosemide, a diuretic known commonly as Lasix, is prescribed to decrease fluid retention and combat swelling in the arms, legs and/or abdomen in patients with heart failure, high blood pressure, and/or kidney and liver disease. The drug, like many other diuretics, causes patients to urinate more than normal, leading to lower levels of potassium in the body. These lower levels can be more dangerous when outdoor temperatures are high, as patients often lose additional potassium through sweating, the release noted.

Researchers for the study looked at 1999 to 2010 data from Medicaid patients in California, Florida, New York, Ohio and Pennsylvania. The data set represented about 40% of total U.S. Medicaid enrollees and made up approximately 20% of the total U.S. population, according to the release. Data were included from those who took furosemide at 40 mg/day or more and had not been prescribed any furosemide nor diagnosed with hypokalemia in the previous year.

Among the 337,885 people who took 40 mg/day or more of furosemide, 32% of them also took potassium when starting the diuretic. The team linked these data to zip code-level daily temperature data from the National Oceanic and Atmospheric Administration and compared two groups — one group included patients who took prescription potassium to prevent hypokalemia when beginning furosemide, and the other included patients who did not take prescription potassium when taking furosemide. The team found that across all temperatures, the potassium-taking group experienced a 9.3% lower risk of death than the group who did not take potassium. This survival benefit was also higher when daily maximum temperatures were higher.

“If this potential relationship between temperature and the survival benefit of empiric potassium is true, it would have important clinical and public health implications,” the authors wrote. “It is well established that high outdoor temperature is associated with increase in mortality and morbidity. Some excess deaths in furosemide users, especially among socioeconomically disadvantaged populations, such as Medicaid enrollees in the U.S.A., might be avoidable through interventions to increase potassium intake on hot days. The number of lives saved by such interventions would be expected to increase as global climate change continues.”

The authors speculated that patients who reside in warmer regions might tolerate increases in temperature better than those in cooler regions.

Young Hee Nam

Young Hee Nam

“Also, a temperature–potassium interaction on mortality, if it exists, might differ across subgroups, such as geographic regions, sociodemographic characteristics including age, comorbidities or degree of frailty. Because we were unable to explore such relationships given the limited number of high-temperature deaths, further research is warranted to investigate these potential relationships in diverse subgroups and health outcomes,” they wrote.

Lead author Young Hee Nam, PhD, a post-doctoral researcher in biostatistics, epidemiology and informatics, told Healio/Nephrology the study results “do not imply that more potassium is better and do not imply that prescription potassium may be beneficial for all patients. Further studies are needed to find out the generalizability of our findings to other patient populations. The best way to reduce harmful effects of high temperatures on mortality might be to avoid exposure to high temperatures if possible.” – by Mark E. Neumann

Reference:

http://www.pennmedicine.org/news/news-releases/2019/february/as-temperatures-rise-patients-taking-diuretics-may-see-benefit-from-upping-potassium-intake

Common Diabetes Meds May Raise Odds for Amputation

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People with type 2 diabetes who are taking common drugs called diuretics may be at a significantly increased risk of losing a foot or leg, according to a new French study.

Researchers found that taking a diuretic raised the odds of having an amputation, or requiring an angioplasty or bypass, by 75 percent or more, compared with those not using the medicines.

Based on the findings, “diuretics should be used cautiously in patients with type 2 diabetes at risk of amputations,” concluded a team led by diabetes specialist Dr. Louis Potier, of Bichat Hospital in Paris.

But one U.S. expert said that restricting the use of diuretics puts diabetic patients “between a rock and a hard place.”

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As Dr. Gerald Bernstein explained, diuretics are used to help “get rid of extra salt and water” in the blood, thereby helping patients control blood sugar and blood pressure.

In turn, that could help ward off a major killer: congestive heart failure.

So, the challenge is to “select the right drugs to prevent worsening of heart failure in order to prevent increased risk for amputations,” said Bernstein, coordinator for the Friedman Diabetes Program at Lenox Hill Hospital in New York City.

As Bernstein explained, “type 2 diabetes is a disease heavily associated with cardiovascular complications, in particular the big arteries from the heart to the rest of the body. When these arteries and the heart are diseased there is abnormal blood flow to all the organs but the lower extremities can be affected most because of how long that artery is.”

When circulation issues to the leg and foot become severe, amputation is often the only option.

How much might particular diabetes medicines affect the odds of needing an amputation?

To help find out, Potier’s team tracked outcomes for nearly 1,500 people with type 2 diabetes. The study specifically focused on amputations, as well as procedures such as angioplasty or the bypassing of blocked or damaged blood vessels. Those procedures are used to improve circulation and prevent leg or foot amputations.

Participants were followed until they had a leg procedure or died. Nearly 700 of the study participants were taking a diuretic drug.

Over a follow-up of about seven years, 13 percent of those taking a diuretic had an amputation or other procedure on their lower leg, compared with just 7 percent of those not taking a diuretic.

Said another way, this meant that taking a diuretic increased the risk of having an amputation or an angioplasty/bypass by 75 percent or more, compared with those not using one.

Most of this increase involved amputations, which nearly doubled for those taking a diuretic.

The results of the study were presented Monday at the meeting of the European Association for the Study of Diabetes, in Berlin.

It’s important to note the study was observational in nature, meaning that while it could point to an association between diuretics and amputation rates, it could not prove cause and effect, and other factors might be at play. Furthermore, research presented at medical meetings is typically considered preliminary until published in a peer-reviewed journal.

According to Bernstein, the take-home message here is not to immediately discontinue the use of diuretics, but to keep in mind that “the patient and physician must be very careful not to overtreat and be very selective” in which drugs are used to fight diabetes.

Diabetes specialist Dr. Robert Courgi agreed. Reviewing the findings, he said that while more study is needed to confirm the results, “if a patient is at risk for amputation then perhaps diuretics should be avoided for other equally effective options.” Courgi is an endocrinologist at Southside Hospital in Bay Shore, N.Y.

Diuretics, ACEIs, ARBs, and NSAIDs: A Nephrotoxic Combination.

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This triple therapy can increase the risk of acute renal failure.

Diuretics, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) represent 3 classes of drugs widely used in the treatment of hypertension and heart failure, often in combination. We previously reviewed the effect of nonsteroidal anti-inflammatory drugs (NASIDs) on the hypotensive response of various antihypertensive agents.1 In addition to blunting the hypotensive effects of diuretics, ACEIs, and ARBs, there is an increased risk of patients developing acute renal failure when an NSAID is co-administered. As hypertension, heart failure, and conditions causing chronic pain are common in the elderly, the risk of exposure to potential interactions between these drugs increases over time.

Mechanism of the Interaction

Diuretics can reduce plasma volume leading to reduced renal blood flow. This may lead to increased serum creatinine concentrations. The kidney can compensate via the renin-angiotensin system by constricting the efferent renal arteriole to increase glomerular filtration pressure and favor water and sodium retention. ACEIs and ARBs inhibit efferent renal arteriolar vasoconstriction that lowers glomerular filtration pressure. NSAIDs, by inhibition of prostaglandins and bradykinin, produce vasoconstriction of the afferent renal arteriole and reduce the ability of the kidney to regulate (increase) glomerular blood flow. The administration of an NSAID plus diuretic or ACEI or ARB may reduce the hypotensive effect of the antihypertensive agent but does not commonly lead to acute renal failure. When triple therapy with an NSAID plus diuretic and an ACEI or ARB is administered, the kidney is unable to use its normal compensatory mechanisms and may suffer an acute reduction in glomerular filtration that is marked by a rising serum creatinine.

Clinical Outcome

Several studies have noted the tendency for patients receiving triple therapy to have elevated serum creatines.2,3 Recently a large case-control study examined the risk of acute renal disease in patients receiving a) double therapy consisting of an NSAID combined with a diuretic or an NSAID with an ACEI or ARB, or b) triple therapy with both a diuretic and ACEI or ARB plus an NSAID.4 Patients were included only if kidney disease was their primary diagnosis upon admission to the hospital. The investigators were careful to control for confounders such as other diseases and drug usage. The study population included nearly 500,000 patients followed for a mean of about 6 years. Acute kidney injury was identified in 2215 patients who were compared with about 22,000 control patients. The overall incidence of acute kidney injury was 7 per 10,000 person-years. The risk of kidney disease in the patients was compared with matched control patients not exposed to the double or triple therapy. The use of double therapy was not associated with an increased risk of kidney injury.

Triple therapy was associated with a 31% increase in risk of injury. The greatest risk was noted within the first 30 days of concurrent therapy, when it was nearly twice as high in patients compared with the controls. Due to the study’s conservative entry criteria, it is possible that the study actually underestimates the risk. For example, increased serum creatinine levels may have caused prescribers to discontinue the combination therapy before kidney injury was severe enough to require hospitalization.

Management

Patients receiving NSAIDs chronically in combination with diuretics, ACEIs, or ARB, are at risk for diminished hypotensive response, elevated serum creatinine, and acute kidney injury. They should be monitored for altered blood pressure and serum creatinine, particularly during the first few months of combination therapy. While it appears that alternative hypotensive agents (eg, calcium channel blockers, centrally acting agents) are less affected by NSAIDs, similar data are not available for the risk of renal injury.

Drs. Horn and Hansten are both professors of pharmacy at the University of Washington School of Pharmacy. For an electronic version of this article, including references if any, visit http://www.hanstenandhorn.com.

References:

  1. Horn J et al. Coadministration of NSAIDs and antihypertensive agents. Pharmacy Times. 2006;72;54.
  2. Thomas MC. Diuretics, ACE inhibitors and NSAIDs – the triple whammy. Med J Aust. 2000;172:184-185.
  3. Loboz KK, Shenfield GM. Drug combinations and impaired renal function – the ‘triple whammy’. Br J Clin Pharmacol. 2004;59:239-243.
  4. Lapi F, Azoulay L, Yin H, Nessim SJ, Suissa S. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study. BMJ. 2013;346:e8525.

– See more at: http://www.pharmacytimes.com/publications/issue/2013/April2013/Diuretics-ACEIs-ARBs-and-NSAIDs-A-Nephrotoxic-Combination#sthash.abgaOg2u.dpuf

Are Your Medications Causing or Increasing Incontinence?

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If you are struggling with urinary incontinence or your existing incontinence is getting worse, take a look at the medications you are taking. They may contribute to the problem.

There are four groups of medications doctors commonly recommend that can cause or increase incontinence. If you are taking any of these, you should let your doctor know about your incontinence and discuss your medications (both prescription and over-the-counter) to see if there is another approach to control or eliminate the problem.
The most common incontinence problems arise from medications in the following four categories:

1. Diuretics to reduce excess fluid

Diuretics, also known as “water pills,” stimulate the kidneys to expel unneeded water and salt from your tissues and bloodstream into the urine. Getting rid of excess fluid makes it easier for your heart to pump. There are a number of diuretic drugs, but one of the most common is furosemide (Lasix®).

According to urologist Raymond Rackley, MD, approximately 20 percent of the U.S. population suffers from overactive bladder symptoms.

“Many of those patients also have high blood pressure or vascular conditions, such as swelling of the feet or ankles,” he says. “These conditions are often treated with diuretic therapies that make their bladder condition worse in terms of urgency and frequency.”

A first step is to make sure you are following your doctor’s prescription instructions exactly. As an alternative to water pills, Dr. Rackley recommends restricting salt in your diet and exercising for weight loss. Both of these can reduce salt retention and hypertension naturally.

2. Alpha blockers for hypertension

Another class of drugs used to reduce high blood pressure or hypertension by dilating your blood vessels can also cause problems. These medicines are known as alpha blockers. Some of the most common are Cardura®, Minipress® and Hytrin®.

These are usually more of an issue for women. Again, discuss this with your physician, because there are alternative drugs you may be able to take.

Men typically take these to treat an enlarged prostate (benign prostatic hyperplasia or BPH) which can restrict urination by putting pressure on the urethra. By relaxing the muscles in the bladder neck, they allow smoother urine flow for those patients.

3. Antidepressants and narcotic pain relievers

Some antidepressants and pain medications can prevent the bladder from contracting completely so that it does not empty. That gives rise to urgency or frequency or voiding dysfunction. They can also decrease your awareness of the need to void.

“Some of these drugs can also cause constipation,” Dr. Rackley says. “Constipation, in turn, can cause indirect bladder incontinence because being constipated takes up more room in the pelvis that the bladder needs to expand.”

4. Sedatives and sleeping pills

Using sedatives and sleeping pills can present a problem, especially if you already have incontinence. They can decrease your awareness of the need to void while you are sleeping.

The best way to address this situation, Dr. Rackley says, is to take other steps to relax and improve your sleep. Getting more exercise to make you tired, for example, can help. It’s also important to maintain a regular bedtime and wake-up schedule. Dr. Rackley says finding other ways to relax before bed — meditation, reading a book or listening to soothing music or sound effects (e.g., rain or waves) — can also help you sleep better.