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Common Painkillers Tied to Kidney Risks for Children: Study

Children taking the common painkillers known as nonsteroidal anti-inflammatory drugs may be at risk for acute kidney damage, particularly when the kids are dehydrated, a new study finds.

Nonsteroidal anti-inflammatory drugs (commonly called NSAIDs), such as ibuprofen (brand names Advil and Motrin), naproxen (Aleve) and ketorolac (Toradol) are used to relieve pain and fever.

“The one thing we did see that seemed to be connected to kidney damage was dehydration,” said lead researcher Dr. Jason Misurac, a nephrologist at Indiana University School of Medicine in Indianapolis.

For the study, which was published in the Jan. 25 online edition of the Journal of Pediatrics, Misurac’s team looked at the medical records of children admitted to Riley Hospital for Children in Indianapolis from 1999 through mid-2010. Over that time, they identified more than 1,000 cases of children being treated for kidney damage.

In nearly 3 percent of the cases, the damage was related to NSAIDs, the study found. Most kids were teens, but four were under 5 years old. All of them had been given NSAIDs before being hospitalized. Since many other cases involved several causes of kidney damage, it is possible some of those also were related to NSAIDs, the researchers said.

Most children who developed kidney damage had been given the recommended dose and had not been taking NSAIDs for more than a week.

In adults, taking NSAIDs regularly for several years has been tied to kidney problems, according to the U.S. National Institute of Diabetes and Digestive and Kidney Diseases. Cases involving children have previously been reported but only rarely.

Misurac noted that most of the children in the study hadn’t been drinking well and also were vomiting and had diarrhea, all of which can lead to dehydration. When someone is dehydrated the kidneys have a way of protecting themselves, which NSAIDs block, resulting in the damage, Misurac explained.

“Certainly in the way NSAIDs affect the kidneys, it’s reasonable to think that dehydration plus an NSAID has more of an effect than just an NSAID by itself,” he said.

Often the signs of kidney problems aren’t apparent, Misurac said. One sign is a decrease in urine; another is stomach pain. “But most kids who have episodes of acute kidney injury have nonspecific symptoms and there’s no one way to tell,” he said.

“If kids are dehydrated and not drinking well, then parents should think twice about using NSAIDs,” Misurac said. Tylenol (acetaminophen), which acts differently than NSAIDs, might be a better choice for children, he said.

For many of the children in the study, the kidney damage was reversed, Misurac said. The damage, however, was permanent for seven patients and they will probably need ongoing monitoring and treatment for declining kidney function, he said.

All the children under age 5 had to undergo dialysis and were more likely to be treated in an intensive-care unit, the researchers said. They also stayed in the hospital longer.

Although the study showed an association between taking NSAIDs and kidney problems in children, it didn’t establish a cause-and-effect relationship.

One expert agreed that NSAIDs can damage the kidneys.

“This is well known. Unfortunately, it is better known among doctors; the public is not as educated regarding this problem,” said Dr. Felix Ramirez-Seijas, director of pediatric nephrology at Miami Children’s Hospital.

Ramirez-Seijas said NSAIDs are “overused and abused, both by doctors and patients.”

For children, most fevers should not be treated; fever is how the body fights infection, he said. “There is a fear of fever that leads to overtreatment,” Ramirez-Seijas said.

In addition, children who take NSAIDs for aches after vigorous exercise also are at risk, because they may be dehydrated, Ramirez-Seijas said.

His advice to parents is to be sure children are well hydrated if they are going take NSAIDs. In addition, he believes that even these over-the-counter drugs should only be used with the advice of a doctor.

“Most people see taking a couple of Advil like taking a sip of water, but it’s not,” Ramirez-Seijas said.

By Steven Reinberg     HealthDay    Jan. 25
 

 

nsaids

 

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

What are NSAIDs and how do they work?

Prostaglandins are a family of chemicals that are produced by the cells of the body and have several important functions. They promote inflammation that is necessary for healing, but also results in pain, and fever; support the blood clotting function of platelets; and protect the lining of the stomach from the damaging effects of acid.

Prostaglandins are produced within the body’s cells by the enzyme cyclooxygenase (COX). There are two COX enzymes, COX-1 and COX-2. Both enzymes produce prostaglandins that promote inflammation, pain, and fever. However, only COX-1 produces prostaglandins that support platelets and protect the stomach. Nonsteroidal anti-inflammatory drugs (NSAIDs) block the COX enzymes and reduce prostaglandins throughout the body. As a consequence, ongoing inflammation, pain, and fever are reduced. Since the prostaglandins that protect the stomach and support platelets and blood clotting also are reduced, NSAIDs can cause ulcers in the stomach and promote bleeding.

What NSAIDs are approved in the United States?

The following list is an example of NSAIDs available:

  • aspirin
  • celecoxib (Celebrex)
  • diclofenac (Cambia, Cataflam, Voltaren-XR, Zipsor, Zorvolex)
  • diflunisal (Dolobid – discontinued brand)
  • etodolac (Lodine – discontinued brand)
  • ibuprofen (Motrin, Advil)
  • indomethacin (Indocin)
  • ketoprofen (Active-Ketoprofen [Orudis – discontinued brand])
  • ketorolac (Toradol – discontinued brand)
  • nabumetone (Relafen – discontinued brand)
  • naproxen (Aleve, Anaprox, Naprelan, Naprosyn)
  • oxaprozin (Daypro)
  • piroxicam (Feldene)
  • salsalate (Disalsate [Amigesic – discontinued brand])
  • sulindac (Clinoril – discontinued brand)
  • tolmetin (Tolectin – discontinued brand)

What are the side effects of NSAIDs?

NSAIDs are associated with several side effects. The frequency of side effects varies among NSAIDs.

Common side effects are

  • nausea,
  • vomiting,
  • diarrhea,
  • constipation,
  • decreased appetite,
  • rash,
  • dizziness,
  • headache, and
  • drowsiness.

Other important side effects are:

  • kidney failure (primarily with chronic use),
  • liver failure,
  • ulcers, and
  • prolonged bleeding after injury or surgery.

NSAIDs can cause fluid retention which can lead to edema, which is most commonly manifested by swelling of the ankles.

WARNING: Some individuals are allergic to NSAIDs and may develop shortness of breath when an NSAID is taken. People with asthma are at a higher risk for experiencing serious allergic reaction to NSAIDs. Individuals with a serious allergy to one NSAID are likely to experience a similar reaction to a different NSAID.

Use of aspirin in children and teenagers with chickenpox or influenza has been associated with the development of Reye’s syndrome, a serious and sometimes fatal liver disease. Therefore, aspirin and non-aspirin salicylates (for example, salsalate [Amigesic]) should not be used in children and teenagers with suspected or confirmed chickenpox or influenza.

NSAIDs increase the risk of potentially fatal, stomach and intestinal adverse reactions (for example, bleeding, ulcers, and perforation of the stomach or intestines). These events can occur at any time during treatment and without warning symptoms. Elderly patients are at greater risk for these adverse events. NSAIDs (except low dose aspirin) may increase the risk of potentially fatal heart attacks, stroke, and related conditions. This risk may increase with duration of use and in patients who have underlying risk factors for heart and blood vessel disease. Therefore, NSAIDs should not be used for the treatment of pain resulting from coronary artery bypass graft (CABG) surgery.

For what conditions are NSAIDs used?

NSAIDs are used primarily to treat inflammation, mild to moderate pain, and fever.

Specific uses include the treatment of:

  • headaches,
  • arthritis,
  • ankylosing spondylitis,
  • sports injuries, and
  • menstrual cramps.
  • Ketorolac (Toradol) is only used for short-term treatment of moderately severe acute pain that otherwise would be treated with narcotics.

Aspirin (also an NSAID) is used to inhibit the clotting of blood and prevent strokes and heart attacks in individuals at high risk for strokes and heart attacks.

NSAIDs also are included in many cold and allergy preparations.

Celecoxib (Celebrex) is used for treating familial adenomatous polyposis (FAP) to prevent the formation and growth of colon polyps.

With which drugs do NSAIDs interact?

NSAIDs reduce blood flow to the kidneys and therefore reduce the action of diuretics (“water pills”) and decrease the elimination of lithium (Eskalith, Lithobid) and methotrexate (Rheumatrex, Trexall). As a result, the blood levels of these drugs may increase as may their side effects.

NSAIDs also decrease the ability of the blood to clot and therefore increase bleeding. When used with other drugs that also increase bleeding (for example, warfarin [Coumadin]), there is an increased likelihood of serious bleeding or complications of bleeding. Therefore, individuals who are taking drugs that reduce the ability of blood to clot should avoid prolonged use of NSAIDs.

NSAIDs also may increase blood pressure in patients with hypertension (high blood pressure) and therefore antagonize the action of drugs that are used to treat hypertension.

NSAIDs increase the negative effect of cyclosporine on kidney function.

Persons who have more than three alcoholic beverages per day may be at increased risk of developing stomach ulcers when taking NSAIDs.

 

Medical and Pharmacy Editor: Jay W. Marks, MD  
Pharmacy Author: Omudhome Ogbru, PharmD 
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Common Painkillers Linked To Increased Risk Of Heart Attack, Study Says

Story highlights
A new study links common painkillers called to increased risk of heart attacks
Researchers urge doctors and patients to weight the risks and benefits
The drugs are not proved to be a a direct cause of heart attacks

(CNN)Taking even over-the-counter doses of common painkillers known as NSAIDs – nonsteroidal anti-inflammatory drugs – has been linked to an increased risk of heart attack in a new study.

The likelihood of experiencing a heart attack was calculated to increase by an average of 20% to 50%, compared with someone not taking the drugs, regardless of the dosage and amount of time the medications are taken.

The findings are observational and based on an association, however, with the drugs not proved to be a a direct cause of heart attack.

This group of drugs includes ibuprofen, diclofenac, celecoxib and naproxen, which are available over the counter or by prescription for higher doses, to relieve pain or fever resulting from a range of causes, including flu, headaches, back pain and menstrual cramps. Their range of uses also means they are often taken as needed, for short periods of time.

The level of risk increased as early as one week into the use of any drug in this category and at any dose, and the risk associated with taking higher doses was greatest within the first month.
“We found that all common NSAIDs shared a heightened risk of heart attack,” said Dr. Michèle Bally, an epidemiologist at the University of Montreal Hospital Research Center, who led the research. “There is a perception that naproxen has the lowest cardiovascular risk (among the NSAIDs), but that’s not true.”

Researchers’ overall finding was that taking any dosage of these drugs for one week, one month or longer was linked to an increased risk of a heart attack. The risk appeared to decline when these painkillers were no longer taken, with a slight decline one to 30 days after use and a greater decline, falling below 11%, between 30 days and one year after use.

Based on the paper, published Tuesday in the BMJ, Bally’s team suggests that doctors and patients weigh the potential harms and benefits before relying on the drugs as a treatment option.

“People minimize the risks because drugs are over the counter and they don’t read labels,” Bally said. “Why not consider all treatment options? … Every therapeutic decision is a balance of benefits and risk.”

Building on previous research

Cardiovascular diseases are the No. 1 cause of death globally, according to the World Health Organization, with 80% of all deaths in this category due to heart attacks and strokes. Each year, it’s estimated that 735,000 people in the United States have a heart attack. In the United Kingdom, more than 200,000 hospital visits each year are due to a heart attack.

Previous research has showed that this class of painkillers could increase the risk of having a heart attack, known as myocardial infarction. In 2015, the US Food and Drug Administration called on drugmakers to update their warnings labels to identify an increased risk of a heart attack or stroke.

But the specifics in terms of timing, dosage and treatment durations were less clear.

Bally and her team reviewed all available studies in this area from Canadian and European databases, analyzing the findings from 446,763 people, with 61,460 of them having had a heart attack. Their goal was to calculate the risk, determinants and time course of heart attacks associated with the use of NSAIDs under typical circumstances.

The team looked at very short-term use and at any dose, said Bally. “In real life, people use drugs at low doses and use them on and off,” she said, adding that this is not reflected in many clinical trials, for example, in which people have often been monitored during prolonged use of these drugs.

When using them for one week, the greatest risk was associated with rofecoxib, followed by diclofenac, ibuprofen and then celecoxib, respectively, though all except celecoxib had similar levels of risk, hovering around 50% increased odds of a heart attack, at any dose.

At higher doses, typically needing a prescription, some drugs had an even greater risk of heart attack between one week and one month of use. For example, naproxen showed a 75% increased likelihood of a heart attack within one month with doses of 1200 milligrams per day or more, and naproxen showed an 83% increased likelihood of a heart attack with doses greater than 750 milligrams per day when taken for one week to one month.

But the level of risk declined, on average, when the drugs were used for longer than one month.

“This is relative to not taking these drugs, your baseline risk,” Bally said. “The risk is not 75%. It’s an increase (maybe) from a tiny baseline risk that they have.”
Millions of these pills are sold every year, Bally said. “Therefore the risk, no matter how small or relative, is important to note from a population viewpoint.”
“We already know that these drugs increase your risk of having a heart attack,” said Dr. Mike Knapton, associate medical director at the British Heart Foundation, in a statement. “However this large-scale study worryingly highlights just how quickly you become at risk of having a heart attack after starting NSAIDs.” Knapton was not involved in the research.

Knapton further added that people must be made aware of the risk and that alternative medication or treatment should be considered where appropriate. For example, physical therapy or yoga could be used to alleviate pain from an injury.

nonsteroidal anti-inflammatory drugs
nonsteroidal anti-inflammatory drugs

Association, not causation

The researchers stress that the findings are purely observational, as they used readily available data about certain populations. Not all potentially influential factors could be taken into account, they say.

Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, commented that a number of lifestyle factors, such as smoking and body mass index, are not available in the data about the study participants. “It leads to uncertainty,” he said.

Tobacco use, unhealthy diet, obesity, alcohol abuse and hypertension are just a few of many factors that can cause a heart attack.

“This is the largest study of its kind, but it is still observational data based on prescription or dispensing information, rather than whether people were actually taking their medication,” said Dr. Amitava Banerjee, senior clinical lecturer in clinical data science at UCL in the UK. “Although these data reflect real-world use of NSAIDs, it is impossible to control for all the factors which may lead to confounding or bias.”

This uncertainty combined with the overall observational nature of the findings means the cause of the increased risk shown in the analysis cannot be explained, nor can the drugs be directly stated as a cause of heart attacks.

Bally thinks a cause could be changes in blood pressure or effects on kidney function, as these areas are poorly studied. But she stresses that all five drugs studied have individual behaviors. “It will be hard to point to one factor,” she said.

Relative, not absolute risk

“The paper has good evidence that there is some risk of a heart attack for all NSAIDs and suggests that the risk starts immediately on starting them, but is only expressed in relative terms,” said Evans, who was not involved in the research. “There is no clear description of the absolute risk.”

The findings are based on the chances of a heart attack occurring in people taking these drugs, compared with those not taking them. If risk was already low in a person, a 20% to 50% increased risk is not that much cause for concern.

“The risks are relatively small, and for most people who are not at high risk of a heart attack, these findings have minimal implications,” Evans said.

It’s also possible that people taking these drugs are, on average, already at higher risk than people not taking the drugs, he said, commenting that the study did not account for these factors in their calculations. For example, the reason someone is prescribed an NSAID, such as for severe pain, may also be the reason they have a heart attack soon after. So while the study shows that risk of a heart attack increases as soon as a few days into taking NSAIDs, the links may not be as clear as suggested, Evans said.

“The most likely mechanisms for action of the drugs would be expected to show a low risk at the start and only have an effect on heart attacks after longer usage. That this wasn’t the case casts some doubt on the findings of an immediate increase in risk,” he said.
“All effective medicines have unwanted effects, and NSAIDs, although easily available, are not without some risks, but this study is no reason to induce anxiety in most users of these drugs,” he said.

But while waiting for more clarity on the true level of risk and its cause, experts still advise caution when prescribing or taking these painkillers.

“The increased risk of heart attack with NSAIDs, regardless of which one, means that both health professionals and the public should weigh up the harm and the benefit when prescribing these medications, especially for more than a day or two,” Banerjee said.
“Despite the over-the-counter availability of the traditional NSAIDs, this caution is still required. The mechanism of this increased risk of heart attack is not at all clear from existing studies.”

By Meera Senthilingam, CNN         May 9, 2017
 source: www.cnn.com


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Just Say No: When It Makes Sense Not to Take Your Medicine

By Alexandra Sifferlin    Oct. 16, 2013
  
It sounds like something a quack would support, but it’s true. There’s growing evidence that lifestyle changes such as eating a healthier diet and exercising more may be enough to prevent and even treat conditions ranging from diabetes to cancer.

The latest comes from a review of studies, published in the Annals of Internal Medicine, that analyzed the effects of a combination of behaviors that reduced the rate of Type 2 diabetes among those at high risk of developing the disease. Making over their diets and boosting their amount of daily exercise, as well as quitting smoking and managing their stress were enough to help the participants, all of whom had high blood-sugar levels that precede diabetes, lower their glucose and avoid getting diagnosed with the disease.

And it’s not the first study to hint at the power of the pharmaceutical-free approach. A study published this month in the journal Cancer Epidemiology, Biomarkers & Prevention reported that brisk walking cut postmenopausal women’s breast-cancer risk by 14% compared with those who didn’t walk. Women who exercised more vigorously enjoyed a 25% drop in risk of developing the disease. Another report in the journal Lancet Oncology found that a plant-based diet, stress management and other lifestyle changes contributed to longer-lived cells among men with prostate cancer. Those results echoed previous work that documented that the same lifestyle-based changes contributed to fewer recurrent tumors among men who had been treated for prostate cancer.

Taken together, the data has more doctors putting away their prescription pads when they see certain patients. The pill-free route isn’t for everyone, however, so it’s important for physicians and patients to understand when it’s appropriate and when it isn’t.

It makes sense, for example, that prescription medications shouldn’t be a first-line treatment for people who are on the verge of developing a condition but can still prevent it — like the participants in the latest diabetes study. Preventing disease is always preferable to treating it, since once symptoms develop, they can cause more complications and additional health issues that require even more drug-based therapies to control. And diabetes is a good example of a disease that can be avoided, with weight management, proper diet and exercise, as the landmark Diabetes Prevention Program, a multicenter trial involving 3,234 people with prediabetes, proved in 2002. In that study, those who changed their diet and exercise habits lost more weight and had a lower rate of developing diabetes than those who took the glucose-controlling medication metformin.

With America’s growing obesity epidemic showing no signs of turning around, understanding how to prevent weight-related chronic disease, such as diabetes, hypertension and heart disease, is even more critical, especially among children, says Dr. David Katz. Katz is the director of the Yale-Griffin Prevention Research Center and author of the new book Disease Proof: The Remarkable Truth About What Makes Us Well. “If you think about the issues that prevail today, they are related to eating too much of all the wrong foods, getting far too little physical activity, toxins we’ve invented like tobacco, inadequate sleep and strained social bonds,” he says.

Treating these ailments with prescription medications can address the symptoms but does nothing to change the forces that drive these diseases. And in some cases, the drugs may cause even more problems, in the form of side effects.


So why aren’t the simpler strategies — exercise and diet changes — as entrenched as the prescription medications? Katz blames muddled messaging. “Unfortunately there has been a lot of bad advice. It has come from people trying to sell products, as well as sound bites and media spin.”

And even good advice, from doctors and public-health officials with good intentions, is often oversimplified to the point where it’s no longer helpful. “Take the ‘just cut fat’ recommendation. What the scientists actually meant was eat more naturally low-fat foods like vegetables. And, frankly, if we had done that, the advice would have been fine. But we didn’t do that, instead we ate low-fat cookies got fatter and sicker,” says Katz. “Essentially what we have done with each attempt to dumb this down is create an opportunity to spin out a whole new set of products that exploit the message.”

And until recently, there hasn’t been much attention paid to what may be driving unhealthy eating — like stress. In the study of men who lowered their risk of recurrent prostate tumors, stress management was part of the lifestyle-based regimen that helped them to keep cancer at bay. Finding a way to address and relieve stress can be an important part of preventing many chronic diseases, says Dr. Dean Ornish, director of the Preventive Medicine Research Institute and clinical professor of medicine at the University of California, San Francisco, who led that study.

According to Dr. Jordan Metzl, a sports-medicine physician at New York City’s Hospital for Special Surgery and author of the upcoming book The Exercise Cure, exercise could be one effective way of coping with stress. And it doesn’t hurt that physical activity also controls symptoms related to heart disease and other metabolic and psychological conditions.

“In my office, I see people from the medical community who are athletic. I see running psychiatrists, running neurologists, running oncologists, cardiologists,” says Metzl. “So I started asking the doctors, What role does exercise play in your treatment of headaches, your treatment of asthma, your treatment of cancer? I found that everyone uses exercise in the care of their patients for both prevention and treatment.”

Granted, Metzl’s patient population may be biased since the doctors he sees already believe in the benefits of physical activity, but he believes more physicians are starting to prescribe exercise as the research to support its benefits continues to grow. “There are studies on exercise and cancer prevention, fatigue, and new neuron formation in the hippocampus,” he says. “There is a nugget for every part of the body from erectile dysfunction, to cancer, to dementia. People are comfortable with the benefits of exercise for obesity or heart disease, but if you look at dementia or anxiety and the data on the role of exercise as prevention and even treatment, it’s amazing how much there is. I think we are seeing a movement toward connecting the dots.”

Doing so will require more than a few enlightened doctors and some scientific data, however. The U.S. health care system is designed to react to disease and treat it once symptoms set in — the reimbursement structure is founded on doctors diagnosing problems and treating them, for example, most often with medications. “The focus of our system is embedded in disease treatment. People make a lot of money off the way it was built, so we give lip service to prevention. But exercise is free.”

At Lincoln Medical Center and Harlem Hospital in New York City, doctors are starting to focus more on prevention by making diet changes a priority for patients — before they find themselves diagnosed with a disease like diabetes or heart trouble. The hospitals have launched the Fruit and Vegetable Prescription, a four-month pilot program, which allows patients with prescriptions — written by their doctors — to get coupons for fresh produce at farmers’ markets and the city’s green carts.

It’s not that prescription medicines aren’t doing their job, or that they don’t have a place in modern medicine. They do, and they are effective in containing disease once they emerge. But if it’s possible to avoid disease altogether, and if patients can do it without expensive medications that can cause complications, why wouldn’t they? Wouldn’t you?

Alexandra Sifferlin

source: Time


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Sharp rise in hospitalizations tied to energy drinks: report

CHICAGO | Tue Nov 22, 2011

(Reuters) – Emergency room visits linked to energy drink consumption have surged in recent years, according to a report released on Tuesday, as more people combine the popular beverages with alcohol and drugs.

The Substance Abuse and Mental Health Services Administration said hospitalizations in the United States tied to energy drinks have jumped tenfold to 13,114 in 2009 from 1,128 visits in 2005. The most recent year for which data is available is 2009.

The agency, a unit of the Department of Health and Human Services, said that 44 percent of the visits involved people who had combined the stimulant-rich drinks with alcohol, pharmaceuticals or illicit drugs.

The vast majority of the visits were made by males between the ages of 18 and 39, the agency said.

The researchers did not say what symptoms drove the people to go to the ER or what underlying medical conditions they may have had.

But they said other studies have indicated that excessive use of the drinks on their own can cause adverse reactions such as arrhythmia, hypertension and dehydration.

“Combining energy drinks with substances of abuse raises the risk of serious, even life-threatening injury, as well as the likelihood of engaging in risky behaviors such as driving under the influence,” the researchers said.

The report was immediately criticized by a trade group for makers of the energy drinks, which usually contain stimulants like caffeine and guarana as well as other additives that can compound the beverages’ effects .

The fact that nearly half the hospitalizations involved people who had also consumed alcohol or taken illegal substances or pharmaceuticals made “their consumption of energy drinks potentially irrelevant,” the American Beverage Association said.

The group also said that most mainstream energy drinks contain just half the caffeine of a similar size cup of coffee.

(Reporting by James Kelleher and Greg McCune)

source: Reuters