Nonsteroidal Anti-inflammatory Drugs and Risk of Atrial Fibrillation: Is There a Relationship?
By Carole Alison Chrvala, PhD
Nonsteroidal anti-inflammatory drugs (NSAIDs), including nonselective NSAIDs and cyclooxygenase-2 (COX-2) inhibitors, frequently are prescribed for the management of pain associated with musculoskeletal conditions and injuries, as well as other sources of mild to moderate pain and inflammation. In fact, an estimated 5% of all physician appointments in the United States involve a prescription for NSAIDs.1 A recent meta-analysis of 31 trials enrolling 116,429 patients examined the risk of cardiovascular events associated with NSAIDs.1 When compared to placebo, significantly increased risks of myocardial infarction, stroke, cardovascular mortality, and death were attributed to NSAID use.1 Of the NSAIDs studies, naproxen was associated with the lowest risk of adverse cardiovascular events.1The relationship between the use of NSAIDs and risk of atrial fibrillation (AF) is not yet clearly understood, although the adverse renal effects associated with NSAIDs, such as fluid retention, electrolyte imbalances, and blood pressure variations, are thought to play a role in AF.2 A meta-analysis that examined the relationship between COX-2 inhibitors and risk of AF evaluated data from 114 trials and reported that rofecoxib was associated with a significantly higher rate of cardiac arrhythmias (relative risk [RR], 2.90; 95% CI, 1.07-7.88). However, the analysis was limited by a low number of arrhythmia events.3
A recent analysis of approximately 3 million patients in the United Kingdom General Practice Research Database revealed that current use of NSAIDs was associated with a RR of 1.44 (95% CI, 1.08-1.91) for chronic AF. Risk declined as more time elapsed since last use of NSAIDs, while risk increased with longer duration of use. The RR for chronic AF was 1.57 (95% CI, 1.15-2.15) for patients taking NSAIDs for more than 30 days, compared with 1.80 (95% CI, 1.20-2.72) among those who used NSAIDs for more than 1 year. No relationship between NSAID therapy and risk of paroxysmal AF was observed, with the exception of patients who used NSAIDs for more than 1 year (RR, 1.74; 95% CI, 1.11-2.71).4
A population-based, case-control study further evaluated whether NSAIDs increased the risk of AF or flutter. The analysis included 32,602 individuals with a first inpatient or outpatient hospital diagnosis of AF or flutter and 325,918 population controls. Compared with no use of NSAIDs, the adjusted incidence rate ratio (IRR) among cases was 1.17 (95% CI, 1.10-1.24) for current nonselective NSAID use. The IRR increased to 1.27 (95% CI, 1.20-1.34) for those who used COX-2 inhibitors, with no significant differences in risk associated with newer versus older COX-2 inhibitors.2
Notably, new users of nonselective NSAIDs and COX-2 inhibitors were at highest risk of AF or flutter. The IRR for new users of nonselective NSAIDs was 1.46 (95% CI, 1.33-1.62) and 1.71 (95% CI, 1.56-1.88) for COX-2 inhibitors. Evaluation of the incidence of AF or flutter by type of NSAID for new users revealed that the risk was greatest for celecoxib (1.83; 95% CI, 1.44-2.34) and lowest for ibuprofen (1.43; 95% CI, 1.28-1.59) and naproxen (1.44; 95% CI, 0.97-2.12).2 Importantly, elderly patients taking NSAIDs were at greatest risk of AF or flutter. In addition, those with chronic kidney disease were at increased risk, with an adjusted IRR of 2.87 (95% CI, 1.53-5.38) for new users of COX-2 inhibitors and 1.75 (95% CI, 1.11-2.77) for long-term users of nonselective NSAIDs. Similarly, the adjusted IRR for patients with rheumatoid arthritis who were new users of a COX-2 inhibitor was 2.49 (95% CI, 1.40-4.42) and 1.44 (95% CI, 1.01-2.03) for long-term users of nonselective NSAIDs.2
As we review these findings, it is important to acknowledge the potential for methodological limitations of these case-control studies, including the possible effects of unmeasured confounders that might affect study results. In addition, the specific biologic mechanism to explain the association between NSAIDs and risk of AF is not yet understood, although one proposed explanation suggests that an underlying inflammatory condition increases both the risk of AF and the use of NSAIDs. Alternatively, it has been suggested that NSAIDs provoke disorders such as heart failure and hypertension, which can lead to AF.5
With these cautions in mind, evidence from these studies suggest that AF is an additional cardiovascular risk associated with NSAIDs,2,5 with the strongest association evident for new users and individuals who take NSAIDs for longer periods of time. These findings have clinically significant implications due to the high rate of administration of NSAIDs to treat pain and inflammation associated with a wide variety of musculoskeletal and other conditions. This is particularly important for older adults, who are at increased risk of AF by virtue of their advanced age. Of greatest concern, of course, are older patients who have been diagnosed with hypertension or heart failure and are already at increased risk for the adverse effects of NSAIDs because of these conditions.5
- Trelle S, Reichenbach S, Wandel S, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011;342:c7086.
- Schmidt M, Christiansen CF, Mehnert F, et al. Non-steroidal anti-inflammatory drug use and risk of atrial fibrillation or flutter: population based case-control study. BMJ. 2011;343:d3450.
- Zhang J, Ding EL, Song Y. Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomized trials. JAMA. 2006;296:1619-1632.
NSAID Painkillers Found To Deplete Vitamin B-6 Levels
New research has determined that COX-inhibitors, which include numerous NSAIDs - Nonsteroidal anti-inflammatory drugs – reduce Vitamin B-6 levels within the body.
The study, published in the American Journal of Clinical Nutrition, tested 150 patients with rheumatoid arthritis. Some of the patients were treated with cyclooxygenase (COX) -inhibitor treatments while some were not.
After six months of treatment, the researchers compared the two groups for their blood levels of pyridoxal-phosphate – the active form of vitamin B-6. The researchers found that the patients taking NSAIDs had significantly reduced levels of circulating vitamin B-6.
Both types of COX-inhibitors reduce B6
Both selective and non-selective COX-inhibitors were found to lower vitamin B6 levels. Laboratory research found this effected both kidney and liver levels of the important B-vitamin as well.
Vitamin B6 is critical for nerve function, fat metabolism, glucose metabolism, and many other functions in the body.
Non-selective COX-inhibitors include aspirin and ibuprofen, while selective COX-inhibitors include celecoxib (Celebrex).
Non-selective COX-inhibitors halt both the cyclooxygenase-1 enzyme and the cyclooxygenase-2 enzyme. While the cyclooxygenase-2 inhibition blocks prostaglandins involved in the pain and inflammatory response, cyclooxygenase-1 inhibition stops the prostaglandins related to producing healthy mucosal membranes, particularly among the stomach and lower esophagus.
This is why aspirin , naproxen (Naprosyn, Naprelan) and ibuprofen can produce ulcerative and bleeding stomach symptoms.
Arthritis, which now affects one in five adult Americans, is a leading reason people take COX-inhibitors.
Research that came to light about a decade ago revealed that selective COX-2 inhibitors can produce cardiovascular issues. This resulted in the removal of Vioxx and Bextra from the market. Celebrex (celecoxib ) still remains in the U.S. market, but has been removed from other markets, such as the European and Australian markets.
So besides the risk of ulcers, gastric bleeding and cardiovascular disease, we can now add blocking vitamin B6 uptake to the list of serious risks of these medications.
Natural COX-inhibitors come without side effects
It should be noted that natural COX-inhibitors such as willow bark and meadowsweet herb block pain-related prostaglandins but they do not cause the negative side effects relating to bleeding ulcers and cardiovascular effects. While this study did not test these with respect to vitamin B6, it is logical to assume that these herbs also do not block B6 as these do as well.
In fact both willow and meadowsweat stimulate the healing of ulcers and gastric bleeding, and are frequently used to help heal ulcers by herbalists.
Why do natural COX-inhibiting herbs not have the same negative effects? Because nature's herbs contain tens and sometimes hundreds of different medicinal compounds, which help balance and buffer the effects of the COX inhibition.
That's because nature is smart.
Chang HY, Tang FY, Chen DY, Chih HM, Huang ST, Cheng HD, Lan JL, Chiang EP. Clinical use of cyclooxygenase inhibitors impair vitamin B-6 metabolism. Am J Clin Nutr. 2013 Oct 23.
Source : LaLeva.org
FDA Tightens Opioid Labeling
The FDA has ordered a class-wide label change for long-acting opioids such as OxyContin (oxycodone) aimed at limiting use of these drugs to patients with severe, refractory pain.The move, announced at press briefing Tuesday, is part of a handful of changes that the agency hopes will curb an ongoing prescription painkiller epidemic, including a label clarification about the risks of abuse and death with the drugs, a requirement for additional postmarketing studies, and a boxed warning about the risks of neonatal opioid withdrawal syndrome.
"Opioids are important pain relieving medications that provide significant benefits when used appropriately," Douglas Throckmorton, MD, deputy director of the FDA's Center for Drug Evaluation and Research (CDER), said during a press briefing. "But they have significant risks associated with inappropriate patient selection and improper use, whether accidental or intentional."
The announcement is the culmination of a series of agency meetings and research on opioid safety that were prompted in large part by a Citizen's Petition from the groups Physicians for Responsible Opioid Prescribing (PROP) and Public Citizen.
The petition was signed by nearly 40 doctors, researchers, and public health officials, and aimed to make it more difficult for drug companies to market opioids for chronic, noncancer pain. Among other criteria, it asked FDA to strike the word "moderate" from opioid labels in chronic pain.
Throckmorton said changing the indication to "pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate" will further discussions between clinicians and patients about their eligibility for the drugs.
"The change reflects a departure from an indication that was based on a severity scale and transitions to a more specific use," Throckmorton said. "Patients in pain will not only be assessed by a rating on a pain scale, but a more thoughtful determination of pain."
Greg Anderson, MD, a primary care physician at the Mayo Clinic in Rochester, Minnesota welcomed the FDA action.
"In the absence of malignancy related pain, examples where long acting opioids can be justified are relatively few and far between," Anderson, wrote in an email.
James A. McGowan, MD, of the center for interventional pain medicine at Mercy Medical Center in Baltimore, said chronic pain treatment is challenging but he warned that "too often these medications are prescribed without adequate thought being given to their serious side effects, their marginal effectiveness in treating long term pain, and the fact that these medications often end up doing more harm than good."
In an email, McGowan acknowledged that "small subsets of patients may benefit from chronic opiate use" but he added that the new labels would serve as a necessary reminder "to both patients and physicians that the use of these medications must be done very cautiously and only after carefully weighing the potential risks and benefits."
Randy Wexler, MD, MPH, of Ohio State University, said the changes were "appropriate" adding that he only "rarely" prescribes long-acting opioids for chronic pain.
"This will have no impact on my practice other than as support for my discussion with patients as to why such medications are often not indicated," Wexler said in an email to MedPage Today.
Kevin Hill, MD, MPH, psychiatrist-in-charge at McLean Hospital's alcohol and drug abuse program in Belmont, Massachusetts, wrote that he has experience treating opioid addiction. "I've seen patients that have been prescribed long-acting opioids inappropriately on an "as-needed" basis, and inappropriate prescribing can have the unintended effect of starting someone on a path to addiction," Hill wrote in an email to MedPage Today. "Opioid addiction is very difficult to treat, so I appreciate the FDA's effort to limit the risk associated with these medications."
The updated label will further clarify that the drugs should be used as a last resort in patients who have no other options, due to their risk of addiction, abuse, and misuse even at recommended doses, as well as greater risk of overdose and death.
The FDA is also requiring postmarketing studies to further assess those risks. Throckmorton said the agency expects companies to collaborate on the requisite trials in order to get more information as efficiently as possible.
He added that it became apparent through earlier meetingson the issue that there were not enough data available on the risks of long-term opioid use, as earlier trials had only been completed through 12 weeks.
Additionally, the agency will now require long-acting opioids to carry a boxed warning describing the risk of neonatal opioid withdrawal syndrome with chronic use during pregnancy.
"By exercising our legal and regulatory authority to take action, the FDA will ensure that the benefits of long-acting opioids will continue to outweigh the risks," FDA Commissioner Margaret Hamburg, MD, said during the briefing.
Michael Von Korff, ScD, of Group Health Research Institute in Seattle, who is also a member of PROP, said the move is a step in the right direction, but said that overall the agency's actions on the opioid epidemic leave something to be desired.
"It is not clear to me why the FDA's actions apply only to long-acting opioids when similar cautions apply to short-acting opioids, like Vicodin," Von Korff said in an email.
Von Korff added that the label now appropriately places "increased emphasis on the risks of chronic opioid therapy. But the current FDA label does not adequately reflect that data are lacking to establish the effectiveness -- and long-term safety -- of long-term or high-dose opioid therapy for chronic pain."
"Prescribing opioids for longer than 90 days for chronic pain should remain an option for physicians and patients, but it should be an off-label use, because there is almost no research establishing that this use is either safe or effective," Von Korff said.
Source : MedPageToday
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Diclofenac Used and Recommended Globally, Despite Cardiovascular Risks
A study in this week's PLOS Medicine finds that the painkiller diclofenac (a non-steroidal anti-inflammatory drug (NSAID) in the same class as aspirin) is the most commonly used NSAID in the 15 countries studied and is included in the essential medicines lists of 74 low-, middle- and high-income countries, despite its known tendency to cause heart attacks and strokes in vulnerable patients. This risk is almost identical to that of Vioxx (rofecoxib), which was withdrawn from worldwide sales in 2004 because of cardiovascular risk. Researchers writing in this week's PLOS Medicine call for diclofenac to be removed from national essential medicines lists and to have its global marketing authorisations revoked.
It has been known for over a decade that some NSAIDs such as diclofenac are associated with more cardiovascular complications than other NSAIDs such as naproxen, but in an analysis of the essential medicines lists of 100 countries, Patricia McGettigan from Barts and The London School of Medicine and Dentistry and David Henry from the Institute for Clinical Evaluative Sciences and the University of Toronto, Canada, found that diclofenac was listed in the essential medicines lists of 74 countries and naproxen, a much safer alternative, in just 27.
Furthermore, in an in-depth analysis of the sales and prescriptions of NSAIDs in a selection of 15 low-, middle-, and high-income countries using information from 2011, they found that diclofenac sales (or prescribing, in the case of England and Canada) were three times higher than that of naproxen. The findings demonstrate that evidence about the risks associated with diclofenac has translated poorly to clinical practice.
McGettigan states: "Diclofenac has no advantage in terms of gastrointestinal safety and it has a clear cardiovascular disadvantage." Henry added: "Given the availability of safer alternatives, diclofenac should be de-listed from national essential medicines lists. McGettigan concludes: "There are strong arguments to revoke its marketing authorisations globally."
In an accompanying Perspective, K. Srinath Reddy from the Public Health Foundation of India and Ambuj Roy from the All India Institute of Medical Sciences (uninvolved in the study) say that the results of this study suggest that immediate action is warranted to remove diclofenac from national drug lists and that the World Health Organization should provide information on the safety of NSAIDs.
However, according to Reddy and Roy, it is not just the case of diclofenac versus naproxen that is at stake but the broader challenge of ensuring that everyone responsible for the safety of patients makes informed decisions in an appropriate and timely manner.
Reddy and Roy conclude: "If we do not collectively rise to that challenge, no NSAID can relieve the pain of that failure."
Source : Science Daily
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FDA Panel Votes for Tighter Controls on Vicodin
An FDA advisory committee voted 19 to 10 on Friday in favor of moving hydrocodone combination drugs such as Vicodin, Lortab, and Norco into the more restrictive schedule II category of controlled substances.The majority of panelists involved in the 2-day hearing believe the evidence suggests that the drugs are pharmacologically similar to and as susceptible to abuse as other opioids, such as oxycodone combination drugs like Percocet, that fall into the more tightly regulated class.
"We've seen the terribly serious consequences of poor prescribing practices stemming from obvious misclassification of hydrocodone combinations," said panelist Mary Ellen Olbrisch, PhD, professor of psychiatry at Virginia Commonwealth University.
"I don't think the reclassification is a panacea for the opiate abuse problem in the U.S.," she added, "but I think it's an important step in getting physicians to rethink prescribing practices and look at other approaches to pain management."
Moving the drugs from schedule III to schedule II would eliminate a clinician's ability to prescribe up to a 6-month supply of the drugs as well as the ability to simply call in a prescription. For schedule II drugs, doctors can write for no more than a 3-month supply, and a written prescription is mandatory.
The decision has been a long time coming -- beginning with a 1999 citizen's petition that ultimately prompted an inter-agency war between the DEA and the FDA.
This week's 2-day hearing was a compromise that resulted from removal of a hydrocodone reclassification provision from last year's PDUFA reauthorization bill. The hearing was originally scheduled for October but was cancelled because of Hurricane Sandy and its attendant damage across the MidAtlantic states.
At the meeting hearing, industry and advocacy organizations -- including pharmacists and pain specialists -- expressed concerns that reducing access to hydrocodone combination products would limit treatment for patients who in pain.
Their message was countered by addiction specialists and bereaved families who had lost children to prescription painkillers.
Looking at the Numbers
Currently, hydrocodone products are the most widely prescribed agents in the U.S., accounting for 131 million prescriptions for 47 million patients in 2011.
To get a handle on their potential for abuse, FDA and Drug Enforcement Administration (DEA) epidemiologists calculated "abuse ratios" that tried to assess whether this volume of prescribed drugs was tied to more severe outcomes, by comparing it with data for oxycodone combination products.
Numerators included ED visits or poisonings, but depending on the denominator used -- the U.S. population, the number of tablets dispensed, or the overall weight of drugs used -- hydrocodone products appeared both more and less abusable than oxycodone products.
Joseph Rannazzisi, deputy assistant administrator of the office of diversion control at the DEA -- which used total weight when calculating its abuse ratio and concluded that hydrocodone was more widely abused than oxycodone products -- spoke out passionately against statistics.
"I'm not going to talk about denominators. I'm not a statistician or a PhD. I'm just a cop," he said. "Every day I deal in reality, and I know these abusers are taking 10, 20, 30, or 40 tablets" of hydrocodone drugs.
"This drug has got a hold of this society and it's just killing us," he said.
Sharon Walsh, PhD, of the Center on Drug and Alcohol Research at the University of Kentucky, who discussed her work looking at how addictive the agents could be, was asked by a panelist for her interpretation of the research.
"I think they're the same, that's the bottom line from a pharmacological perspective," Walsh said about hydrocodone and oxycodone. "One might wonder why the oxycodone products aren't in schedule III."
Several panelists asked whether a schedule change would have any impact on curbing addiction rates given the fact that oxycodone products are in a more tightly regulated class and are still subject to such wide abuse.
But Rannazzisi said hydrocodone often acts as a gateway drug that gets people started on other opioids.
During the open public hearing portion of the meeting, Sen. Joe Manchin (D-W.Va.) who pushed the amendment to reclassify hydrocodone combos in last year's PDUFA reauthorization bill, and groups representing families who'd lost loved ones to addiction, including Save the Michaels of the World led by Avi Israel, addressed the panel.
Balancing Act: Pain Control vs. Abuse
Representatives from the American Cancer Society, the American Academy of Pain Management, National Association of Chain Drug Stores (NACDS), the Healthcare Distribution Management Association (HDMA), and other groups aired their concerns about patient access and challenges to distribution if the drugs were up-scheduled.
Groups such as the American Academy of Pain Medicine, the American Pharmacists Association (APhA), the American Dental Association, and the American Optometric Association, had time in the regular schedule of the meeting to air their concerns about access.
"This is a balancing act," said Lynne Webster, MD, who represented AAPM. "It's a tradeoff between access for people who derive a benefit from hydrocodone and non-medical use that has caused a great deal of harm."
Some panelists asked if there was a third choice, an alternative solution that would provide more benefit than changing the drug's scheduling. They questioned whether greater use of e-prescribing and Prescription Drug Monitoring Programs, as well as better education efforts for both clinicians and patients, would suffice.
Ultimately, the majority decided that a reclassification into schedule II would be appropriate -- but it remains to be seen how the FDA will interpret their conclusions.
Douglas Throckmorton, MD, deputy director of the FDA's Center for Drug Evaluation and Research, said the issues the panel faced "were among the most challenging I've ever worked on" in the 16 years he's been at the agency.
"It's unquestionable, this epidemic of abuse and death [from opioid narcotics], it's something we need to address as a society," he said. "There's also a need for appropriate access to opioids for patients in pain. Finding a balance between those needs is what FDA will be working on."
Source : MedPage Today
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Prescription Drug Misuse Remains a Top Public Health Concern
Prescription drug misuse is second only to marijuana as the nation’s most prevalent illicit drug problem, with approximately 22 million persons nationwide initiating nonmedical pain reliever use since 2002, according to a report by the Substance Abuse and Mental Health Services Administration (SAMHSA). The report also shows variations in use by state, with combined 2010 and 2011 data indicating that rates of past year misuse among those aged 12 or older ranged from 3.6 percent in Iowa to 6.4 percent in Oregon.“Addressing prescription drug misuse remains a top public health priority, as we’ve seen inconsistent progress in addressing the issue across the states,” said SAMHSA Administrator Pamela S. Hyde. “Data from this report helps up better understand geographic variations in use and should help with the development of more targeted and effective prevention and treatment programs. The key is educating the public on the serious health risks involved and ensuring that we are providing the necessary treatment to those who need it.”
“Prescription drug abuse is a major problem throughout our nation,” said Gil Kerlikowske, Director of National Drug Control Policy. “These data reaffirm how vital it is for the public health and public safety communities to work together to reduce the toll prescription drug abuse inflicts on our cities, towns and neighborhoods. As we continue to focus on this challenge at the federal level, we hope people will also endeavor to learn more about the harms associated with prescription drug abuse and take time to empty medicine cabinets of any excess, unneeded or expired prescription medications.”
Seven of the 10 states with the highest rates of nonmedical use of prescription pain relievers were in the West (Arizona, Colorado, Idaho, Nevada, New Mexico, Oregon and Washington). Four of the 10 states with the lowest rates were in the Midwest (Illinois, Iowa, North Dakota and South Dakota), and four were in the South (Florida, Georgia, Maryland and North Carolina).
A comparison of the combined 2009 and 2010 data with combined 2010 and 2011 data revealed a decrease in prescription drug misuse among those aged 12 or older in 10 states (Kentucky, Louisiana, Massachusetts, Mississippi, New Hampshire, New York, Ohio, Oklahoma, Rhode Island and West Virginia). None of the states saw an increase.
SAMHSA has a number of programs designed to address prescription drug misuse, including its Prevention of Prescription Abuse in the Workplace contract which provides technical assistance to help civilian and military workplaces in communities across America to reduce prescription drug abuse problems.
The NSDUH Report: State Estimates of Nonmedical Use of Prescription Pain Relievers: 2010-2011, is based on data from the SAMHSA National Survey on Drug Use and Health (NSDUH). NSDUH is a scientifically conducted annual survey of approximately 67,500 people throughout the country, aged 12 and older. This NSDUH report is available at: www.samhsa.gov/data/2k12/NSDUH115/sr115-nonmedical-use-pain-relievers.htm.
The complete 2010-2011 NSDUH State report presenting estimates for 25 substance use and mental health measures is available at www.samhsa.gov/data/NSDUH/2k11State/NSDUHsae2011/Index.aspx.
Source : Newswise
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Rx Drug Abuse Up, Illicit Drug Use Wanes
As abuse of prescription painkillers continues to rise, patients are using fewer illicit drugs, researchers said here.While the incidence of abuse of oxycodone (OxyContin) and other prescription painkillers rose about 1 percentage point each year between 2007 and 2009, rates of illicit drug use -- that includes marijuana, cocaine, and heroin -- fell 4 percentage points each year during that time, according to Asokumar Buvanendran, MD, of Rush University Medical Center in Chicago, and colleagues.
They reported their findings at a poster session at the American Society of Anesthesiologists meeting here.
The bright side is that less abuse of illicit drugs may eventually translate to decreases in common comorbidities of injection drug use, such as HIV and hepatitis C.
But Buvanendran told MedPage Today it's important that pain specialists "identify and stratify high- to low-risk patients, and aggressively follow prescription monitoring programs."
To assess trends in abuse of prescription and illicit drugs, the researchers looked at data from the Drug Abuse Warning Network (DAWN) for 11 major metropolitan areas between 2007 and 2009.
The database provides estimates of the percentage of emergency department visits that have to do with substance use.
Illicit drugs included cocaine, marijuana, and heroin, while prescription drug visits to the ED typically involved oxycodone, Buvanendran said.
He and colleagues found that overall, illicit drug use is higher than prescription painkiller abuse, with 28% of ED visits involving illicit drugs and 22% involving prescription drugs in 2009.
But use of illicit drugs appeared to be declining between 2007 and 2009 they found, by about 4 percentage points per year -- from 36% in 2007 to 32% in 2008 and finally to 28% in 2009.
On the other hand, ED visits involving abuse of prescription painkillers rose about 1 percentage point each year during that time -- from 20% to 21% to 22%, they reported.
They noted that even though prescription drug abuse appeared to be on the rise, increases weren't as large in magnitude as the decreases in illicit drug use.
Buvanendran told MedPage Today that it's critical for pain medicine specialists to identify which of their patients may be at risk for prescription drug abuse. In addition to screening and taking advantage of prescription drug monitoring programs to track patient use, he urged clinicians to do random urine screenings if they deem them necessary.
"If you have a 30-year-old male with nonspecific back pain and a normal MRI," you have to be suspicious, he said.
Source : MedPage Today
Worrying Trends Confronted in Prescription Drug Abuse
The two young men who showed up retching and wild-eyed in an emergency room in Portland, Ore., last summer insisted they had swallowed nothing but an ordinary soft drink before one collapsed. Yet their odd coloring suggested otherwise. Fifteen minutes after they had downed the drink, their lips and skin turned a startling blue. Their blood was as dark as chocolate.
Eventually one of the men confessed: they had spiked their soda with a bitter liquid they bought online. They meant to order “2C-E,” a man-made hallucinogen that they heard was similar to Ecstasy or LSD. What they received instead from a chemical company in China was aniline, an industrial solvent that ruptured their red blood cells, starved their tissues for oxygen and nearly killed them. Whether the substitution was their mistake or the company's, no one knew. “For quite a while after they got to the ER,” says Zane Horowitz, medical director of the Oregon Poison Center, “we didn't know what exactly they had taken, and neither did they.”
Horowitz and other toxicologists say the range of legal and illegal drugs now available to anyone with a credit card or well-stocked family medicine chest is broader and, in some ways, more dangerous than ever before. Bored teens seeking the latest high are only part of the problem. Patients who double down on long-acting prescription narcotics or mix some medicines with one another or with alcohol are vulnerable, too. The escalating death toll from drug use in the U.S. is startling, as a recent overview from the Centers for Disease Control and Prevention has confirmed. Accidental poisoning has now replaced car crashes as the nation's leading cause of fatal injury, and 89 percent of those poisonings result from drugs.
The magnitude of the problem has legislators, doctors and public health experts searching for solutions. Last July, President Barack Obama signed into law the Synthetic Drug Abuse Prevention Act of 2012, nationally outlawing the manufacture, sale and possession of 2C-E and 25 other “designer” recreational drugs. To try to rein in prescription drug abuse, at least 49 states have authorized funding for electronic databases that ultimately aim to identify physicians who overprescribe narcotics, as well as addicts who “doctor shop” to load up on pain relievers or stimulants.
Meanwhile medical toxicologists have surprising advice for emergency room teams treating overdoses: rely less on standard blood and urine tests when trying to identify drugs of abuse because those lab tests can be grossly misleading. Instead, these medical sleuths say, asking sharper questions will likely save more patients.
Despite the recent increase in deaths from designer drugs—recreational compounds that are chemically tweaked to stay ahead of the law—a less exotic threat accounts for the most common type of drug poisoning. In the most recent analysis of all overdose deaths in the U.S., more than 40 percent involved prescription narcotics. Sales of these strong painkillers, including oxycodone, hydrocodone and methadone, have climbed, too, jumping by 300 percent between 1998 and 2008, according to the CDC, as doctors have prioritized alleviating the severe pain of cancer, surgery and serious injury.
In the past decade research has firmly demonstrated that a short course of prescription narcotics can safely reduce suffering. But the abuse of these potentially addictive drugs, alone or in combination, is particularly deadly. A 2008 study in the Journal of the American Medical Association profiled the problem in West Virginia: 56 percent of 275 people who overdosed on prescription narcotics had not been prescribed the medication that killed them. Another 21 percent had received prescriptions for narcotics from five or more doctors in the year before they died, a pattern that suggests they had doctor shopped to obtain more pills than any one physician would supply. National statistics underscore the risk: legal narcotics now kill more people every year than heroin and cocaine combined.
Not only are prescription narcotics more widely available than ever before, some also stay in the body longer. High-dose, extended-release pills are convenient for patients seeking uninterrupted relief from severe pain throughout the night, for example, but they also make overdose more likely if taken incorrectly. Some recreational abusers pulverize long-acting 60-milligram pills of oxycodone to snort or smoke it, thereby sending a potentially toxic quantity into the bloodstream all at once.
Well-meaning pain patients run afoul of the pills, too. “I get patients who tell me, ‘I ran out of my medicine, so my neighbor gave me some of his,’” Horowitz says. “But it turned out the neighbor was taking a much higher dose.”
The greater availability of prescription drugs also makes it dangerously easy to mix medications. In the JAMA overdose study, nearly 80 percent of those who died were on a medley of drugs that usually included benzodiazepines (commonly prescribed for anxiety or insomnia) and had sometimes imbibed alcohol as well. That pattern of mixing often bespeaks an underlying addiction, the researchers say. In high-enough doses, each of those drugs can slow breathing, and the combination is particularly dangerous, says Jane Prosser, an emergency medicine physician at Weill Cornell Medical Center in New York City. “This is one of those cases where one plus one equals four.”
An overdose in an older patient, who is more likely to be undergoing treatment for multiple chronic conditions, can be especially tough to diagnose in the emergency room, Prosser says. “A confused elderly person comes to the ER and says, ‘I feel very weak and dizzy.’ Is that their cancer? The chemo? The pain meds? The fact that they're dehydrated because they've been vomiting and have diarrhea? It can be very hard to tell.”
When Lab Tests Go Wrong
Although advanced analytical techniques can selectively identify any drug, they are too expensive and slow to be useful in a medical emergency, says Mark B. Mycyk, a medical toxicologist at John H. Stroger, Jr., Hospital of Cook County in Chicago. And the standard panels of quicker screening tests for drugs in blood and urine have not kept up with shifts in the types of drugs people abuse.
“Those core [toxicology] screens were developed for the war on drugs in the workplace in the mid-1970s and are designed mostly to pick up heroin, cocaine and marijuana use,” Mycyk says. The tests will not detect the increasing number of barely legal or illegal recreational drugs such as 2C-E that come in many slightly rejiggered versions because of creative chemists looking to make a buck. Even many legitimate medicines, including the antianxiety pills Ativan and Xanax and the painkillers methadone and oxycodone, do not show up on the standard hospital drug-screening tests. Relying on lab results, Prosser says, can, in this case, foil diagnosis and misguide treatment.
Say a man addicted to methadone comes into the emergency room unconscious after also taking a hefty dose of Xanax. The doctor, trying to figure out why the patient is unconscious, screens his urine for sedating narcotics. The results come back negative because the screen will pick up neither methadone nor Xanax. Misled by the test results, the doctor does not prescribe a medicine that would blunt symptoms of withdrawal as the narcotic wears off—and that decision has fatal consequences. “Suddenly [the patient] starts vomiting from opiate withdrawal but doesn't wake up, because he has OD'd on benzodiazepines,” Prosser says. Inhaling that vomit could kill him.
Improved testing is not necessarily the answer, Mycyk says. When time is critical, taking note of a telltale constellation of symptoms typically triggered by a certain class of drugs—and treating those symptoms—makes more sense than waiting for chemical confirmation.
Federal organizations have started to work on solutions as well. Last July the Food and Drug Administration began requiring drug companies to start educating doctors about the special risks of such prescription drugs. The CDC has called on states to consider monitoring Medicaid or workers' compensation claims “for signs of inappropriate use of controlled prescription drugs.” To help reduce doctor shopping, the CDC says, these state programs might in some cases consider restricting reimbursement for controlled drugs to scripts that come through only one designated prescriber per patient and one designated pharmacy.
Mycyk has started telling the ER physicians he trains that they might save more lives by asking more specific questions than the ones they learned to ask in medical school. “Don't ask, ‘Do you abuse illegal drugs?’” he says. “Most of the drugs people are using today are not illegal. A lot of them are overdosing on drugs that were prescribed by their doctor.”
Instead, Mycyk says, asking questions such as “Have you ever gotten high on cough syrup?” or “Have you ever taken a friend's or relative's pills?” will put you on the right track to more helpful responses. “Most [patients] will do all they can to help you,” he says. “In most cases, landing in the ER was an accident. They don't want to die.”
Source : Scientific American
Study: Dramatic Increase in Abuse of Rx Painkillers
The illicit use of prescription painkillers has increased dramatically in recent years, particularly among men ages 18 to 49, according to a new report.
Between 2002 and 2010, there was a 74.6% overall increase in the number of individuals taking prescription painkillers chronically -- on more than 200 days each year -- for nonmedical purposes, according to Christopher M. Jones, PharmD, of the CDC in Atlanta.
And among men, chronic use increased by 105.3%, Jones reported in a research letter in Archives of Internal Medicine.
"This finding is important because it parallels increases in overdose deaths, treatment admission, and other negative effects associated with opioid pain relievers in recent years," he observed.
For instance, in 2009 alone there were 15,597 fatal overdoses involving drugs such as hydrocodone and oxycodone.
To see if this skyrocketing rate of fatal overdoses was accompanied by an overall increase in nonmedical use of these painkillers, Jones analyzed data from the annual National Survey on Drug Use and Health.
In this survey, individuals who report using these drugs were asked to estimate how many days during the previous years they did so.
The analysis showed no increase in the number of people reporting any nonmedical use of prescription painkillers, or use on 1 to 200 days in the past year.
But the total number of days of use rose by 35% to 612,829,084 in 2010 from 451,031,411 in 2002.
The annual rates of men using these drugs more than 200 days each year rose by 5.1% (P<0.01), the researcher reported.
Moreover, when the data on men's nonmedical use of prescription painkillers were broken down according to age group, these annual increases were identified:
- Ages 18 to 25, 7.4% (P<0.01)
- Ages 26 to 34, 5% (P<0.05)
- Ages 35 to 49, 4% (P<0.01)
Overall, individuals ages 26 to 34 using the drugs for more than 200 days increased by 81%, while the increase among those ages 35 to 49 was 134.6%.
Rates of chronic use also rose, although not significantly, among people 50 and older.
One "encouraging" finding, Jones reported, was a decrease in use by individuals ages 12 to 17.
Among these adolescents, use on 1 to 29 days decreased by 17.4% (P<0.01) and use for more than 200 days fell by 25.7%.
But the sum totals of 4.6 million people taking the drugs for more than 30 days and almost 1 million using painkillers for nonmedical reasons for more than 200 days per year are "concerning," he observed.
"The annual average estimate of 613 million person-days of [past-year nonmedical use] implies that each of the 257 million opioid prescriptions dispensed in the United States annually contributes on average to more than 2 days of [nonmedical use]," he stated.
These findings are a warning signal that greater efforts are needed for public health authorities to focus efforts on preventing the morbidity and mortality associated with illicit pain reliever drug-taking, and particularly among men and high-using age groups, he concluded.