Medication

NSAID Prescribing Precautions
Am Fam Physician. 2009 Dec 15; 80(12):1371-8.
Reprinted with permission from Risser A., Donovan D., Heintzman J., Page T.
School of Medicine, Oregon Health and Science University

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used, but have risks associated with their use, including significant upper gastrointestinal tract bleeding. Older persons, persons taking anticoagulants, and persons with a history of upper gastrointestinal tract bleeding associated with NSAIDs are at especially high risk. Although aspirin is cardioprotective, other NSAIDs can worsen congestive heart failure, can increase blood pressure, and are related to adverse cardiovascular events, such as myocardial infarction and ischemia. Cyclooxygenase-2 inhibitors have been associated with increased risk of myocardial infarction; however, the only cyclooxygenase-2 inhibitor still available in the United States, celecoxib, seems to be safer in this regard. Hepatic damage from NSAIDs is rare, but these medications should not be used in persons with cirrhotic liver diseases because bleeding problems and renal failure are more likely. Care should be used when prescribing NSAIDs in persons taking anticoagulants and in those with platelet dysfunction, as well as immediately before surgery. Potential central nervous system effects include aseptic meningitis, psychosis, and tinnitus. Asthma may be induced or exacerbated by NSAIDs. Although most NSAIDs are likely safe in pregnancy, they should be avoided in the last six to eight weeks of pregnancy to prevent prolonged gestation from inhibition of prostaglandin synthesis, premature closure of the ductus arteriosus, and maternal and fetal complications from antiplatelet activity. Ibuprofen, indomethacin, and naproxen are safe in breastfeeding women. Care should be taken to prevent accidental NSAID overdose in children by educating parents about correct dosing and storage in childproof containers.

Opioid Medications for Back Pain
in Injured Workers?
Reprinted with permission from Charles P. Moore, MD, Oregon Health Services

The use of opioids for control of acute back pain following work injuries is controversial. One study of more than 1800 injured workers with low back pain in the State of Washington revealed a significant association between use of opioids and work disability at one year. (1) The authors of the study recommended caution prescribing opioids in this population, reserving their use for only the most severe cases. A similar study of over 8000 injured workers with new-onset, disabling low back pain found a similar association with prolonged disability and higher medical costs. (2) The authors speculate that the cognitive and emotional side-effects of opioids may predispose to poorer effort in rehabilitation and less motivation to return to work.

It is not unusual for work injuries to occur at a time of high stress levels in workers’ lives. This emotional stress impairs the worker’s ability to cope with pain. Opioid drugs in these workers can provide dramatic relief of both pain and psychological distress but there is potential risk that some of them will become “chemical copers” who avoid facing the real issues in their lives while remaining “too painful” to return to work. True, it is the physician’s responsibility to provide adequate pain relief but our first responsibility is to do no harm. We should not naively assume that controlling the injured worker’s pain automatically leads to normalizing his function. I have reviewed medical histories of numerous injured workers who received escalating doses of opioid medication while continuing to complain of high levels of pain and inability to work.

Physicians treating injured workers should attempt pain control with use of acetaminophen and NSAIDs as the first line of defense. A good physical therapist can teach the worker self-management techniques to control pain. Every effort should be made to avoid use of opioids because, once started, some patients quickly become dependent on them. If opioids are used, it should be made clear that ongoing use depends less on subjective pain control than on improving function. At each visit the treating physician needs to carefully review whether there is objective evidence of improvement. If not, there should be strong consideration of stopping opioid medications.

The bottom line: Physicians need to be aware that opioid medications may hinder rather than promote recovery in injured workers with acute back injuries.

1) Franklin GM et al., Early opioid prescription and subsequent disability among workers with back injuries, Spine, 2008;33:199-204.

2) Webster B et al., Relationship between early opioid prescribing for acute occupational low back pain and disability duration, medical costs, subsequent surgery and late opioid use, Spine, 2007;32:2127-32

NSAID Use Associated With Future Stroke
in Healthy Population
—Sue Hughes

September 8, 2010 (Stockholm, Sweden) — Short-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an increased risk of stroke in a Danish population study including only healthy individuals.
Presenting the study at last week's European Society of Cardiology (ESC) 2010 Congress, Dr Gunnar Gislason (Gentofte University Hospital, Hellerup, Denmark) said the results could have "massive public-health implications."
"First we found an increased risk of MI with NSAIDs. Now we are finding the same thing for stroke. This is very serious, as these drugs are very widely used, with many available over the counter," Gislason told heartwire. "We need to get the message out to healthcare authorities that these drugs need to be regulated more carefully."
Cochair of the session at which the study was presented, Dr Robert Califf (Duke Clinical Research Institute, Durham, NC), agreed that the results raised a major public-health issue, especially in the US, where many NSAIDs were available without a prescription.

For the current study, Gislason and colleagues examined the risk of stroke and NSAID use in healthy individuals living in Denmark. He explained to heartwire that information on each individual in the Danish population is kept in various national registries. His team started with the whole population of Denmark aged over 10 years. To select just the healthy individuals, they excluded anyone admitted to the hospital within the past five years or those prescribed chronic medications for more than two years. This left a population of around half a million, who were included in the study. By linking to prescribing registries, the researchers found that 45% of these healthy individuals had received at least one prescription for an NSAID between 1997 and 2005. They then used stroke data from further hospitalization and death registries and estimated the risk of fatal and nonfatal stroke associated with the use of NSAIDs by Cox proportional-hazard models and case-crossover analyses.

Results showed that NSAID use was associated with an increased risk of stroke. This increased risk ranged from about 30% with ibuprofen and naproxen to 86% with diclofenac.

Gislason noted that there was also a dose-relationship found, with the increased risk of stroke reaching 90% (HR 1.90) with doses of ibuprofen over 200 mg and 100% (HR 2.0) with diclofenac doses over 100 mg. He pointed out that the results were particularly striking, given that this study was conducted in healthy individuals.

He conceded that his results could have some confounding but noted that the data were controlled for age, gender, and socioeconomic status and the patient population did not include those with chronic diseases. "We also have to think about the degree of confounding needed to nullify risk. It would have to increase risk four- to fivefold, which is very unlikely," he commented.

He said he did not find the results that surprising in view of the accumulating evidence of increased MI risk with these drugs, adding that the mechanism was probably the same. There have been several hypotheses about the mechanism linking NSAIDs with cardiovascular events, including increased thrombotic effect on platelets, the endothelium, and/or atherosclerotic plaques; increasing blood pressure; and effect on the kidneys and salt retention.

Gislason told heartwire that there is reluctance among the medical profession to limit the prescribing of these drugs. "The problem is that we don't have randomized trials, and it is very hard to change the habits of doctors. They have been using these drugs for decades without thinking about cardiovascular side effects."

He also stressed that the public needs to be protected by not allowing NSAIDs to be bought without a prescription. He has had some success in this regard in Denmark at least, where diclofenac became available over the counter recently, but after some of the MI data came out, Gislason's group campaigned the health authorities, and it has now become a prescription-only drug again. But he noted that many more NSAIDs are available over the counter in the US.

He believes the harmful effects of these agents are relevant to huge numbers of people. "If half the population takes these drugs, even on an occasional basis, then this could be responsible for a 50% to 100% increase in stroke risk. It is an enormous effect."

These results have been partly published in Circulation: Cardiovascular Quality and Outcomes earlier this year [1]. Gislason told heart wire that the novelty of the results presented at the ESC meeting was that "we had further analyzed our data regarding specific stroke and looked at the risk of ischemic stroke, and we confirmed that the risk of ischemic stroke was substantially elevated." He added: "We are in the process of analyzing these data related to time to risk and the effect of duration of treatment on stroke risk."

References
1. Fosbøl EL, Folke F, Jacobsen S, et al. Cause-specific CV risk associated with NSAIDs among healthy individuals.
Circ Cardiovasc Qual Outcomes 2010; 3:395-405.

Sue Hughes is a journalist for Medscape. She joined theheart.org, part of the WebMD Professional Network, in 2000. She was previously science editor of Scrip World Pharmaceutical News. Graduating in pharmacy from Manchester University, UK, she started her career as a hospital pharmacist before moving as a journalist to a UK pharmacy trade publication. She can be reached at Shughes@webmd.net.