Erin Drewniany, PharmD (Candidate)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are prescription and OTC medications commonly used to relieve pain in the United States.

Pain can present in a number of different ways that are unique to each individual patient. Depending on its level of severity, pain may require pharmacologic therapy.

Whether it’s caused by a headache, menstrual cramps, muscle strain, backache, or cancer, pain is something that practically everyone has experienced and used some class of medication to alleviate. NSAIDs are a popular choice of pharmacologic treatment for pain because of their proven effectiveness.

NSAIDs provide an anti-inflammatory effect and decrease pain sensation, also known as analgesia. The benefits of NSAID analgesia and its anti-inflammatory effects stem from its inhibition of prostanoid biosynthesis.

Prostanoids are synthesized from arachidonic acid. Cyclooxygenase (COX) isozymes convert arachidonic acid to prostanoids, which are then converted through a series of reactions to prostaglandins.

Prostaglandins are responsible for a number of different physiological and pathological pathways that involve the inflammatory response, gastrointestinal (GI) mucosa, blood clotting, and renal control of blood pressure.

There are 2 different forms of COX: COX-1 and COX-2. COX-1 is responsible for the protection of the GI tract and platelet homeostasis, while COX-2 is responsible for the inflammatory response among other things.

Traditional NSAIDs inhibit both of these mechanisms, leading to their efficacy in providing pain relief. Drugs in this NSAID class include ibuprofen, naproxen, meloxicam, diclofenac, and aspirin.

Ibuprofen is available OTC in a 200-mg strength, while 400-mg and 800-mg doses are available by prescription. Naproxen is also available OTC in 220-mg oral tablets, as well as a 500-mg prescription strength. Meloxicam and diclofenac are both prescription-only medications, while all aspirin strengths are available OTC.

These 5 traditional NSAIDs account for nearly 86 million prescriptions dispensed for 44 million patients.

Despite their high proven efficacy, they are also associated with serious side effects and complications.

What Side Effects and Complications Can Result From NSAID Use?

Because of the drugs’ dual effect on COX-1 and COX-2 receptors, there is an increased risk of cardiovascular (CV) events and GI complications. COX-1 has protective factors that are responsible for promoting mucus and bicarbonate secretion, so the inhibition of COX-1 leads to less mucus and a more acidic environment in the GI tract, which can lead to serious bleeds.

NSAIDs’ CV side effects result from excessive COX-2 inhibition. COX-2 is responsible for the conversion of prostaglandin (PGI2), which promotes vasodilation and prevents platelet activation and cell adhesion, leading to a cardioprotective role in the circulatory system. Therefore, its inhibition can lead to an increased risk of hypertension, myocardial infarction (MI), stroke, and heart failure.

The risk for all of these side effects increases when higher doses of NSAIDs are taken for a longer period of time.

How Can Clinicians Curb NSAID Complications?

The discovery of these life-threatening complications spurred a closer look at the COX mechanism in the 1990s.

With the seemingly protective qualities of COX-1, there was a hypothesis that if COX-2 could be selectively inhibited without COX-1 inhibition, then anti-inflammatory effects could be achieved with less GI damage.

This led to a new selective COX-2 inhibition drug class called “coxibs.” One study reviewed the safety of rofecoxib, the first drug in this class, and found a significantly higher MI rate in patients taking rofecoxib compared with those taking naproxen (0.4% vs 0.1%, respectively).

However, as the dose of rofecoxib was increased, an independent thrombotic risk was noted, and the drug was voluntarily removed from the market in 2004 after another trial showed double the number of CV events in patients taking rofecoxib than placebo.

In 2005, at an advisory committee meeting that looked at data addressing these issues, the FDA mandated that all prescription NSAID labels have:

(1) a ‘black box’ warning highlighting the potential for increased risk for CV events and serious life-threatening GI bleeding, ulceration, and perforation; (2) statements indicating patients with, or at risk for, CV disease and the elderly may be at greater risk, and that these reactions may increase with duration of use; (3) a contraindication for use after coronary artery bypass graft surgery on the basis of reports with valdecoxib/parecoxib; (4) language that the lowest dose should be used for the shortest duration possible; and (5) wording in the warning section that there is no evidence that the concomitant use of aspirin with NSAIDs mitigates the CV risk, but that it does increase the GI risk.

This led Pfizer to look at these issues more closely, comparing the different risk factors between specific NSAIDs in the Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION) Trial in 2006.

PRECISION was designed to compare celecoxib—the only coxib still available on the US market&mdash;with naproxen and ibuprofen. The primary endpoint was first occurrence of a composite CV event defined as CV mortality, non-fatal MI, or non-fatal stroke in patients with rheumatoid arthritis (RA) or osteoarthritis (OA) who generally require chronic high doses of NSAIDs.

The trial was intended to compare the side effect profiles of these drugs in the hopes of using the data to distinguish the commonly used NSAIDs in a way that might guide clinical practice more definitively.

Although there is an increasing amount of data on the CV and GI risks associated with NSAIDs, the American Heart Association (AHA) still leaves medication choice up to the discretion of the physician. The AHA recommends that clinicians keep patient risk factors, treatment factors, and COX selectivity in mind when deciding which NSAID may be appropriate.

There are almost no data comparing the nonselective NSAID drugs to each other, making it more difficult for prescribers to make a selection. PRECISION, which is ongoing, is the first trial to examine comparative risk factors, which could change guideline recommendations.

What Are the Current Recommendations for NSAIDs?

In February 2014, the FDA held another advisory meeting looking at recently published analyses assessing the NSAID labeling assumptions. The agency looked at the committee’s opinions and decided to further restrict NSAID label guidelines.

The panel had considered studies that concluded:

Naproxen may have less thrombotic risk that other NSAIDs.

There is CV risk from the start of NSAID therapy.

The relative risk between a healthy individual and one with CV risks is the same; however, the absolute risk is higher in those with CV risk.

Both NSAIDs and coxibs have risk for stroke, though it is less than MI and there is no pattern of relative hazard among NSAIDs.

Aspirin can decrease CV risk with NSAIDs, but naproxen and ibuprofen may inhibit this cardioprotection.

Naproxen may have lower CV risk than ibuprofen, while ibuprofen may have lower GI risk.

The PRECISION trial should be stopped due to lack of balance in interests.

The panel discussed whether there was a clinically significant difference in CV thrombotic events between NSAIDs. Despite the fact that there was differential risk, especially for naproxen, it decided that the data were not strong enough to support a label claim.

The panel also looked at whether there was a relationship between length of time on NSAIDs and increased CV risk. It found that there is a risk of CV thrombotic event from the start of NSAID therapy independent of dose, and the label should reflect this.

Another aspect that the panel addressed was whether the warnings and restrictions for individuals at higher risk for CV thrombotic events are appropriate or should be stricter. Although it could not identify specific population recommendations (except post-MI and RA patients), it determined that labeling specifying higher risk was indeed appropriate.

The last aspect the panel addressed was whether the PRECISION trial should be altered or stopped. It decided that the trial should continue because it may provide the best opportunity to answer the question about differential CV risk between NSAIDs, and suggested that if the trial was causing harm, it would have been stopped.

After reviewing the advisory committee results, the FDA recently decided that it will require stricter labels on both prescription and OTC NSAID medications.

There are already warnings in place for the GI, heart attack, and stroke risks, but the FDA is now requiring these drugs to provide more specific information regarding heart attack and stroke risks. It will also require manufacturers to provide heart attack and stroke risk information on the drug facts label.

How Should Clinicians Approach NSAID Prescribing?

With the PRECISION trial still under way, the specific differences between NSAIDs remain unclear, which may not change clinical practice just yet. Clinicians should continue to follow current guidelines when it comes to prescribing these medications.

The FDA is not yet willing, without proper data, to claim that certain NSAIDs may be safer than others for specific patient populations. With the data that have been released, although controversial, it does seem as though coxibs may have lower risk for GI complications but increased CV risk, while naproxen may have lower CV risk but higher risk for GI complications.

This type of information should be kept in mind when looking at a specific patient’s medical history before recommending one NSAID over another.

For the patient population, it is still acceptable to use OTC NSAIDs for minor pain, but patients need to be aware of the risks and complications. Patients should always read labels closely and follow the directions on the label when it comes to specific doses, so that they do not inadvertently increase their risk for side effects and complications.

Clinicians need to make sure that they assess and discuss with patients what OTC medications they might be taking in order to avoid drug interactions, duplicity in treatment, and to answer any questions patients may have that aren’t answered on the drug labels.

Despite the potential risks, NSAIDs are still very effective in reducing pain and inflammation without the same addictive potential that the stronger prescription opiate medications have. They will always have a place in treatment for minor and moderate pain, but it is important to continue research to ensure patient safety and tolerability.

Clinicians must understand the distinct differences between each NSAID in order to help guide their recommendations for pain relief. Until new data are released, careful administration and understanding of NSAID risk is extremely important for avoiding CV and GI side effects.

1. Brune K and Patrignani P. New insights into the use of currently available non-steroidal anti-inflammatory drugs.

2. Bello AE and Holt RJ. Cardiovacular risk with non-steroidal anti-inflammatory drugs: clinical implications.

3. Bombardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis.

4. Antman EM, Bennett JS, Daugherty A, Furburg C, Roberts H, Taubert KA; American Heart Association. Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association.

Articles

Clinicians must understand the distinct differences between each NSAID in order to help guide their recommendations for pain relief.

Stricter NSAID Guidelines: What Retail Clinicians Should Know

According to the World Health Organization, almost 90% of people with diabetes around the world have type 2 diabetes. This type of diabetes is commonly the result of excess of body weight and lack of physical activity. A

showed that by implementing a combined diet and physical activity program, people with type 2 diabetes can see normoglycemic levels and reduce cardiovascular disease risk factors such as high blood pressure, high cholesterol levels, excess body weight, and suboptimal blood glucose levels.

reviewed 53 studies which combined, evaluated a total of 66 different programs. The programs varied in the number of sessions (median 15 sessions), program length (median 12 months), and diet and exercise program delivery (internet only, or combined, in-person, individual, and group sessions). The programs were led by a variety of trained specialists including diet counselors, dietitians, exercise counselors, physical trainers and physicians or psychologists. The success of the programs was tracked using weight-loss, diet, and physical activity goals. The majority of the programs showed positive results leading to weight loss or reduced risk for diabetes, or both.

has used these results as evidence for recommendations on community-and system-based interventions. These programs provide success in weight loss and reduce diabetes risks for patients, and were economically cost-effective according to the incremental cost effectiveness ratio (ICER) from a health system perspective. Seventeen studies reported other benefits of the programs, such as reduced systolic and diastolic blood pressures and improved lipid levels in participants.

There are a number of organizations that have implemented diet and exercise programs, nationwide. The Centers for Disease Control and Prevention established the National Diabetes Prevention Program (DPP) to coordinate lifestyle change programs to prevent or delay type 2 diabetes. The success of the DPP program influenced other prevention programs. One in particular, designed similarly to the DPP, was through the Montana Cardiovascular Disease and Diabetes Prevention Program, and has shown success in having 45% of those who completed the program achieved their weight-loss goal of 7%. The YMCA also adapted the DPP study program and provided a lower-cost program with group sessions, including 16 weekly core sessions and 8 maintenance monthly follow-up sessions. This program reached 46 communities in 23 states by 2012. Over 16,000 participants have been enrolled in similar programs over 750 community locations in 39 states.

With the rising numbers of patients diagnosed with type 2 diabetes, and the proven benefits of combined diet and exercise to reverse the incidence of type 2 diabetes, it is important for health care providers to be aware of the types of programs offered in their communities. Primary care providers are the initial resource for patients newly diagnosed with type 2 diabetes and so they are in the perfect position to provide their patients with information on how to participate in these programs.

This article was published in the 14 July 2015 issue of

According to the World Health Organization, almost 90% of people with diabetes around the world have type 2 diabetes. This type of diabetes is commonly the result of excess of body weight and lack of physical activity.

Combined Diet and Physical Activity Program Effective Against Diabetes

In the constantly evolving health care world, there many different settings in which advanced practice clinicians, such as nurse practitioners, can choose to work. Advanced practice clinicians can choose a retail clinic setting, the hospital, a primary care physician’s practice, as well as other settings. While the retail clinic setting is usually for minor illnesses and preventative care, the traditional primary care setting is more specialized and tends to be the primary point of care for patients. Choosing a setting is typically based on personal preference, but is there a difference in job satisfaction among the different settings? In a recent study, published in the

Journal of the American Association of Nurse Practitioners

, researchers set out to compare the job satisfaction of nurse practitioners in the retail clinic setting with those in the traditional primary care setting.

The researchers used both the Misener NP Job Satisfaction Scale (MNPJSS) and the Dempster Practice Behavior Scale (DPBS) to determine job satisfaction and autonomy perceptions in a convenience sample of nurse practitioners recruited from the 2013 annual American Association of Nurse Practitioners conference. “Job satisfaction” was defined as how content one is with his or her employer. The researchers also looked at the level of autonomy the nurse practitioners felt, as increased autonomy is known to correlate positively with job satisfaction. “Autonomy” was defined as the feeling of being able to work independently.

Both autonomy and social interaction with patients were positively related to job satisfaction. While the results of the study did not show a difference in overall job satisfaction between the two settings, nurse practitioners in the traditional primary care setting reported higher job satisfaction in relation to social/community interaction. This can provide insight on areas to address when looking to improve job satisfaction for nurse practitioners in the retail setting.

It can be more difficult for nurse practitioners to interact with their patients and build relationships in the retail setting since patients may use multiple retail clinics and may not follow up with the clinicians on a regular basis. An added pressure to see more patients in a day also cuts down on the time practitioners have to spend with their patients to build important relationships, however, research has shown that patient outcomes improve when patients have positive relationships with their primary care provider. In a study published in the

researchers looked at how a patient-centered visit affects recovery, self-reported health, and subsequent medical care. They found that when patients perceive their visit as patient-centered, they find more common ground with the physician, which can be associated with positive health outcomes and decreased levels of discomfort. The researchers also found that patients with a patient-centered visit received fewer diagnostic tests and referrals.

found that when there is good communication between the patient and the physician, the patient’s diabetes and hypertension is under better control (as measured by hemoglobin A1

These results suggest that clinicians should focus on building long-term relationships with their patients, leading to better care for the patients and higher overall job satisfaction for the nurse practitioners.

Lelli VR, Hickman RL Jr, Savrin CL, Peterson RA. Retail clinics versus traditional primary care: employee satisfaction guaranteed?

Published February 20, 2015. doi: 10.1002/2327-6924.12220. Accessed July 28, 2015.

Stewart, Moira et al The impact of patient-centered care on outcomes,

2000; 49(9): 796-804. http://web.a.ebscohost.com.libproxy.temple.edu/ehost/pdfviewer/pdfviewer?sid=d3860810-30e9-4766-bd44-4bcf2f46208b%40sessionmgr4004&vid=1&hid=4114. Accessed July 28, 2015.

Kaplan, Sherrie H et al. Assessing the Effects of Physician-Patient Interactions on the Outcomes of Chronic Disease.

1989; 27(3): S110-S127. http://www,jstor.org/page/info/about/policies/terms.jsp. Accessed July 28, 2015.

In the constantly evolving health care world, there many different settings in which advanced practice clinicians, such as nurse practitioners, can choose to work. Advanced practice clinicians can choose a retail clinic setting, the hospital, a primary care physician's practice, as well as other settings.

Job Satisfaction of Nurse Practitioners in Retail Clinics vs. Primary Care Settings

Obesity is a common issue in the United States. According to the Food Research and Action Center, 68.5% of adults are clinically “overweight” and 34.9% are “obese”. This obesity statistic is an increase from 27.1% in 2013 and 25.5% in 2008, and the trend is continuing upward. Other health conditions can be exacerbated by obesity and so it is important to educate patients on how losing weight can not only increase their health and survival, but also contribute to a better overall quality of life.

In the United States, retail clinics are becoming a more popular option for individuals seeking quick and immediate health care advice that is also convenient and cost-effective. These clinics provide greater access to patients in a more casual environment and creates a perfect opportunity for the advanced practice clinicians who work in these settings to counsel patients on weight loss and the importance of maintaining a healthy lifestyle. A recent article on PharmacyTimes.com outlined 5 weight-loss counseling points for pharmacists that are also applicable to advanced practice practitioners:

1. Weigh yourself at the same time every day

Studies have shown that when patients who are trying to lose weight keep track of their weight on a daily basis, they stay accountable for their diet and exercise throughout the day and are motivated as they lose small amounts of weight (5-10 pounds) each week. In addition, patients who keep track of their weight on a daily basis keep the weight off, in comparison to patients who do not weigh themselves daily.

2. Jenny Craig and Weight Watcher-type programs are effective for losing weight and keeping it off.

Studies have shown that long-term health programs, such as Jenny Craig and Weight Watchers, are effective in promoting weight loss and helping patients keep the weight off. As a clinician in a retail setting, advanced practice clinicians should be aware of the programs in their community and the benefits of such programs for weight loss. Educating patients on the different types of programs can be useful for patients who might not know how to go about weight loss otherwise.

3. Education on Childhood Obesity is important.

Since, almost 95% of parents with an overweight child will report that their child is within the normal weight ranges for their age, and over 80% report that their obese child is within the normal weight ranges, it is extremely important to educate parents on weight norms for children. This information can help parents to identify changes they might need to make in terms of choosing the right foods for their children, as well as lifestyle changes that may help them develop better nutritional habits, and promote overall positive health.

Patients may be unaware that obesity can lead to type 2 diabetes. Advance practice clinicians should educate their patients on the risk factors for obesity, such as type 2 diabetes, high blood pressure, high cholesterol, asthma, and other breathing-related conditions.

5. Set realistic weight loss goals with weight loss medications.

Patients may turn to pharmacotherapy to help supplement their weight loss. Most patients can lose up to 5%-10% of their body weight with weigh loss medications if taken correctly and combined with a healthy diet and exercise routine. It is important to educate patients that although these medications are meant to help boost weight loss, lifestyle changes are still an important aspect to losing weight. Clinicians must help patients set realistic goals for their weight loss plan in order to keep them motivated and on track for a healthier lifestyle.

With the increasing popularity of retail clinic use, retail clinicians have the perfect opportunity to educate patients about the rising health issues that relate to obesity and the importance of maintaining a healthy weight and lifestyle.

was published online July 27, 2015 on PharmacyTimes.com

Obesity is a common issue in the United States. According to the Food Research and Action Center, 68.5% of adults are clinically "overweight" and 34.9% are "obese". This obesity statistic is an increase from 27.1% in 2013 and 25.5% in 2008, and the trend is continuing upward. Other health conditions can be exacerbated by obesity and so it is important to educate patients on how losing weight can not only increase their health and survival, but also contribute to a better overall quality of life.

Erin Drewniany, PharmD (Candidate)

Articles

Stricter NSAID Guidelines: What Retail Clinicians Should Know

Combined Diet and Physical Activity Program Effective Against Diabetes

Job Satisfaction of Nurse Practitioners in Retail Clinics vs. Primary Care Settings

Counseling Points to Drive Down Obesity