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Commonly used nonopioid analgesics in adults

Mallick-Searle, Theresa, MS, NP, APRN-BC

doi: 10.1097/01.NURSE.0000530985.53988.37
Department: CONTROLLING PAIN
Free

Common nonopioid analgesics

Theresa Mallick-Searle is an NP in the pain medicine division of Stanford Health Care in Stanford, Calif.

The author has disclosed that she is currently a paid lecturer for Allergan and Pernix Pharmaceuticals.

ALTHOUGH PAIN is a common reason why patients visit their primary care providers (PCPs), many patients first try self-managing their pain. Even when a patient presents to a PCP's office, initial recommendations are often to try the commonly used over-the-counter (OTC) nonopioid therapies: acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs are generally coupled with other conservative measures, such as alternating heat/ice application and rest.

Many patients and healthcare professionals underestimate the risks of these commonly used OTC products. As OTC analgesics are among the most commonly used nonprescription medications that have potentially unrealized consequences with long-term use, nurses must understand and educate their patients about the appropriate and safe use of these products.1

The widespread availability of these OTC analgesics provides both challenges and opportunities for healthcare professionals, who must be knowledgeable about dosing parameters, potential drug-drug interactions, and the ever-growing body of evidence on drug-disease interactions. Nurses must make time to educate their patients on the safe use of OTC analgesics, as many patients are unaware of adverse drug interactions associated with their long-term use, or the potential for toxicity.2

For optimal patient safety, nurses must be prepared to perform medication reconciliation upon the first encounter with a patient and with every transfer of care. Proper medication reconciliation lets the nurse assess for potential drug-drug interactions, including those associated with the concomitant use of OTC and prescription products with duplicate or overlapping components, such as acetaminophen and salicylates. Medication reconciliation is an ideal opportunity for nurses to educate patients and families about safe medication use.

This article will review the most commonly used OTC nonopioid analgesics, acetaminophen and NSAIDs. The discussion of OTC adjuvant medications, such as capsaicin cream, is beyond the scope of this article.

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Acetaminophen

Commonly used as an analgesic and antipyretic, acetaminophen is available in many OTC preparations for oral, rectal, I.V., and topical use. Acetaminophen is in fact the most commonly used OTC analgesic on the market.3 Although available as a single-agent product, it's also commonly found in cough, cold, and allergy combination products, and in sleep aids. With the recognition and improved understanding about the real risks of liver toxicity with excessive acetaminophen use from all sources, the FDA mandated removing from the market all combination drug products with more than 325 mg of acetaminophen per tablet, capsule, or other dosage unit.4 The rationale was that by limiting the maximum amount of acetaminophen to 325 mg per dosage unit, patients are less likely to overdose on acetaminophen if they mistakenly take too many doses of acetaminophen-containing products.4

Mechanism of action. Although its exact mechanism of action isn't understood, acetaminophen appears to produce analgesia by elevating the pain threshold through central activation of descending serotonergic pathways.5 Acetaminophen has been shown to produce antipyresis through inhibition of the hypothalamic heat-regulating center.6

Safety considerations. In 2014, when the FDA called for manufacturers of combination OTC acetaminophen products to reduce the amount of acetaminophen in each pill/capsule/unit of delivery, a black box warning was implemented to highlight the potential for liver failure.7 Healthcare professionals should advise patients not to exceed the recommended maximum total daily dose of acetaminophen and counsel them about the potential for severe liver injury. Cases of acute liver failure resulting in liver transplant and death have been reported with the use of acetaminophen even at prescribed dosing. Finally, educate patients about the importance of reading all prescription and OTC medication labels to ensure they aren't taking multiple acetaminophen-containing products.7 Nurses should counsel patients who consume three or more alcoholic beverages per day, suffer from malnutrition, have active liver disease or hepatic dysfunction, or have advanced kidney disease to avoid the habitual use of acetaminophen.8,9

Nurses should also teach patients to recognize the signs of acetaminophen toxicity including nausea/vomiting, abdominal pain, jaundice, fatigue, skin rashes/pruritus, and peripheral edema.10 If not identified early, acetaminophen overdose could lead to acute liver failure. Acetaminophen overdose is the most common cause of acute liver failure in the United States, and the symptoms of hepatic toxicity may not present for more than 24 hours.11

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NSAIDs

Aspirin, ibuprofen, naproxen, and other NSAIDs are used as analgesic, antipyretic, and anti-inflammatory agents. They're available in oral, rectal, and topical preparations.12 Naproxen is a longer-acting alternative to ibuprofen.13,14

Mechanism of action. NSAIDs undergo hepatic metabolism through the isoenzymes pathways: CYP2C8, 2C9, 2C19, and/or glucuronidation.3 They exert their analgesic benefits not solely through peripheral inhibition of prostaglandin synthesis but also through peripheral action on the enzyme cyclooxygenase, which plays a central role in inflammatory conditions. It's now known that there are two structurally distinct forms of the cyclooxygenase enzyme (COX-1 and COX-2).3

Safety considerations. Most adverse drug reactions associated with NSAIDs are gastrointestinal (GI), cardiovascular, and renal. NSAIDs can lead to fluid retention and should be prescribed with caution in patients with hypertension, renal insufficiency, or heart failure. Patients with a history of impaired renal function or heart failure should be strongly counseled about the risks of NSAID use.8,15 The most common adverse reactions associated with NSAIDs include dyspepsia, nausea, heartburn, and epigastric pain.16

GI bleeding is the major risk factor associated with NSAIDs and clinical studies indicate that older adults are at greater risk for GI bleeding than younger patients.17,18 These events can occur at any time during use and without warning symptoms. Older adults and patients with a history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.19 To minimize adverse GI reactions, instruct patients to take NSAIDs with food or milk. If used chronically, the healthcare provider may prescribe a GI protective agent, such as a proton pump inhibitor or histamine2-receptor antagonist.

Salicylate toxicity occurs as an adverse effect of aspirin use, as well as due to the intake of methyl salicylate or bismuth subsalicylate; these preparations contain very high quantities of salicylate. Tinnitus, vertigo, vomiting, and diarrhea are all early signs and symptoms of acute salicylate poisoning.20 Severe intoxication can cause altered mental status, hyperpyrexia, coma, noncardiac pulmonary edema, and death.20

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Nursing considerations

Acetaminophen21

Assessment

  • Assess overall health status and alcohol consumption. Patients who are malnourished or who chronically abuse alcohol are at higher risk for developing hepatotoxicity with chronic use of acetaminophen.
  • Assess amount, frequency, and type of drugs taken by self-medicating patients, especially OTC drugs. Prolonged use of acetaminophen increases the risk of hepatotoxicity.
  • Evaluate hepatic, hematologic, and renal function periodically during prolonged, high-dose therapy.
  • Increased serum bilirubin, liver enzymes, and prothrombin time may indicate liver compromise and/or hepatotoxicity.
  • Toxicity and overdose: If overdose occurs, acetylcysteine is the antidote.
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Patient/family teaching

  • Caution patients to use the lowest effective dose for the shortest duration as directed.
  • Caution patients to avoid alcohol, which increases the risk of hepatotoxicity, and to avoid taking concurrently with NSAIDs for more than a few days, unless directed by their PCP.
  • Advise patients to discontinue acetaminophen immediately and notify their PCP if a rash occurs.
  • Advise patients to check with their PCP before taking acetaminophen if they have diabetes because acetaminophen falsely elevates continuous glucose monitor readings by a large margin.
  • Advise patients to check labels on all OTC products and to avoid taking more than one product containing acetaminophen at a time to prevent toxicity.
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NSAIDs22

Assessment

  • Patients who have asthma, aspirin-induced allergy, or nasal polyps are at increased risk for developing hypersensitivity reactions with aspirin use. Assess for rhinitis, asthma, and urticaria.
  • Assess for signs and symptoms of GI bleeding (tarry stools, lightheadedness, hypotension).
  • Watch for renal dysfunction (elevated blood urea nitrogen and creatinine levels, decreased urine output), and hepatic impairment (elevated liver enzymes, jaundice).
  • Assess patient for skin rash frequently during therapy. Discontinue NSAID use at the first sign of rash; life-threatening Stevens-Johnson syndrome or toxic epidermal necrolysis may develop. Monitor blood urea nitrogen, serum creatinine, complete blood cell count, and liver function test results.
  • Aspirin may prolong bleeding time. This may persist for 5 to 7 days following discontinuation, the life span of a functional platelet.
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Patient/family teaching

  • Advise patients to take NSAIDs with a full glass of water and to remain in an upright position for 15 to 30 minutes after administration.
  • Advise patients to inform healthcare professionals of their medication regimen before invasive procedures or surgery. Because NSAIDs can result in excessive bleeding, they should be discontinued beforehand.
  • Caution patients that use of NSAIDs with alcohol may increase the risk of GI bleeding.
  • Advise patients to consult their PCP if they experience rash, pruritus, visual disturbances, tinnitus, weight gain, edema, epigastric pain, dyspepsia, black stools, hematemesis, persistent headache, or influenza-like syndrome.

As many patients and healthcare professionals rely on the safe and efficacious use of nonopioid OTC analgesics, nurses must gain a better understanding of the challenges posed by the broad availability of these products and educate their patients about how to use them safely.

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REFERENCES

1. Consumer Healthcare Products Association. OTC sales by category 2013-2016. The Nielsen Company. http://www.chpa.org/OTCsCategory.aspx.

2. Westerlund T, Barzi S, Bernsten C. Consumer views on safety of over-the-counter drugs, preferred retailers and information sources in Sweden: after re-regulation of the pharmacy market. Pharm Pract (Granada). 2017;15(1):894.

3. Rosenquist E. Overview of the treatment of chronic non-cancer pain. UpToDate. 2017. http://www.uptodate.com.

4. U.S. Food and Drug Administration. All manufacturers of prescription combination drug products with more than 325 mg of acetaminophen have discontinued marketing. 2014. http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm390509.htm.

5. Sharma CV, Mehta V. Paracetamol: mechanisms and updates. Contin Educ Anaesth Crit Care Pain. 2014;14(4):153–158.

6. Graham GG, Davies MJ, Day RO, Mohamudally A, Scott KF. The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings. Inflammopharmacology. 2013;21(3):201–232.

7. U.S. Food and Drug Administration. FDA Drug Safety Communication: Prescription acetaminophen products to be limited to 325 mg per dosage unit; boxed warning will highlight potential for severe liver failure. 2017. http://www.fda.gov/Drugs/DrugSafety/ucm239821.htm.

8. Remington T. Headache. In: Krinsky D, Berardi R, Ferreri S, et al., eds. Handbook of Nonprescription Drugs. 17th ed. Washington, DC: American Pharmacists Association; 2012.

9. American Dental Association. Council for Academic Affairs-Science brief on acetaminophen and liver injury. 2010. http://www.ada.org/~/media/ADA/Science and Research/Files/100531_sci_brief_acetaminophen.pdf.

10. Drugs & diseases—acetaminophen toxicity treatment and management. Medscape. 2017. http://emedicine.medscape.com/article/820200-treatment.

11. Heard K. Acetaminophen (paracetamol) poisoning in adults: Treatment. UpToDate. 2017. http://www.uptodate.com.

12. Bushra R, Aslam N. An overview of clinical pharmacology of ibuprofen. Oman Med J. 2010;25(3):155–1661.

13. Food and Drug Administration. Drugs. Naproxen Information. 2015. http://www.fda.gov/Drugs/DrugSafety/ucm110423.htm.

14. Apo-Napro-Na (naproxen sodium) [product monograph]. Toronto, Ontario, Canada: Apotex Inc; May 2014. http://www.medbroadcast.com/drug/getdrug/apo-napro-na.

15. Antman EM, Bennett JS, Daugherty A, et al Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association. Circulation. 2007;115(12):1634–1642.

16. Labianca R, Sarzi-Puttini P, Zuccaro SM, Cherubino P, Vellucci R, Fornasari D. Adverse effects associated with non-opioid and opioid treatment in patients with chronic pain. Clin Drug Investig. 2012;32(suppl 1):53–63.

17. Fendrick AM, Pan DE, Johnson GE. OTC analgesics and drug interactions: clinical implications. Osteopath Med Prim Care. 2008;2:2.

18. The History of Aspirin. 2017. http://www.thoughtco.com/history-of-aspirin-4072562.

19. Naproxen—drug information. UpToDate. 2018. http://www.uptodate.com.

20. Boyer EW. Salicylate (aspirin) poisoning in adults. UpToDate. 2017. http://www.uptodate.com.

21. DavisPlus: Online Resource for Instructors and Students. Acetaminophen. https://davisplus.fadavis.com/3976/meddeck/pdf/acetaminophen.pdf.

22. DavisPlus: Online Resource for Instructors and Students. Ibuprofen. https://davisplus.fadavis.com/3976/meddeck/pdf/ibuprofen.pdf.

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RESOURCES:

The Acetaminophen Awareness Coalition: http://www.knowyourdose.org/the-acetaminophen-awareness.coalition.

The Alliance for Rational Use of NSAIDs: http://nsaidalliance.com.

National Council on Patient Information and Education (NCPIE): Medication use Safety Training for Seniors: http://www.bemedwise.org/acetaminophen.

U.S. Department of Health and Human Services: Drug Information for Consumers: http://www.fda.gov/Drugs/ResourcesForYou/Consumers.

U.S. Department of Health and Human Services: Using Acetaminophen and Nonsteroidal Anti-inflammatory Drugs Safely: http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/UnderstandingOver-the-CounterMedicines/SafeUseofOver-the-CounterPainRelieversandFeverReducers/ucm164977.htm.

The American Association of Poison Control Centers supports the nation's 55 poison centers in their efforts to prevent and treat poison exposures. Poison centers offer free, confidential, expert medical advice 24 hours a day, 7 days a week through the Poison Help line at 1-800-222-1222 and online at http://www.PoisonHelp.org.

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