14.2: Nonopioid Analgesics

Learning Objectives

By the end of this section, you should be able to:

• 14.2.1 Identify the characteristics of nonopioid analgesic drugs used to treat pain.
• 14.2.2 Explain the indications, actions, adverse reactions, and contraindications of nonopioid analgesic drugs used to treat pain.
• 14.2.3 Describe the nursing implications of nonopioid analgesic drugs used to treat pain.
• 14.2.4 Explain the client education related to nonopioid analgesic drugs used to treat pain.

A nonopioid analgesic refers to any pharmacologic agent that treats the symptoms of pain and does not involve activation of opioid receptors. These agents generally work by inhibiting cyclooxygenase (COX), a major pro-inflammatory enzyme that causes many signs and symptoms of inflammation, including redness, swelling, and sensitization of nociceptors, thereby increasing the transmission of painful signals to the brain. COX causes this increase in inflammation and pain by increasing the production of cytokines such as prostaglandins, prostacyclin, and thromboxane. It is also partly responsible for the pyrexia that occurs with infection, which is why many nonopioid analgesics that block the activity of COX also work as antipyretics to reduce fever.

Cyclooxygenase has two major isoforms: COX-1 and COX-2. COX-1 helps with normal homeostatic functions in the body, including maintaining normal platelet and renal functions. It also is important for producing prostaglandins that stimulate production of the mucosal barrier that protects the stomach from its own acids. If COX-1 is inhibited through the actions of medications such as glucocorticoids or nonsteroidal anti-inflammatory drugs (NSAIDs), this protective barrier can erode, which is a major cause of peptic ulcers. COX-2 is responsible for much of the inflammation and pain brought about by tissue injury.

Other nonopioid analgesics may serve as adjunctive agents for treating neuropathic sources of pain. These include antidepressant drugs (e.g., duloxetine, amitriptyline), antiseizure drugs (e.g., carbamazepine, pregabalin), and local anesthetics (e.g., lidocaine and bupivacaine). These are useful because they target the abnormal neuronal function that is the source of neuropathic pain. These medications are covered in their respective chapters, and health care professionals should keep these additional tools in mind to ensure adequate management of this type of pain.

Acetaminophen

Acetaminophen is a common over-the-counter nonopioid analgesic. It is one of the most popular analgesics due to its low cost, efficacy in treating mild to moderate pain, and excellent safety profile when used within the recommended dosages. Acetaminophen’s complete mechanism of action to relieve pain is not currently known. Some experts theorize that it inhibits COX in the central nervous system (CNS), providing analgesic and antipyretic actions, but notably it does not inhibit COX peripherally, meaning it has no anti-inflammatory action as compared with other nonopioid analgesics.

Acetaminophen comes in a variety of dosage forms, including intravenous and rectal options, to aid clients who cannot take medications by mouth. Acetaminophen is commonly found in combination products with opioid agonists, antihistamines, and medications for coughs and colds. Because acetaminophen is present in so many products, and because its overuse can lead to serious adverse events, nurses must be alert for all sources of acetaminophen that clients may be taking.

Clinical Tip

Check for All Sources of Acetaminophen

Many over-the-counter and prescription medications include acetaminophen, including many cough and cold products. Clients should be aware that they need to count all sources of acetaminophen to ensure they do not exceed the limit of 4000 mg per 24 hours and put themselves at risk for liver injury.

Aspirin, Ibuprofen, and Naproxen Sodium

Aspirin, ibuprofen, and naproxen sodium are classified as nonsteroidal anti-inflammatory drugs (NSAIDs). This classification means they possess analgesic, antipyretic, and anti-inflammatory actions without belonging to the group of medications known as the glucocorticoids (e.g., prednisone and dexamethasone, which are discussed in Introduction to the Immune System and the Inflammatory Response). NSAIDs are often preferred over glucocorticoids as anti-inflammatory agents because they cause fewer adverse drug reactions such as hyperglycemia, hypertension, and increased risk for infection. NSAIDs work by inhibiting the enzyme COX centrally and in peripheral tissues to decrease inflammation and reduce pain. NSAIDs are also very popular analgesics because they are readily available over the counter.

Aspirin is notable for its antiplatelet actions, so it can be used during myocardial infarctions to aid in maintaining coronary blood flow by inhibiting platelet aggregation. (See Cardiac Emergency and Shock Drugs for more about aspirin’s use in cardiovascular emergencies.) The reason for aspirin’s unique actions is that it is an irreversible inhibitor of COX in platelets, preventing them from aggregating and initiating the clotting cascade. Aspirin’s irreversible inhibition of COX means that platelets are affected for their entire lifetime, which is approximately 7–10 days. Nurses should instruct clients taking blood thinners (e.g., warfarin, apixaban) to be cautious about using aspirin to treat pain because of increased risk for bleeding and bruising.

Safety Alert

NSAIDs

Clients reporting severe abdominal pain, dark tarry stools, or vomiting or coughing up of blood should stop using any NSAIDs immediately and be assessed by a health care provider for possible stomach ulcers.

Tramadol

Tramadol is a partial opioid receptor agonist and inhibitor of reuptake of the neurotransmitters norepinephrine and serotonin. These characteristics make tramadol a potential analgesic option for clients with neuropathic pain because they benefit from both the partial opioid effect and the pain-modulating effects of increased norepinephrine and serotonin. However, due to its actions at the opioid receptors, tramadol has been linked to cases of misuse and addiction, leading the Drug Enforcement Administration (DEA) to categorize tramadol as a Schedule IV medication (CIV). The DEA scheduling of a medication puts certain restrictions on who can prescribe the medication and how much of the medication can be prescribed at a time.

Table 14.1 lists common nonopioid analgesics and typical routes and dosing for adult and pediatric clients.

Table 14.1 Drug Emphasis Table: Nonopioid Analgesics (source: https://dailymed.nlm.nih.gov/dailymed/)

Drug	Routes and Dosage Ranges
Acetaminophen (Tylenol)	Pain and/or fever: Adults: 325–650 mg orally every 4–6 hours as needed; maximum dose: 4000 mg/day. Children: 10–15 mg/kg/dose orally every 4–6 hours as needed; maximum dose: 75 mg/kg/day, not to exceed 4000 mg/day.
Aspirin	Pain and/or fever: Adults: 325–1000 mg orally every 4–6 hours as needed; usual maximum dose is 4000 mg/day. Secondary prevention of atherosclerotic cardiovascular disease: Adults: 75–325 mg once daily.
Ibuprofen (Advil, Motrin)	Pain and/or fever: Adults: 200–800 mg orally every 4–8 hours as needed; maximum dose: 3200 mg/day. Children: 10 mg/kg/dose orally every 6–8 hours; maximum dose: 600 mg/dose, not to exceed 2400 mg/day.
Naproxen sodium (Aleve, Naprosyn)	Pain and/or fever: Adults: 200–400 mg orally, followed by 200 mg every 8–12 hours as needed; maximum dose: 600 mg/day.
Tramadol (Ultram)	Pain: Adults: 25–100 mg orally every 6 hours as needed; maximum dose: 400 mg/day.

Adverse Effects and Contraindications

Nonopioid analgesics as a class are relatively safe to use for many clients but do carry some notable adverse effects in susceptible individuals. Acetaminophen is a preferred analgesic for mild to moderate pain because it has relatively few adverse effects, but it must not be taken in amounts greater than those recommended by the drug’s manufacturers. This limit is 4000 mg per 24 hours; taking acetaminophen in doses beyond that increases the chances of developing potentially fatal hepatotoxicity. Clients with a history of liver disease will have lower recommended dosages because they are at greater risk for liver injury when using acetaminophen. Hepatotoxicity from acetaminophen can present as nausea, fatigue, and jaundice (yellowish skin and sclera) and may require antidotal therapy with the drug n-acetylcysteine to help prevent further liver injury.

NSAIDs such as aspirin, ibuprofen, and naproxen sodium are known to increase the risk for bleeding and bruising and can cause kidney injury in older adults and in clients with a history of chronic kidney disease. NSAIDs taken at high doses for long periods of time can also potentially cause stomach ulcers that can progress to bleeding and perforation by eroding the protective stomach lining over time.

Due to its opioid receptor activity, tramadol can cause CNS and respiratory depression in overdose or when mixed with other CNS depressants such as alcohol. It is associated with risk for problematic use and addiction, and individuals with a history of substance use disorder should avoid it. Tramadol can lower the seizure threshold and should be used with caution in clients with a history of seizure disorder.

NSAIDs carry a risk for asthma exacerbations in clients with a history of aspirin-induced asthma. Aspirin should be avoided in children younger than 16 years old with a recent history of viral illness because the medication may cause a potentially fatal condition called Reye’s syndrome.

All of these agents should be avoided in clients with a known allergy to the individual agents or any of their components.

Table 14.2 is a drug prototype table for nonopioid analgesics featuring ibuprofen. It lists drug class, mechanism of action, adult and pediatric dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.

Table 14.2 Drug Prototype Table: Ibuprofen (source: https://dailymed.nlm.nih.gov/dailymed/)

Drug Class Nonsteroidal anti-inflammatory drug (NSAID) Mechanism of Action Inhibits the enzyme cyclooxygenase to decrease the production of inflammatory cytokines and thereby reduce inflammation and pain	Drug Dosage Adults: 200–800 mg orally every 4–8 hours as needed; maximum dose: 3200 mg/day. Children: 10 mg/kg/dose orally every 6–8 hours; maximum dose: 600 mg/dose, not to exceed 2400 mg/day.
Indications Temporarily relieves minor aches and pains Temporarily reduces fever Therapeutic Effects Reduces fever Reduces inflammation Decreases pain	Drug Interactions Angiotensin II receptor blockers (e.g., candesartan) Angiotensin-converting enzyme (ACE) inhibitors (e.g., lisinopril) Lithium Warfarin Food Interactions No significant interactions
Adverse Effects Decreased hemoglobin Edema Skin rash Abdominal cramps Constipation Diarrhea Nausea Gastric ulcer Heartburn Dizziness	Contraindications Hypersensitivity Aspirin-sensitive asthma Allergic reaction to aspirin Caution: Asthma Hepatic impairment Renal impairment Bariatric surgery

Nursing Implications

The nurse should do the following for clients who are taking a nonopioid analgesic:

• Assess the client for pain by using a pain scale before and 15–20 minutes after a dose of a nonopioid analgesic to determine its efficacy.
• Ensure that the client does not receive more than the recommended amount of acetaminophen in 24 hours.
• Check for any contraindications, allergies, or potential drug interactions before beginning therapy with a nonopioid analgesic.
• Ask the client when they last used an analgesic medication.
• Ask the client about any types of nonpharmacologic pain treatment they may be using, such as ice, stretching, or heat/cold therapy.
• Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.

Client Teaching Guidelines

The client taking a nonopioid analgesic should:

• Alert their health care provider about any signs of allergic reactions, including throat swelling, severe itching, rash, or chest tightness.
• Alert their health care provider about any signs of bleeding, including black tarry stools, coffee-ground emesis, or blood-streaked sputum.
• Alert their health care provider that they are taking this medication, including the dose and frequency.
• Avoid drinking alcohol while using acetaminophen.
• Take the drug with food if it causes upset stomach.
• Take a missed dose as soon as they remember it; however, they should not take double doses.
• Contact their health care provider for further advice if pain persists longer than 3 days.

FDA Black Box Warning

Nonopioid Analgesics

Acetaminophen has been associated with cases of acute liver failure, at times resulting in death or the need for liver transplantation.

NSAIDs increase the risk for serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.

NSAIDs increase the risk for serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Older adults and individuals with a prior history of peptic ulcer disease or gastrointestinal bleeding are at greater risk for serious gastrointestinal events.

Unfolding Case Study

Part A

Read the following clinical scenario to answer the questions that follow. This case study will evolve throughout the chapter.

Maria Vega is a 63-year-old client who presents to her health care provider’s office with reports of abdominal pain, diarrhea that is occasionally black and tarry in appearance, and dizziness.

History
Coronary artery disease
Osteoarthritis (both knees and hips are affected)

Current Medications
Aspirin 81 mg orally once daily
Metoprolol 50 mg orally twice daily
Over-the-counter ibuprofen 400 mg orally every 4–6 hours as needed for joint pain

Table 14.3

Vital Signs		Physical Examination
Temperature:	98.8°F	Head, eyes, ears, nose, throat (HEENT): Within normal limits Cardiovascular: No jugular vein distention; no peripheral edema noted bilaterally; S1, S2 auscultated, rhythm regular Respiratory: Lungs clear to auscultation bilaterally GI: Abdomen soft, generalized tenderness, nondistended; normal bowel sounds auscultated in all four quadrants GU: Reports normal urine output Neurologic: Within normal limits Integumentary: No wounds noted; skin appropriate for age
Blood pressure:	126/86 mm Hg
Heart rate:	74 beats/min
Respiratory rate:	16 breaths/min
Oxygen saturation:	97% on room air
Height:	5'3"
Weight:	122 lb

Exercise \(\PageIndex{1}\)

Based on the information above, what is the most important question for the nurse to ask Maria?

“How long have you been taking aspirin?”

“How many stools have you had today?”

“How much ibuprofen do you take each day?”

“Have you lost any weight in the last month?”

Answer

“How much ibuprofen do you take each day?”

Exercise \(\PageIndex{2}\)

The nurse determines that the client is taking 2 or 3 200 mg tablets nine times daily to control her arthritic pain. Which instruction should the nurse give the client?

“This dose is too low to effectively relieve arthritis pain.”

“This dose is appropriate for arthritis pain.”

“This dose may cause respiratory depression.”

“This dose is too high and can cause gastric bleeding.”

Answer

“This dose is too high and can cause gastric bleeding.”