Nonselective NSAIDs

Nonselective NSAIDs are anti-inflammatory drugs that inhibit both COX-1 and COX-2 enzymes, providing effective relief from pain, fever, and inflammation, but with increased risk of gastrointestinal and renal side effects due to COX-1 suppression.

Name of the Nonselective NSAID Drugs

• Acetaminophen
• Indomethacin
• Ketoprofen
• Sulindac

1.Acetaminophen

Mechanism of Action

Inhibits the enzyme cyclooxygenase, blocking prostaglandin production and interfering with pain impulse generation in the peripheral nervous system. Acetaminophen also acts directly on temperature-regulating center in the hypothalamus by inhibiting synthesis of prostaglandin E2.

Pharmacokinetics

• Peak Plasma Time: 10-60 min (PO immediate-release); 60-120 min (PO extended-release); 6 hr (PO 500 mg, conventional tablet); 8 hr (PO 650 mg, extended-release tablet)
• Protein Bound: 10 to 25%
• Metabolism: Liver (microsomal enzyme systems); conjugation (glucuronic/sulfuric acid)
• Half-life elimination: 1.25-3 hr (adolescents); 2-5 hr (children); 4 hr (infants); 7 hr (neonates); 2-3 hr (adults)
• Excretion: urine (principally as acetaminophen glucuronide with acetaminophen sulfate/mercaptate)

Contraindications

Hypersensitivity to acetaminophen or its components

Adverse Reactions

• GI: Abdominal pain, hepatotoxicity, nausea, vomiting
• HEME: Hemolytic anemia (with long-term use), leukopenia, neutropenia, pancytopenia, thrombocytopenia
• SKIN: Jaundice, rash, urticaria
• Other: Angioedema, hypoglycemic coma

Nursing Considerations

• Before and during long-term therapy, monitor liver function test results, including AST, ALT, bilirubin, and creatinine levels, as ordered.
• Monitor renal function in patient on longterm therapy. Keep in mind that blood or albumin in urine may indicate nephritis; decreased urine output may indicate renal failure; and dark brown urine may indicate presence of the metabolite phenacetin.
• Expect to reduce dosage for patients with renal dysfunction.
• Store suppositories under 80° F (26.6° C).

Patient Teaching

• Tell patient that tablets may be crushed or swallowed whole.
• Instruct patient to read manufacturer’s label and follow dosage guidelines precisely. Explain that infants’ and children’s acetaminophen liquid aren’t equal in drug concentration and aren’t interchangeable.
• Advise patient to use manufacturer’s dropper or dosage cup for measuring liquid acetaminophen.
• Advise him to contact prescriber before taking other prescription or OTC products because they may contain acetaminophen.
• Teach patient to recognize signs of hepatotoxicity, such as bleeding, easy bruising, and malaise, which commonly occurs with chronic overdose

2.Indomethacin

Mechanism of Action

Blocks activity of cyclooxygenase, the enzyme needed to synthesize prostaglandins, which mediate inflammatory response and cause local vasodilation, swelling, and pain. By blocking cyclooxygenase and inhibiting prostaglandins, this NSAID reduces inflammatory symptoms and helps relieve pain

Pharmacokinetics

• Bioavailability: ~100%
• Peak plasma time: 0.5-2 hr; 1.67 hr (Tivorbex)
• Protein bound: 99%
• Metabolized in liver
• Half-life: 4.5 hr (prolonged in neonates)
• Excretion: Urine (60%), feces (>33%)

Administration

• Give with food, full glass of water, or antacids to reduce GI upset.
• Don’t open or crush capsules.
• For arthritis, give up to 100 mg of daily dose at bedtime as needed to reduce nighttime pain and morning stiffness.
• Don’t give sustained-release form to patients with gouty arthritis.

Contraindications

• Hypersensitivity to drug, its components, or other NSAIDs
• Active GI bleeding
• Concurrent diflunisal use

Precautions:

• Severe cardiovascular, renal, or hepatic disease
• History of ulcer disease
• Elderly patients
• Pregnant or breastfeeding patients
• Children ages 14 and younger (efficacy not established).

Adverse reactions

• CNS: headache, dizziness, drowsiness, fatigue, vertigo, depression,seizures
• EENT: tinnitus
• GI: nausea, vomiting, diarrhea, constipation, abdominal pain or cramps, dyspepsia, ulcers, GI bleeding
• Other: allergic reactions including anaphylaxis

Patient monitoring

• Assess for dizziness, drowsiness, headache, fatigue, and exacerbation of depression, epilepsy, or parkinsonism.
• Monitor for drug efficacy, indicated by improved joint mobility, pain relief, and decreased inflammation.
• Monitor urine output for marked reduction.
• Watch for signs and symptoms of GI bleeding and ulcers.

Patient teaching

• Tell patient to take with food, full glass of water, or antacid to reduce GI upset.
• Advise patient not to open or crush capsules.
• Inform breastfeeding patient that indomethacin enters breast milk and may cause seizures in infant. Advise her to use a different infant feeding method during therapy.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, balance, and alertness.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.

Nursing Considerations

• Use indomethacin with extreme caution in patients with history of ulcer disease or GI bleeding because NSAIDs such as indomethacin increase risk of GI bleeding and ulceration. Expect to use drug for shortest time possible in these patients. • Be aware that serious GI tract ulceration, bleeding, and perforation may occur without warning symptoms. Elderly patients are at greater risk. To minimize risk, give oral indomethacin with food, a full glass of water (not suspension), or an antacid to reduce GI distress.
• If GI distress occurs, withhold drug and notify prescriber immediately.
• Use indomethacin cautiously in patients with hypertension, and monitor blood pressure closely throughout therapy. Drug may cause hypertension or worsen it.
• Shake suspension well before giving it.
• For arthritis, give up to 100 mg of daily dose (not E.R. capsules) at bedtime to reduce nighttime pain and morning stiffness.
• Make sure suppository stays in rectum at least 1 hour to improve absorption.
• To reconstitute I.V. form, add 1 to 2 ml of preservative-free sodium chloride for injection or preservative-free sterile water to vial. Solution made with 1 ml diluent contains 100 mcg (0.1 mg) indomethacin/0.1 ml. Solution made with 2 ml diluent contains 50 mcg (0.05 mg) indomethacin/0.1 ml. Use solution immediately because it contains no preservatives. Discard unused portion.
• Be aware that scheduled I.V. doses may be withheld if infant or neonate has anuria or a significant decrease in urine output (less than 0.6 ml/kg/hr).
• When using I.V. form, avoid extravasation to protect surrounding tissue.
• Anticipate a second course (3 more doses) of I.V. indomethacin if patent ductus arteriosus fails to close or reopens. After two courses, surgery may be performed.
• Monitor patient—especially if he’s elderly or receiving long-term indomethacin therapy—for less common but serious adverse GI reactions, including anorexia, constipation, diverticulitis, dysphagia, esophagitis, gastritis, gastroenteritis, gastroesophageal reflux disease, hemorrhoids, hiatal hernia, melena, stomatitis, and vomiting.
• Monitor liver function test results because, rarely, elevations may progress to severe hepatic reactions, including fatal hepatitis, liver necrosis, and hepatic failure.
• Monitor BUN and serum creatinine levels in elderly patients, those taking diuretics or ACE inhibitors, and those with heart failure, impaired renal function, or hepatic dysfunction; drug may cause renal failure.
• Monitor CBC for decreased hemoglobin and hematocrit. Drug may worsen anemia
• Assess patient’s skin regularly for signs of rash or other hypersensitivity reaction because indomethacin is an NSAID and may cause serious skin reactions without warning, even in patients with no history of NSAID sensitivity. At first sign of reaction, stop drug and notify prescriber.
• Because indomethacin causes sodium retention, monitor weight and blood pressure, especially if patient has hypertension.
• When drug is used to treat gouty arthritis, expect its action to peak in 24 to 36 hours and significant swelling to gradually disappear over 3 to 5 days.
• Be aware that E.R. form shouldn’t be used to treat gouty arthritis.

3.Ketoprofen

Mechanism of Action

Blocks activity of cyclooxygenase, the enzyme needed for prostaglandin synthesis. Prostaglandins, important mediators of inflammatory response, cause local vasodilation with swelling and pain. By blocking cyclooxygenase and inhibiting prostaglandins, this NSAID reduces inflammatory symptoms and relieves pain.

Pharmacokinetics

• Bioavailability: 90%
• Protein Bound: 99%
• Metabolism: Liver
• Half-life: 2-4 hr (immediate release); 3-7.5 hr (ER)
• Excretion: Urine 50-90% as glucuronide conjugates; feces 1-8%

Contraindications

Angioedema; aspirin-, iodide-, or NSAIDinduced asthma, bronchospasm, nasal polyps, rhinitis, or urticaria; hypersensitivity to ketoprofen or its components

Adverse Reactions

• CNS: Headache, irritability, nervousness, seizures, stroke
• CV: Edema, fluid retention, hypertension, MI, tachycardia
• EENT: Tinnitus, vision changes
• GI: Abdominal pain, anorexia, constipation, diarrhea, diverticulitis, dyspepsia, dysphagia, flatulence, gastritis, gastroenteritis, gastroesophageal reflux disease, GI bleeding and ulceration, hepatic failure, hiatal hernia, indigestion, melena, nausea, perforation of stomach or intestine, stomatitis, vomiting
• GU: Acute renal failure, decreased urine output
• HEME: Agranulocytosis, anemia, easy bruising, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia
• RESP: Asthma, respiratory depression
• SKIN: Erythema multiforme, Stevens Johnson syndrome, toxic epidermal necrolysis, rash
• Other: Anaphylaxis, angioedema, rapid weight gain

Nursing Considerations

• Use ketoprofen with extreme caution in patients with history of ulcer disease or GI bleeding because NSAIDs such as ketoprofen increase risk of GI bleeding and ulceration. Expect to use ketoprofen for shortest time possible in these patients.
• Be aware that serious GI tract ulceration, bleeding, and perforation may occur without warning symptoms. Elderly patients are at greater risk. To minimize risk, give drug with food. If GI distress occurs, withhold drug and notify prescriber immediately.
• Use ketoprofen cautiously in patients with hypertension, and monitor blood pressure closely throughout therapy. Drug may cause hypertension or worsen it to cause stroke, because NSAIDs increase the risk.
• • Monitor patient—especially if he’s elderly or receiving long-term ketoprofen therapy—for less common but serious adverse GI reactions, including anorexia, constipation, diverticulitis, dysphagia, esophagitis, gastritis, gastroenteritis, gastroesophageal reflux disease, haemorrhoids, hiatal hernia, melena, stomatitis, and vomiting.
• Monitor liver function test results because, rarely, elevations may progress to severe hepatic reactions, including fatal hepatitis, liver necrosis, and hepatic failure.
• Monitor BUN and serum creatinine levels in elderly patients, patients taking diuretics or ACE inhibitors, and patients with heart failure, impaired renal function, or hepatic dysfunction; drug may cause renal failure.
• Monitor CBC for decreased hemoglobin level and hematocrit because drug may worsen anemia.
• Assess patient’s skin regularly for signs of rash or other hypersensitivity reaction because ketoprofen is an NSAID and may cause serious skin reactions without warning, even in patients with no history of NSAID sensivitity. At first sign of reaction, stop drug and notify prescriber.
• If patient takes acetaminophen, monitor fluid intake and output, BUN level, and serum creatinine level for evidence of adverse renal effects.

Patient Teaching

• Instruct patient to take ketoprofen with food or after meals to prevent GI upset. Advise him to take drug with a full glass of water and to avoid lying down for 15 to 30 minutes afterward to prevent drug from lodging in esophagus and causing irritation.
• Advise patient to swallow drug whole and not to crush, break, chew, or open capsules.
• Instruct patient to avoid aspirin, aspirincontaining products, and alcohol while taking ketoprofen to decrease risk of adverse GI effects.
• Tell patient not to take more drug than prescribed because stomach bleeding may occur.
• If patient takes an anticoagulant, tell him to watch for and immediately report bleeding problems, such as bloody or tarry stools and bloody vomitus.
• If patient takes insulin or an oral antidiabetic, advise him to monitor blood glucose level closely. Urge him to carry candy or other simple sugars to treat mild hypoglycemia. If he has frequent or severe episodes, instruct him to consult prescriber. • Inform patient that he may be nervous and irritable while taking ketoprofen.
• Instruct patient to notify prescriber immediately if he develops a rash, decreased urine output, dark yellow or brown urine, or signs of fluid retention, including swelling of extremities and unexplained rapid weight gain.
• Caution pregnant patient not to take NSAIDs such as ketoprofen during last trimester because they may cause premature closure of the ductus arteriosus.
• Explain that ketoprofen may increase risk of serious adverse cardiovascular reactions; urge patient to seek immediate medical attention if signs or symptoms arise, such as chest pain, shortness of breath, weakness, and slurring of speech.
• Explain that ketoprofen may increase risk of serious adverse GI reactions; stress importance of seeking immediate medical attention for such signs and symptoms as epigastric or abdominal pain, indigestion, black or tarry stools, or vomiting blood or material that looks like coffee grounds.
• Alert patient to rare but serious skin reactions. Urge him to seek immediate medical attention for rash, blisters, itching, fever, or other indications of hypersensitivity.

4.Sulindac

Mechanism of Action

May block the activity of cyclooxygenase, an enzyme needed to synthesize prostaglandins, which mediate the inflammatory response and cause local vasodilation, swelling, and pain. By blocking cyclooxygenase and inhibiting prostaglandins, this NSAID reduces inflammatory symptoms and pain.

Pharmacokinetics

• Half-life: Sulindac (8 hr); sulfide metabolite (16.4 hr)
• Peak Plasma Time: 2 hr (sulindac); 5-6 hr (sulfide metabolites)
• Concentration: 3-6 mcg/mL
• Excretion: Urine (50%); feces (25%)
• Bioavailability: 90%
• Protein Bound: Approx 93% (sulindac); approx 98% (sulfide metabolite)
• Metabolism: Hepatic reduction; significant enterohepatic circulation
• Enzymes inhibited: Cyclooxygenase

Contraindications

Angioedema, asthma, bronchospasm, nasal polyps, rhinitis, or urticaria induced by aspirin, iodides, or other NSAIDs

Adverse Reactions

• CNS: Aseptic meningitis, cerebral hemorrhage, chills, drowsiness, fever, headache, ischemic stroke, malaise, nervousness, transient ischemic attack
• CV: Deep vein thrombosis, edema, heart failure, hypertension, MI, palpitations, peripheral edema, vasculitis
• EENT: Tinnitus
• ENDO: Hypoglycemia
• GI: Abdominal cramps or pain, anorexia, constipation, diarrhea, esophageal irritation, flatulence, gastritis, gastrointestinal bleeding or ulceration, hepatic failure, hepatitis, hepatotoxicity, indigestion, jaundice, liver failure, nausea, perforation of stomach or intestines, vomiting
• GU: Acute renal failure, decreased urine output, interstitial nephritis, nephrotic syndrome, polyuria, proteinuria
• HEME: Agranulocytosis, aplastic anemia, leukopenia, pancytopenia
• RESP: Bronchial spasm, dyspnea, pulmonary edema, wheezing
• SKIN: Diaphoresis, erythema multiforme, exfoliative dermatitis, maculopapular rash, pruritus, purpura, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
• Other: Anaphylaxis, angioedema, facial edema, hypersensitivity syndrome

Nursing Considerations

• Use sulindac with extreme caution in patients with a history of ulcer disease or GI bleeding because NSAIDs such as sulindac increased risk of GI bleeding and ulceration. Expect to use sulindac for the shortest time possible in these patients.
• Be aware that serious GI tract ulceration, bleeding, and perforation may occur without warning symptoms. Elderly patients are at greater risk. To minimize risk, give drug with food. If GI distress occurs, withhold drug and notify prescriber at once
• Use sulindac cautiously in patients with hypertension and monitor blood pressure closely throughout therapy. Drug may cause hypertension or worsen it.
• If patient has systemic lupus erythematosus and mixed connective tissue disease, monitor him closely because sulindac increases the risk of aseptic meningitis.
• Especially if patient is elderly or taking sulindac long-term, watch for less common but serious adverse GI reactions, including anorexia, constipation, diverticulitis, dysphagia, esophagitis, gastritis, gastroenteritis, gastroesophageal reflux disease, haemorrhoids, hiatal hernia, melena, stomatitis, and vomiting.
• Monitor liver function test results because, in rare cases, elevated levels may progress to severe hepatic reactions, including fatal hepatitis, liver necrosis, and hepatic failure.
• Watch BUN and serum creatinine levels in elderly patients; those with heart failure, impaired renal function, or hepatic dysfunction; and those taking diuretics or ACE inhibitors, because drug may cause renal failure.
• Monitor CBC for decreased haemoglobin and haematocrit because drug may worsen anemia.
• Assess patient’s skin routinely for rash or other signs of hypersensitivity reaction because sulindac and other NSAIDs may cause serious skin reactions without warning, even in patients with no history of NSAID hypersensitivity. Stop drug at first sign of reaction and notify prescriber.
• Expect patient to undergo audiometric examinations before and periodically during prolonged therapy, as ordered.
• Monitor patient for evidence of hypersensitivity syndrome, which could become life-threatening. Report multiple occurring and multi-organ adverse reactions to prescriber and expect drug to be discontinued. Be prepared to provide emergency supportive care, as ordered.

Patient Teaching

• Instruct patient to take sulindac exactly as prescribed. Explain that higher doses don’t increase effectiveness and may increase risk of adverse reactions.
• Advise patient to crush tablet and mix with food, if needed, to aid in swallowing.
• Instruct patient to take drug with or immediately after meals to decrease GI distress, to take with a full glass of water, and to remain upright for 20 to 30 minutes after administration to prevent drug from lodging in esophagus and causing esophageal irritation.
• Urge patient to notify prescriber immediately of chills, fever, rash, or sweating, which may indicate hypersensitivity.
• Advise patient to consult prescriber before using acetaminophen, alcohol, aspirin, other NSAIDs, or any OTC drugs during sulindac therapy.
• Caution patient to avoid hazardous activities until drug’s CNS effects are known.
• Explain the need for periodic physical examinations and laboratory tests during prolonged therapy to monitor drug effectiveness.
• Inform patient that sulindac may increase the risk of serious adverse cardiovascular reactions; urge patient to seek immediate medical attention if signs or symptoms arise, such as chest pain, shortness of breath, weakness, and slurring of speech.
• Tell patient that sulindac also may increase the risk of serious adverse GI reactions; stress the need to seek immediate medical attention for such signs and symptoms as epigastric or abdominal pain, indigestion, black or tarry stools, or vomiting blood or material that looks like coffee grounds.
• Alert patient to the possibility of rare but serious hypersensitivity reactions. Urge him to seek immediate medical attention for rash, blisters, itching, fever, or other indications of hypersensitivity

Cautions

• Use caution in asthma (bronchial), cardiac disease, congestive heart failure , hepatic impairment, hypertension, renal impairment.
• Long-term administration of NSAIDs may result in renal papillary necrosis and other renal injury; patients at greatest risk include the elderly, or those with impaired renal function, hypovolemia, heart failure, liver dysfunction, salt depletion, and individuals taking diuretics, ACE inhibitors, or ARBs.

REFERENCES

1. Robert Kizior, Keith Hodgson, Saunders Nursing Drug handbook,1st edition 2024, Elsevier Publications. ISBN-9780443116070
2. McGraw Hill- Drug Handbook, Seventh Edition, 2013, McGraw Hill Education Publications,9780071799430.
3. April Hazard, Cynthia Sanoski, Davi’s Drug Guide for Nurses -Sixteenth Edition 2019, FA Davis Company Publications,9780803669451.
4. Jones and Bartlet, Pharmacology for Nurses, Second Edition, 2020, Jones and Bartlet Learning Publications, ISBN 9781284141986.
5. Nursebro.com, Search – Nursebro
6. Ghlichloo I, Gerriets V. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK547742/

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