Non-Opioid Analgesics

Introduction

Non-Opioid Analgesics Drugs: Three major classes, salicylates (aspirin), para-aminophenal (Tylenol), and Non-steroidal anti-inflammatory drugs (NSAIDS, e.g., Ibuprofen). All inhibit prostaglandin synthesis which may increase the body’s response to pain. They exhibit an anti-pyretic effect by either peripheral vasodilation or by acting on the thermoregulatory centre.

Name of the Non-Opioid Analgesics Drugs

1. Aspirin
2. Acetaminophen
3. Ibuprofen
4. Ketoprofen
5. Naproxen Sodium

Mechanism Of Action:

Irreversibly inhibits cyclo-oxygenase enzyme, resulting in a decreased formation of prostaglandin precursors. Irreversibly inhibits formation of thromboxane, resulting in inhibiting platelet aggregation. Therapeutic Effect: Reduces inflammatory response, intensity of pain; decreases fever; inhibits platelet aggregation.

Indications:

• Treatment of mild to moderate pain, fever.
• Reduces inflammation related to rheumatoid arthritis (RA), juvenile arthritis, osteoarthritis, rheumatic fever.
• Used as platelet aggregation inhibitor in the prevention of transient ischemic attacks (tias), cerebral thromboembolism, MI or reinfarction.
• Reduce risk of MI in pts with CAD or stroke in pts who have had TIA or ischemic stroke.
• OFF-LABEL: Prevention of preeclampsia
• Alternative therapy for preventing thromboembolism associated with atrial fibrillation when warfarin cannot be used; pericarditis associated with MI
• Prosthetic valve thromboprophylaxis.
• Adjunctive treatment of kawasaki’s disease.
• Complications associated with autoimmune disorders, colorectal cancer.

Cautions & Contraindications:

• Hypersensitivity to NSAIDs.
• Pts with asthma, rhinitis, nasal polyps
• Inherited or acquired bleeding disorders
• Use in children (younger than 16 yrs) for viral infections with or without fever.
• Cautions: Platelet/bleeding disorders, severe renal/hepatic impairment, dehydration, erosive gastritis, peptic ulcer disease, sensitivity to tartrazine dyes, elderly (chronic use of doses 325 mg or greater).
• Avoid use in pregnancy, especially third trimester.

Metabolism and Half- life:

Rapidly and completely absorbed from GI tract; enteric-coated absorption delayed; rectal absorption delayed and incomplete. Protein binding: High. Widely distributed. Rapidly hydrolyzed to salicylate. Half-life: 15–20 min (aspirin); 2–3 hrs (salicylate at low dose); more than 20 hrs (salicylate at high dose).

Drug Interactions:

•Alcohol, NSAIDs (e.g., ibuprofen, ketorolac, naproxen) may increase risk of GI effects (e.g., ulceration).

•Antacids, urinary alkalinizers increase excretion.

•Anticoagulants, (e.g. enoxaparin, warfarin), heparin, thrombolytics, ticagrelor increase risk of bleeding. 

•Herbals with anticoagulant/antiplatelet properties (e.g., garlic, ginger, ginkgo biloba) may increase risk of bleeding.

•LAB VALUES: May alter serum ALT, AST, alkaline phosphatase, uric acid; prolongs prothrombin time (PT) platelet function assay. May decrease serum cholesterol, potassium, T3, T4.

Side- Effects:

• GI distress (including abdominal distention, cramping, heartburn, mild nausea)
• Allergic reaction (including bronchospasm, pruritus, urticaria).
• High doses of aspirin may produce GI bleeding and/or gastric mucosal lesions.
• Dehydrated, febrile children may experience aspirin toxicity quickly.
• Reye’s syndrome, characterized by persistent vomiting, signs of brain dysfunction, may occur in children taking aspirin with recent viral infection (chickenpox, common cold, or flu).
• Low-grade aspirin toxicity characterized by tinnitus, generalized pruritus (may be severe), headache, dizziness, flushing, tachycardia, hyperventilation, diaphoresis, thirst.

NURSING CONSIDERATIONS

Baseline assessment

• Do not give to children or teenagers who have or have recently had viral infections (increases risk of Reye’s syndrome).
• Do not use if vinegar-like odor is noted (indicates chemical breakdown).
• Assess history of GI bleed, peptic ulcer disease, OTC use of products that may contain aspirin.
• Assess type, location, duration of pain, inflammation.
• Inspect appearance of affected joints for immobility, deformities, skin condition.

Intervention/evaluation

• Monitor urinary pH (sudden acidification, pH from 6.5 to 5.5, may result in toxicity).
• Assess skin for evidence of ecchymosis.
• If given as antipyretic, assess temperature directly before and 1 hr after giving medication.
• Evaluate for therapeutic response: relief of pain, stiffness, swelling; increased joint mobility; reduced joint tenderness; improved grip strength.

Patient/family teaching

• Do not, chew, crush, dissolve, or divide enteric-coated tablets.
• Avoid alcohol, OTC pain/cold products that may contain aspirin.
• Report ringing of the ears or persistent abdominal GI pain, bleeding.
• Therapeutic anti-inflammatory effect noted in 1–3 wks.
• Behavioural changes, persistent vomiting may be early signs of Reye’s syndrome, contact physician.

Mechanism of Action:

Analgesic: Activates descending serotonergic inhibitory pathways in CNS. Antipyretic: Inhibits hypothalamic heat regulating center. Therapeutic Effect: Results in antipyresis. Produces analgesic effect.

Metabolism and Half-life:

Rapidly, completely absorbed from GI tract; rectal absorption variable. Protein binding: 20%–50%. Widely distributed to most body tissues. Metabolized in liver. Excreted in urine. Removed by hemodialysis.

 Half-life: 1–4 hrs (increased in pts with hepatic disease, elderly, neonates; decreased in children).

Indications:

• Temporary relief of mild to moderate pain, headache, fever.
• IV: (Additional) Management of moderate to severe pain when combined with opioid analgesia.

Cautions & Contraindications:

• Hypersensitivity
• Severe hepatic impairment or severe active liver disease.
• Cautions: Sensitivity to acetaminophen; severe renal impairment; alcohol dependency, hepatic impairment, or active hepatic disease
• Chronic malnutrition and hypovolemia

Drug Interactions:

Alcohol (chronic use), hepatotoxic medications ,hepatic enzyme inducers may increase risk of hepatotoxicity with prolonged high dose or single toxic dose.

Side- Effects:

Hypersensitivity reaction

Early Signs of Acetaminophen Toxicity: Anorexia, nausea, diaphoresis, fatigue within first 12–24 hrs. Later Signs of Toxicity: Vomiting, right upper quadrant tenderness, elevated LFTs within 48–72 hrs after ingestion

NURSING CONSIDERATIONS

Baseline assessment

• If given for analgesia, assess onset, type, location, duration of pain.
• Effect of medication is reduced if full pain response recurs prior to next dose.
• Assess for fever.
• Assess LFT in pts with chronic usage or history of hepatic impairment, alcohol abuse.

Intervention/evaluation

• Assess for clinical improvement and relief of pain, fever.
• Therapeutic serum level: 10–30 mcg/mL; toxic serum level: greater than 200 mcg/mL.
• Do not exceed maximum daily recommended dose: 4 g/day

Patient/family teaching

• Consult physician for use in children younger than 2 yrs, oral use longer than 5 days (children) or longer than 10 days (adults), or fever lasting longer than 3 days.
• Severe/recurrent pain or high/ continuous fever may indicate serious illness.
• Do not take more than 4 g/ day (3 g/day if using OTC [over-the counter]). Actual OTC dosing recommendations may vary by product and/or manufacturer. Many nonprescription combination products contain acetaminophen. Avoid alcohol.

Mechanism of Action:

Reversibly inhibits COX-1 and COX-2 enzymes, resulting in decreased formation of prostaglandin precursors. Therapeutic Effect: Produces analgesic, anti-inflammatory effects; decreases fever.

Indications:

• Treatment of fever
• Inflammatory disease
• Rheumatoid disorders
• Osteoarthritis
• Mild to moderate pain
• Primary dysmenorrhea
• Severe pain in combination with an opioid analgesic
• To close a clinically significant patent ductus arteriosus (PDA) in premature infants weighing between 500 and 1,500 g who are no more than 32 weeks gestational age when usual medical management is ineffective.
• OFF-LABEL: treatment of cystic fibrosis, pericarditis. Juvenile idiopathic arthritis.

Metabolism and Half- Life:

Rapidly absorbed from GI tract. Protein binding: 90%–99%. Metabolized in liver. Primarily excreted in urine. Not removed by hemodialysis.

Half-life: 2–4 hrs

Cautions & Contraindications:

• History of hypersensitivity to ibuprofen, aspirin, other NSAIDs.
• Treatment of perioperative pain in coronary artery bypass graft (CABG) surgery.
• Aspirin triad (bronchial asthma, aspirin intolerance, rhinitis).
• Neoprofen: Preterm neonates with proven or suspected untreated infection, elevated total bilirubin, congenital heart disease in whom patency of the patent ductus arteriosus is necessary for satisfactory pulmonary or systemic blood flow (e.g., Pulmonary atresia), bleeding, thrombocytopenia, coagulation defects, proven or suspected necrotizing enterocolitis, significant renal impairment.
• Cautions: Patients with fluid retention, HF, dehydration, coagulation disorders, concurrent use with aspirin, anticoagulants, steroids; history of GI disease (e.g., Bleeding, ulcers), smoking, use of alcohol, elderly, debilitated pts, hepatic/ renal impairment, asthma.

Drug interactions:

• May decrease effects of antihypertensives (e.g., amlodipine, lisinopril, valsartan), diuretics (e.g., furosemide). Aspirin, other salicylates may increase risk of GI side effects, bleeding.
• May increase nephrotoxic effect of cyclosporine.
• LAB VALUES: May prolong bleeding time. May alter serum glucose level. May increase serum BUN, creatinine, potassium, ALT, AST. May decrease serum calcium, glucose; Hgb, Hct, platelets.

Side- Effects:

• Nausea, vomiting
• Dyspepsia
• Dizziness
• Rash
• Overdose may result in metabolic acidosis.
• Rare reactions with long-term use include peptic ulcer, GI bleeding, gastritis, severe hepatic reaction (cholestasis, jaundice), nephrotoxicity (dysuria, hematuria, proteinuria, nephrotic syndrome), severe hypersensitivity reaction (particularly in pts with systemic lupus erythematosus or other collagen diseases).

NURSING CONSIDERATIONS

Baseline assessment

• Assess onset, type, location, duration of pain, inflammation.
• Inspect appearance of affected joints for immobility, deformities, skin condition. Assess temperature. 

Intervention/evaluation

• Monitor for evidence of nausea, dyspepsia.
• Assess skin for rash.
• Observe for bleeding, bruising, occult blood loss.
• Evaluate for therapeutic response: relief of pain, stiffness, swelling; increased joint mobility; reduced joint tenderness; improved grip strength.
• Monitor for fever.

Patient/family teaching

• Avoid aspirin, alcohol during therapy (increases risk of GI bleeding).
• If GI upset occurs, take with food, milk, antacids.
• May cause dizziness.
• Report ringing in ears, persistent stomach pain, respiratory difficulty, unusual bruising/ bleeding, swelling of extremities, chest pain/palpitations.

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.

Indications:

• Pain Management
• Rheumatoid Arthritis or Osteoarthritis
• Dysmenorrhea

Cautions & Contraindications:

• Angioedema
• Aspirin-, iodide-, or NSAID induced asthma
• Bronchospasm
• Nasal polyps
• Rhinitis, or urticaria
• Hypersensitivity to ketoprofen or its components

Metabolism and Half- life:

• Bioavailability: 90%
• Metabolized in Liver ; Half-life:2-4 hr (immediate release); 3-7.5 hr (ER)
• Excretion: Urine 50-90% as glucuronide conjugates; faeces 1-8%

Drug Interactions:

• ACE inhibitors: possibly decreased hypotensive effect of ACE inhibitors
• Aspirin, other NSAIDs: increased risk of bleeding and adverse GI effects, increased and prolonged blood ketoprofen levels
• Alcohol use: increased risk of adverse GI effects
• Heparin, oral anticoagulants, thrombolytics: Increased anticoagulant effects, increased risk of haemorrhage

Side-effects:

• Increased liver function test
• Dyspepsia
• Dizziness
• Headache
• Impaired renal function disorder
• Upper GI ulcers, 3-6 months treatment​
• Nausea ​
• Diarrhoea ​ Ketoprofen-induced peptic ulcer, GI bleeding (>2% in long-term studies)

Nursing Considerations

• Use ketoprofen with extreme caution in patients with history of ulcer disease or GI bleeding because NSAIDs such as ketoprofen increased risk of GI bleeding and ulceration. 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.
• Monitor patient closely for thrombotic events, including MI and stroke, because NSAIDs increase the risk.
• Monitor liver function test, BUN, creatinine CBC and decreased Hb levels 
• 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 sensitivity. 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 And Family 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.
• Instruct patient to avoid aspirin, aspirin containing products, and alcohol while taking ketoprofen to decrease risk of
• Adverse GI effects.
• 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.​
• 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.​

Mechanism of Action:

Blocks cyclooxygenase, the enzyme needed to synthesize prostaglandins, which mediate the inflammatory response and cause local vasodilation, swelling, and pain. Thus, naproxen, an NSAID, reduces symptoms of inflammation and relieves pain. Antipyretic action probably stems from effects on the hypothalamus, which increases peripheral blood flow, causing vasodilation and heat dissipation.

Indications:

• Treatment of acute or long-term mild to moderate pain
• Primary dysmenorrhea
• Rheumatoid arthritis (RA) & Juvenile rheumatoid arthritis (JRA)
• Osteoarthritis
• Ankylosing spondylitis
• Acute gouty arthritis
• Bursitis; Tendonitis
• Fever.
• OFFLABEL: migraine prophylaxis

Cautions & Contraindications:

• History of asthma, urticaria
• Hypersensitivity to naproxen, other nsaids.
• Perioperative pain in setting of CABG surgery.
• Cautions: GI disease (bleeding, ulcers), fluid retention, renal/ hepatic impairment, asthma, HF, concurrent use of anticoagulants, smoking, use of alcohol, elderly pts, debilitated pts.

Metabolism and Half- life:

Completely absorbed from GI tract. Protein binding: 99%. Metabolized in liver. Primarily excreted in urine. Not removed by hemodialysis.

Half-life: 13 hrs.

Drug Interactions:

• Bile acid sequestrants (e.g., cholestyramine) may decrease absorption. 
• HERBAL: Glucosamine, herbals with anticoagulant/antiplatelet properties (e.g., garlic, ginger, ginseng, ginkgo biloba) may increase concentration/effect.
• LAB VALUES: May prolong bleeding time. May increase serum BUN, creatinine, ALT, AST, alkaline phosphatase. May decrease Hgb, Hct, leukocytes, platelets, uric acid.

Side effects:

• Nausea
• Constipation
• Abdominal cramps/pain
• Heartburn
• Dizziness, headache, drowsiness.
• Occasional: stomatitis, diarrhea, indigestion.
• Rare: vomiting, confusion

NURSING CONSIDERATIONS

Baseline assessment

• Assess onset, type, location, duration of pain/ inflammation.
• Inspect appearance of affected joints for immobility, deformities, skin condition.
• Question history of GI bleeding, gastric or duodenal ulcers, hypertension.

Intervention/evaluation

• Assist with ambulation if dizziness occurs.
• Periodically monitor renal function test during chronic use.
• Monitor daily pattern of bowel activity, stool consistency.
• Evaluate for therapeutic response: relief of pain, stiffness, swelling; increased joint mobility, reduced joint tenderness, improved grip strength.

Patient/family teaching

• Avoid tasks that require alertness, motor skills until response to drug is established.
• Take with food, milk.
• Avoid aspirin, alcohol during therapy (increases risk of GI bleeding).
• Report headache, rash, visual disturbances, weight gain, black or tarry stools, bleeding, persistent headache.

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

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