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NSAIDs

6 min read

NSAIDs

Key Points

  • NSAIDs inhibit COX-1 and COX-2 enzymes → block prostaglandin synthesis → analgesia, antipyresis, and anti-inflammation
  • COX-1 inhibition → decreased gastric mucosal protection → GI bleeding risk — always administer with food
  • All NSAIDs (except low-dose aspirin) increase risk of cardiovascular events (MI, stroke, heart failure) — Black Box Warning
  • Ketorolac: Maximum 5 days; reduce dose in patients ≥65 years; last nonopioid before initiating opioids
  • Aspirin: Irreversible COX inhibitor → antiplatelet effect lasts 7–10 days (platelet lifespan); use in acute MI
  • NSAIDs are contraindicated in renal impairment and late pregnancy (premature ductal closure)
  • In neonatal PDA pathways, ibuprofen/indomethacin may support ductal closure but are contraindicated in ductal-dependent critical CHD.

Drug Class Overview

NSAIDs are among the most widely used medications worldwide, available both over-the-counter and by prescription. They possess three therapeutic properties: analgesia (pain relief), antipyresis (fever reduction), and anti-inflammation. Unlike acetaminophen, NSAIDs effectively reduce inflammation and platelet aggregation. All NSAIDs carry significant risk profiles requiring careful patient assessment before and during administration.

Mechanism of Action

NSAIDs inhibit cyclooxygenase (COX) enzymes centrally and peripherally:

  • COX-1: Homeostatic functions — maintains gastric mucosal barrier (prostaglandin E2), regulates platelet function, supports normal renal blood flow
  • COX-2: Primarily activated by tissue injury — responsible for pain, inflammation, and fever

Inhibiting COX-1 → loss of gastric mucosal protection → GI irritation and ulcers. Inhibiting COX-2 → decreased prostaglandins → anti-inflammatory and analgesic effects.

Major NSAID Agents

Non-Selective NSAIDs (COX-1 + COX-2 Inhibition)

DrugRoutesAdult DosingKey Notes
AspirinOralAnalgesia: 325–1000 mg q4-6h (max 4000 mg/day); Antiplatelet: 75–325 mg dailyIrreversible COX inhibition; antiplatelet effect lasts 7–10 days
Ibuprofen (Advil, Motrin)Oral200–800 mg q4-8h (max 3200 mg/day); ≥6 months safe in childrenMost common OTC NSAID; take with food
Naproxen (Aleve, Naprosyn)Oral200–400 mg, then 200 mg q8-12h (max 600 mg/day OTC)Longer duration than ibuprofen; less frequent dosing
Ketorolac (Toradol)IV/IM, oral15–30 mg IV/IM q6h; oral continuationLast nonopioid on WHO pain ladder; max 5 days total

COX-2 Selective NSAIDs

Celecoxib (Celebrex): Selectively inhibits COX-2 → reduced GI risk compared to non-selective NSAIDs; however, cardiovascular risk remains.

Indications for COX-2 selective agents: Patients at high GI risk who require anti-inflammatory therapy; osteoarthritis, rheumatoid arthritis.

Aspirin — Special Antiplatelet Properties

Unlike other NSAIDs, aspirin irreversibly inactivates COX in platelets. Since platelets cannot synthesize new COX, the antiplatelet effect persists for the platelet’s entire 7–10 day lifespan. This makes aspirin essential in:

  • Acute MI management: 162–325 mg chewed immediately → prevents further platelet aggregation
  • Secondary prevention: Low-dose aspirin (75–325 mg daily) for cardiovascular risk reduction
  • Reye’s syndrome risk: Aspirin contraindicated in children/adolescents with viral illness

Adverse Effects

GI Effects (Major Risk)

  • Mechanism: COX-1 inhibition → decreased prostaglandin E2 → loss of gastric mucosal protection
  • Risks: Dyspepsia, gastritis, peptic ulcer disease, GI bleeding, GI perforation (can be fatal)
  • Concomitant warfarin or corticosteroid therapy further increases GI bleeding risk
  • Prevention: Always administer with food; use proton pump inhibitors in high-risk patients
  • Warning signs: Severe abdominal pain, dark tarry stools, vomiting blood — STOP NSAID and notify provider

Cardiovascular Risk (All NSAIDs)

NSAID Cardiovascular Risk — Black Box Warning

All NSAIDs (except low-dose aspirin) increase risk of 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. Ketorolac is contraindicated post-CABG surgery.

Renal Effects

  • NSAIDs reduce renal prostaglandin production → decreased renal blood flow → acute kidney injury
  • Risk increases with: pre-existing renal impairment, volume depletion, older adults, concurrent ACE inhibitors/ARBs
  • Monitor BUN, serum creatinine, and urine output; ensure adequate hydration

Platelet/Bleeding Effects

  • Reversible platelet inhibition with most NSAIDs (effect ends when drug is metabolized)
  • Increased bleeding time — hold before surgery per protocol
  • Avoid concurrent use with anticoagulants (warfarin, heparin) — additive bleeding risk

Other Adverse Effects

  • Ketorolac: GI bleeding, renal failure, hypersensitivity (anaphylaxis), Stevens-Johnson syndrome, edema
  • Aspirin allergy: Hypersensitivity reactions (bronchospasm) — cross-reactivity possible with other NSAIDs
  • Tinnitus with aspirin toxicity (salicylism)

Ketorolac — The Last Nonopioid

Ketorolac occupies a unique position: it provides opioid-level analgesia without opioid adverse effects, making it the final step on the WHO pain ladder before initiating opioids.

Maximum Duration: 5 days total (combined IV/IM and oral) — longer use dramatically increases GI and renal risk.

Dose Reduction: Required in patients ≥65 years due to increased GI and renal risk.

Route: Initial therapy always via IM or IV; oral can continue as replacement for parenteral.

Contraindications: Active peptic ulcer disease, GI bleeding, renal impairment, cerebrovascular bleeding, pre/perioperative pain, CABG surgery.

Nursing Assessment

Before Administration:

  • Assess pain level, location, and character; verify appropriate NSAID use for the pain type
  • Check renal function (BUN, creatinine), history of peptic ulcer, GI bleeding, or aspirin allergy
  • Review concurrent medications: anticoagulants, antihypertensives (NSAIDs reduce effectiveness), corticosteroids
  • Verify pregnancy status — contraindicated in third trimester (risk of premature ductal closure)
  • In neonatal PDA treatment context, verify whether systemic or pulmonary flow is ductal-dependent before giving closure-directed NSAID therapy.

During/After Administration:

  • Monitor for GI symptoms (pain, nausea, dark stools) — administer with food or milk
  • Assess renal function with prolonged use
  • Monitor blood pressure — NSAIDs can raise BP and reduce antihypertensive efficacy
  • Ketorolac: monitor BUN, creatinine, CBC, and liver function tests per protocol

Patient Education:

  • Take with food or milk to reduce GI irritation
  • Avoid alcohol — increases GI bleeding risk
  • Do not combine multiple NSAIDs (increased toxicity)
  • Consult provider before combining with anticoagulants or aspirin
  • Report GI pain, blood in stool, decreased urination, or unusual bruising immediately
  • Ketorolac: do not exceed 5 days; reduce activity if dizzy or drowsy

Self-Check

  1. A patient with a history of peptic ulcer disease needs anti-inflammatory therapy for osteoarthritis. Which NSAID subclass has reduced GI risk, and what GI protective agent may also be prescribed?
  2. A patient is receiving ketorolac IV for postoperative pain. On day 6, the provider continues the prescription. What is the priority nursing action?
  3. What is the mechanism by which aspirin provides antiplatelet effects, and how long does this effect last?

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