Ibuprofen
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ibuprofen pharmacology mechanism of action indications dosing
Opioid Prescribing for Analgesia After Common Otolaryngology Operations
Page 19
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ibuprofen adverse effects contraindications drug interactions
GradeResponse
GradeResponse
Here is a comprehensive overview of ibuprofen:
Ibuprofen
Drug Class
Non-steroidal anti-inflammatory drug (NSAID); propionic acid derivative
Mechanism of Action
Ibuprofen nonselectively and reversibly inhibits the cyclooxygenase isoenzymes COX-1 and COX-2, which convert arachidonic acid into prostaglandins and thromboxane A₂. By suppressing prostaglandin synthesis, ibuprofen reduces pain, inflammation, and fever. (Opioid Prescribing for Analgesia After Common Otolaryngology Operations, p. 19)
- COX-1 inhibition → reduced thromboxane A₂ → antiplatelet effect; also reduces gastroprotective prostaglandins (source of GI side effects)
- COX-2 inhibition → anti-inflammatory and analgesic effects
Indications
| Indication | Notes |
|---|---|
| Mild-to-moderate pain | Headache, dental pain, musculoskeletal pain, dysmenorrhea |
| Fever (antipyretic) | Adults and children |
| Inflammation | Arthritis (OA, RA), bursitis, tendinitis |
| Patent ductus arteriosus (PDA) | IV formulation in neonates |
| Postoperative analgesia | Often combined with acetaminophen (opioid-sparing) |
Dosing
| Population | Dose | Frequency | Max Daily Dose |
|---|---|---|---|
| Adults (OTC) | 200–400 mg | Every 4–6 hours | 1,200 mg |
| Adults (Rx) | 400–800 mg | Every 6–8 hours | 3,200 mg |
| Children (≥6 months) | 5–10 mg/kg | Every 6–8 hours | 40 mg/kg/day |
- Take with food or milk to reduce GI irritation
- Use the lowest effective dose for the shortest duration
Adverse Effects
| System | Effect |
|---|---|
| GI | Nausea, dyspepsia, peptic ulcer, GI bleeding (COX-1 mediated) |
| Renal | Acute kidney injury, fluid retention, hypertension, reduced GFR |
| Cardiovascular | Increased risk of MI and stroke (especially with prolonged use) |
| Hematologic | Reversible platelet inhibition, increased bleeding time |
| Hepatic | Transaminase elevation (rare hepatotoxicity) |
| Hypersensitivity | Urticaria, bronchospasm, anaphylaxis (especially in aspirin-sensitive asthma) |
| CNS | Headache, dizziness (less common) |
Contraindications
- Absolute: Known hypersensitivity to ibuprofen or any NSAID; aspirin-exacerbated respiratory disease (AERD/"aspirin triad")
- Third trimester pregnancy: Risk of premature closure of ductus arteriosus, oligohydramnios
- Perioperative CABG: Increased cardiovascular risk
- Active GI ulcer or bleeding
- Severe renal or hepatic impairment
Drug Interactions
| Drug | Interaction |
|---|---|
| Aspirin | NSAIDs (especially ibuprofen) may block aspirin's irreversible COX-1 inhibition — take aspirin 30+ min before ibuprofen |
| Anticoagulants (warfarin, DOACs) | Additive bleeding risk |
| Antihypertensives (ACEi, ARBs, diuretics) | Reduced efficacy; increased risk of AKI ("triple whammy") |
| Lithium, methotrexate | NSAIDs reduce renal clearance → toxicity |
| SSRIs | Additive GI bleeding risk |
| Corticosteroids | Additive GI ulceration risk |
Special Populations
- Elderly: Higher risk of GI bleeding, renal impairment, cardiovascular events — use with caution; consider gastroprotection (PPI)
- Pregnancy: Avoid in first trimester (some evidence of miscarriage risk) and avoid in third trimester (fetal renal toxicity, ductal closure)
- Renal/hepatic disease: Reduce dose or avoid; monitor closely
- Asthma: Use cautiously — up to 20% of asthmatics may experience NSAID-triggered bronchospasm
Comparison to Other NSAIDs
| Feature | Ibuprofen | Naproxen | Celecoxib (COX-2 selective) |
|---|---|---|---|
| Duration | Short (4–6 h) | Long (8–12 h) | Intermediate |
| GI risk | Moderate | Moderate | Lower |
| CV risk | Moderate | Lower | Higher |
| Platelet effect | Reversible | Reversible | Minimal |
| OTC availability | Yes | Yes | No (Rx only) |
Key takeaway: Ibuprofen is a versatile, widely available NSAID effective for pain, fever, and inflammation. Its risk-benefit profile is generally favorable at low doses for short durations, but caution is warranted in elderly patients, those with renal/cardiovascular disease, and in pregnancy.
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