Generic Name

Ibuprofen

Mechanism

• Ibuprofen is a non‑selective cyclo‑oxygenase (COX‑1 and COX‑2) inhibitor.
• By blocking COX enzymes, it ↓ the conversion of arachidonic acid to prostaglandins, which are key mediators of inflammation, pain, and fever.
• The resulting ↓ prostaglandin synthesis alleviates acute pain and reduces inflammation, while also decreasing fever by acting on the hypothalamic thermoregulatory center.

Pharmacokinetics

• Absorption: Rapid oral uptake; peak plasma levels within 1–2 h (≈ 3 h for extended‑release).
• Distribution: Highly protein‑bound (~ 99 %); extensive distribution to inflamed tissues and cerebrospinal fluid.
• Metabolism: Hepatic via CYP2C9; major pathway is hydroxylation and glucuronidation.
• Excretion: Renal elimination (≈ 70 % unchanged urine, 30 % metabolites).
• Half‑life: 2–4 h (≈ 6 h for extended‑release formulations).
• Drug interactions: May increase plasma levels of other NSAIDs, warfarin, and diuretics; caution with CYP2C9 inhibitors.

Indications

• Mild‑to‑moderate pain (musculoskeletal, dental, dysmenorrhea).
• Acute inflammatory disorders (e.g., rheumatoid arthritis flare‑up).
• Fever reduction in infectious, post‑operative, or rheumatic etiologies.
• Post‑operative analgesia when combination with acetaminophen is indicated.

Contraindications

• Absolute contraindications:
• Known hypersensitivity to NSAIDs or any excipient.
• Active peptic ulcer disease or history of GI bleeding.
• Severe hepatic or renal impairment.
• Relative contraindications / warnings:
• Pregnancy (especially 3rd trimester) → uterine irritability, fetal ductus arteriosus constriction.
• History of asthma or severe allergic reactions (possible anaphylactoid bronchospasm).
• Cardiac disease (risk of fluid retention, hypertension, heart failure).
• Untreated hypertension.
• Special populations: Elderly, children under 6 mo, or those on chronic steroids require dose adjustment.

Dosing

• Administration tips: Take with food or milk to reduce GI upset; avoid simultaneous ingestion of high‑phosphorus foods when on chronic therapy.
• Transdermal use: Not approved; topical NSAIDs may be used for localized pain.

Adverse Effects

• Common:
• Gastro‑intestinal dyspepsia, nausea, dyspepsia.
• Minor rash or pruritus.
• Headache, dizziness.
• Serious:
• GI ulceration, bleeding, perforation (particularly with ≥ 3 months use).
• Acute kidney injury or chronic renal insufficiency.
• Hepatotoxicity (rare).
• Hypersensitivity reactions: urticaria, angioedema, bronchospasm.
• Cardiovascular events (MI, stroke) with long‑term high‑dose use, especially in older adults.

Monitoring

• Baseline & periodic labs: CBC, liver panel, serum creatinine & BUN, electrolytes (especially K⁺ in older adults).
• Cardiovascular monitoring: BP, signs of fluid overload, ECG if indicated.
• GI surveillance: Monitor for abdominal pain, melena, hematochezia; consider upper GI endoscopy if symptoms persist.
• Drug‑drug interactions: Monitor INR in patients on warfarin; adjust dosing accordingly.

Clinical Pearls

• Pain–Fever ↔ COX‑Inhibition: Because ibuprofen blocks both COX‑1 and COX‑2, it offers dual anti‑inflammatory and antipyretic effects—ideal for acute pain with a febrile component.
• NSAID “Holiday” Strategy: In patients on chronic NSAIDs, a temporary interruption (“holiday”) during acute infections or surgery can reduce GI toxicity without compromising baseline disease control.
• Low‑Dose, Short‑Course is Safe: A 2–3 day course of 400 mg q6 h (≤ 1200 mg/24 h) is generally free of major adverse effects, making it the preferred regimen for acute migraine or dental procedures.
• COX‑1 Suppression → GI Protection: The risk of GI bleeding is dose‑ and duration‑dependent; adding a proton‑pump inhibitor or misoprostol is recommended for patients with ulcer risk factors.
• Use with Acetaminophen as Add‑On: Combining ibuprofen with acetaminophen (≤ 650 mg BID) can provide synergistic pain relief while keeping individual drug doses lower—useful in post‑operative patients.
• Renal‑Dose Adjustment: In chronic kidney disease stage 3–4 (eGFR 15–59 mL/min/1.73 m²), limited evidence supports a 200 mg q8 h dose; avoid chronic use beyond 5 days.
• Avoidance in Gout: Ibuprofen promotes uric acid retention; patients with gout should use alternative analgesics or add allopurinol if NSAIDs are necessary.
• Pregnancy Precautions: Safe in 1st–2nd trimester, but avoid in 3rd trimester due to risk of premature ductus arteriosus closure; in lactation, low concentration in breast milk but generally considered safe.

--
• Keywords: ibuprofen pharmacology, ibuprofen mechanism of action, ibuprofen dosing, ibuprofen side effects, ibuprofen contraindications, ibuprofen clinical pearls.