Ibuprofen

Mechanism

💊 Common Business Names

Neobrufen, Espidifen, Advil, Motrin, Algiasel.

🔬 Pharmacological Group

Derived from arylpropionic acid. Classic non-selective NSAID.

Mechanism of Action

Ibuprofen acts as a reversible and competitive inhibitor of cyclooxygenases:

• Reversible inhibition of COX-1 and COX-2: Non-selectively blocks the synthesis of inflammatory prostaglandins by reversibly occupying the hydrophobic entry channel of arachidonic acid in the active site of both enzymes. In this way, it reduces tissue inflammation by reducing vasodilation and local edema, and mitigates pain by attenuating the sensitization of peripheral nociceptive endings induced by the prostaglandin PGE₂.
• Central Thermoregulatory Effect: Inhibits the synthesis of PGE₂ induced by pyrogens in the hypothalamus, readjusting the body thermostat and causing peripheral heat dissipation through vasodilation and sweating.

Pharmacokinetics

Key Pharmacokinetics

Indicators and dose

Dosage and Adjustment

• Adults:
  • Analgesic/Antipyretic Effect: 400 mg orally every 6 to 8 hours.
  • Anti-inflammatory Effect (Rheumatology): 600 mg to 800 mg every 8 hours. Maximum recommended daily dose: 2400 mg/day.
• Pediatrics: 5 - 10 mg/kg per dose every 6 or 8 hours orally. Not recommended for infants under 6 months or weighing less than 5-7 kg.
• Adjustment in Kidney Failure:
  • Cl_cr ≥ 30 mL/min: No adjustment is required for sporadic use, but avoid chronic treatments if clearance is less than 60 mL/min.
  • Cl_cr < 30 mL/min: Absolutely contraindicated due to the risk of inducing oligoanuric acute renal failure.
• Adjustment in Liver Failure: Avoid in decompensated cirrhosis due to the increased risk of varicose bleeding and hepatorenal syndrome.

Security

Contraindications

• Absolute: Active peptic ulcer, history of recurrent gastrointestinal bleeding or perforation associated with the use of NSAIDs; severe renal failure (Cl_cr < 30 mL/min); severe liver failure; severe congestive heart failure (NYHA III-IV); active hemorrhagic diathesis. Triad of asthma, rhinitis and nasal polyps triggered by aspirin or other NSAIDs.
• Relative: Uncontrolled arterial hypertension; established ischemic heart disease; peripheral arterial disease; history of ulcerative colitis or Crohn's disease.

Adverse Effects (ADR)

• Frequent / Mild: Dyspepsia, epigastralgia, heartburn, nausea, mild diarrhea, postural dizziness, hydrosaline retention with mild peripheral edema.
• Rare / Serious: Gastrointestinal ulceration and perforation, massive upper gastrointestinal bleeding. Acute renal failure of hemodynamic origin. Aseptic meningitis (mainly in patients with systemic lupus erythematosus). Hemolytic anemia, agranulocytosis.
• Mechanism of Renal Toxicity: Renal prostaglandins (PGE₂ and PGI₂) act as vasodilators of the glomerular afferent arteriole, counteracting the constrictor tone induced by angiotensin II and norepinephrine. By inhibiting renal COX with ibuprofen, this homeostatic balance is broken and vasoconstriction of the afferent arteriole predominates, causing a sudden drop in the glomerular filtration rate, papillary necrosis and chronic interstitial nephropathy in prolonged treatments.

Cardiovascular Risk and Platelet Interaction with Aspirin

Ibuprofen can competitively block the binding site of low-dose aspirin in the platelet COX-1 channel, preventing the irreversible acetylation of serine-529 of the enzyme and nullifying the cardioprotective antiplatelet effect. In patients at high cardiovascular risk taking prophylactic aspirin, low-dose aspirin should be administered at least 2 hours before taking ibuprofen, or space ibuprofen at least 8 hours after the aspirin dose.

Drug Interactions

• Anticoagulants (Warfarin, Acenocoumarol, DOACs): Synergistic increase in the risk of bleeding due to alteration of platelet hemostasis added to the toxicity of the gastric mucosa caused by the NSAID.
• Antihypertensives (ACEI, ARB, Beta-blockers): Ibuprofen reduces the hypotensive effect of these drugs by inhibiting the synthesis of vasodilatory prostaglandins and promoting renal retention of sodium and water.
• Lithium: Decreased renal clearance of lithium due to interference with renal plasma flow, increasing lithium concentrations and the risk of neurological toxicity. It requires close monitoring of lithemia.

Pregnancy and Breastfeeding

Classified in FDA Category C during the first and second quarters. Absolutely contraindicated during the third trimester of pregnancy (Category D). The use of NSAIDs from the 20th week of gestation can cause fetal renal dysfunction leading to severe oligohydramnios, and their administration in the third trimester induces premature closure of the fetal ductus arteriosus, primary neonatal pulmonary hypertension and inhibition of uterine contractions during childbirth. Breastfeeding: Compatible and safe choice; It is excreted in minute quantities that do not pose a risk to the infant.