Nepafenac, Ketorolac, Bromfenac

Prostanoid Synthesis Inhibitors

Topical ophthalmic NSAIDs reversibly inhibit local cyclooxygenase enzymes, stopping the synthesis of prostaglandins involved in postoperative pain, intraoperative miosis and macular edema.

Mechanism

💊 Commercial Names

Nevanac, Acular, Acuvail, Yellox, Bromfenaco Kern, Voltaren Ofta.

🔬 Pharmacological Group

Inhibidores reversibles de la ciclooxigenasa-1 y ciclooxigenasa-2 (AINEs). Nepafenaco (prodroga de amida).

🧪 Standard Presentations

Nepafenaco 0.1% y 0.3% (suspensión), Ketorolaco trometamina 0.5%, Bromfenaco sódico 0.09%.

Mechanism of Action

Los AINEs tópicos actúan bloqueando de forma selectiva o no selectiva el sitio activo de las ciclooxigenasas:

Inhibición Reversible de COX-1 y COX-2: Bloquean de forma competitiva el acceso del ácido araquidónico al canal de la COX, impidiendo la síntesis de prostanoides inflamatorios como la PGE₂, PGI₂ y tromboxanos.
Prevención de la Miosis Transoperatoria: El traumatismo físico sobre el iris durante la cirugía de catarata provoca una síntesis masiva local de PGE₂ que induce una constricción pupilar (miosis) involuntaria. Los AINEs tópicos aplicados antes de la cirugía bloquean esta respuesta, manteniendo la midriasis estable y facilitando el procedimiento quirúrgico.
Prevención del Edema Macular Cistoideo (Sindrome de Irvine-Gass): La inflamación del segmento anterior tras la cirugía libera citocinas inflamatorias que difunden a través del vítreo hacia el polo posterior. Los AINEs, especialmente las prodrogas como el nepafenaco (que penetra rápidamente la córnea y es hidrolizado por hidrolasas del iris, cuerpo ciliar y retina a amfenaco, un inhibidor de COX extremadamente potente), suprimen esta síntesis inflamatoria en el polo posterior, protegiendo las uniones estrechas del endotelio capilar macular retinal.
Alivio del Dolor Ocular y Fotofobia: Suprime la sensibilización de las terminaciones libres del nervio oftálmico (rama trigémina) inducida por prostaglandinas locales.

Pharmacokinetics

Quantitative Ocular and Systemic Pharmacokinetics

Parameter	Nepafenac 0.3%	Ketorolac Tromethamine 0.5%	Bromfenac 0.09%
Lipophilicity and Structure	Highly lipophilic neutral amide prodrugs. P ≈ 2.1.	Polar water-soluble tromethamine salt; intermediate penetration. P ≈ 0.5.	High affinity lipophilic bromophonil structure. P ≈ 1.8.
Transcorneal Passage	Rapid and complete epithelial permeation. Conversion to active free amfenac.	Preferential stromal penetration; lower intracellular penetration rate.	Complete penetration; excellent accumulation in the anterior and posterior pole.
T_max in Aqueous and Iris	T_max ≈ 1.0 hour for active amfenac.	T_max ≈ 45 - 60 minutes in anterior chamber.	T_max ≈ 1.5 - 2 hours average.
Half-life and Clearance	Prolonged elimination of the amfenac metabolite by the aqueous humor. t_1/2 ≈ 4 h.	Rapid clarification of the basal aqueous. t_1/2 ≈ 1.5 - 2.0 h.	High ocular biological stability. t_1/2 ≈ 5 hours.

Security

Risk of Corneal Keratolysis (Corneal Melting) due to Topical NSAIDs

The uncontrolled application of topical NSAIDs, especially in the presence of previous risk factors (neuropathic keratopathy, severe dry eye, herpetic keratitis or systemic rheumatoid arthritis), can induce a catastrophic ocular dermal complication: corneal keratolysis or corneal melting (perforation and thinning of the cornea). NSAIDs inhibit the synthesis of corneal trophic prostaglandins and decrease dural sensitivity, which drastically delays keratocyte mitosis, simultaneously favoring the local overexpression of matrix metalloproteinases collagenases (MMP-8 and MMP-1) of neutrophils. This causes accelerated self-digestion of the collagen stroma, with the risk of perforation and loss of the eyeball.

Contraindications

Absolute: Documented hypersensitivity to the salt components of NSAIDs, acetylsalicylic acid or other systemic NSAIDs; personal history of aspirin-induced bronchospasm or asthma triad and nasal polyps.
Relative: Active extensive corneal epithelial defects; dry eye of moderate to severe course; patients wearing therapeutic silicone hydrogel contact lenses (they may retain preservatives and exacerbate epitheliotoxicity).

Adverse Effects (ADR)

Ocular Sites: Sensation of stinging and immediate dural burning (associated with osmolarity); diffuse superficial punctate keratitis; delay in re-epithelialization of ulcers; conjunctival hyperemia; pathological corneal thinning and descemetocele in extreme cases of melting.
Systemic: Mild headaches, dryness of the nasal mucosa. Very low systemic absorption and no gastrointestinal or platelet effect at usual doses.

Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.

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System: Ophthalmology
Cluster: Prostanoid Synthesis Inhibitors

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