EpistemisLatanoprost, Travoprost, Bimatoprost
Prostaglandin analogues are the first line of treatment for open-angle glaucoma and ocular hypertension. They effectively reduce intraocular pressure (IOP) by increasing uveoscleral drainage of aqueous humor without interfering with its basal physiological production.
Mechanism
💊 Commercial NamesXalatan, Travatan, Lumigan, Monoprost, Ganfort (coformulación con Timolol).
🔬 Pharmacological GroupAgonistas selectivos del receptor de prostaglandinas F (FP). Análogos de prostanoides.
🧪 Standard PresentationsColirios oftálmicos: Latanoprost 0.005%, Travoprost 0.004%, Bimatoprost 0.01% y 0.03%.
Mechanism of Action
Los análogos de prostaglandinas actúan como agonistas potentes y altamente selectivos del receptor transmembrana de prostanoides de tipo FP:
- Activación de Receptores FP: El acoplamiento del fármaco al receptor FP, acoplado a la subunidad de proteína G Gq/11, activa la fosfolipasa C (PLC). Esto genera inositol trifosfato (IP3) y diacilglicerol (DAG), induciendo la liberación de calcio intracelular en las células del cuerpo ciliar.
- Remodelación de la Matriz Extracelular: Este incremento de calcio estimula la síntesis y secreción de metaloproteinasas de matriz (MMP-1, MMP-2, MMP-3 y MMP-9). Las MMP degradan enzimáticamente de forma controlada el colágeno intersticial (tipos I y III) en los espacios interhaces del músculo ciliar y la esclera.
- Reducción de la Resistencia Uveoescleral: Al incrementarse los espacios intercelulares en el músculo ciliar, se reduce sustancialmente la resistencia al flujo saliente. El humor acuoso drena a través de la vía uveoescleral no convencional (hacia el espacio supracorideo y los vasos esclerales), disminuyendo la PIO entre un 25% y un 35% de los valores basales. El bimatoprost posee además actividad agonista directa sobre receptores de prostamidas, optimizando esta vía.
Pharmacokinetics
Quantitative Ocular and Systemic Pharmacokinetics
| Parameter | Latanoprost | Travoprost | Bimatoprost |
|---|---|---|---|
| Chemical Structure | Isopropyl ester type prodrug to maximize lipophilicity. | Highly fluorinated isopropyl ester. | Synthetic amide type prostamide (not direct prodrug). |
| Corneal Papp and P | P ≈ 4.4 (High epithelial permeability). | P ≈ 4.6 (Optimal permeability). | P ≈ 3.2 (Lower lipophilicity, intermediate hydrophilic penetration). |
| Ocular Activation | Enzymatic hydrolysis forced by corneal esterases towards the active free carboxylic acid. | It functions in the intact amide form or undergoes partial hydrolysis to bimatoprost acid. | |
| Tmax in Aqueous Humor | 1.5 - 2 hours | 1.5 - 2 hours | 1.0 - 1.5 hours |
| Clearance and Half-Life (t1/2) | t1/2 in aqueous: 2 - 3 h. Ultrafast plasma elimination (t1/2 ≈ 17 min). | t1/2 plasma ≈ 45 min. Metabolism by beta-oxidation. | t1/2 plasma ≈ 45 min. Mixed biliary and renal excretion. |
Indicators and dose
Clinical Indications and Dosing Protocols
Treatment of primary open-angle glaucoma, pseudoexfoliative glaucoma, pigmentary glaucoma and isolated ocular hypertension:
- Standard Dosage Guideline: 1 drop in the conjunctival sac of the affected eye once a day, administered strictly at night.
- Rationale for Evening Dosing: Morning administration paradoxically reduces long-term hypotensive efficacy due to phenomena of tachyphylaxis and FP receptor desensitization. The IOP reaches its physiological peak in the early hours of the morning; nocturnal dosing synchronizes the peak of the drug in aqueous humor with this increase.
Phenomenon of Hypertrichosis and Periocular Aesthetic Changes
FP receptors are abundant in the follicular sheath of the eyelashes and orbital adipocytes. The daily application of prostaglandin analogues progressively induces notable histological changes: 1) Stimulation of the passage of hair follicles from the telogen phase to the anagen phase, causing hypertrichosis (growth, thickening and hyperpigmentation of the eyelashes). This has given rise to aesthetic formulations such as bimatoprost 0.03% (Latisse); 2) Activation of stromal melanocytes of the iris and eyelid skin, inducing heterochromia and reversible eyelid hyperpigmentation; 3) Periorbital fat atrophy (prostaglandin-associated orbitopathy) due to inhibition of adipocyte differentiation mediated by PPAR-γ, inducing functional enophthalmos and deepening of the palpebral sulcus.
Security
Contraindications
- Absolute: Documented hypersensitivity to the active ingredient or preservative (commonly benzalkonium chloride); history of active or recurrent anterior uveitis (prostaglandins are inflammatory mediators and can reactivate the breakdown of the blood-aqueous barrier).
- Relative: Active cystoid macular edema or a history of it; aphakia or pseudophakia with rupture of the posterior capsule of the lens (facilitates the diffusion of the drug towards the vitreous and macula, promoting macular edema); Active herpes simplex virus keratinitis (risk of herpetic reactivation).
Adverse Effects (ADR)
- Ocular Sites: Conjunctiva with marked hyperemia (dural vasodilation mediated by endothelial nitric oxide, more common with bimatoprost); eye itching; superficial punctate keratopathy; foreign body sensation; Post-dosing transient blurred vision.
- Systemic: Tension headache, flu-like symptoms, mild allergic skin rash. Very low incidence of cardiorespiratory effects thanks to ultra-rapid systemic plasma clearance by hepatic beta-oxidation.
Drug Interactions
- Other Prostanoids (Topical NSAIDs): The concomitant use of NSAID eye drops (such as ketorolac or nepafenac) can modestly reduce the hypotensive effect of prostaglandin analogues by competition in local metabolic cascades or by altering the response of FP receptors. It is advisable to space the administration of both eye drops by a minimum of 15 minutes.
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.
- System
- Ophthalmology
- Cluster
- Prostaglandin Analogs (FP)