Latanoprost, Travoprost, Bimatoprost

Prostaglandin Analogs (FP)

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 Names

Xalatan, Travatan, Lumigan, Monoprost, Ganfort (co-formulation with timolol).

🔬 Pharmacological Group

Selective prostaglandin F (FP) receptor agonists. Prostanoid analogs.

🧪 Standard Formulations

Ophthalmic eye drops: latanoprost 0.005%, travoprost 0.004%, bimatoprost 0.01% and 0.03%.

Mechanism of Action

Prostaglandin analogs act as potent, highly selective agonists of the FP-type prostanoid transmembrane receptor:

FP Receptor Activation: Docking of the drug to the FP receptor, coupled to the G protein G subunit_q/11, activates phospholipase C (PLC). This generates inositol trisphosphate (IP₃) and diacylglycerol (DAG), inducing the release of intracellular calcium in the ciliary body cells.
Extracellular Matrix Remodeling: This increase in calcium stimulates the synthesis and secretion of matrix metalloproteinases (MMP-1, MMP-2, MMP-3 and MMP-9). MMPs enzymatically degrade interstitial collagen (types I and III) in the interbundle spaces of the ciliary muscle and sclera in a controlled manner.
Reduced Uveoscleral Resistance: By increasing the intercellular spaces in the ciliary muscle, the resistance to outflow is substantially reduced. The aqueous humor drains through the unconventional uveoscleral pathway (towards the suprachoroidal space and scleral vessels), decreasing IOP between 25% and 35% of baseline values. Bimatoprost also has direct agonist activity on prostamide receptors, optimizing this pathway.

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 P_app 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.
T_max in Aqueous Humor	1.5 - 2 hours	1.5 - 2 hours	1.0 - 1.5 hours
Clearance and Half-Life (t_1/2)	t_1/2 in aqueous: 2 - 3 h. Ultrafast plasma elimination (t_1/2 ≈ 17 min).	t_1/2 plasma ≈ 45 min. Metabolism by beta-oxidation.	t_1/2 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 Regimen: 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.

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System
Ophthalmology

Group
Prostaglandin Analogs (FP)

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