Pharmacological mechanisms, clinical effectiveness, and side-effects of prostaglandin analogues as anti-glaucoma agents

Pharmacological mechanisms, clinical effectiveness, and side-effects of prostaglandin analogues as anti-glaucoma agents
Shigeo Tsukahara and Kenji Kashiwagi (Japan)

Prostaglandin (PG)-related ophthalmic solutions, which only recently became available for clinical use, are currently the most widely used solutions in the treatment of glaucoma, because they have excellent ocular hypotensive effects with little adverse effects. With respect to the pharmacological mechanism of action of these solutions, the mechanism of intraocular pressure (IOP) reduction for latanoprost, the first drug in this class to become available, is to promote the outflow of aqueous humor through the uveoscleral route, an important aqueous humor outflow tract. Molecular and cellular studies have shown that latanoprost affects the extracellular matrix metabolism in the uveoscleral route. For other PG-related ophthalmic solutions, there is no consensus opinion on their effects on the aqueous humor outflow tract, and how they reduce the IOP remains largely unclear. The docosanoid, isopropyl unoprostone, has excellent ocular hypotensive effects, despite having extremely low affinities to the known PG receptors. Many basic and clinical studies have demonstrated that PG-related ophthalmic solutions themselves cause not only a decrease in the IOP, but also induce endogenous PGs which could lead to secondary effects that may account in part for the IOP reduction. PG-related ophthalmic solutions have essentially no clinically important systemic adverse effects, but often have local adverse effects. The most characteristic is the pigment deposition in the iris or eyelid. Corneal epitheliopathy is also relatively common. In addition, as an adverse effect that affects vision, cystoid macular edema can be seen. Current studies are aimed at elucidating the mechanisms of development of these adverse effects, and thus to establish measures to prevent them. We compare the mechanisms of action of PG-related ophthalmic solutions and review the adverse effects and their mechanisms.
Biomed Rev 2002; 13:17-27.
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Received 16 September 2002 and accepted 30 October 2002.

Correspondence and reprint requests to Dr Kenji Kashiwagi, Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Tamaho, Yamanashi 409-3898, Japan. Tel: 81-552-73-9657, Fax: 81-552-73-6757
E-mail: kenjik@res.yamanashi-med.ac.jp

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