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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Pharmacological and ocular hypotensive properties of topical carbonic anhydrase inhibitors.

There was a time gap of over 40 years between the demonstrated oral effectiveness of acetazolamide in lowering the intraocular pressure (IOP) of glaucoma patients and the introduction of a topical carbonic anhydrase (CA) inhibitor. This is due to the fact that CA-II, the isoenzyme which most likely plays an important role in the production of aqueous humor in humans, must be essentially inhibited by 100% to elicit a pharmacological response. The lack of success with earlier attempts to obtain a topical agent stems from an inability to attain and maintain a sufficiently high intraocular concentration of drug to achieve the required inhibition of CA. Dorzolamide and brinzolamide are two topical CA inhibitors which are currently available to treat ocular hypertension and/or glaucoma. Dorzolamide is a very potent inhibitor of CA-II and its site of action is local within the eye. Like oral CA inhibitors, topically applied dorzolamide lowers IOP by decreasing the production of aqueous humor. The drug is used in monotherapy as a 2% solution administered three times daily. Its ocular hypotensive effect is comparable to that of timolol at peak but is somewhat less at trough. The IOP lowering effect of timolol is enhanced by the twice daily administration of 2% dorzolamide either concomitantly or in combination. Topically applied dorzolamide is generally well tolerated and had a low drop-out rate in clinical studies. The most frequent ocular adverse experience is burning and/or stinging. Corneal and lenticular problems have generally not been encountered with long-term therapy with dorzolamide. Topically applied dorzolamide penetrates directly to the posterior segment of the eye and its presence is consistent with the initial report that dorzolamide increases retinal blood flow velocity in patients with normal tension glaucoma. The most frequent systemic adverse experience is a transient bitter taste. Biochemical changes indicative of the systemic inhibition of CA have not been observed in monotherapy studies lasting up to 2 years. This is in harmony with the inability of dorzolamide at steady-state to saturate CA in the red blood cell and the failure to detect its presence in plasma. A 1% suspension of brinzolamide is comparable to 2% dorzolamide in lowering IOP, both drugs being administered three times daily. Although brinzolamide has a lower incidence of burning/ stinging, it elicits more blurred vision.[1]


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