What is the mechanism of action of dorzolamide (Trusopt), a carbonic anhydrase inhibitor?

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From the Guidelines

Dorzolamide works by inhibiting the enzyme carbonic anhydrase in the eye, reducing the production of aqueous humor and subsequently lowering intraocular pressure (IOP). This mechanism is crucial for treating conditions like open-angle glaucoma and ocular hypertension, where elevated eye pressure can damage the optic nerve and potentially lead to vision loss 1. The medication is typically administered as eye drops, often as a 2% solution, applied to the affected eye(s) three times daily.

Key Points about Dorzolamide

  • It begins working within about 2 hours after administration, with maximum effect occurring after 3 hours 1.
  • The pressure-lowering effect can last for 8-12 hours.
  • Some patients may experience mild stinging or burning upon application.
  • The medication should not be used by individuals with certain kidney or liver conditions or those allergic to sulfonamides, as dorzolamide is a sulfonamide derivative.

Clinical Considerations

  • The decision to use dorzolamide should be individualized, taking into account the amount of damage, the level of IOP, age, and other patient characteristics 1.
  • While dorzolamide is effective in lowering IOP, other medications like latanoprost may be more effective in certain cases 1.
  • The clinical and cost-effectiveness of contemporary medication compared with primary surgery is not well established, and further research is recommended 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Mechanism of Action Carbonic anhydrase (CA) is an enzyme found in many tissues of the body including the eye. It catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid In humans, carbonic anhydrase exists as a number of isoenzymes, the most active being carbonic anhydrase II (CA-II), found primarily in red blood cells (RBCs), but also in other tissues Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. The result is a reduction in intraocular pressure (IOP). Dorzolamide HCl Ophthalmic Solution contains dorzolamide hydrochloride, an inhibitor of human carbonic anhydrase II

Dorzolamide works by inhibiting carbonic anhydrase II (CA-II) in the ciliary processes of the eye, which decreases aqueous humor secretion and subsequently reduces intraocular pressure (IOP). The main mechanism involves slowing the formation of bicarbonate ions with a subsequent reduction in sodium and fluid transport. 2

From the Research

Mechanism of Action

  • Dorzolamide is a topical carbonic anhydrase (CA) inhibitor that lowers intraocular pressure (IOP) by reducing aqueous humour formation 3, 4, 5, 6, 7
  • It penetrates the sclera and cornea to reach the ciliary process and inhibits carbonic anhydrase II, leading to a decrease in the formation of HCO3 and aqueous humor 4, 6
  • The inhibition of carbonic anhydrase in the ciliary body reduces the production of aqueous humor, resulting in a decrease in IOP 5, 6

Pharmacokinetics

  • After topical administration, dorzolamide is absorbed into the eye and binds to carbonic anhydrase in the ciliary process 4, 7
  • It is slowly metabolized to N-de-ethyldorzolamide, which is also stored in red blood cells 7
  • The elimination of dorzolamide and its metabolite occurs via the renal route, with a half-life of more than 4 months 7
  • The plasma concentration of dorzolamide is very low, approximately 1/700 of the concentration in red blood cells, which reduces the risk of systemic adverse effects 4

Efficacy and Safety

  • Dorzolamide has been shown to be effective in lowering IOP in patients with open-angle glaucoma or ocular hypertension 3, 5, 6
  • It has a good safety profile, with the most common adverse effects being bitter taste and transient local burning or stinging 3
  • Dorzolamide does not appear to produce the acid-base or electrolyte disturbances and severe systemic adverse events associated with oral CA inhibitors 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Ocular absorption, blood levels, and excretion of dorzolamide, a topically active carbonic anhydrase inhibitor.

Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics, 1997

Research

The preclinical pharmacology of dorzolamide hydrochloride, a topical carbonic anhydrase inhibitor.

Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics, 1996

Research

Clinical pharmacokinetics of dorzolamide.

Clinical pharmacokinetics, 2002

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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