Carbonic Anhydrase Inhibitors

EVE J. HIGGINBOTHAM and ROBERT C. ALLEN

For more than 50 years, carbonic anhydrase inhibitors (CAIs) have remained consistent and critical components in the armamentarium of the clinician. Despite systemic toxicity observed in some glaucoma patients, this category of medication has emerged as an important option for those patients who remain resistant to alternative intervention. Although beyond the reach of those individuals who have demonstrated a legitimate allergy to sulfa drugs in the past, CAIs have exhibited versatility in use across a broad range of ages and coexistent systemic comorbidities. It is the only category that can be administered as either a topical or a systemic agent, and patients rarely present with complaints of ocular hyper-emia, shortness of breath, fatigue, or loss of libido when the topical agents are administered. This chapter provides an updated evidence-based review of the efficacy and safety of CAIs in an effort to provide the clinician a suitable guide for determining when best to use CAIs given the availability of more effective treatment alternatives.

The history of CAIs dates back to 1954 when oral acetazolamide was first introduced for the treatment of glaucoma. Investigators proposed minor modifications in the original acetazolamide molecule, and thus created methazolamide, which had clear pharmacologic and clinical advantages. Although this molecular innovation led to better gastric absorption, less serum protein binding, and longer duration of action, systemic side effects still prompted uneven compliance. Continued research efforts led to two effective topical agents that are now available to glaucoma patients. Although the availability of topical CAIs has significantly diminished the use of oral agents, a brief discussion of the oral agents is warranted given their continued importance in the medical armamentarium of the clinician.

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