Topical carbonic anhydrase inhibitors (CAIs), which do not incite ocular inflammation, are common first-line treatments for feline primary and secondary glaucoma. Cats are uniquely sensitive to the adverse effects (eg, metabolic acidosis, hyporexia, vomiting, lethargy) of systemic CAIs; therefore, use of topical CAIs (eg, dorzolamide, brinzolamide) has largely replaced oral formulations.1,2
CAIs reduce intraocular pressure by inhibiting carbonic anhydrase enzyme activity in the ciliary body epithelium of the uvea, reducing aqueous humor production. Carbonic anhydrase isoenzymes are also present in extraocular sites, including RBCs, kidneys, and the respiratory tract.3 Systemic absorption of topical ocular medications occurs. Given the important metabolic functions of carbonic anhydrase and case reports of clinical signs associated with hypokalemia and metabolic acidosis in cats receiving topical CAIs,4,5 the authors of this study reviewed records of feline glaucoma patients that received topical CAIs and then prospectively evaluated the effect of topical dorzolamide in healthy cats.
In the retrospective portion of the study, 8 out of 27 (29.6%) cats developed hypokalemia by the first reported screening (median, 67.5 days) after medical treatment was initiated. The degree of hypokalemia varied widely. Information on the development of clinical signs in cats with hypokalemia was limited, but inappetence, anorexia, and vomiting were reported in 4 cats, and alterations in mentation or energy level were reported in 3 cats. Clinical signs occurred in cats with or without concurrent systemic disease and with or without intraocular pressure control; female cats were more commonly affected. The severity of observed clinical signs did not coincide with the degree of hypokalemia identified on blood work.
Prospectively, 10 healthy cats were treated with dorzolamide in both eyes 3 times daily for 6 weeks. Serum potassium values were significantly lower than baseline at all evaluated time points, and serum chloride was significantly increased at weeks 2 and 4; however, all values remained within reference ranges. Adverse effects (including lip licking, hypersalivation, decreased appetite, and local irritation) were reported in half of the study cats. All reported clinical signs were transient and lasted <2 weeks.
In this study, topical dorzolamide applied to the eyes of healthy cats resulted in a measurable effect on serum electrolytes. Electrolyte changes may be the result of impaired secretion of hydrogen from the kidneys, resulting in distal renal tubular acidosis.4 Further studies evaluating the impact of topical CAIs on systemic health of glaucomatous cats and those with concurrent systemic disease are needed.