Safety of carbonic anhydrase inhibitors

Carbonic anhydrase (CA) inhibitors have an impressive safety record despite the multiple functions that CA isozymes serve because they are not fully inhibited with most dosing. While reducing the targeted CA-dependent process sufficiently for disease control, residual activity and uncatalyzed rates in combination with compensations are adequate to avoid lethal consequences. Some drugs have in vitro selectivity differences against the 13 active isozymes, but none are convincingly selective in vivo or clinically. Efforts to synthesize selective inhibitors should result in safer drugs with fewer side effects.

This review will focus on approved drugs with CA-inhibiting activity, whether used directly for this purpose or others. Side effects are discussed in relation to various organ systems and the disease being treated. Causes of side effects are considered, and strategies for symptom reduction are given.

Common side effects of paresthesias, dyspepsia, lassitude and fatigue in 30 - 40% of patients are generally tolerable or abate, but if not can be partially relieved by bicarbonate supplementation. The most important safety concerns are severe acidosis, respiratory failure and encephalopathy in patients with renal, pulmonary and hepatic disease where caution is critical, as is also the case in persons with sulfa drug allergies.