carbonic anhydrase inhibitor

Methazolamide, an intraocular pressure-lowering agent, reduces intraocular pressure elevations associated with glaucoma and other ocular disorders. Demetrius Ellis, in Smith's Anesthesia for Infants and Children (Eighth Edition), 2011. This enzyme is abundant in the proximal tubule and therefore represents the major site of action of these diuretics. We use cookies to help provide and enhance our service and tailor content and ads. This phenomenon reflects the fact that approximately one third of proximal tubule Na+ reabsorption occurs in exchange for H+ (through the Na+-H+ antiporter) and thus depends on the activity of carbonic anhydrase (see Chapter 8). Acetazolamide, a carbonic anhydrase inhibitor that induces a metabolic acidosis, thereby increasing ventilation, has been studied primarily in patients with central sleep apnea secondary to high altitude exposure or heart failure, who often have unstable ventilatory control (i.e., high loop gain). 9-3). 26-1). Systemic administration of CAIs produces diuresis and metabolic acidosis. In a 5-day randomized trial involving 15 patients with heart failure and CSR-CSA, theophylline reduced the AHI but did not improve left ventricular ejection fraction.135-137 However, although once used widely for therapy of acute heart failure, theophylline is no longer used for this purpose because it increases the risk of cardiac arrhythmias and sudden death.138,139 Consequently, neither of these agents can be recommended for therapy of CSR-CSA. A study of these agents at a simulated altitude of 4000 meters (13,123 ft) and another in trekkers at 3613 meters (11,854 ft) showed that, compared with placebo, both agents increased sleep efficiency and decreased wakefulness and that zolpidem increased slow wave sleep. Overall, bicarbonate reabsorption in the proximal tubule decreases by 80%, leading to the possibility of acidosis. Susheel P. Patil, ... Michael T. Smith, in Principles and Practice of Sleep Medicine (Sixth Edition), 2017. This carbonic anhydrase inhibitor causes sodium bicarbonate diuresis and a reduction in total body bicarbonate stores. If the cerebral mantle is less than 15 mm isosorbide is of no value. No randomized controlled trial has been performed to confirm these findings. Department of Pharmacy, University of Pisa, Pisa, Italy. All CAIs influence ocular perfusion, but the clinical significance of the CAI-induced increase of ocular blood flow remains to be specified. CAIs are widely used in the treatment of glaucoma, both as systemic and topic agents. Case reports suggest that acetazolamide decreases the number of attacks in episodic ataxia 2 in 66% of cases (Jen et al., 2004; Ilg et al., 2014). Carbonic anhydrase (CA) inhibitors block CA on the luminal membrane and inside proximal tubule cells (Fig. Among them, molecules synthesized with the “tail approach,” or hybrid CAI drugs incorporating NO-donating moieties, conjugated with PG agonists and β-blockers have been developed. Sodium reabsorption in the distal tubule provides the electrogenic driving force to facilitate K+ secretion into the tubule lumen. The drug is contraindicated in those with sulfonamide hypersensitivity. In order to increase the ocular penetration, dorzolamide is formulated with an acidic pH, which may explain the more frequent and severe local side effects as compared to brinzolamide. Although this proposed mechanism has generated considerable discussion, there is no direct proof to support the hypothesis. Acetazolamide is a carbonic anhydrase inhibitor that causes CO2 to accumulate within the brain, blocking anion transport and increasing γ-aminobutyric acid (GABA) levels, leading to a modulation of firing rate (Wyllie et al., 2010). Overall, the enhanced urinary excretion of Na+ and K+ leads to increased urine flow. Emanuela Masini, ... Laura Lucarini, in Carbonic Anhydrases, 2019. By inhibiting the reaction catalysed by this enzyme in the renal tubules, acetazolamide increases the excretion of bicarbonate and of cations, chiefly sodium and potassium, and so promotes alkaline diuresis. Carbonic acid is acted upon by carbonic anhydrase, regenerating CO2 which is reabsorbed and forms carbonic acid once again. Finally, mono- and DTCs have been described as new classes of CAIs and selected molecules have shown very attractive as future antiglaucoma drugs. This drug has been examined as a treatment for both central and obstructive sleep apnea. However, larger clinical trials have shown a smaller benefit. Several studies suggest the safety and potential utility of benzodiazepines for the treatment of sleep disturbance of high altitude.88-90 Temazepam shortened sleep latency, decreased arousals, increased sleep efficiency, and increased REM sleep, with subjectively better quality sleep in climbers sleeping above 4000 meters (13,123 ft).89,90 The nonbenzodiazepine sedative agents zolpidem and zaleplon have each been found to be effective in improving sleep architecture and consolidation at high altitude.

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