PubMed · 11711845
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R Hitchings. 2001. Traumatic glaucoma.. https://doi.org/10.1097/00061198-200110000-00014
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The accuracy of the acetazolamide (ACZ) challenge test using semiquantitative SPECT in detecting Stage II hemodynamic failure, i.e. cerebral misery perfusion, in patients so diagnosed with PET has yet to be determined. This study was carried out in 53 patients who had a unilateral occlusion or severe stenosis of their cerebral artery. Asymmetry index (AI) was used to determine relative CBF distribution on each SPECT image. DeltaAI (regional vasodilatory capacity) values were compared with the values of several PET parameters. We also repeated SPECT and PET studies in 15 patients after a mean interval of 2.6 years from entry. The correlation between changes in DeltaAI and PET data were examined. The DeltaAI value closely correlated with the ipsilateral OEF value (r=-0.64, p<0.001). Sensitivity-specificity curve analysis revealed that the optimal cut-off value for detecting Stage II hemodynamic failure was -13.5% of DeltaAI, at which point the diagnostic accuracy was 82%. In follow-up studies, changes in DeltaAI correlated significantly with changes in OEF values (r=-0.68, p<0.01). Semiquantitative SPECT examination with ACZ challenge detects Stage II hemodynamic failure with a diagnostic accuracy of 82%. An improvement in reduced vasodilatory capacity as determined by SPECT coincides with a reduction in OEF values.
Through this review it is contemplated that acetazolamide (ACZ), an age-old treatment for glaucoma with a myriad of side effects and inadequate topical effectiveness, may be formulated into a topically effective agent by utilizing various newer formulation approaches of ocular drug delivery. Even though it has a poor solubility and penetration power, various studies mentioned in the review indicate that it is possible to successfully formulate topically effective ACZ by using: (i) high concentration of the drug, (ii) surfactant gel preparations of ACZ, (iii) ACZ loaded into liposomes, (iv) cyclodextrins to increase the solubility and hence bioavailability of ACZ, and (v) viscolyzers and other polymers either alone or in combination with cyclodextrins. With the advent of newer topical carbonic anhydrase inhibitors (CAIs) like dorzolamide and brinzolamide, a localized effect with fewer side effects is expected. But whenever absorbed systemically, a similar range of adverse effects (attributable to sulphonamides) may occur upon use. Furthermore, oral ACZ is reported to be more physiologically effective than 2% dorzolamide hydrochloride administered topically, even though in isolated tissues dorzolamide appears to be the most active as it shows the lowest IC(50) values for CA-II and CA-IV [M.F. Surgue, J. Ocular Pharmacol. Ther. 12 (1996) 363-376]. Hence, there exists considerable scope for the development of more/equally effective and inexpensive topically effective formulations of ACZ. The use of various formulation technologies discussed in this review can provide a fresh impetus to research in this area.
Acetazolamide (Acz) is used at altitude to prevent acute mountain sickness, but its effect on exercise capacity under hypoxic conditions is uncertain. Nine healthy men completed this double-blind, randomized, crossover study. All subjects underwent incremental exercise to exhaustion with an inspired O(2) fraction of 0.13, hypoxic ventilatory responses, and hypercapnic ventilatory responses after Acz (500 mg twice daily for 5 doses) and placebo. Maximum power of 203 +/- 38 (SD) W on Acz was less than the placebo value of 225 +/- 40 W (P < 0.01). At peak exercise, arterialized capillary pH was lower and Po(2) higher on Acz (P < 0.01). Ventilation was 118.6 +/- 20.0 l/min at the maximal power on Acz and 102.4 +/- 20.7 l/min at the same power on placebo (P < 0.02), and Borg score for leg fatigue was increased on Acz (P < 0.02), with no difference in Borg score for dyspnea. Hypercapnic ventilatory response on Acz was greater (P < 0.02), whereas hypoxic ventilatory response was unchanged. During hypoxic exercise, Acz reduced exercise capacity associated with increased perception of leg fatigue. Despite increased ventilation, dyspnea was not increased.