PubMed · 16358192
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K Helling, H Scherer. 2005. [Vertigo attacks -- current therapy].. https://doi.org/10.1055/s-2005-870499
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Idiopathic intracranial hypertension (IIH) is a syndrome of unknown etiology characterized by elevated intracranial pressure (ICP). Although a stenosis of the transverse sinus has been observed in many IIH patients, the role this feature plays in IIH is in dispute. In this paper, a lumped-parameter model is developed for the purpose of analytically investigating the elevated pressures associated with IIH and a collapsible transverse sinus. This analysis yields practical predictions regarding the degree of elevated ICPs and the effectiveness of various treatment methods. Results suggest that IIH may be caused by a sufficiently collapsible transverse sinus, but it is also possible that a stenosed sinus may persist following resolution of significant intracranial hypertension.
Acetazolamide, a potent carbonic anhydrase (CA) inhibitor, is the most commonly used and best-studied agent for the amelioration of acute mountain sickness (AMS). The actual mechanisms by which acetazolamide reduces symptoms of AMS, however, remain unclear. Traditionally, acetazolamide's efficacy has been attributed to inhibition of CA in the kidneys, resulting in bicarbonaturia and metabolic acidosis. The result is offsetting hyperventilation-induced respiratory alkalosis and allowance of chemoreceptors to respond more fully to hypoxic stimuli at altitude. Studies performed on both animals and humans, however, have shown that this explanation is unsatisfactory and that the efficacy of acetazolamide in the context of AMS is likely due to a multitude of effects. This review summarizes the known systemic effects of acetazolamide and incorporates them into a model encompassing several factors that are likely to play a key role in the drug's efficacy. Such factors include not only metabolic acidosis resulting from renal CA inhibition but also improvements in ventilation from tissue respiratory acidosis, improvements in sleep quality from carotid body CA inhibition, and effects of diuresis.
The possibility of preparation of ophthalmic drug delivery systems using compressed anti-solvent technology was evaluated. Eudragit RS 100 and RL 100 were used as drug carriers, acetazolamide was the model drug processed. Compressed anti-solvent experiments were carried out as a semi-continuous or a batch operation from a liquid solution of polymer(s)+solute dissolved in acetone. Both techniques allowed the recovery of composite particles, but the semi-continuous operation yielded smaller and less aggregated populations than the batch operation. The release behaviour of acetazolamide from the prepared microparticles was studied and most products exhibited a slower release than the single drug. Moreover, the release could be controlled to some extent by varying the ratio of the two Eudragit used in the formulation and by selecting one or the other anti-solvent technique. Simple diffusion models satisfactorily described the release profiles. Composites specifically produced by semi-continuous technique have a drug release rate controlled by a diffusion mechanism, whereas for composites produced by the batch operation, the polymer swelling also contributes to the overall transport mechanism.