The histopathology of iris pigment changes induced by miotics.
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We investigated the use of commercially available intraocular preparations of acetylcholine chloride and carbachol for their effects on the physiological function and anatomical appearance of the corneal endothelium. Cornea endothelial cells that were perfused for 15 minutes in the specular microscope with 1% acetylcholine demonstrated no alteration in physiology or ultrastructure. Cornea endothelial cells perfused for 15 minutes with 0.01% carbachol demonstrated alterations in physiology during the first hour; however, physiological function returned to normal during the remaining two hours of perfusion in modified Krebs-Ringer bicarbonate solution. Electron microscopy demonstrated no cellular alterations.
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The time variation of changes in the chlorpromazine-induced pupil diameter decrease was studied following varying bolus and slowly infused intravenous doses administered to rabbits. The observed pharmacological response data were coverted, via, the use of a dose-effect curve, to values theoretically corresponding to relative biophasic drug levels. These values were, in turn, used to construct a linear pharmacokinetic model of the drug bioavailability input equilibrium pharmacological response output dynamics of the system. The use of a time domain, MULTIFIT, computerized method of fitting the data to obtain a pharmacokinetic model was compared to the use of a frequency response, PLTEST, approach. The fidelity of the model in quantitatively relating the time course of systemic drug bioavailability to observed pupil response was verified by the satisfactory agreement obtained by directly comparing experimentally known amounts of drug intravenously infused with corresponding values computed from observed changes in pupil size. The applicability of using pharmacological data for quantitative bioavailability and pharmacokinetic analysis of chlorpromazine is demonstrated. This finding is particularly significant because no suitable chemical or radiological direct assay technique exists for determining levels of chlorpromazine, except for high doses, in body fluids.
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