Farmakologiia i toksikologiia最新文献

On the 3rd day after the last administration of phenobarbital (50 mg/kg orally, 4 days), benzonal (35 mg/kg orally, 4 days), zixorine (200 mg/kg orally, 4 days) and 3-methylcholanthrene (20 mg/kg subcutaneously, 2 days) the rats exhibited a decrease of iodamide secretion in the kidneys. The administration of zixorine to the dog (200 mg orally, 6 days) led to a significant decrease of iodamide transport in the first two weeks after discontinuation of the drug administration.

Gentamicin distribution in some tissues of the abdominal cavity one hour after the intralymphovasal and intranodular administration to 32 rabbits was studied. The experiments were performed under conditions of the blocking and external drainage of the thoracic lymphatic duct. It was found that the optimal bacteriostatic concentrations were reached at both intralymphovasal and intranodular administration.

The effectiveness of the anti-ischemic effect of verapamil was studied on models of coronary spasm (the test with dihydroergotamine) and microthrombosis of the coronary arteries (the test with ADP). The results of the performed studies showed that verapamil exerts the anti-ischemic effect at administration of dihydroergotamine and ADP. The most pronounced effect of verapamil was demonstrated on the model of myocardial ischemia due to coronary spasm.

In experiments on dogs and cats with disorders of the atrial and ventricular rhythms of various genesis the combination of N-propylaymalinebromide and trimecaine (the antiarrhythmic drugs of classes IA and IB) was found to potentiate the antiarrhythmic action. This effect was studied in electrophysiological experiments by using the microelectrode technique or on the dog and rat myocardium tissue. The combination of the antiarrhythmic drugs was shown to exert a more significant effect on some electrophysiological parameters determining the arrhythmic readiness of the myocardium.

The anticonvulsant activity of digoxin was studied on rats of different ages and mice. Cramps were simulated by using electroshock or a subcutaneous administration of bemegrid or corasol. The effect of digoxin (in the doses amounting to 1/10 or 1/2 of LD50) on the time of the onset of cramps, the duration of tonic and clonic phases as well as the number of the deceased animals was evaluated. The detected anticonvulsant effect of digoxin is explained by its influence on the activity of the membrane Na+, K+, ATP-ase and K+ conductivity.

The review presents the literature data on the mechanism of the protective action of diuretics in ischemic damage of the kidneys. The role of changes in the renal blood flow, glomerular filtration, oxidative metabolism of the kidney epithelium in the increase of resistance of the kidneys to circulatory hypoxia is analyzed. Great importance of sodium excretion and the corresponding change in hydrodynamics of nephrons in prevention of the damage of the specialized structures of the kidney cells, nephrons, in normalization of the kidney function in the postischemic period is emphasized.

The effect of the long-term use of prolonged medicinal forms containing nitroglycerin (NG)--trinitrolong and nitroderm-TTS on the pharmacokinetics of sublingual NG was studied. A significant change of the pharmacokinetic parameters at the sublingual use of NG both after the long-term treatment with trinitrolong and after therapy with nitroderm was observed: in both cases the time of half-release of NG from plasma and the average time of retention increased, the area under the curve of concentration-time significantly increased and the drug clearance decreased (for trinitrolong the difference in the clearance parameter is significant). While combining the data on both drugs the difference in the last two parameters also becomes significant. The observed slowing of elimination is probably the cause of the development of tolerance to NH at the long-term treatment, since according to the modern notions the degree of the effect is determined by the rate of NG metabolism.

The experiments on different species of animals (mice, cats) showed the lack of parallelism between the antihypoxic and anti-ischemic effects of pharmacological agents. Of four studied antihypoxic agents (lithium oxybutyrate, piracetam, glyo-6, a derivative of pyrimidine S-207) only GABA derivatives showed an increase of the lactate/pyruvate ratio in the blood of the venous sinus under occlusion of the coronary artery and consequently possessed the anti-ischemic properties. Such difference in the effects of the antihypoxic agents on the myocardium was determined to a certain degree by their different influences on the collateral coronary blood circulation.