Pharmacokinetics and pharmacodynamics of torasemide and furosemide in patients with diuretic resistant ascites.

BACKGROUND/AIM: To evaluate the pharmacokinetics and pharmacodynamics of furosemide and torasemide in patients with cirrhosis and diuretic resistant ascites. METHODS: Eighteen patients were randomly allocated to receive intravenous torasemide (40 mg) or furosemide (80 mg). The renal response to these drugs was assessed in baseline conditions and in the 24 h following drug administration together with plasma and urinary concentrations of furosemide, torasemide and its metabolites. RESULTS: Torasemide induced significantly greater diuretic and natriuretic effects than furosemide in the first hour after drug administration. No other significant differences between the two drugs were observed with respect to the renal response to these drugs. Torasemide reached a lower maximum plasma concentration than furosemide, but the former drug had a longer apparent terminal half-life and lower renal and non-renal clearances. Comparing these results with those previously reported in healthy subjects, both drugs showed a reduced elimination rate through renal and non-renal routes, and a larger distribution to body fluids. As a consequence, the half-life of both drugs was longer than in healthy subjects. Urinary excretion of pharmacologically active species, however, was quantitatively unchanged after torasemide administration, whereas it was reduced after furosemide. Finally, the natriuretic potency of both drugs was markedly reduced in these patients. CONCLUSIONS: The pharmacokinetics and pharmacodynamics of torasemide and furosemide are markedly altered in patients with diuretic resistant ascites.

[Association of pulmonary and portal hypertension]. / Associazione tra ipertensione arteriosa polmonare ed ipertensione portale.

The association between portal venous hypertension and pulmonary arterial hypertension has received scarce attention in the italian medical literature. Nevertheless the association is relatively frequent, it needs a multidisciplinary approach and it is a stimulus for the search of causes of so-called primary pulmonary hypertension. The purpose of the article is to review the frequency of the association, the main pathogenetic hypothesis formulated to explain the appearance of pulmonary hypertension, the clinical and the laboratory findings, the evolution of the association and to present briefly a personal series of cases. The pulmonary arterial hypertension has been found in approximately 2% of patients with portal hypertension due to either hepatic cirrhosis or extraepatic lesions. Microembolism from the portocavat system or a number of vasoactive substances which enter the pulmonary circulation without being inactivated by the liver have been held responsible for the appearance of pulmonary hypertension in predisposed patients. Clinical and laboratory findings do not differ from those a patients with primary pulmonary hypertension. Also the prognosis is similar. In conclusion on accurate examination of the pulmonary circulation by noninvasive methods, in particular by echocardiography, appears to be mandatory in patients with chronic hepatic lesions. When pulmonary arterial hypertension is detected the study of the biochemical factors which at present are known to determine pulmonary hypertension may be warranted. The study may enhance our knowledge of the pathogenesis of the so-called primary pulmonary hypertension.

Cirrhosis associated with homozygous alpha-1 antitrypsin deficiency in the adult: a case report.

A 34 year old woman admitted to the department of Gastroenterology of Florence hospital was diagnosed as suffering from liver cirrhosis with an alpha-1 antitrypsin deficiency (PiZZ phenotype). Liver biopsy showed the presence of intra-hepatocyte PAS-positive inclusions and the presence of alpha-1 antitrypsin was confirmed using the immunoperoxidase technique. No other organ appeared to be affected and respiratory function tests were within normal limits. The quantitative assay of alpha-1 antitrypsin was higher than values reported in the literature for PiZZ homozygotes. The authors report the case and discuss some aspects of this disease.