Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacodynamics of torasemide (1-isopropyl-3- ([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea), a new potent loop diuretic, were compared to those of furosemide in a double-blind controlled study in 18 patients with oedema of various origin. Torasemide behaved like furosemide in exerting a potent diuretic effect which culminated during the first 4 h after its administration. Nevertheless, torasemide was about 8 times more potent, exerted a longer lasting diuretic effect and was more potassium sparing than furosemide. Torasemide did not accumulate during repeated administration (5 days). It was well tolerated and efficient in the treatment of oedema due to congestive heart failure and hepatic cirrhosis. The long duration of action and the potassium sparing effect of torasemide compared to furosemide are promising features of this new potent loop diuretic.
 ...
PMID:Comparative pharmacodynamics of torasemide and furosemide in patients with oedema. 328 31

Triamterene is a potassium-sparing diuretic used in patients with cirrhosis for the treatment of ascites. It is extensively metabolized by the liver and is subject to an important first-pass effect after oral dosing. We examined the disposition and diuretic effect of triamterene after repeated oral administration (200 mg daily for 10 days) in 7 healthy controls and 6 patients with cirrhosis and ascites. In the controls the average plasma concentration of triamterene during a dosage interval was 45 +/- 8 ng/ml and that of hydroxy-triamterene sulfate, an active metabolite of triamterene, was 967 +/- 177 ng/ml. In the cirrhotics, the mean concentration of triamterene was 586 +/- 126 ng/ml (a 13-fold increase as compared with the controls) and that of hydroxy-triamterene sulfate was 747 +/- 502 ng/ml. Sodium excretion was correlated with hydroxy-triamterene sulfate levels in the controls (r = 0.81), but in the cirrhotics the diuretic response was correlated with basal sodium excretion (r = 0.86) and was not related to either triamterene or hydroxy-triamterene plasma concentrations. Our results indicate that chronic treatment with triamterene in patients with cirrhosis and ascites results in markedly elevated plasma levels, but these changes do not have a major influence on the magnitude of the diuretic response.
 ...
PMID:Kinetics and dynamics of triamterene at steady-state in patients with cirrhosis. 336 82

It has been postulated that diminished renal prostaglandin E2 (PGE2) production, whether basal or in response to stimulation by diuretic treatment, determines the intensity of sodium retention in cirrhosis. Urinary PGE2 excretion (as an index of renal PGE2 production) as well as urine volume, urinary sodium and potassium excretion, and creatinine clearance were examined in 19 patients with cirrhosis and either no ascites, diuretic-responsive ascites, or diuretic-resistant ascites. Measurements were made both before (all patients) and after (ascitic patients) stimulation of renal PGE2 synthesis by 80 mg of furosemide intravenously. Urinary PGE2 excretion was similar in the three groups both before and after furosemide. Baseline urine volume and creatinine clearance were similar in all groups but were significantly less after furosemide in patients with diuretic-resistant ascites as compared to the other two groups. The natriuretic response to intravenous furosemide was significantly less in patients with diuretic-resistant ascites. Insertion of the peritoneovenous shunt to aid in the management of diuretic-resistant ascites resulted in a marked, immediate increase in urine volume and urinary PGE2 excretion in the four patients who were serially evaluated, but natriuresis occurred in only two. Overall, urinary PGE2 excretion correlated with urine volume but not with sodium excretion or creatinine clearance. Diminished renal PGE2 production, as reflected by urinary PGE2 excretion, does not appear to be a determinant of the severity of renal sodium retention in cirrhosis.
 ...
PMID:Urinary prostaglandin E2 excretion, sodium retention, and diuretic responsiveness in patients with chronic liver disease. 347 Oct 82

Muzolimine is a loop diuretic with both the dose-dependent increasing effectiveness of loop diuretics and the long-lasting effect of thiazides. This is a potential advantage in the treatment of ascites in advanced cirrhosis since these patients have a low tolerance to sudden reductions of blood volume. Equivalent single, oral doses of furosemide (40 mg) and muzolimine (30 mg) were given to 10 cirrhotic patients with ascites and reduced renal perfusion (glomerular filtration rate = 30 to 75 ml per min). The study was preceded by 4 days of equilibration (dietary sodium 40 mmoles per day), and the drugs were alternated via a single-blind, cross-over protocol after a wash-out period of 3 days. Renal function was monitored under basal conditions and after diuretic administration through 4-hr clearance periods for 24 hr. The renin-aldosterone axis was evaluated before diuretic administration and after 8 and 24 hr. Muzolimine led to a 12-hr cumulative diuresis [AUC0-12 = 2.52 +/- 0.42 (S.E.) ml per min] and natriuresis (5.14 +/- 1.05 mmoles per hr), which were comparable to those of furosemide (2.85 +/- 0.29 ml per min and 6.75 +/- 1.63 mmoles per hr). Its effect, however, was distributed over a longer period (8 hr) than furosemide (4 hr). Muzolimine activity mainly differed from furosemide because of: significantly lower 12-hr potassium excretion (AUC0-12 = 0.28 +/- 0.82 vs. 2.69 +/- 0.46 mmoles per hr; p less than 0.005); greater sodium/chloride excretion ratio (0.45 +/- 0.08 vs. 0.26 +/- 0.06; p less than 0.025), and absence of rebound phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of a new loop diuretic (muzolimine) in cirrhosis with ascites: comparison with furosemide. 351 16

We studied the mechanisms leading to derangement of aldosterone secretion in cirrhosis. The circadian patterns of plasma renin activity (PRA), aldosterone, cortisol, sodium, and potassium were studied in 16 nonazotemic cirrhotics (group 1 without ascites, 7 cases; group 2 with ascites, 9 cases) and 7 healthy controls. Group 1 did not differ from controls in aldosterone, sodium, and potassium mean daily levels (mesors), but had reduced PRA mesor (p less than 0.05). Moreover, minor derangements in circadian patterns of PRA, aldosterone, and potassium were also found. Group 2 not only showed an increased mesor of PRA (p less than 0.05), aldosterone (p less than 0.001), and reduced sodium (p less than 0.005), but also achronia in daily fluctuations of PRA, aldosterone, and potassium. In all groups the mesors of PRA and aldosterone were correlated (r greater than or equal to 0.82; p less than 0.01 or less), but the regression line slopes of patients were steeper than those of controls (group 1, p less than 0.05; group 2, p less than 0.01). Moreover, although in controls and some group 1 patients aldosterone paralleled cortisol rhythmicity, most group 2 patients had aldosterone daily patterns correlated with those of PRA. Finally, no relationships between plasma potassium and aldosterone concentrations were found in patients, whereas they were strictly related in controls. These results suggest that the renin-angiotensin system is the prevalent determinant of aldosterone secretion in cirrhosis.
 ...
PMID:Chronobiological study of factors affecting plasma aldosterone concentration in cirrhosis. 352 16

In order to assess the prognostic value of clinical and laboratory variables in liver cirrhosis, 36 of these variables were statistically analyzed in 151 patients followed up for 8 years. The 'survival time' was taken as the reference variable. In a first step we analyzed by log-rank test and by Cox's proportional hazard regression model the data of 98 patients (study group), obtaining 7 prognostically significant variables (age, leukocytes, calcium, potassium, globulins, cholesterol and previous diagnosis). From the regression coefficients of these variables, a risk score was obtained for each patient. To validate the prognostic value of this score, we computed it, using the same coefficients obtained in the study group, in 53 subsequently examined patients (control group) showing that the prognostic score allows the classification of these patients in 3 risk classes with different observed survival times.
 ...
PMID:Prognostic score in liver cirrhosis developed using the Cox's proportional hazard regression model. 358 4

This chapter reviews the disturbances of the serum sodium and potassium concentrations, acid-base imbalances, and acute renal dysfunction that are seen frequently in alcoholic patients. The hyponatremia common in decompensated cirrhotics is caused by an impairment of renal free water clearance and concomitant water ingestion. Excessive proximal renal tubular sodium reabsorption and nonosmotic vasopressin release underlie the defect in renal water excretion in cirrhosis. Restriction of water intake is the principal therapeutic measure for hyponatremia. Hypokalemia is common in alcoholics but when observed does not always represent true potassium depletion. Although most cirrhotics have a diminished total body potassium content, intracellular potassium concentration is usually normal. In some patients gastrointestinal and renal potassium losses and nutritional potassium deficiency may cause true potassium depletion. Respiratory and metabolic alkalosis are the acid-base disturbances seen most frequently in alcoholics. Acidosis is relatively uncommon and is usually due to renal insufficiency, lactic acid or keto-acid accumulation. Toxin ingestion (methanol, ethylene glycol, or isopropanol) may also cause severe acidosis. Rhabdomyolysis, common in severe alcoholism, may produce various electrolyte disturbances and acute renal failure. The prognosis for recovery is good although temporary dialysis may be necessary.
 ...
PMID:Disorders of the serum electrolytes, acid-base balance, and renal function in alcoholism. 370 21

One thousand seventy-two 24-hr diet duplicate samples were collected from inhabitants of 49 regions in various parts of Japan during the winters of 1977-1981. An additional 238 samples were collected in an adjacent summer. The samples were analyzed for sodium (Na) and potassium (K) by flame atomic absorption spectrometry and for chloride (Cl) with a chloride counter. The winter-summer differences in Na, Cl, and Na/K were essentially negligible. When the regional means of Na, K, Cl, and Na/K were compared with the 1969-1978 standardized mortality ratios of each region, positive and significant correlations were observed between winter Na and the standardized mortality ratios for cerebrovascular disease (P less than 0.01), cerebral infarction (P less than 0.01), and subarachnoid hemorrhage (P less than 0.05) in both males and females. The correlation (P less than 0.01) with the cerebrovascular disease standardized mortality ratio was further confirmed by the values for 1978-1982. In the case of the Na/K ratio, the correlation with the standardized mortality ratio for each of the three diseases was significant for men (P less than 0.01 or 0.05, depending on the disease) but not for women (P greater than 0.05). Both Na and Na/K showed significant associations with the ischemic heart disease standardized mortality ratio in men (P less than 0.05) but not in women (P greater than 0.05). In contrast, no positive association was found between Na, K, Cl, or Na/K and standardized mortality ratios for diabetes mellitus, liver cirrhosis, tuberculosis, or liver cancer (P greater than 0.05). Current blood pressure did not appear to correlate with any of the Na, K, Cl, or Na/K measurements. The validity of the present observation is discussed.
 ...
PMID:Correlation of cerebrovascular disease standardized mortality ratios with dietary sodium and the sodium/potassium ratio among the Japanese population. 371 59

We have suggested that cirrhotic patients with high uric acid clearances had an increased effective vascular volume. This hypothesis was tested by studying the relationship between the excretion of uric acid, sodium, potassium, and aldosterone in cirrhosis. In 29 consecutive cirrhotic patients, of whom 17 had ascites, and in a control group, the logarithm of urinary sodium and aldosterone excretion highly correlated in control (r = -0.79, p less than 0.001) and cirrhotic patients without (r = -0.72, p less than 0.01) and with (r = -0.80, p less than 0.001) ascites. The regression line significantly shifted to the left in the cirrhotic patients (p less than 0.001). The urinary ratio K/K + Na also correlated with urinary aldosterone in controls (r = +0.66, p less than 0.001) and in cirrhotic patients (r = +0.77, p less than 0.001); this regression line shifted to the right in cirrhosis patients (p less than 0.02). The fractional uric acid excretion significantly correlated with urinary aldosterone only in cirrhotic patients (r = -0.76, p less than 0.001). These data confirmed the existence of hypoaldosteronism in many cirrhotic patients and are consistent with tubular hypersensitivity to aldosterone and emphasize the major role of the effective vascular volume in the control of urid acid clearance in cirrhosis.
 ...
PMID:Relationship between aldosterone and sodium, potassium, and uric acid clearance in cirrhosis with and without ascites. 378 85

Plasma renin activity (PRA), plasma renin concentration (PRC), plasma angiotensin II concentration (AII), plasma and urinary aldosterone (PA, UA) and urinary sodium excretion (UNaV) were measured in 51 normal controls, 16 patients with decompensated cirrhosis (i.e. ascites and/or oedema present) in sodium equilibrium (Group 1) and 13 patients with decompensated cirrhosis in a phase of active sodium retention (Group 2). In Group 1 the mean supine and erect values, although lower, were not significantly different from controls. In Group 2 the mean values were significantly elevated, but several individual values were within the normal range; there were significant direct relationships between plasma renin activity and plasma renin concentration (r = 0.85, p less than 0.001 erect), plasma renin concentration and plasma angiotensin II concentration (r = 0.86, p less than 0.001 erect), and plasma angiotensin II concentration and plasma aldosterone (r = 0.70, p less than 0.01 erect). In Group 2 there was an inverse correlation between urinary sodium excretion and both urinary aldosterone (r = -0.50) and erect plasma aldosterone (r = -0.36) but, perhaps because of the narrow range of sodium excretion rates, significance was not reached. The normal values in Group 1 indicate that hyperaldosteronism is not essential for the maintenance of established ascites, but do not exclude a role for aldosterone in the control of sodium excretion if it is accepted that renal tubular sensitivity to aldosterone is increased in these patients. In Group 2, the raised mean plasma and urinary aldosterone levels and the trend towards an inverse relationship with urinary sodium excretion suggests a role for aldosterone in the active retention of sodium. It appears that stimulation of the renin-angiotensin system is the major factor in the elevation of plasma aldosterone; there was no relationship between plasma aldosterone and either plasma sodium or potassium levels. The mechanism of renin hypersecretion is unclear but this may represent part of a sympathetically mediated response in order to maintain blood pressure. The close relationship between plasma renin activity and plasma renin concentration indicates that the former is a valid measure of circulating renin levels in cirrhosis, despite low renin-substrate levels.
 ...
PMID:The renin-angiotensin-aldosterone system in decompensated cirrhosis: its activity in relation to sodium balance. 390 Oct 77


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>