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PubMed1992

The effects of two different local anaesthetic solutions administered for oral surgery on plasma potassium levels in patients taking kaliuretic diuretics.

The effects of two different dental local anaesthetic solutions, administered for oral surgery, on the plasma potassium levels of patients taking non-potassium sparing diuretics has been investigated. There was a significant reduction in plasma potassium concentration in eight subjects who received 4.4 ml of 2% lignocaine with 1:80,000 adrenaline; the mean reduction from baseline being 0.30 mmol.l-1 10 min following intraoral extravascular injection of the local anaesthetic. There was no significant difference from the pre-treatment plasma potassium concentration 10 min following similar injections of 3% prilocaine with 0.03 IU.ml-1 felypressin in 8 patients; the mean change in these subjects being -0.05 mmol.l-1. It is suggested that the use of adrenaline-free local anaesthetics would seem to be appropriate in patients receiving kaliuretic diuretics.

Aged↗
PubMed1977

Effects of a new diuretic on cerebrospinal fluid pressure in patients with supratentorial tumors.

The effect of a new, powerful diuretic on biochemical parameters, urine output, central venous pressure, blood pressure, and cerebrospinal fluid pressure in patients with supratentorial intracerebral tumors who showed signs and symptoms of increased intracranial pressure was tested. When compared to an untreated control group and to the steady-state data of each patient, CSF pressure was significantly reduced using a dose of 240 mg of the diuretic. The 120 mg dosage did not produce significant results. Normalization of increased cerebrospinal fluid pressure was not completely obtained using either dose. Used alone, this substance is not suitable for treatment of increased intracranial pressure due to brain edema in patients with intra-cerebral tumors. It might, however, be useful in combination with other medications.

Brain Edema↗
PubMed1979

Effects of modern loop diuretics on the inner ear a quantitative evaluation using computer technics.

The effects of some modern high ceiling loop diuretics on the guinea-pig's inner ear are tested. Short-time experiments are run registrating the cochlear microphonic potentials (CMP) before and after i.v. bolus injections of a diuretic. A 100-point matrix program is performed by automatic sampling of the CMPs after stimulating by five frequencies at 20 sound pressure levels each. Data can be plotted in different scales within 10 min after the end of a whole-day experiment. The data are on-line processed by a IBM 1800 computer.

Animals↗
PubMed1986

Effects of spironolactone on serum and muscle electrolytes in patients on long-term diuretic therapy for congestive heart failure and/or arterial hypertension.

The effect of adding spironolactone (Aldactone) on muscle electrolytes was studied in 48 patients with arterial hypertension and/or congestive heart failure who had received conventional diuretic treatment, including a potassium supplement, for more than 1 year. After 6 months on spironolactone 100 mg/day as well as the original conventional diuretic therapy, there was a significant increase in both skeletal muscle potassium and magnesium. At the same time these parameters decreased in the control group. In the spironolactone group there was also a significant increase in the mean serum potassium and creatinine levels. There was a significant fall in blood pressure in the spironolactone-treated group.

Aged↗
PubMed1988

Effects of triamterene on serum and skeletal muscle electrolytes in diuretic-treated patients.

The effects on plasma and skeletal muscle electrolytes of the combination of triamterene 37.5 mg and hydrochlorothiazide 25 mg daily were studied in 19 patients on prior long-term (greater than 1 year) diuretic therapy for arterial hypertension and/or congestive heart failure. A further 20 patients fulfilling the same admission criteria were used as controls. Blood samples and skeletal muscle biopsies were taken before the study and after 6 months on therapy. The diuretic-treated group had a significant increase in skeletal muscle potassium and magnesium after 6 months on therapy as compared to the controls. Thus, the combination of triamterene and hydrochlorothiazide appeared effective in preserving the cellular content of potassium and magnesium on a long-term basis in the type of patient studied.

Aged↗
PubMed1982

Variance comparison as a tool in clinical pharmacology: an example with two loop diuretics.

Comparison of variances can be usefUl in assessing the regularity of drug effects. In order to compare the variances of the saluretic effects of piretanide and frusemide, two loop diuretics with different bioavailabilities, a double-blind cross-over study was carried out in 34 normal volunteers. The diuretics were given in randomized order, with an interval of 7 days, in single equipotent doses (frusemide 6.25 mg and piretanide 1.0 mg chosen from previous results) adjusted by body weight. The dispersion of individual values (comparison of variances from paired measures) for Na+, Cl- and Ca++ excretion, urine osmolality and excretion of the drugs, was significantly smaller for piretanide than for frusemide. It is concluded that the saluretic effect of a single dose of piretanide varies less than that of an equipotent dose of frusemide. The methodology may be useful in trials of drugs for which regularity of effect is important.

Biological Availability↗
PubMed1980

Pharmacokinetics of diuretics and methylxanthines in the neonate.

The elimination of diuretics and methylxanthines is considerably slower in the neonate than in the adult. Dose guidelines, especially during long term maintenance, must be adjusted to account for this slower drug elimination. Pharmacokinetic studies and the requisite pharmacologic evaluation on diuretics such as hydrochlorothiazide, spironolactone, ethacrynic acid and others should be done. Furosemide undergoes biotransformation in the newborn producing an acid metabolite and a glucuronide conjugate. Methylxanthines are effective in the treatment of neonatal apnea. Plasma elimination of theophylline is exceedingly slow, more so with caffeine. Decreased elimination is partly explained by decreased oxidative biotransformation. Caffeine is excreted in the urine of the newborn mainly unchanged (85%) in contrast to the adult where caffeine is a minor portion of urinary excretion (2%). Theophylline is methylated to caffeine and may possibly exert additive pharmacologic effects.

Bilirubin↗
PubMed1980

Disposition and pharmacodynamics of diuretics and antihypertensive agents in renal disease.

The pharmacodynamic actions and disposition of diuretic and antihypertensive agents may be significantly modified in subjects with renal disease. Most studies on this question have dealt with alterations in the elimination kinetics of these drugs and, while they generate descriptive data, minimal insight about changes in dose-response relationships or mechanisms of drug action are provided by such investigations. Several basic principles which may serve as useful guidelines in determining how renal failure will influence the response to drugs have been considered. They include the following: degree of renal malfunction, intrinsic toxicity of the drug, alternative pathways for drug metabolism and elimination, elimination pharmacokinetics and dose-response characteristics. Several classes of diuretic agents (thiazides, furosemide) and antihypertensive drugs (hydralazine, methylopda, propranolol, prazosin, and clonidine) have been used as models to define how basic knowledge of renal and non-renal pathways for elimination of drugs and their pharmacodynamic actions may assist in establishing rational therapeutic regimens for these agents in patients with renal failure.

Antihypertensive Agents↗
PubMed1976

Diuretic action of bumetanide in advanced chronic renal insufficiency.

The effect of bumetanide, a new potent diuretic, was studied in twelve patients with severe chronic renal failure (GFR 2.7 - 10.7 ml/min). Bumetanide 8 mg i.v. caused increased excretion of water and sodium in all patients. In some patients sodium excretion was greater than 50% of filtered load indicating an effect on proximal tubules. Bumetanide 2 mg i.v. was significantly less effective than 8 mg and a greater diuretic effect was produced by bumetanide 16 mg. In a comparative study bumetanide 8 mg was less potent than furosemide 250 mg, a finding in contrast to the potency rate ratio of 1/40 in other conditions. Side effects consisted of mild to moderate muscle pain and stiffness, especially localized in the neck, shoulders and calves. These side effects occurred only in patients with a GFR less than 5.3 ml/min. They were noted in all patients receiving 16 mg and in 3 out of 12 patients who took bumetanide 8 mg. There was no relationship between the occurrence of side effects and plasma bumetanide levels, electrolyte levels or the renal excretion of bumetanide and electrolytes.

Adult↗
PubMed1980

Effects of a new diuretic (piretanide) compared with furosemide on renal diluting and concentrating mechanisms in patients with the nephrotic syndrome.

The mode and site of action of the new diuretic agent piretanide were investigated in man. The effect of a single oral dose of 12 mg was compared with that of furosemide 80 mg p.o. iin 6 patients with the nephrotic syndrome. Piretanide showed a greater diuretic and natriuretic response than furosemide during maximal water diuresis, but the effect was similar in the hydropenic state. Like furosemide, piretanide decreased free water clearance relative to delivery during water diuresis and the reabsorption of solute-free water during hydropenia. This inhibitory action on both the concentrating and diluting urinary mechanisms demonstrates an effect of piretanide localized in the ascending limb of Henle's loop. Consistent alterations in glomerulur filtration rate, renal blood flow or filtration fraction were not observed.

Body Water↗
PubMed1981

Haemodynamic and hormonal changes during acute and chronic diuretic treatment in essential hypertension.

The short- and long-term effects of diuretic treatment with chlorthalidone 50 mg/day on haemodynamic and hormonal parameters in patients with essential hypertension (WHO grade I) were investigated. After three days of treatment, all patients showed a rise in plasma renin activity (PRA), plasma aldosterone (PA), urinary norepinephrine excretion (UNE) and heart rate (HR), and a decrease in body weight (BW) and extracellular volume (ECV) and blood volume (BV); the change in blood pressure (BP) was variable. The changes in BP were correlated with those in BV. After three months of therapy, the signs of volume depletion tended to fade, but the lower ECV persisted. In contrast to the 4-day study, after three months the change in BP correlated inversely with changes in ECV and renin dependency (saralasin response), and positively with PRA and changes in UNE. It is concluded that the BP response to diuretic treatment is determined by the adaptation with time of the haemodynamic reactions to the volume-depleted state. Whether this adaptation will take place cannot be predicted from the control values of the parameters studied, or from acute changes observed during the first days of treatment.

Adolescent↗
PubMed1975

Effect of inhibitors and diuretics on electrical potential differences in rat kidney proximal tubule.

Active transport potentials were studied across early loops of rat proximal tubule during luminal perfusion and peritubular superfusion with HCO3- Ringer's solution of identical ionic composition. From the effects of the carbonic anhydrase inhibitor acetazolamide and of ouabain it is concluded 1. that the lumen-positive active transport potential indicates an excess of active H+ secretion/HCO3- absorption over active Na+ absorption and 2. that the lumen-negative active transport potential, which develops in the presence of glucose (and/or aminoacids) in the tubular lumen, indicates stimulation of active Na+ absorption. Ouabain did not abolish the lumen-positive potential difference suggesting that active H+/HCO3- transport and active Na+ transport may be to some extent independent. Among the diuretics tested the mercurial diuretic mersalyl acted primarily on Na+ transport, and furosemide acted on HCO3- transport, whereas the effect of ethacrynic acid appeared to be unspecific.

Animals↗
PubMed1980

Studies with the optically active isomers of the new diuretic drug ozolinone. I. Differences in stereoselectivity of the renal target structures of ozolinone.

The renal actions of the optically active isomers of the new diuretic drug ozolinone were studied by clearance, flowmeter and micropuncture techniques in rats. The levorotatory, but not the dextrorotatory isomer of ozolinone increased urine flow, urinary sodium and chloride excretion and enhanced sodium and chloride concentrations in early distal tubular fluid as checked by in situ microperfusion of Henle's loops. This indicates stereospecificity of the drug's diuretic action. However, both isomers of ozolinone equally inhibited maximal tubular secretion of paraaminohippurate and increased renal blood flow as measured by an electromagnetic flowmeter. Thus, the different renal target structures of ozolinone differ markedly with respect to stereoselectivity.

Animals↗
PubMed1987

The effects of prazosin and propranolol in combination with thiazide diuretics on blood pressure and serum lipids: a multicentre study.

We have carried out randomized 12-week multicentre study to compare the effects of prazosin and propranolol on blood pressure and serum lipids in 70 patients with essential hypertension after a 4 week minimum period of treatment with thiazide diuretics. After 12 weeks treatment with prazosin (n = 40, 1.5-12.0 mg per day) or propranolol (n = 30, 30-120 mg per day) with diuretics there was a significant blood pressure reduction from 165.1/97.9 mmHg to 151.2/90.6 mmHg and from 167/96.5 mmHg to 153/91.9 mmHg, respectively. In the 12th week a significant decrease was noted in triglyceride and in low-density lipoprotein cholesterol (LDL + VLDL-C), but no significant effects were seen in high-density lipoprotein cholesterol (HDL-C) in patients receiving prazosin. On the other hand, a significant decrease in lecithin cholesterol acyltransferase (LCAT) was seen in patients receiving propranolol. Twenty-six of 40 patients receiving prazosin were given an additional 12 weeks of treatment. Twenty-two of 30 patients initially treated with propranolol were switched from propranolol to prazosin after 13 weeks and given prazosin up to the 24th week. At 24 weeks, the blood pressure was 149/93.0 mmHg in the prazosin group and 155/89.2 mmHg in the group which switched from propranolol to prazosin. Triglyceride remained reduced in the prazosin group at the 24th week. In the group which switched from propranolol to prazosin, triglyceride decreased significantly over the next 12 weeks.

Benzothiadiazines↗
PubMed1977

Acute acetylsalicylic acid poisoning: treatment with forced alkaline diuresis and diuretics.

101 patients were treated for acute acetylsalicylic acid (ASA) poisoning in the Nephrological Unit Trondheim between 1971-1975. On admission 33 of them had a serum salicylic acid (SA) concentration greater than 400 microgram/ml (mean 588 +/- 40 microgram/ml). This group was compared with a group of 11 children less than 5 years old with ASA poisoning and a mean serum SA on admission of 550 +/- 34 microgram/ml. Blood pH on admission was normal or elevated in all patients more than 12 years old (mean 7.43 +/- 0.01), whereas 7 of the 11 children suffered from metabolic acidosis. The results of forced alkaline diuresis produced by loop diuretics (bumetanide, furosemide) in ASA poisoned patients older than 12 years are reported. The mean T 1/2 of SA was 9.6 h in the treated group as compared to 18-22 h in untreated patients. There was no apparent difference between the diuretic effect of bumetanide and furosemide.

Acid-Base Equilibrium↗
PubMed1993

Postinfarct heart failure: role of diuretic therapy.

There can be no doubt that ACE inhibitors prolong survival in patients with a low ejection fraction. There is no evidence whether or not diuretics have the same effect. The pathophysiology of asymptomatic patients with poor left ventricular function differs from that of patients with the clinical syndrome of heart failure, and different treatments may well be needed. Diuretics still have a crucial role in the relief of symptoms.

Cardiac Output, Low↗
PubMed1993

Renal and extrarenal sites of action of diuretics.

This paper provides (a) a survey of the basic tubule transport mechanisms of sodium and potassium ions along the nephron, (b) a comparison of the overall renal effects of two diuretic agents (torasemide and furosemide), as assessed by renal clearance techniques, (c) an analysis of the tubule sites of action of torasemide evaluated by free-flow micropuncture and microperfusion techniques, and (d) a brief evaluation of some extrarenal transport effects of loop diuretics.

Animals↗
PubMed1977

Intractable diarrhea. Intestinal perfusion studies and plasma VIP concentrations in patients with pancreatic cholera syndrome and surreptitious ingestion of laxatives and diuretics.

Small-intestinal perfusion studies with a triple-lumen tube were performed in the jejunum and ileum of 11 patients with a presumptive diagnosis of pancreatic cholera syndrome (PCS). Ultimately PCS was proven to be present in only 3 patients, whereas 6 were discovered to be taking either laxatives or diuretics surreptitiously. In 2 of the 11 patients the cause of the diarrhea could not be determined. In PCS the major abnormality which we observed was that the jejunal mucosa secreted rather than absorbed when perfused with a plasma-like solution. By contrast, the ileum of the PCS patients absorbed a plasma-like solution in a normal fashion; however, one patient failed to absorb sodium and chloride when a solution with low (50 mM) sodium chloride concentration was perfused in the ileum. The volume of endogenous fluid was high in both the jejunum and ileum, presumably because of proximal small-intestinal secretion. Glucose stimulated sodium movement in an absorptive direction in each patient. Studies were repeated in one PCS patient after tumor removal, and his intestinal absorption of water and electrolytes was normal. Patients with diarrhea due to surreptitious ingestion of laxatives and diuretics showed normal absorption in the jejunum and ileum. This study shows that proximal small-bowel secretion was the major cause for diarrhea in our 3 patients with PCS. This cannot be a consequence of diarrhea per se since it was not found in patients with long-standing diarrhea due to surrepitious drug ingestion. Small-intestinal perfusion studies may be helpful in the diagnosis and management of selected cases of severe chronic diarrhea. On the other hand, measurement of plasma VIP concentration, especially by methods currently used in the United States, is of little use and may be misleading.

Adult↗