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PubMed1979

Sequential method for combined screening antihypertensive and diuretic agents in the same spontaneously hypertensive rat (SHR).

A combined method for detecting compounds with antihypertensive and diuretic activity simultaneously in the same spontaneously hypertensive (SH) rat is described. The present method, utilizing the advantages of sequential probability test analysis, the spontaneously hypertensive rats and the direct measurement of arterial blood pressure, proves to be feasible and efficient in detecting both activities. This ia s 3-stage sequential test requires one to three rats per compound. One adult SH rat was dosed by gavage with compound at 100 mg/kg, p.o. and loaded with 0.9% NaCl at 25 ml/kg, p.o. at 0-hr. The rat was put in a metabolism cage. The 0-5 hr. urine was collected and urinary Na+, K+ and CL- were determined. A second identical dose was given without NaCl loading at 24-hr. Mean arterial blood pressure (MABP) of conscious rats was measured directly by fermoral-iliac artery puncture at 28-hr. The criteria to accept, retest or reject a compound were based on the testing of known antihypertensives and diuretics. A 2nd and 3rd rat may be needed for a test compound depending on the outcome of the MABP and urinary electrolytes of the 1st rat. Based on MABP, guancydine, hydralazine, clonidine, reserpine, alpha-methyldopa, guanethidine and parglyine were accepted as active. Based on urinary sodium excretion, furosemide, quinethazone, acetazolamide, hydrochlorothiazide, metolazone, triamterene and clonidine were accepted as active.

Animals↗
PubMed1982

Enantiomers of indacrinone: a new approach to producing an isouricemic diuretic.

Racemic indacrinone is a potent loop diuretic with transient uricosuric properties in certain nonhuman primates and in man. After chronic treatment, hyperuricemia develops presumably because of enhanced proximal tubular urate reabsorption secondary to extracellular fluid volume contraction. The natriuretic and uricosuric activities are associated with both enantiomers, but the (-)-enantiomer is significantly more potent as a natriuretic agent than the (+). Acutely, in Cebus monkeys, both enantiomers appear to have similar uricosuric activity. The difference in the natriuretic potency between the two enantiomers provides the possibility of altering the enantiomer ratio from its naturally occurring 1:1 ratio to another combination which would enhance the uricosuric action [more (+) relative to (-)] while preserving the potent natriuretic action of the (-). In healthy volunteers, a 1:4 ratio [(-):(+)] was isouricemic after 7 days of treatment and a 1:8 mixture lowered mean serum urate by 13%. Presumably, the desired ratio of (-):(+) will be in the range 1:4-1:9. Further enhancement of the diuretic profile of this compound may be obtained by adding sufficient amiloride to produce isokalemia.

Amiloride↗
PubMed1983

Side effects of diuretics.

Diuretics are amongst the most widely used drugs. Fortunately enough, there are rather few clinically relevant side effects. The following side effects are discussed in this paper: disturbances of electrolyte, acid-base- and water balance, metabolic changes (uric-acid, carbohydrate-metabolism, lipid metabolism), unspecific side effects and drug interactions. Finally the prevention of side reactions of diuretics is briefly mentioned.

Calcium↗
PubMed1991

The effects of sulindac and diclofenac in essential hypertension controlled by treatment with a beta blocker and/or diuretic.

A placebo-controlled, double blind crossover study of the non-steroidal anti-inflammatory drugs (NSAIDs) sulindac and diclofenac was conducted in 16 patients with essential hypertension that was controlled by treatment with a beta blocker, a diuretic or co-administration of both. In 4 cases, another antihypertensive agent (prazosin or verapamil) was also co-administered. In every patient, plasma creatinine concentration was less than 0.14 mmol/l (normal range 0.07-0.12 mmol/l). Sulindac and diclofenac were each given for 7 weeks. Diclofenac caused a decrease of borderline significance in plasma aldosterone concentration. Neither NSAID altered the mean values for systolic or diastolic blood pressure, body weight, plasma electrolyte concentrations, urate clearance, creatinine clearance or plasma renin activity. However, rises in plasma creatinine concentration and falls in creatinine clearance occurred during NSAID therapy in three individual subjects. No significant differences were observed in this study between the effects on renal function or blood pressure of sulindac and diclofenac, both of which appear not to interfere with the antihypertensive actions of beta blockers and diuretics.

Adrenergic beta-Antagonists↗
PubMed2002

Combining renin-angiotensin-aldosterone system blockade with diuretic therapy for treatment of hypertension.

The rationale for using angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) in combination with thiazide diuretic therapy has centred formerly around antihypertensive synergy and counter-balancing adverse metabolic effects, particularly on potassium homeostasis. However, two recent landmark clinical trials that included high-risk hypertensive patients have now provided an evidence base for this form of combination therapy by demonstrating the efficacy of perindopril/indapamide and losartan/ hydrochlorothiazide in reducing vascular morbidity and mortality, a proportion of the benefit being unaccounted for by blood pressure reduction alone. Several unresolved issues remain concerning class effects versus specific drug effects, optimal dosing, potential differences in efficacy between ACE-I and ARBs, whether elderly mild hypertensives benefit from this form of combination therapy, and the possibility that the optimal regimen may be a triple combination of ACE-I, ARB and thiazide diuretic. These issues will be resolved by ongoing and future major endpoint trials in hypertension.

Angiotensin Receptor Antagonists↗
PubMed2004

How do thiazide and thiazide-like diuretics lower blood pressure?

Thiazide diuretics are widely used for the treatment of hypertension, but the mechanism by which these drugs lower blood pressure in the long term remains unknown. This article reviews current knowledge about the hypotensive actions of thiazides and thiazide-like diuretics and discusses possible mechanisms of action.

Animals↗
PubMed2002

Attenuated renal excretion in response to thiazide diuretics in Gitelman's syndrome: a case report.

Gitelman's syndrome is a variant of Bartter's syndrome characterized by hypocalciuria and hypomagnesemia. The administration of thiazide diuretics may induce a subnormal increase of urinary Na+ and Cl- excretion in patients with Gitelman's syndrome, consistent with the hypothesis that less Na+ and Cl- than normal is reabsorbed by the thiazide-inhibitable transporter in Gitelman's syndrome. Specific mutations of NaCl cotransporter, coupled with mutant NaCl cotransporter expression studies clearly demonstrated that many of the characteristics of individuals with Gitelman's syndrome are explained by lack of function of NaCl cotransporter. We recently diagnosed a patient with Gitelman's syndrome by performing the thiazide and furosemide tests, and it is suggested that the clearance studies by diuretic administration may be of diagnostic help in Gitelman's syndrome.

Adolescent↗
PubMed2007

[Diuretic effect of injecting furosemide into low hydraulic resistance point Shuifen along the conception meridian in pigs with acute edema].

OBJECTIVE: To observe whether injection of medicine into low hydraulic resistance point along meridian brings about higher medicinal effect and to explore the efficacy of the theory that meridians are made up of channels featuring low hydraulic resistance by observing the diuretic effect of injecting furosemide or saline into the low hydraulic resistance point Shuifen (CV 9), vein and Zusanli (St 36) respectively. METHODS: Acute edema was induced in pigs by rapid intravenous injection of 2 000 ml normal saline. The pigs were divided into four groups: Shuifen (CV 9) injection of half dose furosemide group (SFF group), intravenous injection of full dose furosemide group (VF group), Zusanli (St 36) injection of full dose furosemide group (ZSLF group), and Shuifen (CV 9) injection of half dose normal saline group (SFS group). The accumulated urine quantity and the urine quantity generated in every 15-minute period were measured in each group respectively, every 15 minutes after injection, and the measurement lasted for two hours at one experiment. Each group involved eight times of experiments with one pig used for one experiment, which means the whole observation involved 32 times of experiments. RESULTS: The accumulated urine quantities observed in both SFF group and VF group were higher than those in the ZSLF group and the SFS group all through the measurement, showing significant differences during the period from the 15th minute to the 45th minute (P<0.05). But no significant difference was observed between the SFF group and the VF group during the whole 2-hour measurement (P>0.05). Analysis of urine quantity generated in every 15-minute period showed that diuretic effect climaxed during the 15th minute to the 30th minute in both SFF group and VF group. By contrast, ZSLF group reached diuresis climax during the 45th minute to 60th minute and no diuresis climax was observed in the SFS group all through the measurement. CONCLUSION: Injection of medicine into low hydraulic resistance point along meridian generates faster and more powerful medicinal potency, and this is likely to be applied to clinical practice. The theory that meridians are channels featuring low hydraulic resistance is important to the elucidation of meridians.

Acupuncture Points↗
PubMed2003

Thiazide diuretics and the risk for hip fracture.

BACKGROUND: Since most hip fractures are related to osteoporosis, treating accelerated bone loss can be an important strategy to prevent hip fractures. Thiazides have been associated with reduced age-related bone loss by decreasing urinary calcium excretion. OBJECTIVE: To examine the association between dose and duration of thiazide diuretic use and the risk for hip fracture and to study the consequences of discontinuing use. DESIGN: Prospective population-based cohort study. SETTING: The Rotterdam Study. PARTICIPANTS: 7891 individuals 55 years of age and older. MEASUREMENTS: Hip fractures were reported by the general practitioners and verified by trained research assistants. Details of all dispensed drugs were available on a day-to-day basis. Exposure to thiazides was divided into 7 mutually exclusive categories: never use, current use for 1 to 42 days, current use for 43 to 365 days, current use for more than 365 days, discontinuation of use since 1 to 60 days, discontinuation of use since 61 to 120 days, and discontinuation of use since more than 120 days. RESULTS: 281 hip fractures occurred. Relative to nonuse, current use of thiazides for more than 365 days was statistically significantly associated with a lower risk for hip fracture (hazard ratio, 0.46 [95% CI, 0.21 to 0.96]). There was no clear dose dependency. This lower risk disappeared approximately 4 months after thiazide use was discontinued. CONCLUSIONS: Thiazide diuretics protect against hip fracture, but this protective effect disappears within 4 months after use is discontinued.

Age Factors↗
PubMed1976

Heat tolerance following diuretic induced dehydration.

In an effort to assess the effects of acute fluid loss on body temperature regulation during exercise, seven subjects (one female and six males) were studied on two occasions during two hours of cycling (35% Vo2max) in a hot environment (39 degrees C = DB, 35% = RH). One trial (D) was conducted following a 3% body weight reduction, achieved with 40-80 mg oral administration of a diuretic "lasix." A control exercise bout was performed with the subject normally hydrated (H). As a result of the diuresis, plasma volume (PV) decreased 15.3% (SE +/- 1.3), while heart rates during exercise increased 20-25 beats/min when compared to the H condition. Although significantly greater increases (P less than 0.05) in rectal and muscle temperatures occurred during exercise in the D trial, mean skin temperature (TS) was lower. Skin blood flow estimated from conductance values averaged 800 ml/min less during the D condition than during exercise in the H trial. Since the preliminary diuresis had no affect on sweat rate during exercise (D = 0.80 vs. H = 0.80 liters/hr), body heat dissipation appeared limited mainly by a reduction in peripheral blood flow. The diuretic induced dehydration was found to increase the sensitivity of some subjects to the exercise-heat stress, producing symptoms of heat exhaustion.

Adult↗
PubMed1998

A patient-focused approach to managing diuretic therapy.

The use of diuretic therapy has been shown to be efficacious in a variety of patient populations. However, its use is not without untoward side effects. Knowledge about the indications for and possible complications resulting from diuretic therapy is imperative to any practitioner prescribing and administering these medications. Informing your patients about why they are on these medications and any side effects will help to prevent the incidence of complications.

Adult↗
PubMed1999

[A case of significant natriuresis and improvement of proteinuria by Temocapril, an ACE inhibitor with biliary excretion, in loop diuretics resistant edema in membranous nephropathy].

A 50-year-old man with WPW syndrome and chronic atrial fibrillation controlled by digoxin exhibited nephrotic syndrome due to membranous nephropathy in 1994. For massive edema resistant to loop diuretics, administration of 2 mg/day of Temocapril, an ACE inhibitor with biliary excretion, was started. It provided marked natriuresis and rapid improvement of massive anasarca. Moreover, 6 months later at the time of writing this report, nephrotic proteinuria has decreased and abnormally depressed Ccr level has elevated. For massive edema resistant to loop diuretics in nephrotic syndrome, Temocapril might bring about a beneficial effect possibly through the induction of natriuresis, which has been suppressed by the over-expression of angiotensin II in tubulointerstitium.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Diuretic MAG3 scintirenography in children with HIV nephropathy: diffuse parenchymal dysfunction.

UNLABELLED: HIV nephropathy (HIVN) is prevalent in 15%-56% of HIV-infected children and induces mild to severe progressive nephropathy. METHODS: A total of 33 renal diuretic scintirenographic studies with 99mTc-mercaptoacetyltriglycine (MAG3) were reviewed and analyzed from 23 HIV pediatric patients, 21 of whom had HIVN with varying degrees of renal impairment. Results were compared with 10 studies of control patients of matching ages. Visual interpretation of images and renograms as well as semiquantitative analyses were performed. Variables compared were size of kidneys, time of peak and one-half peak activities, residual (or retained) cortical activity at 20 min, ratio of cortical activity at 2.5-20 min, and ratio of kidney activity to kidney plus background activity at 2 min. The results of MAG3 renal studies were also compared with laboratory data pertaining to creatinine clearance in all patients and with sonography in 17 patients. RESULTS: In most patients with HIVN (18/21), the kidneys were larger than normal, with a diffuse parenchymal dysfunction (decreased uptake, slow processing, and increased retention of activity) and flat renograms, findings similar to those observed in other diffuse parenchymal diseases. In all patients with HIVN, semiquantitative analysis (paired t test) showed statistically significant differences from control patients for all variables. On ANOVA, a statistically significant correlation was found between most scintigraphic parameters and the severity of renal impairment. Of the 17 concurrent sonographic studies in HIVN patients, 7 showed no abnormalities, whereas the results of scintigraphy were abnormal. CONCLUSION: Diuretic MAG3 scintirenography shows nonspecific diffuse parenchymal dysfunction in pediatric patients with HIVN. Such dysfunction may provide corroborative evidence of HIVN and should be recognized when the test is performed for standard indications. Further work is necessary to prove that the test has indeed the high sensitivity and good correlation with the seventy of HIVN suggested in this population; the test may be useful to follow up the progression of disease and the effect of treatment.

AIDS-Associated Nephropathy↗
PubMed2000

Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera, Dunal) root.

Hypoglycemic, diuretic and hypocholesterolemic effects of roots of W. somnifera (ashvagandha) were assessed on human subjects. Six mild NIDDM subjects and six mild hypercholesterolemic subjects were treated with the powder of roots of W. somnifera for 30 days. Suitable parameters were studied in the blood and urine samples of the subjects along with dietary pattern before and at the end of treatment period. Decrease in blood glucose was comparable to that of an oral hypoglycemic drug. Significant increase in urine sodium, urine volume, significant decrease in serum cholesterol, triglycerides, LDL (low density lipoproteins) and VLDL (very low density lipoproteins) cholesterol were observed indicating that root of W. somnifera is a potential source of hypoglycemic, diuretic and hypocholesterolemic agents. Clinical observations revealed no adverse effects.

Adult↗
PubMed2001

[Hyponatremic crisis--a serious side effect of diuretics in the elderly].

BACKGROUND: Treatment with thiazide diuretics is among the most frequent causes of severe hyponatremia. Previous reports indicate that elderly women develop more severe manifestations than men. The risk of developing hyponatremia increases when thiazide diuretics are given simultaneously with NSAIDs. MATERIAL AND METHODS: Three typical case-stories are presented, all cases being admitted to hospital with a tentative diagnosis of cerebrovascular stroke. RESULTS: It is shown that hyponatremia can give rise to a broad spectrum of symptoms, ranging from unspecific dizziness and headache to alarming neurological symptoms involving lethargy and severe confusion. As far as therapy is concerned, it is important to eliminate the cause of hyponatremia, and to carry out a controlled correction with isotonic or hypertonic saline. Too rapid correction can precipitate a serious complication called osmotic demyelination syndrome. INTERPRETATION: Differential diagnoses of hyponatremic conditions are discussed. Prescription of drugs that involve risk of hyponatremia should be preceded by a precise evaluation of the condition and the indication for such treatment.

Aged↗
PubMed1975

Marked elevation of plasma renin activity during post diuretic sodium conservation in furosemide stimulated subjects.

Plasma renin activity (PRA) was measured in 3 subjects during control period, after 3 days of oral furosemide (40 mg B.I.D.) and on the 2nd, 3rd and 5th days post diuresis. PRA, ng of angiotensin per ml plasma per 3-hour incubation was 8, 0.4 ng during the control period and rose to 51, 6 and 16 respectively. During the post diuretic phase, PRA rose to 99 in the first and 49 in the second subject. Urinary sodium was drastically reduced during this period. By 5th post diuretic day PRA returned to normal values. Striking elevations of PRA during intense sodium conservation are in accord with a concept of reduced Na load to macula densa stimulating renin release.

Aged↗
PubMed2001

[Biological factors influencing response to diuretics in patients with cirrhosis and ascites].

PURPOSES: To examine the biological factors influencing response to diuretics in patients with cirrhosis and ascites. METHODS: Sixty-nine patients were evaluated. Patients were classified into 3 groups: group 1: "good responders" (responding to spironolactone 200 mg/day), group 2: "bad responders" (responding to spironolactone doses above 200 mg/day or requiring addition of furosemide), and group 3: "non-responders" (not responding to spironolactone 400 mg/day and furosemide 160 mg/day). RESULTS: There were 30 patients in group 1, 24 in group 2 and 15 in group 3. The degree of activation of the renin-aldosterone and sympathetic system in group 2 was significantly higher than in group 1 and lower than in group 3. Natriuresis in group 2 (11 +/- 0.7 mEq/24h) was significantly below group 1 (20 +/- 2 mEq/24h) and above group 3 (5 +/- 0.6 mEq/24h). CONCLUSIONS: In patients with cirrhosis and ascites, the degree of activation of the renin-aldosterone and sympathetic nervous system influences diuretic response of ascites and is estimated by measured baseline natriuresis.

Aldosterone↗
PubMed2000

Spironolactone in severe heart failure: enhances efficacy of diuretic + ACE inhibitor combinations.

(1) In patients with heart failure who remain symptomatic despite combination therapy with a diuretic and an angiotensin-converting-enzyme (ACE) inhibitor, a strictly conducted trial has shown that adding spironolactone at a mean dose of 25 mg/day reduces overall mortality by approximately 5% per year, and reduces the incidence of hospitalisation for heart disease and disability. (2) There is a risk of gynaecomastia (9%) and potentially severe hyperkalaemia. (3) It is crucial to follow the protocol used in the clinical trial, i.e. this treatment is contraindicated in severe renal failure or hyperkalaemia; creatinine and potassium levels must be monitored strictly; and spironolactone must be combined with a loop diuretic.

Angiotensin-Converting Enzyme Inhibitors↗