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PubMed1994

Diuretic therapy for hypertension and the risk of primary cardiac arrest.

BACKGROUND: The results of trials of the primary prevention of coronary heart disease have suggested that treating hypertension with high doses of thiazide diuretic drugs might increase the risk of sudden death from cardiac causes. In contrast, treatment with low doses of thiazide reduces the risk of coronary heart disease. METHODS: To examine the association between thiazide treatment for hypertension and the occurrence of primary cardiac arrest, we conducted a population-based case-control study among enrollees of a health maintenance organization. The case patients were 114 persons with hypertension who had a primary cardiac arrest from 1977 through 1990. The control patients were a stratified random sample of 535 persons with hypertension. The patients' treatment was assessed with the use of a computerized pharmacy data base. Records of their ambulatory care were reviewed to determine other clinical characteristics. RESULTS: The risk of primary cardiac arrest among patients receiving combined thiazide and potassium-sparing diuretic therapy was lower than that among patients treated with a thiazide without potassium-sparing therapy (odds ratio, 0.3; 95 percent confidence interval, 0.1 to 0.7). As compared with low-dose thiazide therapy (25 mg daily), moderate-dose therapy (50 mg daily) was associated with a moderate increase in risk (odds ratio, 1.7; 95 percent confidence interval, 0.7 to 4.5), and high-dose therapy (100 mg daily) was associated with a larger increase in risk (odds ratio, 3.6; 95 percent confidence interval, 1.2 to 10.8) (P value for trend, 0.02). The addition of a potassium-sparing drug to low-dose thiazide therapy was associated with a reduced risk of cardiac arrest (odds ratio, 0.4; 95 percent confidence interval, 0.1 to 1.5). CONCLUSIONS: Both the dose of thiazide drugs and the addition of potassium-sparing drugs influence the risk of primary cardiac arrest. These results may explain the differences in the effect of antihypertensive therapy on mortality from coronary heart disease in previous clinical trials.

Aged↗
PubMed1989

ACE inhibitors and diuretics. The benefits of combined therapy for hypertension.

Hypertension and its consequences continue to threaten the health of as many as 60 million Americans. Effective control of blood pressure can be achieved in some patients with a single agent and in many of the remainder with combination therapy. The ideal combination regimen is one that is at least as effective as a single agent, has minimal or no side effects, has a wide therapeutic index, is simple to administer, and is effective in a wide variety of patient populations. When used in combination, the thiazide diuretics and the angiotensin-converting enzyme inhibitors have been shown to improve blood pressure reduction over either drug used alone. In addition, the combination is effective in a wide range of patient populations (blacks and whites, young and old) and is accompanied by fewer adverse metabolic effects than the thiazides alone. Finally, the combination has a more positive impact on quality of life than other combinations involving the thiazide diuretics.

Aged↗
PubMed2004

Effects of nifedipine GITS and diuretics in isolated systolic hypertension--a subanalysis of the INSIGHT study.

AIMS: This study tested the effects on cardiovascular outcomes of treatments based on nifedipine gastrointestinal therapeutic system (GITS) compared with the diuretic combination co-amilozide in a pre-specified subset of patients with isolated systolic hypertension (ISH) enrolled in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) study. MAJOR FINDINGS: Of 6321 randomized patients, 1498 (23.7%) had ISH with a baseline mean BP of 173/88 mmHg in both treatment groups. Mean BP fell by 29/10 mmHg in the nifedipine and 30/10 mmHg in the diuretic group to a mean BP of 144/78 mmHg and 143/79 mmHg, respectively, at endpoint. The percentage of primary outcomes in patients with ISH was not significantly different between the two treatment groups (nifedipine GITS 6.0%, co-amilozide 6.6%). The number of ISH patients with composite secondary outcomes was 90 (12.2%) in the nifedipine GITS group and 110 (14.5%) in the co-amilozide group (not significant). The incidence rates of primary and secondary outcomes were similar in patients without ISH. CONCLUSION: In patients with ISH, nifedipine GITS and co-amilozide had similar effects on clinical outcomes and BP lowering. They lend support to international guidelines for the treatment of hypertension recommending the use of long-acting dihydropyridine calcium-channel blockers as one treatment option for patients with ISH.

Aged↗
PubMed2005

Angiotensin-receptor blockers and diuretics--advantages of combination.

Surveys have shown that in as many as half of patients treated for hypertension, blood pressure (BP) is not controlled to target levels; many more persons have undertreated hypertension. Uncontrolled hypertension is a serious risk factor for cardiovascular events such as stroke, heart failure, myocardial infarction and target-organ diseases. Studies have shown that strict BP control significantly reduces the occurrence of these cardiovascular outcomes, in the majority of patients, effective BP control requires two or more antihypertensive agents. The combination of an angiotensin-receptor blocker (ARB) and a thiazide diuretic is appealing, since these agents have complimentary effects on BP reduction, left ventricular hypertrophy and progression of renal diseases. In addition, this combination provide excellent tolerability. The combination of an ARB and a thiazide diuretic may be of particular value in patient populations who tend to have poor BP control on monotherapy, or have additional cardiovascular or renal risk factors.

Angiotensin II Type 1 Receptor Blockers↗
PubMed1988

Effects of oral magnesium on blood pressure and red cell sodium transport in patients receiving long-term thiazide diuretics for hypertension.

Twenty patients receiving long-term (1.0 to 10.3 years) thiazide diuretic treatment for essential hypertension (Th group) received magnesium supplementation as MgO (600 mg Mg/day) for 4 weeks and placebo for another 4 weeks. Before and at the end of each period, we measured blood pressure; intraerythrocyte magnesium, sodium, and potassium (R-Mg, R-Na, and R-K); and erythrocyte ouabain (10-4 M) sensitive sodium efflux rate constant (Kos). The same measurements were also performed in 21 untreated age-matched essential hypertensives (EHT group). In the Th group, R-Mg was lower, R-Na was higher, and Kos was lower than in the EHT group before magnesium supplementation. Oral magnesium resulted in a significant increase in R-Mg (p less than 0.005) and a decrease in R-Na (p less than 0.01), together with an increase in Kos (p less than 0.005) in the Th group. During magnesium supplementation, the increased Kos was correlated negatively with the lowered R-Na (r = -0.57, p less than 0.01) and positively with the increased R-Mg (r = 0.61, p less than 0.005). Systolic, diastolic, and mean blood pressures were reduced significantly during magnesium administration by a mean of 7.5, 3.0, and 4.5 mm Hg. The results indicate that long-term diuretic treatment may give rise to an intracellular magnesium deficiency and a suppression in cell membrane active transport for sodium, with a resultant increase in intracellular sodium content.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed2005

Examples of doping control analysis by liquid chromatography-tandem mass spectrometry: ephedrines, beta-receptor blocking agents, diuretics, sympathomimetics, and cross-linked hemoglobins.

The application of modern and powerful analytical instruments consisting of liquid chromatographs (LCs), sophisticated atmospheric pressure ion sources, and sensitive mass analyzers has improved quality as well as speed of doping control analyses markedly during the last 5 years. Numerous compounds such as beta-receptor blocking agents or diuretics require derivatization prior to gas chromatographic (GC) and mass spectrometric (MS) measurement, which is the reason for extended sample preparation periods. In addition, several substances demonstrate poor GC-MS properties even after chemical modification, and peptide hormones such as cross-linked hemoglobins cannot be analyzed at all by means of GC-MS. With the availability of electrospray ionization and robust tandem MSs (e.g., triple-stage quadrupole or ion trap instruments) many new or complementary screening and confirmation assays have been developed, providing detailed qualitative and quantitative information on prohibited drugs. With selected categories of compounds (ephedrines, beta-blockers, b2-agonists, diuretics, and bovine hemoglobin-based oxygen therapeutics) that are banned according to the rules of the World Anti-Doping Agency and International Olympic Committee, the advantages of LC-MS-MS procedures over conventional GC-MS assays are demonstrated, such as enhanced separation of analytes, shorter sample pretreatment, and identification of substances that are not identified by GC-MS.

Adrenergic beta-Antagonists↗
PubMed1991

Antihypertensive drug therapy and regression of left ventricular hypertrophy: a review with a focus on diuretics.

Regression of LVH is a reasonable adjunctive goal of blood pressure treatment, given the well described risks of hypertrophy and the possible benefits inherent in its reversal. Data suggest that any of the presently recommended agents for initial monotherapy, i.e. diuretics, beta adrenergic inhibitors, ACE inhibitors, or calcium blockers, are effective in achieving regression of hypertrophy if blood pressure lowering is achieved. While there may be other factors that play a role in the genesis and maintenance of cardiac hypertrophy in the hypertensive subject, it would appear that blood pressure elevation is probably the most important one. If reduction of blood pressure to normotensive levels can be achieved and maintained by the use of any of the antihypertensive agents (including the vasodilators, if used in combination with adrenergic inhibitors and/or diuretics), there is a reasonable chance that cardiac hypertrophy can be prevented or reversed and prognosis improved.

Antihypertensive Agents↗
PubMed1992

Modulation of electrolyte excretion by potassium retaining diuretics.

Triamterene and amiloride belong to the potassium retaining diuretics of the cycloamidine type. These agents exert natriuretic as well as antikaliuretic effects. After administration of high doses an additional magnesium-sparing property also becomes evident. Whereas amiloride is only metabolized to a minor extent, triamterene is rapidly bio-transformed to the phase-I metabolite, hydroxytriamterene, and the phase-II metabolite, hydroxytriamterene sulphuric acid ester. This acidic phase-II metabolite is still diuretically active, but its electrolyte excretion profile is different from the parent compound: although the natriuretic properties are not altered, the potassium retention is very weak. Further studies in rats with cycloamidine derivatives of the triamterene type containing neutral, acidic or basic side chains at the phenyl moiety as well as with basic pteridine derivatives, revealed further evidence that the natriuretic, antikaliuretic and antimagnesiuretic effects can be influenced almost independently by structural variations of the parent drug. Thus, it was possible to obtain compounds predominantly increasing sodium excretion without affecting potassium or magnesium excretion. On the other hand, substances could be developed with mainly antikaliuretic effects, or compounds, which enhanced sodium and reduced magnesium excretion and did not interfere with the potassium elimination. Based on these findings, it can be concluded that distal tubular transport of sodium, potassium and magnesium may be influenced independently from each other. These renal effects of triamterene and its derivatives seem to be independent of their antiarrhythmic actions, as suggested by recent studies.

Animals↗
PubMed1992

Effect of diuretic therapy on hypertensive left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) has been identified as a major independent risk factor for cardiovascular morbidity in patients with essential hypertension. It is also established that antihypertensive drug therapy is associated with regression of LVH in many patients. However, it is unclear whether all antihypertensive agents are equally effective in regressing LVH and whether this process is drug-specific or primarily related to blood pressure control. There is no universal agreement on the influence of diuretics on LVH in hypertension. Several major trials have shown consistent reversal of electrocardiographic manifestations of LVH during diuretic-based therapy. The results of studies employing echocardiographic measurements have been more variable; however, most echocardiographic studies have been flawed by lack of controls or blinding, short duration of follow-up, small sample size, inclusion of patients without LVH, and lack of consideration of previous or concomitant therapy. This review provides a critical examination of the available data on both sides of the question.

Diuretics↗
PubMedDate not supplied

Experience with a sulfonamide diuretic in a large urine drug testing program.

Gas chromatography/mass spectrometry (GC/MS) with selected ion monitoring is a common confirmation method for tetrahydrocannabinol (THC) metabolites in urine. Department of Defense laboratories use this method for analysis of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THCA) following ion exchange column purification and methylation. Furosemide, a common diuretic which is excreted into urine, will be isolated with THCA in the extraction procedure, will appear in the chromatographic window [retention time relative to 11-nor-delta-9-tetrahydrocannabinolmethyl ether-9-carboxylic acid methyl ester (THCA-Me) of 1.13], and will exhibit the six ions monitored for THCA-Me and its trideuterated analog. The results indicate that methylated furosemide and other common diuretics can easily be distinguished from THCA-Me. They also allow one to explain in court the extraneous peaks in a chromatogram and to correct for the overutilization of derivatizing reagent.

Diuretics↗
PubMed1997

A double-blind, cross-over comparison of the effects of a loop diuretic and a dopamine receptor agonist as first line therapy in patients with mild congestive heart failure.

We compared the effects of the orally active dopamine agonist ibopamine with the loop diuretic frusemide as first-line therapy in patients with mild congestive heart failure. Fourteen patients with New York Heart Association class II congestive heart failure were enrolled in a double-blind, cross-over study. After baseline measurements of clinical and symptomatic status, modified Bruce exercise time, high-level exercise time, corridor walk time, regional blood flow, pedometer scores, 24 h urine volume and sodium excretion and neurohumoural factors, patients were randomly allocated to receive either frusemide 40 mg o.d. or ibopamine 100 mg t.d.s. for 8 weeks. Assessments were performed at 2 weekly intervals. After 8 weeks, patients crossed over into the alternate treatment arm for a further 8 weeks, with further assessments performed every 2 weeks. There were four exacerbations of heart failure during ibopamine treatment and none during frusemide treatment. After 8 weeks of treatment, modified Bruce exercise time was 901 +/- 73 s with frusemide and 646 +/- 134 s with ibopamine (P < 0.05). Twenty-four hour urinary sodium excretion at weeks 2 and 4 (P < 0.05), and 24 h urinary volume at week 2 (P = 0.0001) were lower during ibopamine treatment. At week 8, supine (P = 0.076) and erect renin (P = 0.05) were lower with ibopamine treatment. In conclusion, ibopamine is ineffective as first line therapy for congestive heart failure, probably because of a lesser diuretic potency than frusemide.

Adult↗
PubMed1984

Cardiac arrhythmias following acute myocardial infarction: associations with the serum potassium level and prior diuretic therapy.

The relationship between the initial serum potassium level and the incidence of cardiac arrhythmias following myocardial infarction has been reviewed in a coronary care unit setting. The incidence of arrhythmias in general, and ventricular fibrillation, ventricular tachycardia and frequent ventricular ectopic beats in particular, were inversely related to the initial serum potassium level. Hyperkalaemia was also significantly associated with ventricular fibrillation and ventricular tachycardia. Hypokalaemia was significantly more common in patients previously treated with diuretics, though most patients with hypokalaemia had not been so treated. The occurrence of an acute hypokalaemic syndrome, independent of, but exacerbated by, diuretic therapy, is further supported by these results.

Arrhythmias, Cardiac↗
PubMed1985

Diuretic-induced gout in elderly women.

During a 21/2-year period, gout was diagnosed in 51 men and 9 women at the Rheumatology Unit in Bristol. The men had a mean age of 52 years and mean age of onset of gout of 46 years, whereas the women had a mean age of 82 years and a mean age of onset of 77 years. All the women were on long-term diuretic therapy compared to 33% of the men; 77% had mild impairment of renal function and 44% had tophi. The men could recall four times as many attacks of acute gout as the women. Elderly women are particularly prone to diuretic-induced tophaceous gout but less likely to present with acute gout than men.

Age Factors↗
PubMed1994

Diuretic effect of clonidine during isoflurane, nitrous oxide, and oxygen anesthesia.

BACKGROUND: Because clonidine, a relative selective alpha 2-agonist, inhibits the action of arginine vasopressin (AVP), the authors examined whether clonidine as an oral preanesthetic medication would induce diuresis and also would affect AVP release and its action during general anesthesia. METHODS: Fifty-seven patients (aged 18-65 yr) randomly received oral clonidine either approximately 5 micrograms.kg-1 (n = 19), approximately 2.5 micrograms.kg-1 (n = 19), or none (n = 19) in addition to oral famotidine 20 mg, 90 min before arrival at operating room. Urine volume, urine osmolality, and amount of sodium and potassium excreted into urine were examined every hour for 3 h during minor surgery under general anesthesia with isoflurane and nitrous oxide in oxygen. For 5 patients of each group, plasma AVP and atrial natriuretic peptide concentrations and urine cyclic adenosine monophosphate concentrations as an index of AVP action were also assayed. RESULTS: Urine output indices (calculated as hourly urine output [milliliters per hour] divided by body weight [kilograms]) were significantly greater in the all periods (P < or = 0.035) after the initiation of anesthesia in the patients receiving clonidine 5 micrograms.kg-1 and only in the 3rd h in those receiving clonidine 2.5 micrograms.kg-1 (P = 0.047) as compared with those in the patients given famotidine alone. The peak effects of diuresis and natriuresis induced by oral clonidine 5 micrograms.kg-1 were both observed at the 2nd h (mean +/- SEM, 2.4 +/- 0.4 ml.kg-1.h-1 and 5.7 +/- 1.5 mEq.h-1 vs. 0.6 +/- 0.1 ml.kg-1.h-1 and 2.2 +/- 0.5 mEq.h-1 in the control subjects; P = 0.001 and P = 0.049). Kaliuresis also increased in the patients receiving clonidine 5 micrograms.kg-1 in the 2nd and 3rd h (P < or = 0.003). Urine osmolality showed a significant reduction over time in patients given clonidine but not in the control subjects. However, plasma AVP and atrial natriuretic peptide levels, and urine cyclic adenosine monophosphate concentrations did not significantly differ among the three groups. CONCLUSIONS: Oral preanesthetic medication of clonidine 2.5 or 5 micrograms.kg-1 caused a significant diuretic effect during surgery under general anesthesia, though it did not apparently relate to AVP action. This effect of clonidine could be related to its pharmacological action as an alpha 2-adrenoceptor agonist not necessarily restricted to the kidney. The diuretic effect of clonidine implicates its clinical importance in the management of patients during anesthesia.

Administration, Oral↗
PubMed1987

Calcium antagonists and diuretics as combined therapy.

Whether a diuretic confers an additional antihypertensive effect on patients receiving treatment with calcium channel blocking drugs remains controversial. The results of seven recently reported trials are summarized, with the conclusion that much of the confusion arises because of inadequacies in trial design, particularly the failure to take into account placebo responses and period effect, and the inclusion of too few subjects to give the trial sufficient power to demonstrate a significant fall in blood pressure. Further difficulties in comparing one trial with another include differences with respect to age, race, severity of hypertension and renin status in the patient populations under investigation, since all these factors may influence responsiveness to therapy with both classes of agent. Although there may be theoretical grounds for believing that, under circumstances of optimal calcium entry blockade in vascular smooth muscle, diuretics might not cause any further reduction in blood pressure, until such time as full dose-response relationships are established for each class of agent alone and in combination, the problem will remain unresolved.

Calcium Channel Blockers↗
PubMed1989

Effects of thiazide diuretic on vascular eicosanoid system of spontaneously hypertensive rats.

To assess the role of the vascular eicosanoid system in thiazide therapy, we examined the aortic eicosanoid system of spontaneously hypertensive rats (SHR) treated with trichloromethiazide for 2 weeks. The blood pressure reduction caused by the thiazide treatment was associated with a significant decrease in vascular vasodepressor prostacyclin (PGI2) generation, whereas neither nifedipine nor captopril treatment lowered vascular PGI2 generation. The thiazide diuretic directly lowered PGI2 synthase activity in cultured vascular smooth muscle cells (VSMC), thereby decreasing PGI2 generation in the VSMC and probably in the aortic wall. This direct inhibitory effect on vascular PGI2 generation was not observed with either furosemide or indapamide. Thus, vascular PGI2 generation is reduced with trichloromethiazide, partly through its direct inhibition of PGI2 synthase; this has possible relevance to the non-beneficial effects of thiazide diuretics on the vascular sclerotic changes.

Animals↗
PubMed1990

Diuretics for elderly patients.

Diuretics compare well with the large number of other classes of antihypertensive agents now available as first-line treatment in the elderly. Other drugs might be considered for first-line treatment in elderly patients with diabetes, untreated gout, or renal failure, a previous myocardial infarction or multiple ventricular ectopics and for men concerned about potency. A thiazide with a potassium-sparing agent may be preferred in the elderly population. The most telling feature in favor of diuretics is that they comprise the only group of drugs for which a beneficial effect in reducing cardiovascular disease in the elderly has been demonstrated in clinical trials. Although compliance may decline somewhat with age, compliance rates of 80% or more can be expected, even among very elderly patients.

Aged↗
PubMed2000

Serum uric acid, diuretic treatment and risk of cardiovascular events in the Systolic Hypertension in the Elderly Program (SHEP).

OBJECTIVE: To assess longitudinally the association of serum uric acid and its change due to diuretic treatment with cardiovascular events in hypertensive patients. DESIGN: Cohort study in a randomized trial. SETTING: Cohort of hypertensive patients. PARTICIPANTS: A total of 4327 men and women, aged > or = 60 years, with isolated systolic hypertension, randomized to placebo or chlorthalidone, with the addition of atenolol or reserpine if needed, were observed for 5 years. MAIN OUTCOME MEASURES: Major cardiovascular events, coronary events, stroke and all-cause mortality. RESULTS: Cardiovascular event rates for quartiles of baseline serum uric acid were: I, 32.7 per 1000 person-years; II, 34.5 per 1000 person-years; III, 38.1 per 1000 person-years; and IV, 41.4 per 1000 person-years (P for trend = 0.02). The adjusted hazard ratio (HR), of cardiovascular events for the highest quartile of serum uric acid versus the lowest quartile was 1.32 (95% CI, 1.03-1.69). The benefit of active treatment was not affected by baseline serum uric acid. After randomization, an increase of serum uric acid < 0.06 mmol/l (median change) in the active treatment group was associated with a HR of 0.58 (0.37-0.92) for coronary events compared with those with a serum uric acid increase > or = 0.06 mmol/l. This difference was not explained by blood pressure effects. Those with a serum uric acid increase > or = 0.06 mmol/l in the active treatment group had a similar risk of coronary events as the placebo group. CONCLUSIONS: Serum uric acid independently predicts cardiovascular events in older persons with isolated systolic hypertension. Monitoring serum uric acid change during diuretic treatment may help to identify patients who will most benefit from treatment.

Adrenergic beta-Antagonists↗