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Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antihypertensive effect of indapamide, a new thiazide derivative, has a low diuretic effect and a primary action on vascular smooth muscle. It was evaluated in a series of 20 patients with non-insulin-dependent diabetes (age range 47-75 years) who had arterial hypertension of mild to moderate degree treated with hypoglycemic agents and/or diet. Indapamide, 2.5 mg, was given as a single daily dose for 6 months. A statistically significant reduction of systolic and diastolic pressures was observed in both supine and upright positions. This decrease was significant beginning in the first month of therapy (p less than 0.001). No significant modifications of fasting glycemia, postprandial glycemia, and glycosylated hemoglobin were noted. No significant changes were observed in serum sodium, potassium, chloride, calcium, and uric acid. Indapamide is an effective and practical treatment of hypertension of mild to moderate degree in patients with diabetes. The absence of effect on glucose metabolism makes it an especially interesting drug.
Hypertension
PMID:Indapamide in the treatment of hypertension in non-insulin-dependent diabetes. 407 34

Indapamide, a new methylindoline diuretic that appears to act on the distal renal tubules, is also reported to reduce vascular smooth muscle vasopressor reactivity and possibly to have a calcium-antagonist effect. Since 1973, sixteen studies by a number of European investigators who treated 301 patients with indapamide have revealed satisfactory control in 53% of patients with mild hypertension (standing diastolic pressures less than 90 mm Hg) and in 43% of patients with moderate hypertension when the drug was used without other agents. Multiple American clinical trials of indapamide in hypertension have been conducted, including double-blind, placebo-controlled protocols and trials comparing indapamide with traditional diuretic agents. A cooperative, double-blind, 40-week study compared antihypertensive response to indapamide, 2.5 mg and 5 mg daily, with response to hydrochlorothiazide, 50 mg daily, in the treatment of mild to moderate hypertension. Pretreatment diastolic blood pressures averaged 101 mm Hg. At 40 weeks of treatment, indapamide, 2.5 mg daily, had produced a fall in diastolic pressure of 15 mm Hg; indapamide, 5 mg daily, a reduction of 16 mm Hg; and hydrochlorothiazide, 50 mg daily, a fall of 15 mm Hg. Seventy-five percent of patients taking 2.5 mg of indapamide daily and 88% of those taking 5 mg achieved satisfactory blood pressure reduction. Hypokalemia may occur with indapamide but is a minor problem and seldom necessitates potassium supplementation. Serum uric acid increases were observed in only a few subjects, and clinical side effects are infrequent and mild. Indapamide is a useful antihypertensive agent with good patient tolerance in mild or moderate hypertension and may offer advantages over traditional diuretics in view of its possible vasodilator and calcium-antagonist properties, once-a-day dosage, and good therapeutic effect with prolonged usage.
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PMID:Clinical efficacy and safety of indapamide in essential hypertension. 634 46

Indapamide, 2.5 mg administered once daily for periods up to 36 months, was found to be safe and effective for the long-term control of mild to moderate hypertension. The effects of hydrochlorothiazide, 50 mg, and indapamide, 2.5 mg, were studied in two randomized, double-blind, multicenter trials. Data from the two multicenter trials (20 study sites) were pooled for purposes of comparison. Significant reductions in systolic and diastolic blood pressure, with patients in both supine and standing positions, occurred in both groups within the first 8 weeks of treatment. This effect was maintained throughout the active treatment period. Success, as determined by the therapeutic success rate (percentage of patients with decreases of standing phase V diastolic blood pressure of at least 10 mm Hg or to below 90 mm Hg), occurred in 53% of the patients given hydrochlorothiazide and in 56% of the indapamide-treated patients. During the study period, the nature, frequency, and severity of adverse reactions were similar for both groups. There was no clinically significant difference between the treatment groups for the laboratory assessments. Patients who completed the multicenter trials were eligible for participation in an ongoing long-term extension study of the safety of indapamide. Data are available for periods up to 36 months and demonstrate neither augmentation of clinical or laboratory adverse effects nor any potentially harmful indicators that could be attributed to prolonged treatment.
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PMID:Long-term experience with indapamide. 634 48

Indapamide, a new indoline antihypertensive agent, has been the subject of a worldwide programme to develop this drug for general clinical use. The results are described of the multi-centre U.S. clinical programme demonstrating the effectiveness and tolerance of indapamide for the treatment of hypertension. All work was conducted under U.S. Federal Food and Drug Administration guidelines, and resulted recently in a New Drug Application. A total of 1891 subjects or patients participated in 27 separate studies conducted by 91 investigators. In controlled clinical trials comparing 2.5 mg indapamide once daily with 50 mg hydrochlorothiazide once daily for 40 weeks in patients with mild to moderate essential hypertension, indapamide produced a reduction of supine blood pressure of -9.5/-14.3 mmHg as compared with -7.6/-11.4 mmHg for hydrochlorothiazide. In combination with methyldopa, propranolol, clonidine, guanethidine and hydralazine, indapamide consistently produced a greater decrease in arterial pressure than did those agents given alone. Indapamide added to these step-care agents did not result in a meaningful increase in adverse reactions. Indapamide has been the subject of a long-term safety study in which over 100 hypertensive patients have been followed up for 2 years or longer. During this period of time, indapamide was well tolerated and remained effective. No biochemical, electrocardiographic or ophthalmological changes were associated with its use. Other studies with indapamide are discussed describing the systemic and renal haemodynamic effects, pharmacokinetic properties and special safety studies conducted with this agent. The use of indapamide in patients with hepatic or renal impairment is reviewed in detail.
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PMID:Multi-centre clinical investigation of indapamide in the United States: a review. 635 83

Indapamide (Natrilix; Servier) is an antihypertensive diuretic which is used at a dose of 2.5 mg/d as first-line single-drug treatment of essential arterial hypertension. Indapamide effectively controls blood pressure in about 65% of cases of mild and moderate hypertension. The time-course of the antihypertensive effect of this drug consists of a clinically significant fall in blood pressure after the 1st week of treatment and of a further reduction that follows a decreasing power function of time thereafter. When an epidemiological approach to the mass treatment of hypertension is considered, the time-course of the antihypertensive effect of indapamide constitutes an advantage over diuretics such as the thiazides that lower blood pressure mildly during the 1st week of treatment and then proceed to lower it in a linear pattern thereafter. Indapamide does not increase magnesium excretion when given in single doses to normal volunteers. This distinguishes it from most diuretic formulations in current use, which increase renal magnesium excretion. The difference could be explained by the fact that the dose of indapamide usually employed is devoid of major diuretic activity although it still exhibits power antihypertensive properties. Since magnesium depletion provoked by diuretics seems to be the principal causative factor in the development of sudden cardiac death in patients under treatment with diuretics, indapamide should be regarded as one of the best options from this point of view.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Indapamide: a review. 635 2

Indapamide is an orally active sulphonamide diuretic agent. Although some evidence appears to indicate that the antihypertensive action of indapamide is primarily a result of its diuretic activity, only a limited diuresis occurs with the usual antihypertensive doses of 2.5 mg daily, and in vitro and in vivo data suggest that it may also reduce blood pressure by decreasing vascular reactivity and peripheral vascular resistance. In mild to moderate hypertension it is as effective as thiazide diuretics and beta-adrenergic blocking agents in lowering blood pressure when used as the sole treatment. Indapamide has been successfully combined with beta-adrenergic blocking agents, methyldopa, and other anti-hypertensive agents. While such findings need confirmation, it appears that indapamide shares the potential with other diuretic agents to induce electrolyte and other metabolic abnormalities, although it may do so with less frequency or severity. Thus, indapamide appears to offer a suitable alternative to more established drugs as a 'first-line' treatment in patients with mild to moderate hypertension. Whether it differs significantly from other diuretics when used as antihypertensive therapy, either in its mode of action or its side effect profile, needs further clarification.
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PMID:Indapamide. A review of its pharmacodynamic properties and therapeutic efficacy in hypertension. 648 95

The hemodynamic effects of indapamide were evaluated in an open clinical trial of nine patients with mild to moderate hypertension. Hemodynamic and echocardiographic measurements were made before and after six weeks of treatment with single daily doses of 2.5 mg of indapamide. Indapamide significantly reduced the mean standing systolic blood pressure (P less than 0.025), the mean standing diastolic blood pressure (P less than 0.01), the mean arterial blood pressure (P less than 0.001), and the mean total peripheral vascular resistance (P less than 0.01). Cardiac output increased 12% (P less than 0.05) during treatment. The heart rate, left ventricular end-diastolic and end-systolic volumes, systolic volume, and ejection fraction were not markedly altered after treatment with indapamide, although the systolic wall stress index fell slightly. Six weeks of indapamide administration was well tolerated with no notable adverse effects of the drug. The results suggest that indapamide reduces arterial blood pressure in hypertensive patients by decreasing total peripheral resistance.
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PMID:A systemic hemodynamic evaluation of indapamide. 661 23

A double-blind study was carried out in obese patients with moderately severe hypertension to assess the efficacy and tolerability of 2.5 mg indapamide as a once-a-day Step 1 drug compared to 50 mg hydrochlorothiazide also as a once-a-day Step 1 drug; to assess the efficacy and tolerability of a fixed daily dose of 2.5 mg indapamide administered concomitantly with methyldopa starting at 500 mg daily; and to compare the findings of efficacy and tolerability of 2.5 mg indapamide daily with those of 50 mg hydrochlorothiazide daily as Step 1 agents when methyldopa is the Step 2 drug. Twenty-nine patients completed the study and were evaluated. Nine patients achieved the study criterion of reduction of average standing diastolic pressure to 90 mmHg or less when treated with Step 1 medication only. Twenty patients required the addition of methyldopa to their Step 1 medication: 10 patients took 2.5 mg indapamide with an average constant daily dose of 1100 mg methyldopa and 10 patients took 50 mg hydrochlorothiazide with an average constant daily dose of 1575 mg methyldopa to achieve blood pressure control. All groups had mean diastolic pressure controlled at or below the 90 mmHg criterion during the period of constant methyldopa dosage for those patients who required Step 2 therapy. There were no significant differences between groups with respect to diastolic pressure during the constant dosage period. The indapamide patients required significantly (p less than 0.05) less methyldopa than did the hydrochlorothiazide patients in order to maintain satisfactory control of diastolic blood pressure. The number of responders was greater in the 2.5 mg indapamide + methyldopa group than it was in the 50 mg hydrochlorothiazide + methyldopa group, and responses were achieved more rapidly in the former group than in the latter. Indapamide (2.5 mg per day) was effective and well tolerated when used alone or as Step 1 medication in combination with methyldopa as Step 2 medication, and it compared favourably in this regard with hydrochlorothiazide.
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PMID:Indapamide in the stepped-care treatment of obese hypertensive patients. 661 42

Indapamide (Lozol) is a new diuretic and antihypertensive agent. The drug appears to have a unique mechanism of action, combining diuretic effects with a direct vascular action, presumably secondary to calcium channel blockade. Available studies indicate that indapamide is comparable to hydrochlorothiazide, chlorothiazide, furosemide, and other diuretic agents in the management of hypertension and edema. The drug produces toxicity similar to that of the thiazide and loop diuretics; however, it does not appear to increase cholesterol levels. Although it is claimed that indapamide produces no effect on glucose levels, hyperglycemia has been reported. Indapamide is safe and effective for treatment of hypertension in mild to severe renal impairment, but advantages over furosemide are questionable. Indapamide is a unique diuretic, but does not appear to offer advantages over other available agents.
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PMID:Indapamide: a unique diuretic? 665 5

Indapamide is a new antihypertensive diuretic agent indicated for the treatment of hypertension and edema. Indapamide shows an alteration in vascular reactivity to calcium and other agonists, suggesting the possibility of a direct vascular effect. The drug is recommended in doses of 2.5 to 5 mg once a day. It is rapidly and completely absorbed from the gastrointestinal tract, resulting in maximal blood levels in approximately 2.3 hours. Coadministration of indapamide with food or antacids does not reduce bioavailability. Linear proportionality of blood concentration with increasing doses is evident following both single and multiple doses. Other pharmacokinetic parameters are not dose related. Indapamide is widely distributed in the body with extensive binding to erythrocytes. Binding to plasma proteins is approximately 76%. Disappearance of indapamide from the blood is biphasic, with a terminal half-life of approximately 16 hours. Renal clearance represents less than 10% of the total systemic clearance of the parent drug, showing the dominant role of hepatic clearance. Studies of 14C-labeled indapamide in humans demonstrate that 70% of the radioactivity is excreted in urine and 23% in feces. Indapamide is extensively metabolized; less than 7% of the dose is excreted in urine as unchanged compound. Studies of patients with renal impairment showed little or no accumulation of indapamide in the blood in comparison to patients with normal renal function. Clinical studies demonstrate that indapamide has diuretic properties. Free water clearance studies indicate a site of action in the cortical diluting segment of the distal tubules. No adverse effect of indapamide on renal function is evident in normal volunteers, hypertensive patients, or geriatric hypertensive patients, as determined by glomerular filtration rate or effective renal plasma flow. Hemodynamic studies of indapamide in patients with mild to moderate hypertension show a significant (p less than 0.05) decrease in mean blood pressure (16%) and total peripheral resistance (15%). No other significant hemodynamic effects are evident. The data suggest that indapamide may produce antihypertensive activity through a dual mechanism of action--diuretic and direct vascular. Additionally, it appears to be safe even for patients with impaired renal function.
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PMID:Pharmacokinetics and clinical pharmacology of indapamide. 686 3


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