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

Despite the beneficial therapeutic effects of antihypertensive drugs, some agents--particularly diuretics--seem to go in the "wrong direction" chemically. In fact, these changes could counteract some of the benefits resulting from lowering a patient's blood pressure. In the absence of hard evidence of the efficacy of long-term diuretic treatment of mild hypertension, we must be maximally sure that such therapy causes no harm. Thiazide and related diuretics have been associated with four distinct wrong-way chemical changes: increases in plasma concentrations of cholesterol, glucose, and uric acid, and a decrease in plasma potassium levels. The potential ramifications of such changes are well understood. The increase in circulating cholesterol, an established risk factor of myocardial infarction and stroke, is of particular concern--each year approximately one million hypertensive patients have myocardial infarctions. As a result, the search for safer and more effective diuretics must continue. Indapamide, a new antihypertensive drug, appears to meet these criteria. It is an effective diuretic with a considerable peripheral vasodilatory effect. Additionally, it does not appear to induce any significant change in circulating cholesterol, whereas chlorthalidone has been found to increase total cholesterol by 5%. Hydralazine is the only antihypertensive agent that seems to lower total cholesterol levels significantly. Neither indapamide nor hydralazine appears to affect plasma glucose levels; benzothiadiazines, however, have been found to induce an increase in circulating glucose.
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PMID:Some wrong-way chemical changes during antihypertensive treatment: comparison of indapamide and related agents. 686 7

Indapamide and methyldopa were compared in an open parallel study in patients with mild or moderate hypertension. Both drugs showed an antihypertensive effect significantly different from placebo but with indapamide the blood pressure response occurred sooner, after 2 weeks, as opposed to 4 weeks with methyldopa. Indapamide was better tolerated than methyldopa, producing fewer side effects.
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PMID:Indapamide in ambulant treatment of hypertension: a comparative study with alpha-methyldopa. 732 58

In an open study 30 hypertensive outpatients have been treated with Indapamide in a dosage of 2,5 mg daily in the morning for eight weeks. In the course of this treatment a highly significant decrease of blood pressure could be observed. The antihypertensive effect came up gently in the beginning. Indapamide has been well tolerated by all patients. The rate of adverse reactions was low. Syncopal episodes did not occur. The biochemical data monitored (fasting glucose level, creatinine, urea, potassium, sodium, calcium, chloride) did not show any significant deviation. According to the present data Indapamide may be used as basic medication in the treatment of genuine hypertension. The gentle effect in the beginning prevents syncopal episodes, however a sufficient period of treatment, at least eight weeks, is needed to assess the success of the therapy.
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PMID:[Ambulatory treatment of hypertension]. 740 72

We evaluated the mechanical properties of the carotid artery in anesthetized Dahl rats with or without long-term treatment with the diuretic compound indapamide. The mechanical properties of the carotid artery were evaluated by establishing pressure-volume curves in situ in vivo before and after total relaxation of arterial smooth muscle by potassium cyanide. Dahl salt-sensitive and salt-resistant rats were fed either a low (0.4%) or high (7%) NaCl diet for 5 weeks. In each group, half the rats received for the same period of time oral treatment with indapamide (3 mg/kg per day). Blood pressure, heart rate, and pressure-volume curves were studied at the end of the 5-week period. In untreated Dahl salt-sensitive rats, the pressure-volume curve of the carotid artery was shifted to the right compared with that in untreated Dahl salt-resistant rats. The finding was observed even after potassium cyanide and regardless of the NaCl diet (P < .01 between Dahl salt-sensitive and -resistant rats). Indapamide was able to prevent the development of hypertension in Dahl salt-sensitive rats receiving a high NaCl diet (185 +/- 7 versus 146 +/- 8 mm Hg in untreated and treated Dahl salt-sensitive rats with a high NaCl diet, P < .0005). In the other groups, indapamide had no effect on blood pressure. Indapamide treatment increased carotid arterial static compliance in Dahl salt-sensitive rats with a high or low NaCl diet and to a lesser extent in Dahl salt-resistant rats. The increase was observed even after total relaxation of carotid arterial smooth muscle by potassium cyanide.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Feb
PMID:Carotid artery mechanical properties of Dahl salt-sensitive rats. 784 78

This review discusses the pathophysiology and treatment of hypertension in the elderly. Evidence of the risks associated with systolic hypertension in particular is discussed in relation to the elderly population. The results of recent large-scale, placebo-controlled trials of hypertension in the elderly, including the Systolic Hypertension in the Elderly Program, the Swedish Trial in Old Patients with Hypertension, and the Medical Research Council trials, confirm the benefits of treatment in this population. However, pathophysiologic processes in the elderly may predispose them to drug side effects; therefore, selection of appropriate therapy is critical to the success of treatment. Various treatment options are available that may be suitable in subsets of the elderly population, particularly when low-dose regimens are used. Indapamide, a sulfonamide diuretic, may be particularly well suited for treatment of hypertension in the elderly because of its demonstrated efficacy and safety at low doses.
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PMID:Treatment of hypertension in the elderly. 785 34

Diuretics are widely used antihypertensive agents, and although their renal actions have been well characterized, the extent of their vascular effects remains to be defined. Because hypertension is associated with numerous vascular complications whose incidences are not always lowered once blood pressure is regulated, this study was undertaken to evaluate the effects of five selected diuretics on capillary permeability to see if they could contribute in some way to these vascular abnormalities. Extravasation of Evans blue dye (EB: 20 mg/kg) injected in the caudal vein of male Wistar rats was used to assess capillary permeability to albumin. Indapamide (0.04 mg/kg), cicletanine (2.0 mg/kg), amiloride (0.3 mg/kg), hydrochlorothiazide (0.5 mg/kg) and furosemide (0.5 mg/kg) were administered by acute i.v. injection or by 10-day "chronic" gavage. EB extravasation was increased in the upper bronchi, lung parenchyma and kidney after acute administration of indapamide (54, 41 and 31%, respectively) and hydrochlorothiazide (45, 41 and 19%, respectively), and increased in all tissues but the duodenum (upper bronchi, lung parenchyma, heart, liver, kidney and muscle; 57-118%) after furosemide. In contrast, capillary permeability was reduced after acute cicletanine in the heart (31%), duodenum (49%) and muscle (58%) and after amiloride in the heart (25%) and muscle (63%). Pretreatment with indomethacin abolished most changes in EB extravasation induced by acute injection of the diuretics. After 10-day gavage, however, changes in capillary permeability were null after amiloride or hydrochlorothiazide treatment, attenuated after cicletanine or furosemide or even reversed after indapamide. Arterial pressure was not affected by diuretic treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute and chronic diuretic treatment selectively affects vascular permeability in the unanesthetized normal rat. 801 52

Indapamide, a molecule with moderate diuretic effect, is an efficient antihypertensive drug. Blood pressure control is mostly explained by a direct action on peripheral vascular resistance. This action on peripheral resistances, as opposed to that on sodium balance, has rarely been indisputably substantiated. In order to dissociate its diuretic effect from its activity on peripheral resistances, we undertook a study on the efficacy of adding indapamide to the antihypertensive regimen of 12 patients suffering from chronic renal failure complicated by hypertension, and in whom control of high blood pressure had not been achieved with one to four antihypertensive drugs, plus furesemide in case of overhydration. Renal insufficiency was defined by serum creatinine levels of (m +/- SD) 271 +/- 171 mumol/l and a glomerular filtration rate of 36.7 +/- 18.6 ml/min. Before indapamide was introduced, blood pressure was 172.4 +/- 23.1 mmHg/109.6 +/- 9.55 mmHg. After 1 to 6 months of treatment, blood pressure was normalised. Systolic BP was 141.6 +/- 19 mmHg (p < 0.001) and diastolic BP was 89.7 +/- 8.6 mmHg (p < 0.001). Absence of diuretic effect and/or of modification of water and electrolytes was verified by the stability of body weight and serum electrolytes. At end point, body weight, electrolytes and renal function were unchanged. This study confirms that indapamide exerts an antihypertensive effect by lowering peripheral vascular resistances and not by diminishing the volume of extracellular fluid. Indapamide can be listed among antihypertensive agents that are advisable in the treatment of high blood pressure in patients with chronic renal insufficiency. Its antihypertensive effect in such patients is independent of any natriuretic action.
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PMID:[Antihypertensive action of indapamide in hypertension of chronic renal failure]. 817 77

Indapamide (Fludex) administered in daily doses of 2.5 mg resulted in optimal improvement of the blood pressure in patients with mild or moderate hypertension. During the period of 6 months treatment that was tolerated well by the patients, no influence of indapamide on the levels of glucose, cholesterol, triglycerides, and creatinine in blood was observed. A mild decrease of serum potassium in blood was clinically not relevant. Using echocardiography and electrocardiography a regression of the hypertrophy of the left ventricle of the heart was observed.
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PMID:[Regression of hypertrophy of the left ventricle in patients with hypertension after 6-month treatment with Fludex]. 831 Jul 1

Indapamide is a diuretic prescribed in the treatment of hypertension at the dosage of 2.5 mg per day. In accordance with international recommendations concerning the need to use low doses of antihypertensives, a new lower-dose form of indapamide has been developed to achieve the best safety/efficacy ratio by decreasing the incidence of hypokalemia. A new pharmaceutical sustained-release (SR) form was developed to give a smooth pharmacokinetic profile in comparison with the indapamide instant release (IR) form. The aim of this study was to determine the lowest new dosage of the SR form producing similar hypertensive efficacy as the LR form, and decreasing the percentage of patients with a serum potassium concentration below 3.4 mmol/l. This multicenter study was designed as a single-blind, run-in, placebo period of 1 month, followed by a double-blind, active treatment period of 2 months, using parallel groups: 285 patients with essential uncomplicated mild-to-moderate hypertension (95 mmHg < or = supine diastolic blood pressure (sDBP) < or = 114 mmHg) were included and randomly treated by either IR indapamide (2.5 mg) or SR indapamide (1.5, 2.0, 2.5 mg). After 2 months of active treatment, the one-way analysis of variance on the principal criterion (difference in sDBP between M2 and M0) revealed a significant treatment effect (p = 0.016). The mean drop in sDBP (+/- standard deviation) was 5.8 mmHg (+/- 8.6) after 2 months of placebo; 10.1 mmHg (+/- 7.0) after indapamide IR 2.5 mg; and 11.0 mmHg (+/- 9.4), 8.9 mmHg (+/- 9.4), and 10.5 mmHg (+/- 8.5) after indapamide SR 1.5 mg, 2 mg, and 2.5 mg, respectively. The difference between the placebo and indapamide treatment was significant (p < or = 0.05). No significant difference was detected between the various indapamide treatments, i.e., no difference between the IR and SR formulations, no difference between the various dosages of the SR form, and therefore no dose/effect relationship in the dose interval tested (SR 1.5, 2, and 2.5 mg). The incidence of patients with a serum potassium concentration less than 3.4 mmol/l was lower with indapamide SR 1.5 mg (11%) than with indapamide 2.5 mg, SR 2 mg, and SR 2.5 mg, respectively: 29%, 18% and 14%. These results show the interest of a low dose of indapamide in improving the safety while producing the same antihypertensive efficacy.
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PMID:[Therapeutic benefit of a low dose of indapamide: results of a double-blind against placebo European controlled study]. 857 50

Thiazide diuretics in high dosage adversely affect the lipid profile. The non-thiazide indoline, indapamide, appears to be free of this effect, but it is unclear whether this apparent metabolic advantage of indapamide is superior to thiazides used in low dose. Since there are no large direct comparative studies to test this distinction, I surveyed the literature and pooled the findings of all published reports giving data on lipid and blood pressure effects of thiazides in various doses and of both indapamide, 2.5 mg daily, used as monotherapy of hypertension. I found 31 reports of thiazides; 12 of them examined low-dose regimens, i.e., < or = 25 mg/day of hydrochlorothiazide or its equivalent in other thiazides. Larger doses of thiazides were tested in 19 studies (median daily dose of 50 mg, maximum dose of 112.5 mg). There were 430 subjects in the low-dose studies and 559 subjects in the high-dose regimens. There were 13 studies of indapamide, comprising 558 subjects. Regarding lipids, total cholesterol increased from baseline by 1.4% on indapamide, 3.8% on low-dose thiazides, and 6.3% on high-dose thiazides, The change from baseline was significantly greater for high-dose thiazides than for indapamide (p<0.01). Changes in high-density lipoprotein cholesterol did not differ among groups. The change in triglycerides differed among regimens, -0.5%, 10.8%, and 19.5% for indapamide, low-dose thiazides, and high-dose thiazides, respectively (p<0.01). Systolic blood pressure (SBP) decreased by 13 and 18 mm Hg on low-dose and high-dose thiazides, respectively (p<0.05 between doses). Indapamide lowered SBP by 16 mm Hg, not different from either thiazide dose. Diastolic blood pressure did not differ among groups. From these noncomparative studies, I conclude that (1) indapamide has no adverse lipid effect and lowers blood pressure equally to thiazides; (2) thiazide effects on lipids and SBP are dose-dependent; and (3) thiazides adversely affect the lipid profile even in low dose.
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PMID:A comparison of blood lipid and blood pressure responses during the treatment of systemic hypertension with indapamide and with thiazides. 884 87


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