SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Photo-onycholysis due to indapamide presented in a 75-year-old woman who was being treated with the diuretic for hypertension. The onset of her photo-onycholysis was delayed because of inadvertent photoprotection in the form of artificial nails and occurred in the absence of a generalized photosensitive eruption. Her nails returned to normal after withdrawal of the drug and application of opaque nail polish.
Clinical efficacy is not the sole criterion today in the drug treatment of hypertension, a condition which is so often asymptomatic and one which demands prolonged, usually lifetime, management of the patient. Patient compliance with treatment is essential and the practical usefulness of a drug can be determined by its side-effect liability, convenience and simplicity of administration and low possible long-term risk potential. There is growing experimental and clinical evidence that indapamide, an antihypertensive agent with only limited diuretic activity at low dosage (2.5 mg as a single dose per day), is proving to be a consistently effective and well-tolerated alternative to the thiazides and beta-blockers as a first-line treatment, and a useful addition in multi-drug regimens. Some of the recent data, particularly from U.S. and Canadian studies, are briefly reviewed.
An antioxidant activity of indapamide (IDP) and its metabolite (OH-IDP) is demonstrated in this study. Both IDP and OH-IDP were found to scavenge 1,1-diphenyl-2-picryl-hydrazyl free radical. The scavenging effect of OH-IDP was stronger than that of IDP. Lipid peroxidation of rat liver microsomes initiated by reduced nicotinamide adenine dinucleotide phosphate (NADPH) and adenosine diphosphate (ADP)-Fe3+ was inhibited by IDP and OH-IDP with IC50 values of about 6 and 2 microM, respectively. The lipid peroxidation in human erythrocyte membrane, induced by 2,2'-azobis-(2-amidinopropane dihydrochloride) treatment, was also inhibited by 10 microM IDP. The antioxidant capacity of OH-IDP was at almost the same level as that of alpha-tocopherol, tested for comparison. The present data show that IDP and OH-IDP at micromolar concentrations are able to trap the free radicals involved in the lipid peroxidation.
Clinical and epidemiological studies suggest that thiazide diuretics can prevent bone loss and decrease the incidence of hip fractures. However, the mechanism of the effect of diuretics on bone is not clearly established. Indapamide (IDP), a sulfonamide diuretic related to thiazides, is used to treat hypertension. Sixty spontaneously hypertensive rats (SHRs) were divided into four groups and treated with or without IDP (1.5 mg/kg/day) during 8 weeks in the presence or absence of a high sodium load (8% NaCl supplementation in the diet). Sodium and calcium excretions were increased in the rats receiving the high sodium load (SHR + 8% NaCl) comparatively with control rats (SHR). IDP decreased and increased, respectively, calcium and sodium excretions. Serum parathyroid hormone (PTH) was unchanged in any group. Bone density was measured at the femur, tibia, and vertebrae, and bone morphometry was performed at the metaphysis of the femur to evaluate bone architecture. Rats fed a high sodium diet had an average 5.5% decreased bone density at every site except the femoral diaphysis. The trabecular bone volume was also decreased (SHR + 8% NaCl vs. SHR, 11.99+/-0.78 vs. 17.51+/-1.5%, p < 0.05). An increase in trabecular separation suggested that these changes were due to increased bone resorption. In the SHR + 8% NaCl + IDP group, IDP increased bone density and trabecular bone volume (SHR + 8% NaCl + IDP vs. SHR + 8% NaCl, 16.52+/-1.04 vs. 11.99+/-0.78%, p < 0.05). Trabecular separation and pyridinoline/creatinine excretion (SHR + 8% NaCl + IDP vs. SHR + 8% NaCl, 136.39+/-9.62 vs. 195.18+/-22.34 nmol/mmol, p < 0.05) were also decreased by IDP. These results show that in rats receiving a high sodium diet, IDP can reverse sodium-induced bone loss and increased bone resorption independently of changes in serum PTH.
We recently showed that indapamide (IDP), a thiazide-related diuretic, increases bone mass and decreases bone resorption in spontaneously hypertensive rats supplemented with sodium. In the present study, we evaluated the in vitro effects of this diuretic on bone cells, as well as those of hydrochlorothiazide (HCTZ), the reference thiazide, and acetazolamide (AZ), a carbonic anhydrase (CA) inhibitor. We showed that 10(-4) M IDP and 10(-4) M AZ, as well as 10(-5) M pamidronate (APD), decreased bone resorption in organ cultures and in cocultures of osteoblast-like cells and bone marrow cells in the presence of 10(-8) M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. We investigated the mechanism of this antiresorptive effect of IDP; IDP decreased osteoclast differentiation as the number of osteoclasts developing in coculture of marrow and osteoblast-like cells was decreased markedly. We then investigated whether IDP affected osteoblast-like cells because these cells are involved in the osteoclast differentiation. Indeed, IDP increased osteoblast-like cell proliferation and alkaline phosphatase (ALP) expression. Nevertheless, it did not modify the colony-stimulating factor 1 (CSF-1) production by these cells. In addition, osteoblast-like cells expressed the Na+/Cl- cotransporter that is necessary for the renal action of thiazide diuretics, but IDP inhibited bone resorption in mice lacking this cotransporter, so the inhibition of bone resorption and osteoclast differentiation did not involve this pathway. Thus, we hypothesized that IDP may act directly on cells of the osteoclast lineage. We observed that resorption pits produced by spleen cells cultured in the presence of soluble osteoclast differentiation factor (sODF) and CSF-1 were decreased by 10(-4) M IDP as well as 10(-5) M APD. In conclusion, in vitro IDP increased osteoblast proliferation and decreased bone resorption at least in part by decreasing osteoclast differentiation via a direct effect on hematopoietic precursors.
Indapamide conferred effective blood pressure control over the six-month period of study. Blood sugar was elevated slightly in some patients. Hypokalemia occurred commonly within four to six weeks of initiating therapy and was corrected with oral potassium supplementation. There were no changes in cholesterol or triglyceride. There was an increase in plasma renin activity, probably diuretic induced. The antihypertensive efficacy and the low side effect profile may both be related in part to the observed net reduction in neural tone.
Most patients with hypertension will need, at some stage, more than one drug to lower their blood pressure. Although monotherapy is still the preferred option for first-line treatment of hypertension, low-dose combination therapy as the initial medication has been increasingly recommended by National and International Guidelines. The use of perindopril/indapamide is an example of such a combination which contains 2 mg of the angiotensin converting enzyme inhibitor perindopril and 0.625 mg of the diuretic indapamide, these doses being respectively half and a quarter of the usual doses in monotherapy. This combination appears to lower blood pressure effectively with a good safety profile. It can be used in the elderly and also in patients with reduced renal function. Studies are underway to assess its efficacy on target organ damage.
The hemodynamics and myocardial contractility were studied in 64 patients with Stages I-II hypertensive disease during 12-week monotherapy with indapamide agents (Fludex, Arifon, Lorvas). Their antihypertensive effect occurred 7-8 days later, with its peak at week 4, and was recorded in 64% patients, by normalizing the above parameters in 48% who had mainly lower or normal ejection and higher peripheral resistance. Improvement of hemodynamic and myocardial contractile parameters was parallel to a reduction in blood pressure.
A series of N-(4-chloro-3-sulfamoylbenzamido)-1,2,3,4-tetrahydroquinoline++ + (IV-1) and isoquinoline (IV-2) have been synthesized and their diuretic and antihypertensive activities evaluated. While none of the test compounds was found to be provided with antihypertensive properties, most of them displayed a diuretic activity comparable to (IV-2 a) or higher (IV-1 a,b) (IV-2 c) than those of indapamide and clopamide, taken as reference drugs.
S 5984 is a combination of tertatolol (S 2395-1) and indapamide. A positive synergism between these two constituents with regard to antihypertensive activity was demonstrated in the rat and the dog.
Epidemiologic studies evaluating arterial pulse wave velocity together with blood pressure indicate that: (1) salt intake has an independent effect on arteriolar tone and arterial wall properties, with the former indirectly and the latter directly contributing to increased arterial stiffness with age; and (2) normotensive adult subjects who follow a low sodium diet have reduced arterial stiffness and this effect is independent of blood pressure. Conversely, in elderly persons with isolated systolic hypertension, isotonic saline infusion causes a predominant increase in systolic pressure due to an increase in the stiffness of the arterial wall. The diuretic indapamide produces a decrease in blood pressure without significant change in brachial artery diameter. The result indicates a shift of the pressure-diameter curve, reflecting for the first time in humans a pharmacologic effect of the drug on arterial vessel. Furthermore, diuretic drugs may increase arterial distensibility and compliance in hypertensive patients, but this effect seems to be more pronounced in older than in younger subjects. In the latter, either activation of the sympathetic nervous system or potassium depletion, or both, might counteract the improvement in arterial distensibility caused by blood pressure reduction and sodium depletion. Based on epidemiologic, clinical, and pharmacologic studies, this critical review suggests that, in patients with essential hypertension, changes of sodium intake in diet or administration of diuretics, or both, affect the status of large arteries independently of blood pressure changes.
Since hypertension is an important risk factor of cardiovascular morbidity and mortality that can be at least in part decreased by pharmacologic reduction in elevated blood pressure, it is necessary that an antihypertensive agent be effective, but at the same time well tolerated and, according to some recent hypotheses, have no deleterious effect on serum electrolyte levels, as well as lipoprotein and glucose tolerance. However, due to different cultural and social backgrounds, lifestyles, and so on, the tolerability may differ from one population to another and the conclusions drawn from a population cannot be extrapolated to people of other countries. For these reasons, the well-being of patients, as well as the tolerability of indapamide, a non-thiazide diuretic, have been investigated in patients with hypertension of mild and moderate degree from different parts of Italy with a satisfactory blood-pressure response to this drug (-22.8 +/- 0.6/-17.1 +/- 0.5 mm Hg). Simultaneous to the significant blood-pressure reduction, the only significant change among the metabolic effects was a slight reduction in plasma potassium levels (-0.37 +/- 0.03 meq/liter). The tolerability was, on the whole, very good with a tendency toward an improvement of well-being in patients, the majority of whom were already asymptomatic before starting the treatment.
Two-months' administration of 2.5 mg/day indapamide, preceded and followed by 2 weeks of a placebo, led to a significant fall in pressure values and normalisation of diastolic pressure in a high percentage of 47 subjects, mostly with essential hypertension, in a controlled multi-centre trial. Absence of toxic effects, tolerance and therapeutic activity at low doses recommend the drug for most cases of arterial hypertension.
In pursuing earlier studies, the synthesis of a series of 1 and 1,3- substituted 2-(4-chloro-3-sulfamoylbenzamido)isoindolines (V a-e), related to indapamide, is described. These compounds were evaluated for diuretic and antihypertensive activities.
For this study hypertensive patients were selected who were taking at least a diuretic, a beta-blocker and a vasodilator. The diuretic was replaced by indapamide 2.5 mg daily. The objective was to assess the effect on blood pressure control and if possible reduce the total dose of the drugs administered, and also the side effects. 25 patients were admitted to the study. Four withdrew because of side effects. Of the remainder, blood pressure control improved in 10 patients, and in 7, some of the concomitant therapy was either withdrawn or reduced. Transient hypokalaemia developed in one patient byt the patient recovered without therapy. There was no significant increase in either serum uric acid or blood glucose.
In a double blind crossover double dummy study, 17 hypertensive patients who were not adequately controlled on atenolol alone were additionally given either bendrofluazide 5 mg or indapamide 2.5 mg for 12 weeks. Both drugs produced a similar modest improvement in blood pressure. No differences were seen on either treatment in body weight, plasma electrolytes, urea or uric acid.
Left ventricular function was evaluated non-invasively in hypertensive patients treated with indapamide by means of echographically determined velocity of circumferential fibre shortening (VCF). A statistically significant reduction in mean systolic and diastolic blood pressure in both the standing and supine position (P less than 0.001) and after exercise, systolic (P less than 0.001) diastolic (P less than 0.05) occurred but no alteration in left ventricular function was found. Blood lipids showed no change from pre-treatment levels. Serum uric acid demonstrated a significant elevation and serum potassium a significant fall but each remained within the normal range. Three patients required potassium supplementation. A significant rise in serum sodium and fall in serum chloride, both remaining within the normal range, occurred.
Patients with chronic obstructive airways disease (COAD) who also have hypertension present a particular therapeutic problem, since beta-blockers are likely to cause or aggravate bronchospasm. In this study, 25 patients with COAD and moderate benign essential hypertension were treated with indapamide 2.5 mg daily. Over the 28 week study period, blood pressure had fallen by 48/30 mmHg (mean value). With standardized bronchodilator therapy respiratory function improved over the same period.