Pressural - Indapamide

The LIVE (Left ventricular regression, Indapamide Versus Enalapril) study was a 1-year, prospective, randomized, double-blind comparison of modified-release indapamide 1.5 mg and enalapril 20 mg in reducing left ventricular mass in 411 hypertensive patients with left ventricular hypertrophy (9). For equivalent reductions in blood pressure, indapamide was significantly more effective than enalapril in reducing left ventricular mass index. 

Indapamide has been shown to possess diuretic and iadependent vasodilatory effects (16). It lowers the elevated blood pressure and reduces total peripheral resistance without an iacrease ia heart rate. ladapamide antagoni2es the vasocoastrictiag effects of the catecholamiaes and angiotensin II (16), a property not shared by other thia2ide-type diuretics. Tripamide is also reported to have direct vasodilatory effects (13). 

Diuretics have become the cornerstone of all treatment regimens of CHF (III—II3). They can reheve symptoms of pulmonary and peripheral edema. In mild CHF, the thia2ide-type diuretics are adequate unless the GFR falls below 30 ml,/min, as compared to 120 ml,/min in normal subjects. Diuretics improve left ventricular function in CHF due in part to decrease of preload. Indapamide has been shown to cause reduction of pulmonary arterial pressure and pulmonary wedge pressure. 

All ACE-I + diuretic or ARB blood pressure lowering Peridopril 2-8 mg daily Indapamide 1.25-5 mg daily Statin therapy ... 

This indoline derivative has antihypertensive and diuretic actions. Indapamide (233) in methanol under nitrogen was irradiated with a medium-pressure mercury lamp through a copper sulphate filter solution for 12 h. The filter removed wavelengths below 300 nm. Products were separated by preparative TLC and identified as 2-methylindoline (234), the formylhydrazide (235), the amide (237) and semicarbazide. The procedure was repeated under oxygen to give the above products plus the urethane (236), acid (238), ester (239) and TV-acetylanthranilic acid [146]. 

Indapamide is a derivative of benzolsulfonamide and its mechanism of action is analogous to that of thiazides. It is intended for lowering arterial blood pressure and as an adjuvant drug for treating edema caused by cardiac insufficiency. Synonyms of this drug are lozol and others. 

Quantification. High Pressure Liquid Chromatography. In blood, plasma or urine sensitivity 25 ng/ml in plasma, 50 ng/ml in blood and urine, UV detection—R. L. Choi et al., J. Chromat., 1982, 230 Biomed. AppL, 19, 181-187. In urine indapamide and 4-chloro-3-sulphamoylbenzoic acid, sensitivity 25 ng/ml, UV detection—P. Pietta et al., J. Chromat., 1982, 228 , Biomed. Appl.,17, 377-381. 

Indapamide is structurally related to chlortalidone but lowers blood pressure at subdiuretic doses, perhaps by altering calcium flux in vascular smooth muscle. It has less apparent effect on potassium, glucose or uric acid excretion (see below). 

Once-daily administration of 2.5 mg of indapamide has shown the drug to be a safe and effective agent to use in lowering blood pressure of hypertensive patients with normal renal function as well as patients with various degrees of renal impairment and those undergoing long-term maintenance hemodialysis (4). Results from clinical trials indicate that indapamide effectively reduces arterial blood pressure in approximately two-thirds of patients with mild to moderate hypertension, is well tolerated and does not induce biochemical abnormalities that constitute cardiovascular risk factors (3). Indapamide has also been shown to produce a clinically significant decrease in edema (5) as well as a reduction in total peripheral resistance (6). 

Another Beecham compound, BRL 13776 (25) has shown antihypertensive properties due to noradrenaline depletion in DOCA rats and renal hypertensive cats.98 Only the medulla/pons region of brain showed significant drops in noradrenaline, in contrast to reserpine. There were no behavioural effects and the compound is being taken to clinical trial. A novel hypotensive peptide, hypotensin, has been isolated from the venom of the Western diamondback rattlesnake.99 It contains approximately 20 amino-acid residues and appears unrelated to the kinins. The hypotensive effect is said to be dose-related after oral administration in normal rats and SHRs and is not consequent upon histamine release. Brief details of a clinical trial of a PGEp analogue (26) are available.100 Eleven of seventeen hypertensives responded with lower blood pressure to oral doses (10-20 pig) of 26. A recent studylOl of the marked antihypertensive properties of the diuretic Indapamide (27)(SE 1520, Servier) in rats and cats shows it to reduce vascular reactivity on chronic dosing. 

Indapamide, although differing structurally from thiazides, is not so pharmacologically. It can be viewed chemically as consisting of a polar sulfamoylchlorobenzamide and a highly lipoidal methylindolyl moiety. It is a potent drug that may owe only part of its antihypertensive effectiveness to natriuresis since it also has vasodilator properties. Its full potential in blood pressure reduction can take several weeks to develop. 

Thiazides reduce the blood pressure (Chapter 11). Initially, the reduction reflects the reduction of blood volume, but with continued use these agents appear to reduce vascular resistance as well. The antihj rtensive effect is modest but significant and is maximal at doses lower than the maximal diuretic dosage. Compared with older thiazides and thiazide-like agents, indapamide may have a greater ratio of vasodilating effect relative to its sodium diuretic effect. 

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