The pharmacology and clinical pharmacology of indapamide

At low doses indapamide is a potent and long acting antihypertensive agent in various hypertensive animals and in man, but is without activity in normotensive subjects. A daily dose of 2.5 mg produces a minimal diuresis but at higher doses this increases without any significant augmentation of hypotensive activity. It appears to have no effect on most blood biochemical parameters, including glucose, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, noradrenaline, adrenaline, but potassium levels may decrease and uric acid and renin increase. Indapamide had no effect on renal function nor does it alter left ventricular function, electrocardiograph (ECG) or heart rate, although cardiac output may marginally increase. Total peripheral resistance is significantly decreased and it may exert its antihypertensive effect by reducing vascular reactivity to various pressor stimuli by inhibiting the net inward flow of calcium and resultant phasic contractions in vascular smooth muscle. Indapamide differs from the diuretics in that it has a comparatively high lipid solubility; it is also bound to blood proteins and elastin in vascular smooth muscle and little is eliminated in the urine. It may be for these reasons that the drug has less diuretic activity but more pronounced effect on vascular smooth muscle than compounds of similar structure.