Thiazide diuretics inhibit the cotransport of symport type Cl/Na+ in the initial part of the distal tubule, after having been secreted in the lumen of the proximal tubule.
Thiazides reduce the reabsorption of Cl- and Na+, primarily by inhibiting their cotransport, especially at the level of the initial part of the distal convoluted tubule where less than 10% of Na+ and Cl filtered by the glomerulus remains. The mechanism and their location of action explain their relatively moderate diuretic effect because they act on a low proportion of the sodium filtered by the glomerulus.
Thiazide diuretics increase also urinary potassium elimination but to a lesser extent than sodium. This increase, which remains moderate, is badly explained; it could be the indirect effect of the increase in its secretion by the distal tract.
Thiazide diuretics also increase the urinary magnesium elimination.
They increase the elimination of bromide and of iodide parallel to that of chloride like that of bicarbonates and the pH of the urine rises.
They decrease the urinary calcium elimination, which improves the calcium balance. Used over a long time, they decrease in the elderly the risks of fracture of the hip.
They increase the aqueous diuresis moderately.
In plasma, they decrease the potassium concentration, they are hypokalemic diuretics. They slightly increase plasma uric acid concentration by decreasing its tubular secretion.
The paradoxical antidiuretic action of thiazide diuretics observed in patients with diabetes insipidus is not well explained, sodium depletion could be responsible.
The principal thiazide diuretics are hydrochlorothiazide, chlortalidone (Hygroton*), clopamide, bendroflumethiazide, xipamide and altizide. The most frequently used is hydrochlorothiazide (Esidrex*). Their principal therapeutic use is the treatment of arterial hypertension.
Indapamide (Natrilix*, Lozol*) and cicletanine have a low diuretic activity but some vasodilator effect. They are indicated only for the treatment of arterial hypertension where their direct effect on vascular smooth muscle could override their diuretic effect.
There are many drugs associating a thiazide diuretic and another drug, an ACE inhibitor, an inhibitor of AT1 receptors (angiotensin II) (See “Angiotensin”) or a beta-blocker.
Thiazides can induce various adverse effects: hypokalemia, discrete rise in uricemia, LDL (low density lipoproteins) cholesterol, decrease of glucose tolerance, probably by decreasing the secretion of insulin, aggravation of renal impairment and possibility hyponatremia in the elderly. Cutaneous eruptions, leukopenias were reported exceptionally.
Thiazide diuretics are largely used, in particular for the treatment of arterial hypertension where, correctly prescribed, they are well tolerated and effective.
The secretion of thiazide diuretics in the lumen of the proximal tubule can be inhibited by certain compounds such as probenecide which is not used any more.