Thiazidic Diurétique

The thiazidic diuretic as all the Diurétique S cause to increase the Diurèse i.e. the drainage of water via the Urine S.

The reference product is the hydrochlorothiazide (ESIDREX).

At the origin, the thiazidiques ones were developed for their property of inhibition of the carbonic Anhydrase in alternative to the Acétazolamide but their effect diuretic appeared higher.

They all are of derived sulphamides.

Products (corresponding DCI and specialities)

Hydrochlorothiazide (ESIDREX)
Bendrofluméthiazide (NATURINE)
Hydrofluméthiazide (LEODRINE)
Chlortalidone (HYGROTON)
Indapamide (FLUDEX)

Mechanism of action

After a rapid absorption by oral way, the thiazidiques ones are secreted on the level of the Tube circumvented proximal where they enter in competition with the Uric acid .

They inhibit the Cotransporteur Na+/Cl- located in the part initial of the distal Tube circumvented. On this level, 15% of Na+ filtered by the Glomérule are reabsorbed.

Thus, they increase the urinary excretion of sodium and chlorides and, with a less degree, the excretion of potassium and magnesium, increasing kind the diuresis and exerting a antihypertensive action.

The time of the appearance of the diuretic activity is of approximately 2 hours. This activity is maximum at the end of 4 a.m. and is maintained from 6 to 12 noon. Their duration of action higher than the Diurétiques of the handle makes them more interesting in the treatment of the arterial Hypertension.

The therapeutic effect of diuretic thiazidic is proportional to the amount and the power of each product. But beyond a certain amount, the maximum effect is the same one for all the products. On the other hand the undesirable effects continue to increase: in the event of inefficiency of the treatment, it useful, and is not often badly tolerated, to increase the amounts beyond posologies recommended.

Undesirable effects

They are close to those of the Diurétiques of the handle which are also derivatives Sulfamidé S.

orthostatic Hypotension and Giddinesses, often consecutive with an overdose causing a Hypovolémie worsened by a reduction of the hydrous contributions and which can lead to a functional Impaired renal function
Hypokaliémie
metabolic Alcalose hypochloremic by increased elimination of H+ ions on the level of the exchanger located in the final part of the distal circumvented tube, had with the increased presence of Na+ on this level
Hyponatrémie
Intolerance with the glucids due to a reduction in the light insulin release
Hyperuricémie giving crises of drop only among patients having antecedents
Reactions of over-sensitiveness (allergies) in particular reactions crossed with the sulphamides

Indications

HTA
Edema S

Counter-indications

Over-sensitiveness
hepatic Encephalopathy
Impaired renal function
Syndrome of malabsorption glucose/galactose

Disadvised use

Pregnancy and breast feeding
Lithium (risk of overdose because the urinary excretion of Li is decreased)
Sultopride and other drugs giving of the Torsades of point (risk raised by the hypokaliemy)
AINS (diuretic reduction in the effect by reduction of glomerular filtration)
Digitalique (risk of toxicity raised by the hypokaliemy)

Precautions for use

Balance hydroelectrolytic and the renal function must be supervised.

renal Function: the diuretic thiazidiques ones are fully effective only when the renal function is normal or not very faded. (evaluated by the clearance of the Creatinin corrected by the Formula of Cockroft for the old subject)
Hyponatrémie: the Natrémie must be controlled before the startup of the treatment, then with regular intervals thereafter
Hypokaliémie: the potassic déplétion with hypokaliemy constitutes the main risk of diuretic thiazidic and related the
hepatic Atteinte: risk hepatic Encéphalopathie at the insufficient hepatic one and the cirrhotique one, in this case the stop must be immediate.

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