Initial reduction in blood pressure results from this agent’s diuretic-induced reduction in plasma volume and cardiac output with a slight increase in peripheral resistance followed by a decrease in vascular resistance, perpetuating the lowered blood pressure.

Its use is associated with a reduction in plasma volume, which is associated with increased activity in the renin-angiotensin system activity.

Inhibits the reabsorption of luminal sodium in the early distal convoluted tubule, initially promoting natriuresis and diuresis.

Thiazide diuretics act on the sodium chloride cotransporter in the distal convoluted tubule,  which is the diluting segment in the cortex of the nephron.

Thiazide diuretics limit the capacity of the kidneys to produce maximally dilute urine, thus limiting water excretion.

After a few days of use there is reequilibration  of sodium homeostasis by the kidney, and blood pressure lowering process through vasodilation in the absence of volume depletion.

Thiazide diuretics can be differentiated into today is a thiazide type, hydrochlorothiazide and thiazide-like chlorthalidone, indapamide, based on  molecular structure, mechanism of action and efficacy.

With the size sides there is a flat those response curve with a greater risk of adverse metabolic problems without significant improvement in blood pressure and doses exceeding 2.5 or 25 mg, depending on the diuretics.

Hydrochlorothiazide as a short duration of action of six-12 hours compared with chlorthalidone at 48-72 hours or indapamide the being 10 times as potent as the other 2, with about a 24 hour half life.

Chlorthalidone 25 mg per day is more effective in lowering systolic blood pressure at hydrochlorothiazide 50 mg a day.

As approximately 30 to 40% of individuals are salt sensitive, responding to high sodium intake with hypertension and to sodium restriction with a decrease in blood pressure, making thiazideas capable to promote diuresis and control of blood pressure.

Hyponatremia is seen in 22% and hypokalemia in 19% in patients taking thiazide diuretics.

In the study comparing chlorthalidone with hydrochlorothiazide there was more likelihood for hypokalemia and hyponatremia with the former than the latter.

The use of chlorthalidone leads the significantly fewer cardiovascular events than hydrochlorothiazide.

There is better lowering of blood pressure and cardiovascular outcomes with thiazide-like than thiazide type diuretics.

Thiazide like diuretics show statistically significant reduction in coronary heart disease, stroke, and hypertension.

Thiazides and increasing age are risk factors for syncope and falls.

Prescribing diuretics in elderly should be used with caution.

The elderly and black individuals are more salt sensitive and respond better to thiazides than whites and younger individuals with hypertension.

Patients of all ages and all ethnic groups will respond to some extent with lowering of blood pressure, when exposed to thiazides.

The Veterans Cooperative study established that antihypertensive intervention was beneficial in moderate to severe hypertension, with decreases in the incidence of death, strokes and other cardiovascular events in patients with diastolic blood pressures above 105 mmHg-this study utilized reserpine, hydralazine and thiazides.

Chlorthalidone has a longer half-life of 40 to 60 hours and is 1.5 to 2 times as potent is hydrochlorothiazide with a half-life of 6 to 12 hours, and its associated with more potassium loss.

Chlorthalidone explain, hitting the sodium-chloride symporter in the distal, convoluted tubule, and also inhibits carbonic anhydrase.

Hydrochlorothiazide act similarly and promotes diuresis and lowers plasma volume, but long-term use is also associated with vasodilatation.



Leave a Reply

Your email address will not be published. Required fields are marked *