Thiazide Diuretics - Loop Diuretics

Diuretic drugs augment the kidney's urine production by the kidney. This is achieved by altering the way in which the kidney handles sodium. If the kidney discharges more sodium, then water excretion will also increase. Most diuretics cause diuresis by arresting the reabsorption of sodium at different sections of the renal tubular system. Sometimes a combination of two is given because this can be remarkably more effective than either compound alone. The reason for this is that one nephron segment can equalize for altered sodium reabsorption at another nephron segment; therefore, blocking multiple nephron sites notably boosts efficacy. Thiazide diuretics, like Moduretic, Hydrochlorothiazide and Esidrex, are the most frequently used diuretic, and block the sodium-chloride transporter in the distal tubule. Because this transporter normally only reabsorbs about 5% of filtered sodium, thiazide diuretics are less effective than loop diuretics in producing diuresis and natriuresis. Nonetheless, they are powerful enough to fulfill most therapeutic needs requiring such a medication. Their mechanism is based on on renal prostaglandin production.

Loop diuretics, such as Lasix and Frusemide obstruct the sodium-potassium-chloride cotransporter in the thick ascending limb. This transporter normally reabsorbs about 25% of the sodium load; therefore, inhibition of this pump can cause a significant increase in the distal tubular accumulation of sodium, decreased hypertonicity of the surrounding. This modified manipulation of sodium and water leads to both diuresis (increased loss off water) and natriuresis (increased sodium loss). By working on the thick ascending limb, which handles a considerable fraction of sodium reabsorption, loop diuretics are very strong diuretics. Antihypertensive therapy with this meds is particularly effective when joined by reduced dietary sodium intake. The success of these drugs is derived from their competence to lower blood volume, cardiac output, and with long-term therapy, systemic vascular resistance.

The great majority of hypertensive patients are treated with thiazide diuretics. The primary use for diuretics in heart failure is to decrease pulmonary and/or systemic congestion and edema, and related clinical symptoms (e.g., shortness of breath - dyspnea). Long-term treatment with diuretics may also reduce the afterload on the heart by improving systemic vasodilation, which can lead to improved ventricular ejection. Capillary hydrostatic pressure and therefore capillary fluid filtration is strongly affected by venous pressure. Therefore, by diminishing blood volume and venous pressure, this medicines are able to lower capillary hydrostatic pressure, which lessens net capillary fluid filtration and tissue edema.