Loop diuretics vascular effects

Loop diuretics may cause direct vascular effects. They, particularly furosemide, acutely increase systemic venous capacitance and thereby decrease left ventricular filling pressure. This effect, which may be mediated by prostaglandins and requires intact kidneys, benefits patients with pulmonary edema even before diuresis ensues. Furosemide... 

Diuretics are covered in greater detail in Chapter 15 but are mentioned in this chapter because of their importance in hypertension. These drugs lower blood pressure by reduction of blood volume and by a direct vascular effect that is not fully understood. The diuretics most important for treating hypertension are the thiazides (eg, hydrochlorothiazide) and the loop diuretics (eg, furosemide). Thiazides may be adequate in mild hypertension, but the loop agents are used in moderate, severe, and malignant hypertension. Compensatory responses to blood pressure lowering by diuretics are minimal (Table 11-2). When thiazides are given, the maximum antihypertensive effect is often achieved with doses that are below the maximum diuretic doses. 

In addition to their diuretic activity, loop agents appear to have direct effects on blood flow through several vascular beds. Furosemide increases renal blood flow. Furosemide and ethacrynic acid have also been shown to reduce pulmonary congestion and left ventricular filling pressures in heart failure before a measurable increase in urinary output occurs, and in anephric patients. 

The three main diuretic classes are thiazide, loop, and potassium-sparing diuretics (Table 10-1). Thiazide diuretics are considered one of the first-line agents for the treatment of HTN. Acutely, thiazide diuretics lower blood pressure by inhibiting sodium chloride cotransporters in the ascending loop of Henie and distal tubule, increasing sodium excretion and causing diuresis. The reduction in plasma volume decreases cardiac output and consequently reduces blood pressure. However, with continued therapy, the plasma volume returns to pretreatment level and there is a decrease in peripheral vascular resistance, which is responsible for the long-term anti hypertensive effects. The most common indication for thiazide diuretics is HTN. 

Indapamide is a sulfonamide diuretic that has been used for treatment of hypertension (2.5 to 5.0 mg/day). It has been proposed as an alternative antihypertensive agent with both diuretic and vasodilatory capability and a more favorable side-effect profile than the thiazides. Indapamide exerts its antihypertensive effect by two mechanisms. It appears to have a modest diuretic effect while also relaxing vascular smooth muscle. As a diuretic, indapamide increases the excretion of sodium, chloride, and water by interfering with the transport of sodium across the renal tubular epithelium. Its principal site of action remains controversial but is probably either at the diluting segment of the loop of Henle or the proximal segment of the distal tubule (see also Table 25 and Figure 17). 

The mercurial diuretics essentially contain in an organic molecule. They usually inhibit sodium reabsorption in the proximal tubuler and ascending loop of Henle. There may be slight effect in the distal tubule where inhibition of chloride reabsorption also occurs. The mercurials have been foimd to enhance excretion though potassium loss is less than that produced by many other diuretics. However, the overall action of mercurial diuretics is invariably increased by acidification of urine. The mercurial diuretics are not very much used in clinical practices due to their pronormced and marked side-effects viz., mercurialism, hypersensitivity and excessive diuresis which may lead to electrolyte depletion and vascular complications. Most of the mercurials are administered by intramuscular route and the availability of orally active diru etics has limited their use. 

---