1. E. There is no evidence that the thiazides have any effect on blood sugar. Initial reductions of blood pressure are due to decreased extracellular volume and cardiac output. The beneficial effect of the sustained reduction of blood pressure is due to reduced vascular resistance. Extracellular volume remains modestly reduced and cardiac output returns to pretreatment levels. Hypokalemia does not ameliorate over time and is associated with an increased risk of ventricular fibrillation and malignant arrhythmias. The magnitude of hypokalemia produced by thiazide and thiazidelike diuretics is dose dependent. However, the degree to which individual patients are affected varies, though chronic administration of even small doses causes some K+ depletion. Hyperuricemia is thought to have two causes. One is competition of the thiazide class of diuretics, which are weak organic acids, with uric acid for secretion by proximal tubules. This leads to diminished uric acid excretion. Serum concentrations of uric acid are further elevated by the reduced extracellular volume. Diuretic-induced hyperuricemia may cause acute gouty attacks.
2. D. Increased Na+ excretion is a direct consequence of diuretic treatment. In thick ascending limbs, the site of furosemide action, calcium and magnesium transport is largely determined by the magnitude of sodium absorption. Decreases of Na+ absorption are accompanied by diminished Ca++ and Mg++ absorption. K+ wasting is due to increased K+ secretion by late distal tubules and collecting ducts. Uric acid excretion decreases as a consequence of competition for the proximal tubule organic acid secretory mechanism.
3. C. Although still highly controversial, the initial use of a thiazide diuretic for monotherapy has been recommended by the Joint National Committee on Detection, Evaluation and treatment of High Blood Pressure. Triamterene and Aldactone are rarely used alone and exhibit no antihypertensive activity. A recent study found that the loop diuretics bumetanide and furosemide effectively reduced blood pressure. Serum lipid levels were less affected than with thiazide diuretics or chlorthalidone. However, thiazide diuretics are a more conservative and approved approach for the initial treatment of hypertension that avoid the more dramatic fluid and electrolyte shifts that occur with loop diuretics.
4. B. Intravenous furosemide causes a significant decrease in pulmonary capillary wedge pressure and right atrial pressure, concomitantly decreasing stroke volume and increasing vascular resistance. This effect in many cases occurs before diuresis begins.
5. D. Metolazone would be expected to be very effective, particularly in combination with a loop diuretic.
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