Question

Research the mechanism of action of the diuretics furosemide (Lasix) and hydrochlorothiazide (thiazide).  Explain the main mechanism of action of each drug and describe how it produces diuresis.  List a few of the therapeutic uses for each of these diuretics.  Which is more likely to cause an acid/base imbalance and why?

Answer 1

Furosemide is a loop diuretic. It acts on the ascending limb of loop of henle. Of all the diuretics, the loop diuretics have the highest efficacy in mobilizing Sodium and chloride from the body. It inhibits the Na-K-2Cl-symporter on luminal membrane of ascending limb of loop of Henle. Therefore reabsorption of these ions is decreased. It acts promptly, even in patients with a poor renal function or the lack of response to other diuretics. It increases the calcium content of the urine. Loop diuretics may increase renal blood flow possibly by enhancing prostaglandin synthesis. Uses:-

• This is drug of choice for reducing acute pulmonary edema and acute or chronic peripheral edema caused by heart failure or renal impairment.
• It is useful in emergency situations.
• It is also used to treat hypercalcemia.
• It is also used to treat hyperkalemia.

Hydrochlorothiazide (thiazide diuretics). This drug acts mainly in the cortical region of the ascending loop of henle and a distal convoluted tubule to decrease reabsorption of sodium apparently by inhibiting Na-Cl cotransporter on the luminal membrane of the tubules. This increases the concentration of Na and Cl in the urine. It also increases the loss of K and Mg. It decreases the urinary calcium excretion. It also reduces the peripheral vascular resistance. Uses:-

• It is used in mild to moderate essential hypertension
• It is used in heart failure, though drug of choice is furosemide.
• It is used in hypercalciuria.
• It is used in diabetes insipidus.

Thiazide is more likely to cause acid-base imbalance as compared to the furosemide. When the thiazides are given, the body tries to reabsorb more sodium. In order to reabsorb more sodium, the body secrets more H and more K. As the H is lost more, there will be more metabolic alkalosis and hypokalemia. These changes are seen more with thiazide diuretics than furosemide.