12.03.3 Diuretics for Heart Failure

In hypertension, there is no accumulation of excessive fluid, but diuretics reduce blood pressure. In heart failure, there is an accumulation of excessive fluid, so that it is much more logical to use diuretics in heart failure to remove excessive fluid. By increase water loss from the body, diuretics decrease the oedema (Figure 12.3.1).

Figure 12.3.1 Diuretics and heart failure (Copyright QUT, Sheila Doggrell)

Diuretics decrease the oedema in the peripheral tissues, which leads to a reduced swelling of the legs. Diuretics also decrease the pulmonary oedema, which has two effects. Firstly, there is improved breathing, and secondly there is a decreased pulmonary resistance, which allows an increased cardiac output (Figure 12.3.1).

The diuretic combination most commonly used in heart failure is a Loop/High Ceiling Diuretic (usually furosemide), often in combination with a K⁺-sparing diuretic (e.g. amiloride). Amiloride has already been discussed. The thiazide diuretics, which are used in the treatment of hypertension, are often not potent enough to give a good clearance of fluids, and the more potent furosemide is used. Furosemide inhibits the Na⁺K⁺2Cl^- cotransporter in the thick ascending limb of Henle (Figure 12.3.2).

Figure 12.3.2 Mechanism of action of furosemide (Copyright QUT, Sheila Doggrell)

Furosemide (which is also known as frusemide) is active after oral or intravenous administration. After oral administration, frusemide is readily absorbed from the gastrointestinal tract to give a diuretic effect within 30 minutes. In an emergency, intravenous furosemide can be used to have an effect within 2 to 10 minutes. Frusemide is actively secreted into the proximal tubule of the kidney, and passes along the kidney tubule to the thick ascending limb of Henle, where it inhibits the Na⁺K⁺2Cl^- cotransporter (Na⁺ reabsorption). As water reabsorption follows ion reabsorption, inhibition of the Na⁺K⁺2Cl^- cotransporter leads to retention of ions and water, to increase the amount of water loss from the kidney. Frusemide has a greater maximum diuretic effect than thiazide diuretics, and this is commonly needed in congestive heart failure. Frusemide has a duration of action of 4 to 8 hours, and is excreted in urine.

Unfortunately, the increase diuretic potency with frusemide comes with increased adverse effects. An extension of the beneficial effects of frusemide leads to too much sodium being lost from the body producing hyponatremia (low levels of sodium in the body) and too much loss of fluid leading to hypotension.

Frusemide can cause excessive K⁺ loss from the kidney, as increasing the volume of luminal fluid/Na⁺ in distal tubule promotes secretion of K⁺ into the kidney tubule, and K⁺ loss. This hypokalaemic (low levels of potassium) can promote cardiac arrhythmias. Thus, when frusemide is being used on an ongoing basis, it may be necessary to determine plasma K⁺ levels. If excessive K⁺ is being lost from the body, frusemide can be given with potassium supplements or in combination with the K⁺ sparing diuretic amiloride.

Frusemide can cause hyperuricemia (high levels of uric acid). This is due to furosemide and uric acid being secreted into the proximal tubule by the same mechanism, and consequently furosemide can inhibit uric acid secretion and excretion. When uric acid excretion is inhibited, the levels rise, and this precipitates attacks of gout, especially in people with a previous history of gout. Thus, frusemide use should be avoided in this group, if possible. Frusemide can cause ototoxicity (hearing loss) by an unknown mechanism. Fortunately, hearing loss with frusemide is reversible. Finally, frusemide can increase the loss of magnesium from the body, and the resulting hypomagnesemia can promote cardiac arrhythmias. There hypomagnesemia-induced arrhythymias can be prevented with oral magnesium supplements.