Diuretics in cardiology

Diuretics in cardiology

Diuretics increase excretion of Na+ ions from the kidney. As a result water is excreted as well, which lowers plasma volume, extra cellular fluid, cardiac output, and, hence, blood pressure. Three classes of diuretics are applied in the treatment of hypertension: loop diuretics, thiazide diuretics, and potassium-sparing diuretics. Loop diuretics act in the ascending loop of Henle and block the Na+/K+/2Cl–cotransporter.

Example: furosemide is an efficacious drug mainly acting in the ascending limb of the loop of Henle. It almost completely inhibits reabsorption of Na+ and Cl– ions in the ascending loop by blocking the Na+/K+/2Cl–cotransporter. Neither Na+ nor K+ are reabsorbed. As a result, the NaCl concentration drops, which leads to decreased reabsorption of water and thus more diuresis. By changing the exchange of ions, the loop diuretics also cause a potential difference between the apical and basal membrane. Positive ions such as Mg2+ and Ca2+ cannot flow down the gradient into the interstitium anymore. Furosemide is used in the treatment of heart failure in order to decrease symptoms of oedema and dyspnoea by the mechanism of lowering preload. Thiazide diuretics act in the distal

tubule by inhibiting the Na+/Cl– cotransporter.

Example: hydrochlorothiazide inhibits the transport of Na+ and Cl– in the distal tubule. By blocking the Na+/Cl– cotransporter, the NaCl concentration in the tubular fluid remains high and more water will be lost. Hydrochlorothiazide is used in the treatment of heart failure in order to decrease symptoms of oedema and dyspnoea by the mechanism of lowering preload. Potassium-sparing diuretics in the late distal tubule and collecting duct, where they block a sodium channel.

Example: spironolactone is a specific antagonist of the mineralocorticoid receptor (MR) in the distal tubules and collecting ducts of the kidney. Binding to the mineralocorticoid receptor changes the conformation of the complex, rendering it unable to bind the mineralocorticoid receptor responsive element (MRE) on the DNA in the nucleus. Spironolactone thus counteracts the actions of aldosterone and thus has a natriuretic and potassium-sparing effect. Spironolactone is often used in combination with other diuretics in the treatment of oedema in heart failure. Further decrease of the aldosterone concentration is a beneficial additive effect of spironolactone.

1

Overdosing of loop diuretics can lead to

2

Which diuretic works best in a patient with decreased renal function?