Diuretics lower blood pressure by reducing body sodium levels. Initially, they achieve this by decreasing blood volume and cardiac output, though peripheral vascular resistance may initially rise. Over a period of 6-8 weeks, cardiac output tends to normalize while peripheral vascular resistance decreases. Sodium contributes to vascular resistance by increasing vessel stiffness and neural reactivity, likely through changes in sodium-calcium exchange that lead to higher intracellular calcium levels. Diuretics or sodium restriction can reverse these effects.
Diuretics can effectively reduce blood pressure by 10-15 mm Hg in most patients and are often sufficient for treating mild to moderate essential hypertension. In cases of severe hypertension, diuretics are combined with sympathoplegic and vasodilator drugs to counteract the sodium retention caused by these agents. Sympathoplegic and vasodilator drugs decrease vascular responsiveness, making the blood pressure highly sensitive to blood volume. Hence, in severe hypertension, where multiple drugs are used, blood pressure can be well controlled with diuretics.
Use of Diuretics
Different diuretics act at various sites within the kidney and have distinct pharmacokinetic profiles. Thiazide diuretics are suitable for most patients with mild to moderate hypertension and normal kidney and heart function. Stronger diuretics, such as those acting on the loop of Henle (e.g., furosemide), are needed for severe hypertension, especially when combined with other sodium-retaining drugs, in renal insufficiency with a glomerular filtration rate below 30 or 40 mL/min, and in cases of heart failure or cirrhosis where sodium retention is significant.
Potassium-sparing diuretics help prevent excessive potassium loss and enhance the natriuretic effects of other diuretics. Aldosterone receptor antagonists also positively impact cardiac function in heart failure patients.
Toxicity of Diuretics
The most common side effect of diuretics (except potassium-sparing ones) in treating hypertension is potassium depletion. While mild hypokalemia is generally well-tolerated, it can be dangerous for patients on digitalis, those with chronic arrhythmias, acute myocardial infarction, or left ventricular dysfunction. Since potassium loss is linked to sodium reabsorption, reducing dietary sodium intake can help minimize potassium loss. Diuretics may also lead to magnesium depletion, impaired glucose tolerance, and increased serum lipid levels. Additionally, they can raise uric acid levels, potentially triggering gout. Using low doses can minimize these adverse metabolic effects without reducing the antihypertensive efficacy. Potassium-sparing diuretics, on the other hand, may have their own side effects.
Classification of diuretics
Diuretics are classified into several categories based on their mechanism of action and the specific part of the nephron where they act. The main classes of diuretics include:
1. Thiazide Diuretics:
– Mechanism of Action: Inhibit sodium reabsorption in the distal convoluted tubule.
– Examples: Hydrochlorothiazide, chlorthalidone, indapamide, metolazone.
– Uses: Primarily for hypertension and mild to moderate fluid retention.
2. Loop Diuretics:
– Mechanism of Action: Inhibit sodium-potassium-chloride co-transporter in the thick ascending limb of the loop of Henle.
– Examples: Furosemide, bumetanide, torsemide, ethacrynic acid.
– Uses: Used for severe fluid retention, such as in heart failure, renal insufficiency, and pulmonary edema.
3. Potassium-Sparing Diuretics:
– Mechanism of Action: Inhibit sodium channels in the distal convoluted tubule and collecting duct, preventing potassium loss.
– Subtypes:
– Aldosterone Antagonists: Spironolactone, eplerenone.
– Sodium Channel Blockers: Amiloride, triamterene.
– Uses Often used in combination with other diuretics to prevent hypokalemia; spironolactone and eplerenone also have beneficial effects in heart failure.
4. Carbonic Anhydrase Inhibitors:
– Mechanism of Action: Inhibit carbonic anhydrase in the proximal convoluted tubule, reducing bicarbonate reabsorption.
– Examples: Acetazolamide, methazolamide.
– Uses: Mainly for glaucoma, altitude sickness, and metabolic alkalosis.
5. Osmotic Diuretics:
– Mechanism of Action: Increase the osmolarity of the glomerular filtrate, inhibiting water reabsorption in the proximal tubule and loop of Henle.
– Examples: Mannitol, glycerin, urea.
– Uses: Reduce intracranial and intraocular pressure, manage acute kidney injury.
6. Vasopressin Antagonists (Aquaretics):
– Mechanism of Action: Inhibit the action of antidiuretic hormone (ADH) on the collecting ducts, increasing free water excretion.
– Examples: Conivaptan, tolvaptan.
– Uses: Treat hyponatremia, particularly in cases of syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Conclusion
Diuretics are an essential class of medications primarily used to manage hypertension and conditions associated with fluid retention. They work by reducing body sodium levels, initially lowering blood pressure through a decrease in blood volume and cardiac output, with subsequent normalization of cardiac output and reduction in peripheral vascular resistance over time. This mechanism makes diuretics effective in lowering blood pressure by 10-15 mm Hg in most patients, proving sufficient for treating mild to moderate essential hypertension.
There are various types of diuretics, each acting at different sites within the nephron and having distinct mechanisms of action. Thiazide diuretics are commonly used for mild to moderate hypertension. In more severe cases or conditions with significant sodium retention, loop diuretics are preferred. Potassium-sparing diuretics are used to prevent hypokalemia and can have additional benefits in heart failure. Other classes, such as carbonic anhydrase inhibitors and osmotic diuretics, are used for specific conditions like glaucoma and reducing intracranial pressure.
However, diuretics can have side effects, the most common being potassium depletion (except in potassium-sparing diuretics), which can be hazardous in certain patient populations. Other potential adverse effects include magnesium depletion, impaired glucose tolerance, increased serum lipid levels, and elevated uric acid concentrations, which can lead to gout.
In summary, diuretics are versatile and powerful drugs essential for managing hypertension and fluid retention, with careful consideration required to balance their therapeutic benefits against potential side effects.
