Diuretics, commonly known as “water pills,” are prescribed to manage conditions characterized by excess fluid, such as high blood pressure or edema. These drugs work by encouraging the kidneys to excrete more water and salt from the body, which reduces overall fluid volume. While effective, a potential side effect is hyponatremia, defined as an abnormally low concentration of sodium in the blood, specifically a serum sodium level below 135 millimoles per liter. Sodium is responsible for maintaining the balance of water inside and outside the body’s cells.
The Highest Risk: Thiazide Diuretics
Thiazide diuretics are the class of medication most frequently associated with causing hyponatremia; virtually all cases of severe diuretic-induced low sodium are linked to them. Medications such as hydrochlorothiazide and chlorthalidone are common examples. This class interferes with sodium transport in the distal convoluted tubule of the kidney, but it does not inhibit the kidney’s ability to maintain the medullary concentration gradient necessary for water reabsorption.
The resulting effect is a combination of sodium loss and a reduced capacity to excrete free water, leading to water retention that dilutes the remaining sodium. This side effect can occur relatively soon after therapy begins, with a majority of cases developing within the first two weeks to three months of starting the drug or increasing the dose. Older adults, particularly women, and individuals with a low body mass are at a greater risk. Furthermore, chlorthalidone carries an increased risk of hyponatremia compared to hydrochlorothiazide when prescribed at an equal dose.
Risk Profiles of Other Diuretic Types
While thiazides pose the highest risk, other diuretic classes carry different profiles. Loop diuretics, such as furosemide, are significantly less likely to cause chronic hyponatremia compared to thiazides. This is due to their mechanism of action in the loop of Henle, where they actively impair the kidney’s ability to concentrate urine.
By interfering with the medullary concentration gradient, loop diuretics promote the excretion of excess water, helping the body maintain a balanced loss of both water and sodium. Potassium-sparing diuretics, including spironolactone, generally carry a very low risk of causing hyponatremia. However, the risk increases when they are used at higher doses or in combination with other diuretics. Osmotic diuretics are another class, but they are not typically used for long-term management of conditions like hypertension or edema.
How Diuretics Cause Low Sodium
Diuretics contribute to this imbalance through a two-part physiological process involving both salt loss and water regulation. The initial effect is the intended increase in the excretion of sodium and chloride salts through the urine, a direct consequence of the drug’s action in the kidney tubules.
The more complex issue, especially with thiazides, is the disruption of the body’s ability to excrete free water. Thiazides prevent the normal reabsorption of sodium in the distal tubule, but they do not inhibit the kidney’s ability to reabsorb water further down the nephron. This selective effect results in a “diluting defect,” where the body retains excess water despite the continued loss of sodium.
Furthermore, the mild volume depletion from diuretic use may trigger the release of Antidiuretic Hormone (ADH), also known as vasopressin. ADH signals the kidneys to hold onto water, which exacerbates the dilutional effect by causing the body to retain more water and further lowering the concentration of sodium in the blood.
Recognizing Symptoms of Hyponatremia
The clinical presentation of hyponatremia can vary widely, ranging from no noticeable symptoms to a life-threatening medical emergency. Mild cases, where the sodium level has dropped slowly, may be asymptomatic or present with vague complaints. Common mild symptoms include a persistent headache, nausea, or generalized fatigue and drowsiness.
As the sodium level drops more rapidly or becomes significantly low, the symptoms become more serious due to the effect on brain cells. Patients may experience altered mental status, characterized by confusion, restlessness, or irritability. In the most severe instances, hyponatremia can lead to muscle weakness, seizures, or even a coma. Anyone taking a diuretic who develops these symptoms should seek immediate medical attention.