Metolazone

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Metolazone

Kidney nephron

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Metolazone

Metolazone is a type of medication known as a diuretic, specifically a thiazide-like diuretic, which is used primarily to treat hypertension (high blood pressure) and edema (swelling) associated with congestive heart failure, chronic kidney failure, and nephrotic syndrome. It works by inhibiting the kidneys' ability to retain water and sodium, thereby increasing the production of urine and reducing blood volume to lower blood pressure and decrease swelling.

Mechanism of Action

Metolazone acts on the distal convoluted tubules and the proximal part of the distal tubule of the nephron, a structure in the kidney. Unlike the more common thiazide diuretics, metolazone can retain its efficacy even when the kidney function is significantly impaired. It inhibits the sodium-chloride symporter in these tubules, preventing water reabsorption and promoting diuresis (the production of urine). This action results in a decrease in blood volume, leading to a reduction in blood pressure and alleviation of edema.

Clinical Uses

Metolazone is primarily used for the treatment of:

• Hypertension - to lower high blood pressure, which helps prevent strokes, heart attacks, and kidney problems.
• Edema - particularly in cases related to congestive heart failure, chronic kidney failure, and nephrotic syndrome, where it helps reduce swelling and fluid retention.

Side Effects

Common side effects of metolazone include:

• Electrolyte imbalances, such as low potassium (hypokalemia), low sodium (hyponatremia), and high calcium (hypercalcemia)
• Dizziness or lightheadedness, especially when standing up quickly
• Gastrointestinal issues such as nausea or vomiting
• Increased blood sugar levels (hyperglycemia)
• Increased uric acid levels, which can exacerbate or lead to gout

Patients are advised to monitor for signs of electrolyte imbalance and to have regular blood tests to check kidney function and electrolyte levels while taking metolazone.

Interactions

Metolazone can interact with a variety of medications, including:

• Lithium - metolazone can increase lithium levels in the blood, leading to toxicity.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) - can reduce the effectiveness of metolazone.
• Digitalis - the risk of digitalis toxicity may be increased due to electrolyte imbalances caused by metolazone.

Pharmacokinetics

Metolazone is well absorbed from the gastrointestinal tract, with its diuretic effect beginning within one hour of oral administration and peaking in about two to four hours. Its effects can last up to 24 hours, making it suitable for once-daily dosing. The drug is metabolized in the liver and excreted primarily by the kidneys.

Conclusion

Metolazone is an effective medication for managing hypertension and edema, particularly in patients with reduced kidney function. However, its use requires careful monitoring of electrolytes and kidney function to avoid potential side effects and interactions with other medications.