Metolazone is a quinazoline sulfonamide diuretic, structurally related to the thiazide class, which was patented in 1966 and received U.S. FDA approval in 1974.It is primarily used to treat hypertension (high blood pressure), heart failure, and fluid retention (edema) associated with conditions affecting the heart, liver, kidneys, or lungs. Additionally, it may be used in the management of kidney stones. Metolazone works by promoting the excretion of excess water and certain electrolytes from the body, thereby reducing fluid overload and lowering blood pressure. Over time, it also helps relax blood vessels and improve blood flow, contributing to its long-term antihypertensive effects.
BRAND NAMES:
Zytanix – It is available as tablets with strengths 2.5mg & 5mg containing Metolazone as the main active ingredient.
Zaroxolyn – Metolazone the main active ingredient present in the Zaroxoly, it available in the market in the form of oral tablets with strength 2.5mg.
MECHANISM OF ACTION:
Metolazone acts by inhibiting sodium transport across the epithelial cells of the renal tubules, primarily in the distal convoluted tubules. This inhibition reduces sodium reabsorption, leading to increased excretion of sodium, chloride, and water. The resulting loss of fluid and electrolytes causes hypovolemia, which helps lower peripheral vascular resistance and restore normal cardiac output. This diuretic action helps resolve edema and contributes to metolazone’s effectiveness in managing hypertensionWhile metolazone has a mechanism of action similar to thiazide diuretics, it is more effective in patients with impaired renal function. Unlike thiazides, which can reduce the glomerular filtration rate (GFR) and become less effective in renal impairment, metolazone has minimal impact on GFR and remains useful in patients with reduced kidney function. Additionally, unlike loop diuretics, metolazone does not stimulate renin release at the macula densa, avoiding activation of the renin-angiotensin-aldosterone system. When combined with loop diuretics, metolazone enhances sodium excretion by blocking compensatory sodium reabsorption in the distal tubules, resulting in greater natriuresis.
PHARMACOKINETICS:
Absorption: Metolazone is rapidly absorbed when taken orally, although food can delay its absorption. Peak plasma concentrations are typically reached around 1.5 hours after administration.
Distribution: Metolazone has a volume of distribution ranging from 108.7 ± 21.3 liters to 126.3 ± 53.4 liters at doses between 0.5 mg and 2 mg. It is also highly bound to plasma proteins, with about 95% of the drug bound in circulation.
Metabolism: Metolazone undergoes enterohepatic circulation. Studies have also shown that it influences hPXR-mediated expression of CYP3A4 and MDR1 in human hepatocytes and enhances CYP3A4 activity in various cell lines.
Excretion: The mean elimination half-life of metolazone is about 6 to 8 hours, and it is mainly excreted in the urine.
PHARMACODYNAMICS:
Metolazone is a thiazide-like diuretic that primarily targets the distal convoluted tubules of the nephron. Its main pharmacodynamic action involves inhibiting the reabsorption of sodium and chloride, resulting in enhanced excretion of these ions along with water. This promotes diuresis, helping to reduce edema and lower blood pressure.
DOSAGE AND ADMINISTRATION:
Metolazone is administered orally and is available in tablet strengths of 2.5 mg, 5 mg, and 10 mg. The dose recommended for the patients will be vary from one to another depending on the severity of the disease and age.
The starting dose of metolazone for managing edema linked to congestive heart failure or kidney disease is 5 to 20 mg once daily. The dose should be modified according to the patient's individual response.
and then maintained at the lowest effective dose to sustain diuresis.
For managing hypertension, an initial dose of 2.5 to 10 mg once daily is advised, with subsequent adjustments based on the patient’s blood pressure response.
DRUG INTERACTIONS:
Some drugs should be avoiding while taking metolazone, as it interacts with other drugs it may cause adverse effects. Below are the few drugs that are should be avoid while using metolazone.
- Corticosteoid – Prednisone, Methylprednisolone, Dexamethasone
- Opioid – Oxycodone, Morphine, codeine
- NSAID – Ibuprofen, naproxen, aspirin
- Irregular heartbeat medicines – Digoxin(Lanoxin)
- Urinary tract infections – Methenamine(Hiprex)
- Blood thinners
- Diuretic medicines which reduces edema and blood pressure.
FOOD INTERACTIONS:
Avoid taking alcohol.
CONTRAINDIATIONS:
Metolazone is contraindicated in patients with hypersensitivity to thiazides or sulfonamides, anuria, severe electrolyte imbalances, or hepatic coma. Caution is advised during pregnancy and lactation due to potential risks to the fetus or nursing infant.
ADVERSE EFFECTS:
- Hypokalemia
- Hyponatremia
- Hypomagnesemia
- Dehydration
- Dizziness
- Pancreatitis
- Blood dyscrasias
- Photosensitivity
- Orthostatic hypotension
- Muscle cramps
- Renal impairment
OVERDOSE:
Taking overdose of metolazone can leads to toxic effects like
- Increased haematocrit due to plasma volume depletion
- Hypotension
- Hypokalemia
- Reduced renal function
- Hyponatremia
