metolazone

the booster

A potent thiazide-like diuretic that remains effective even at low GFR. Used almost exclusively as a synergist with loop diuretics to overcome “diuretic resistance.”

• Mechanism: Inhibits $N{a}^{+}-C{l}^{-}$ cotransporter (NCC) in the Distal Convoluted Tubule.
• Dosing: 2.5 mg – 5 mg PO. Timing: Administer 30–60 minutes BEFORE the loop diuretic for maximal synergy.
• PK: Long half-life (14–24 hours). Slow onset.

indications

• Refractory Edema: Heart failure or Nephrotic syndrome resistant to high-dose loops.

adverse effects

• Massive Electrolyte Derangement:
  • Severe Hypokalemia (Monitor K+ daily).
  • Hyponatremia (Blocks the diluting segment).
  • Hypomagnesemia.
• Hypovolemia: Can cause rapid, massive fluid shifts (“diuretic crash”).