Loop Diuretics

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Mechanism of Action - Loop's Power Play

  • Site: Thick Ascending Limb (TAL) of Loop of Henle.
  • Target: $Na⁺$-$K⁺$-$2Cl⁻$ (NKCC2) cotransporter (luminal membrane).
  • Action: Reversible inhibition of NKCC2.
  • Key Effects:
    • Potent ("high-ceiling") diuresis; blocks reabsorption of ~25% filtered $Na⁺$.
    • ↓ Medullary hypertonicity → impairs urine concentration.
    • ↑ Renal prostaglandin synthesis ($PGE_2$) → renal vasodilation (NSAIDs blunt this).

    ⭐ Induce hypokalemic metabolic alkalosis. Unique among diuretics for causing significant calcium excretion (hypocalcemia), making them useful in hypercalcemia. 📌 Mnemonic: "LOOPs Diuretics make you LOSE $Ca^{2+}$ (and $K^{+}$, $Mg^{2+}$)".

Loop Diuretics Mechanism on NKCC2

Pharmacokinetics & Examples - The Loop Lineup

  • Agents: Furosemide, Bumetanide, Torsemide, Ethacrynic acid.
  • Routes: Oral (PO), Intravenous (IV).
  • Onset (IV): Rapid, ~5 min; PO: 30-60 min.
  • Duration:
    • Furosemide: 4-6 hrs.
    • Torsemide: Longer, 12-24 hrs.
  • Excretion: Renal (tubular secretion). High protein binding (>90%).
  • Relative Potency (Furosemide = 1):
    • Bumetanide: 40 (Most potent)
    • Torsemide: 2-4
  • Clinical Pearls:
    • Torsemide: ↑Bioavailability, ↑Duration.
    • Ethacrynic acid: Higher risk of ototoxicity.

⭐ Ethacrynic acid is the only non-sulfonamide loop diuretic, suitable for patients with sulfonamide allergy.

Therapeutic Uses - When to Call the Loops

  • Acute Pulmonary Edema (APE): Drug of choice (DOC) for rapid symptom relief.
  • Edema (refractory): Associated with:
    • Congestive Heart Failure (CHF)
    • Cirrhosis (ascites)
    • Nephrotic syndrome
  • Hypertension:
    • Especially with renal insufficiency or heart failure.
    • Hypertensive emergencies (e.g., with fluid overload).
  • Acute Renal Failure (ARF):
    • To ↑ urine output; may convert oliguric to non-oliguric ARF.
  • Hypercalcemia (Acute):
    • Promotes renal Ca²⁺ excretion (adjunct to saline hydration).
  • Forced Diuresis:
    • Certain drug overdoses/poisonings.

⭐ Loop diuretics are the most potent diuretics and are first-line for managing acute pulmonary edema.

Adverse Effects & Interactions - The Downside Drip

  • Electrolyte Depletion:
    • ↓K⁺ (critical!), ↓Mg²⁺, ↓Na⁺, ↓Ca²⁺ (chronic)
    • Hypochloremic metabolic alkalosis
  • Volume Depletion: Dehydration, hypotension.
  • Ototoxicity ⚠️: Dose-dependent; risk ↑ with rapid IV, renal failure, aminoglycosides. Ethacrynic acid highest risk.
  • Metabolic:
    • Hyperuricemia (gout risk)
    • Hyperglycemia (mild)
  • Allergy: Sulfa drugs (Furosemide, etc.). Use Ethacrynic acid if allergic.
  • Drug Interactions:
    • Aminoglycosides: ↑ Ototoxicity
    • NSAIDs: ↓ Diuretic action
    • Digoxin: ↑ Toxicity (via ↓K⁺)
    • Lithium: ↑ Toxicity
    • Antihypertensives: Additive hypotension

⭐ Severe hypokalemia from loop diuretics potentiates digoxin toxicity, risking arrhythmias.

High‑Yield Points - ⚡ Biggest Takeaways

  • Act by inhibiting the Na⁺-K⁺-2Cl⁻ cotransporter in the thick ascending limb (TAL).
  • Most potent diuretics, known as "high-ceiling" diuretics.
  • Key drugs: Furosemide, Bumetanide, Torsemide; Ethacrynic acid is non-sulfa.
  • Primary uses: Pulmonary edema, CHF, cirrhotic ascites, nephrotic syndrome, and hypercalcemia.
  • Adverse effects: Hypokalemia, hypomagnesemia, ototoxicity, hyperuricemia, sulfa allergy.
  • Ethacrynic acid is the choice for patients with sulfa allergy.
  • Caution with NSAIDs (reduce diuretic effect) and aminoglycosides (increased ototoxicity).

Practice Questions: Loop Diuretics

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Mechanism of action of thiazides is by -

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Flashcards: Loop Diuretics

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_____ and HCTZ are diuretics that may cause pancreatitis as an adverse effect.

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_____ and HCTZ are diuretics that may cause pancreatitis as an adverse effect.

Furosemide

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