Overview
This lecture reviews loop diuretics, focusing on renal physiology, mechanisms of action, pharmacology, clinical uses, side effects, and considerations for patient management.
Renal Physiology & Diuretic Sites of Action
- The nephron is the kidney's functional unit; major sodium and water reabsorption sites include proximal tubule, loop of Henle, distal tubule, and collecting duct.
- About 60% of sodium and water is reabsorbed in the proximal tubule; 20-40% in the thick ascending loop of Henle (site of action for loop diuretics).
- The distal convoluted tubule reabsorbs 5–10% of sodium; the collecting duct adjusts water reabsorption based on hydration.
Loop Diuretics: Drugs and Pharmacology
- Common loop diuretics: furosemide (Lasix), bumetanide (Bumex), torsemide (Demadex); ethacrynic acid is rarely used.
- Oral bioavailability: furosemide is lowest (30-50%), greatly affected by gut edema; bumetanide and torsemide have higher, more reliable oral absorption.
- Potency: bumetanide is 40x, torsemide 4x more potent than furosemide.
- IV dosing bypasses absorption issues; 20 mg oral furosemide ≈ 10 mg IV.
- Duration: torsemide acts longest; "Lasix" named for 6-hour action duration.
Mechanism of Action & Effects
- Loop diuretics inhibit the Na⁺-K⁺-2Cl⁻ cotransporter in the thick ascending loop of Henle.
- This action increases urine sodium and water loss, also reducing reabsorption of magnesium and calcium.
- Electrolyte effects: risk of hypokalemia, hyponatremia, hypocalcemia, hypomagnesemia; hypomagnesemia can make potassium replacement ineffective.
Clinical Considerations & Pearls
- Dose adjustments may be needed in renal impairment.
- Diuretic resistance occurs as distal tubule compensates by upregulating sodium reabsorption; strategies: increase loop dose/frequency, or add a thiazide diuretic.
- Co-administering both loop and thiazide diuretics can cause profound diuresis and pre-renal failure if not managed carefully.
- Over-diuresis can result in contraction alkalosis (elevated bicarb from extracellular fluid loss).
- Side effects: electrolyte disturbances, ototoxicity at high doses, renal failure from over-diuresis, metabolic alkalosis from increased hydrogen ion loss.
Sulfonamide Allergy & Special Considerations
- Most loop diuretics contain a sulfonamide group, but true cross-reactivity with sulfa antibiotics is rare (1–3%).
- Ethacrynic acid lacks the sulfonamide group, but is seldom needed for allergy.
- IV administration is preferred in patients with gut edema to ensure drug delivery.
Key Terms & Definitions
- Loop Diuretic — Drug that inhibits the Na⁺-K⁺-2Cl⁻ cotransporter in the thick ascending loop of Henle.
- Bioavailability — Fraction of administered drug reaching systemic circulation.
- Ototoxicity — Ear damage leading to hearing loss, risk increases at high loop diuretic doses.
- Diuretic Resistance — Reduced response to typical doses due to nephron adaptation.
- Contraction Alkalosis — Alkalosis caused by loss of extracellular fluid, increasing bicarbonate concentration.
Action Items / Next Steps
- Review renal physiology and nephron diagrams.
- Practice converting equivalent doses between loop diuretics.
- Understand signs/symptoms and management of electrolyte disturbances related to loop diuretics.
- Read about sulfonamide allergies and implications for prescribing.