In this episode, we review the pharmacology, pharmacokinetics, adverse effects, monitoring, medicinal chemistry, and more of loop diuretics.

Key Concepts

1. Loop diuretics (furosemide, torsemide, bumetanide, ethacrynic acid) are the most potent type of diuretic and are used to relieve edema.
2. Loop diuretics cause an increased loss of sodium, chloride, potassium, hydrogen, magnesium, and calcium ions into the urine. Excessive loss of these ions manifests as hypokalemia, hypomagnesemia, and metabolic alkalosis.
3. Loop diuretics have an S-shaped dose response curve – a minimum dose is required for diuresis and a “ceiling” effect occurs at higher doses (leading to more ADRs). Doses should be individualized based on the clinical response of the patient.
4. Ethacrynic acid is incorrectly used in patients with a “sulfa” allergy. The other loop diuretics contain a sulfa moiety but are safe for use in patients with “sulfa” allergy (e.g. allergy to sulfamethoxazole-trimethoprim).
5. The TRANSFORM-HF trial strongly suggests that there is no clinical difference between furosemide and torsemide.

References

• Rachoin JS, Cerceo EA. Four nephrology myths debunked. J Hosp Med. 2011;6(5):E1-E5. doi:10.1002/jhm.703
• Strom BL, Schinnar R, Apter AJ, et al. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. N Engl J Med. 2003;349(17):1628-1635. doi:10.1056/NEJMoa022963
• Buggey J, Mentz RJ, Pitt B, et al. A reappraisal of loop diuretic choice in heart failure patients. Am Heart J. 2015;169(3):323-333. doi:10.1016/j.ahj.2014.12.009
• Mentz RJ, Anstrom KJ, Eisenstein EL, et al. Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure: The TRANSFORM-HF Randomized Clinical Trial. JAMA. 2023;329(3):214-223. doi:10.1001/jama.2022.23924