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Diuretics

Last updated: June 2, 2021

Summarytoggle arrow icon

Diuretics are a group of drugs that increase the production of urine. Diuretics are categorized according to the renal structures they act on and the changes they lead to in the volume and composition of urine, as well as electrolyte balance. Some of these effects are useful in treating disorders such as hypercalcemia, hypocalcemia, and hyperaldosteronism. The most commonly used diuretics with a pronounced diuretic effect are thiazides, loop diuretics, and potassium-sparing diuretics. Osmotic diuretics and carbonic anhydrase inhibitors are used in acute settings to lower intracranial and/or intraocular pressure (e.g., cerebral edema, acute glaucoma). The most serious side effects of the majority of diuretics include volume depletion and excessive changes in serum electrolyte levels (particularly of sodium and potassium), which increases the risk for cardiac arrhythmias.

Summary of diuretic drug effects

Main diuretic agents
Agents Main characteristics and mechanisms Water elimination Effects on serum
pH Na+ K+ Ca2+
Thiazide diuretics [1]
  • Inhibition of Na+-Cl- cotransporters in the early distal tubule
  • Effects compared to loop diuretics
    • Greater loss of potassium
  • ↑ Calcium reabsorption → urine calcium
  • Reduced effectiveness if GFR < 30 mL/min
  • Increased
  • Increased [2]
  • Decreased
  • Decreased
  • Increased

Loop diuretics

  • Significantly increased
  • Increased
  • Normal/slightly decreased
  • Decreased
  • Decreased

Potassium-sparing diuretics

  • Slightly increased
  • Decreased
  • Decreased
  • Increased
  • No change

Osmotic diuretics

  • Significantly increased

Carbonic anhydrase inhibitors

  • Slightly increase
  • Decreased
  • Slightly decreased
  • Slightly decreased
  • No change

Mechanisms of blood acid-base balance changes

Alkalosis

  • Agents: loop diuretics and thiazides
  • Mechanisms
    • Diuresis → volume contraction (i.e., volume loss) ; RAAS ↑ ATII → Na+/H+ exchanger in the PCT HCO3- reabsorption (contraction alkalosis)
    • K+excretion → hypokalemia, leading to the following effects:
      • Induction of H+ excretion (instead of K+ excretion) in exchange for Na+ reabsorption in the collecting duct → ↑ HCO3- reabsorption → alkalosis with paradoxical aciduria
      • Induction of H+/K+-ATPases in all cells; in order to counteract the decrease in serum K+ K+ outflow from the cells in exchange for H+ ↓ serum H+ metabolic alkalosis

Acidosis

Agents

  • Hydrochlorothiazide (HCTZ)
  • Chlorthalidone
  • Chlorothiazide
  • Metolazone

Mechanism of action

Side effects [4]

To avoid hypokalemia, thiazide diuretics may be combined with potassium-sparing diuretics (e.g., aldosterone receptor antagonists).
To remember the side effects of thiazide diuretics, think of “hyperGLUC”: hyperGlycemia, hyperLipidemia, hyperUricemia, and hyperCalcemia.

Indications

Contraindications

Thiazides should be used with caution in patients with prediabetes and diabetes mellitus because they can cause hyperglycemia and changes in glucose concentration.

Interactions

Agents

  • Sulfonamides: furosemide, torsemide, bumetanide
  • Other: ethacrynic acid

Mechanism of action [11]

  • Blockage of Na+-K+-2Cl- cotransporter in the thick ascending loop of Henle
    • Diminishing concentration gradient between the (usually hypertonic) renal medulla and the cortex → concentration of urine is no longer possible → increased diuresis
    • Decreased reabsorption of Ca2+ and Mg2+
  • Increased PGE release (can be inhibited by NSAIDs)
    • Dilation of renal afferent arterioles diuresis
    • General venodilation (rapid venous pooling) → ↓ cardiac preload
  • See “Mechanism of blood pH” changes in “Overview of diuretics” for mechanism of alkalosis.

To recall that loop diuretics cause increased excretion of calcium, think: loops lose calcium!

Side effects [12]

To recall the side effects of loop diuretics, think of “GO PANDA”: Gout, Ototoxicity, low Potassium, Allergy, Nephritis, Dehydration, Alkalosis.

To remember that loop diuretics are ototoxic, imagine a vertical loop of a roller coaster and deafening screams of people passing through it.

Hypokalemia and/or hypomagnesemia can lead to life-threatening arrhythmias!

Indications [13]

Because of the increased risk of hypokalemia and _Definitions"#Z2c4b7b192fbfa8d2679ddc134ed0e9c5" data-lxid="Ig0Y92">hypovolemia during forced diuresis, rigorous monitoring is necessary.

Contraindications

Contraindications for loop diuretics
Condition Furosemide Torsemide Bumetanide Ethacrynic acid
Anuria
  • Yes
  • Yes
  • Yes
  • Yes
Sulfonamide hypersensitivity
  • Yes
  • Yes
  • Yes
  • No
Hepatic coma or severe electrolyte depletion
  • No
  • No
  • Yes
  • No

History of severe watery diarrhea (caused by the drug)

  • No
  • No
  • No
  • Yes

Agents

To remember that Spironolactone, Triamterene, Eplerenone, and Amiloride are K+-sparing, think of STEAK!

Mechanism of action

Although the molecular pathways differ, both types of potassium-sparing diuretics have very similar clinical effects.

Spironolactone and eplerenone are aldosterone receptor antagonists.

Side effects

Indications

Contraindications

General

Specific

Agents

  • Mannitol
  • Urea [16]

Mechanism of action

Side effects

Indications

Contraindications

Agents

  • Acetazolamide

Mechanism of action

Side effects

Indications

Contraindications

ACetazolamide causes ACidosis.

  1. Shankar SS, Brater DC. Loop diuretics: from the Na-K-2Cl transporter to clinical use. Am J Physiol Renal Physiol. 2003; 284 (1): p.F11-21. doi: 10.1152/ajprenal.00119.2002 . | Open in Read by QxMD
  2. Sica DA. Diuretic-Related Side Effects: Development and Treatment. J Clin Hypertens. 2004; 6 (9): p.532-40.
  3. Oh SW, Han SY. Loop Diuretics in Clinical Practice. Electrolyte Blood Press. 2015; 13 (1): p.17-21. doi: 10.5049/EBP.2015.13.1.17 . | Open in Read by QxMD
  4. Ravnan SL, Ravnan MC, Deedwania PC. Diuretic Resistance and Strategies to Overcome Resistance in Patients With Congestive Heart Failure. Congest Heart Fail. 2002; 8 : p.80–85. doi: 10.1111/j.1527-5299.2002.0758.x . | Open in Read by QxMD
  5. Shorr et al. Drugs for the Geriatric Patient. Elsevier ; 2007
  6. Huang EA, Feldman BJ, Schwartz ID, Geller DH, Rosenthal SM, Gitelman SE. Oral urea for the treatment of chronic syndrome of inappropriate antidiuresis in children. J Pediatr. 2006; 148 (1): p.128-131. doi: 10.1016/j.jpeds.2005.08.031 . | Open in Read by QxMD
  7. Ellison DH, Loffing J. Thiazide effects and adverse effects: insights from molecular genetics. Hypertension. 2009; 54 (2): p.196-202. doi: 10.1161/HYPERTENSIONAHA.109.129171 . | Open in Read by QxMD
  8. Greenberg A. Diuretic complications.. Am J Med Sci. 2000; 319 (1): p.10-24.
  9. Finch CK, Kelley KW, Williams RB. Treatment of Lithium-Induced Diabetes Insipidus with Amiloride. Pharmacotherapy. 2003; 23 (4): p.546-550. doi: 10.1592/phco.23.4.546.32121 . | Open in Read by QxMD
  10. Katzung BG, Masters S, Trevor A. Basic and Clinical Pharmacology 12/E. McGraw Hill Professional ; 2012
  11. Pickkers et al. Thiazide-induced hyperglycaemia: A role for calcium-activated potassium channels?. Diabetologia. 1996; 39 (7): p.861-864. doi: 10.1007/s001250050522 . | Open in Read by QxMD
  12. Becker MA. Diuretic-induced hyperuricemia and gout. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/diuretic-induced-hyperuricemia-and-gout.Last updated: April 20, 2016. Accessed: February 22, 2017.
  13. Hwang KS, Kim GH. Thiazide-induced hyponatremia. Electrolyte Blood Press. 2010; 8 (1): p.51-57. doi: 10.5049/EBP.2010.8.1.51 . | Open in Read by QxMD
  14. Rehman A, Setter SM, Vue MH. Drug-Induced Glucose Alterations Part 2: Drug-Induced Hyperglycemia. Diabetes Spectrum. 2011; 24 (4): p.234-238. doi: 10.2337/diaspect.24.4.234 . | Open in Read by QxMD
  15. Boussemart T, Nsota J, Martin–Coignard D, Champion G. Nephrogenic diabetes insipidus: treat with caution. Pediatric Nephrology. 2009; 24 (9): p.1761-1763. doi: 10.1007/s00467-009-1187-9 . | Open in Read by QxMD
  16. Magaldi AJ. New insights into the paradoxical effect of thiazides in diabetes insipidus therapy. Nephrol Dial Transplant. 2000; 15 (12): p.1903-1905. doi: 10.1093/ndt/15.12.1903 . | Open in Read by QxMD
  17. Wulf NR, Matuszewski KA. Sulfonamide cross-reactivity: Is there evidence to support broad cross-allergenicity?. American Journal of Health-System Pharmacy. 2013; 70 (17): p.1483-1494. doi: 10.2146/ajhp120291 . | Open in Read by QxMD
  18. Katzung B,Trevor A. Basic and Clinical Pharmacology. McGraw-Hill Education ; 2014