What are diuretics?

What Are Diuretics?

Diuretics are medications that increase urine output by inhibiting the reabsorption of sodium or chloride at specific sites in the renal tubules, thereby promoting fluid elimination from the body. 1

Types of Diuretics

Diuretics are classified based on their site of action in the nephron:

Loop Diuretics

• Mechanism: Act at the loop of Henle
• Examples: Furosemide, bumetanide, torsemide
• Characteristics:
  • Increase sodium excretion up to 20-25% of filtered load
  • Enhance free water clearance
  • Maintain efficacy even with severe renal impairment
  • Rapid onset of action (hours to days)
  • Preferred in most heart failure patients 1

Thiazide Diuretics

• Mechanism: Act in the distal convoluted tubule
• Examples: Hydrochlorothiazide, chlorthalidone, metolazone
• Characteristics:
  • Increase sodium excretion to 5-10% of filtered load
  • Tend to decrease free water clearance
  • Lose effectiveness when creatinine clearance falls below 40 mL/min
  • Preferred in hypertensive patients with mild fluid retention 1

Potassium-Sparing Diuretics

• Mechanism: Act in the distal tubule and collecting duct
• Examples: Spironolactone (aldosterone antagonist), triamterene, amiloride
• Characteristics:
  • Weak diuretic effect when used alone
  • Help conserve potassium
  • Spironolactone has additional benefits in heart failure 1, 2

Other Diuretic Classes

• Osmotic diuretics: Increase osmotic pressure in the tubule (e.g., mannitol)
• Carbonic anhydrase inhibitors: Inhibit reabsorption in proximal tubule (e.g., acetazolamide)
• Newer agents: SGLT2 inhibitors, vasopressin receptor antagonists 3, 4

Clinical Applications

Diuretics are used in various clinical conditions:

1. Heart Failure:

   • Loop diuretics are first-line for fluid overload
   • Relieve pulmonary and peripheral edema rapidly
   • Should be combined with ACE inhibitors and beta-blockers for optimal outcomes 1
   • Torsemide may be preferred over furosemide in some patients due to better bioavailability 1

2. Hypertension:

   • Thiazides are preferred first-line agents
   • Chlorthalidone may be more effective than hydrochlorothiazide 5
   • Evening dosing may provide better cardiovascular outcomes 5

3. Edematous States:

   • Used in nephrotic syndrome, cirrhosis, and other conditions with fluid retention
   • Loop diuretics preferred for severe edema 6

4. Resistant Edema:

   • Sequential nephron blockade (combining loop and thiazide diuretics)
   • Metolazone (2.5-10 mg) is often combined with loop diuretics for resistant cases 2

Important Clinical Considerations

1. Rapid Symptom Relief: Diuretics produce symptomatic benefits more rapidly than other heart failure medications (hours to days vs. weeks to months) 1

2. Essential for Fluid Control: Diuretics are the only drugs that can adequately control fluid retention in heart failure; ACE inhibitors or other agents cannot substitute for diuretics 1

3. Combination Therapy: In heart failure, diuretics should not be used alone but combined with ACE inhibitors and beta-blockers 1

4. Dose Optimization:

   • Underdosing leads to fluid retention that can diminish response to other medications
   • Overdosing causes volume contraction, hypotension, and renal insufficiency 1

5. Adverse Effects:

   • Electrolyte disturbances (hypokalemia, hypomagnesemia, hyponatremia)
   • Metabolic alkalosis
   • Dehydration and hypotension
   • Renal impairment
   • Hyperuricemia 7

6. Monitoring Requirements:

   • Regular assessment of electrolytes, especially potassium
   • Renal function monitoring
   • Daily weight measurements to guide dosing adjustments 2, 7

Practical Dosing Guidelines

For heart failure patients:

• Initial approach: Start with low doses and increase until urine output increases and weight decreases (typically 0.5-1.0 kg daily)
• Maintenance: Once fluid retention resolves, continue with the lowest effective dose to prevent recurrence
• Adjustment: Consider having patients record daily weights and adjust diuretic doses accordingly 1

Common Pitfalls to Avoid

1. Inappropriate dosing:

   • Underdosing leads to persistent edema and reduced efficacy of other heart failure medications
   • Overdosing causes dehydration, hypotension, and renal dysfunction 1

2. Ignoring electrolyte imbalances: Diuretics, especially loop diuretics, can cause dangerous electrolyte disturbances that may lead to arrhythmias 7

3. Using diuretics alone in heart failure: Diuretics should be part of a comprehensive heart failure regimen including ACE inhibitors and beta-blockers 1

4. Not considering renal function: Thiazides lose effectiveness with significant renal impairment (CrCl <40 mL/min); loop diuretics are preferred in these patients 1

5. Failing to adjust therapy: Diuretic requirements often change over time and need regular reassessment 1, 2