Pharmacology of Diuretics

Pharmacology of Diuretics

• Diuretics are used to remove extra fluid and minerals through urine.
• Goals include reducing edema, treating hypertension, managing vascular congestion in heart failure, and increasing urination.
• Diuretics should be taken in the morning to avoid nocturia (frequent urination at night).
• Sequential nephron blockade is a potent combination for refractory congestion.
• This combination is effective but increases the risk of renal dysfunction.

Learning Objectives

• List major diuretics and their clinical indications.
• Explain the mechanism of action of major diuretics.
• Discuss pharmacokinetics and major drug interactions of diuretics.
• Describe common and severe adverse effects of commonly used diuretics.
• Summarize patient management with edema.

Goal of Diuretic Drugs

• Remove extra fluid and minerals through urine
• Reduce edema
• Treat hypertension
• Manage vascular congestion in all forms of heart failure
• Increase urination
• Take diuretics in the morning to avoid nocturia (minimize nighttime urination).

Indications

• Heart failure, renal disease, cirrhosis
• Edema, hypertension, ascites diuresis, fluid overload

Classes of Diuretics

• Carbonic anhydrase inhibitors (e.g., Acetazolamide)
• Osmotic diuretics (e.g., Mannitol)
• Loop diuretics (e.g., Furosemide, Ethacrynic acid)
• Thiazide diuretics (e.g., Hydrochlorothiazide, Chlorthalidone)
• Potassium-sparing diuretics (e.g., Spironolactone, Triamterene)

Acetazolamide

• Carbonic anhydrase inhibitor
• Weaker diuretic, acting on the eye, brain, and kidneys
• Indications include glaucoma, high-altitude pulmonary edema, and metabolic alkalosis
• Prophylaxis of acute mountain sickness

Osmotic Diuretics (Mannitol)

• Pharmacologically and metabolically inert substances
• Filtered in the glomerulus, not reabsorbed
• Massive diuresis
• Best drug to reduce intracranial pressure (cerebral edema) and intraocular pressure (glaucoma)
• Creates a powerful osmotic gradient in the kidneys
• Draws water out of brain parenchyma to intravascular space and excreted
• Useful in reducing vitreous humor
• Rapidly excreted via kidneys (IV administration)

Loop Diuretics

• Powerful, rapid onset diuretics
• Act on the ascending limb of the loop of Henle
• Inhibit Na-K-2Cl cotransporter, reducing sodium reabsorption
• Potent for chronic kidney disease and heart failure
• Types: sulfa drugs (furosemide, torsemide, bumetanide) and non-sulfa drugs (ethacrynic acid)
• Common adverse effects: sulfa allergies, hypokalemia, metabolic alkalosis, increased Li clearance, aminoglycoside enhanced toxicity, and reduced efficacy with NSAIDs.

Furosemide (Loop Diuretic)

• Very effective, commonly used loop diuretic
• First-line therapy for heart failure
• Blocks Na-K-2Cl cotransporter, inhibiting NaCl reabsorption, increasing water and electrolyte excretion
• Causes loss of calcium and magnesium
• Bioavailability is variable; better absorbed when taken before meals
• Excreted through kidneys as unchanged compound or glucuronide.
• Short half-life (1.5 hours)

Torsemide (Loop Diuretic)

• More potent than furosemide
• Advantage: mitigation of cardiac fibrosis
• Higher bioavailability, greater absorption regardless of edema
• Eliminated via hepatic pathway
• Longer half-life (4 hours) compared to furosemide

Bumetanide (Loop Diuretic)

• High bioavailability
• Extremely well absorbed, undergoes substantial hepatic elimination
• Similar efficacy to Furosemide and Torsemide

Ethacrynic Acid (Loop Diuretic)

• Non-sulfa loop diuretic
• Suitable for patients with sulfa allergies
• Adverse effect: ototoxicity (damage to inner ear hair cells)

Thiazide Diuretics

• Reliable class of antihypertensive diuretics
• Best for essential hypertension and renal stones
• Enhance calcium reabsorption, reducing calcium excretion
• Common: Hydrochlorothiazide, Chlorthalidone
• Risk of hyperglycemia, gout
• AE: electrolyte derangement, hyperglycemia, decreased K+

Chlorthalidone (Thiazide Diuretic)

• More potent than Hydrochlorothiazide, long half-life

Potassium-Sparing Diuretics

• Include both steroid and non-steriod drugs
• Examples: Spironolactone and Amiloride.
• Effective regardless of aldosterone status
• Spironolactone- also blocks Na channels on cells that reabsorb Na+
• Helps prevent potassium loss, useful in cases of hyperkalemia
• AE: Gynecomastia, hyperkalemia

Eplerenone (Potassium-Sparing)

• Mineralocorticoid receptor blocker
• Higher selectivity for mineralocorticoid receptors than spironolactone
• Used to treat LV systolic dysfunction, congestive heart failure, and hypertension after acute MI.

SGLT2 Inhibitors

• Used as diuretics in Type 2 diabetes and cardiovascular diseases.
• Prevent adverse cardiorenal events in diabetic patients.
• Keep you from reabsorbing glucose, which leads to water and sodium elimination. They inhibit SGLT-2
• Examples include Canagliflozin, Dapagliflozin

Diuresis and Pregnancy

• Diuretics can sometimes be used safely during pregnancy to treat severe illnesses and life-threatening conditions, or to replace a drug with noted fetal effects.

Summary of Diuretic Action

• A detailed diagram of the nephron and the location of various diuretic actions.

Additional Considerations

• The presentation discusses specific diuretics more thoroughly
• Including their mechanisms of action, side effects, and specific indications for specific medical conditions.

This quiz covers the pharmacology of diuretics, including their mechanisms of action, clinical indications, and pharmacokinetics. Explore how diuretics help manage conditions like hypertension and heart failure, as well as their potential adverse effects. Test your knowledge on patient management related to edema and fluid balance.