Diuretics, ACE

Diuretics Overview

  • Diuretics are used for various medical conditions such as high blood pressure (HBP), edema, heart failure, and ascites.

  • They aid in the elimination of toxins from the body.

Use of Diuretics in Hypertension

  • First-Line Therapy: Used as the first-line drug therapy for hypertension unless contraindicated.

  • Benefits:

    • Safe and inexpensive.

    • Effective in preventing serious cardiovascular events such as stroke and myocardial infarction.

    • Recent evidence shows they are superior to β-blockers in treating hypertension in older adults.

Mechanism of Action

  • Relieve pulmonary congestion and peripheral edema.

  • Reduce symptoms of volume overload (e.g., orthopnea).

  • Decrease plasma volume leading to reduced venous return (preload) to the heart, thus reducing cardiac workload and oxygen demand.

  • May decrease blood pressure by reducing afterload.

Sites of Action of Diuretics

  • Proximal Tubule:

    • Osmotic diuretics, Carbonic anhydrase inhibitors.

  • Loop of Henle:

    • Loop diuretics.

  • Distal Tubule:

    • Thiazide diuretics.

  • Collecting Duct:

    • Potassium-sparing diuretics, Aldosterone antagonists.

Types of Diuretics and Their Mechanisms

  • Osmotic Diuretics

    • Example: Mannitol; acts at the proximal tubule, enhancing Na+ reabsorption via osmotic action.

  • Carbonic Anhydrase Inhibitors

    • Example: Acetazolamide; inhibits carbonic anhydrase, increasing bicarbonate excretion.

  • Thiazide Diuretics

    • Example: Hydrochlorothiazide; decreases sodium chloride reabsorption in early distal tubule.

  • Loop Diuretics

    • Examples: Furosemide, Ethacrynic acid; work at the cortical and medullary TALH to inhibit Na+/K+/2Cl-symporter.

  • Potassium-Sparing Diuretics

    • Examples: Spironolactone, Amiloride; reduce potassium loss and may prevent cardiac remodeling.

Thiazide Diuretics: Mechanism of Action

  • Initially lower blood pressure by increasing sodium and water excretion.

  • Decrease extracellular volume, affecting cardiac output, renal blood flow, and peripheral resistance.

  • Often combined with potassium-sparing diuretics to alleviate potassium loss.

Therapeutic Uses of Thiazide Diuretics

  • Effectively lower blood pressure in supine and standing positions.

  • Useful in combination therapy with various antihypertensive agents.

  • Not effective in patients with low kidney function (creatinine clearance <50 mL/min).

Adverse Effects of Thiazide Diuretics

  • Common Side Effects:

    • Hypokalemia, hyperuricemia, hyperglycemia, acute gout attacks, hypomagnesemia.

    • Monitor potassium levels in susceptible patients.

    • Dose reductions required when used with lithium and digoxin.

    • Avoid use with quinidine and quinine.

Loop Diuretics

  • Fast-acting even in patients with poor renal function.

  • Lower renal vascular resistance and increase renal blood flow.

  • Cause increased calcium content in urine, unlike thiazides which decrease calcium.

Side Effects of Loop Diuretics

  • Common Side Effects:

    • Hypokalemia, hypomagnesemia, hypocalcemia, hyperuricemia.

    • Ototoxicity and hypotension may occur.

Osmotic Diuretics: Mannitol

  • Increase urinary excretion of electrolytes, decrease blood viscosity, and inhibit renin release.

  • Used in acute renal failure, brain edema, and transient effects on the blood-brain barrier.

  • Side effects include pulmonary edema and dehydration risks.

Potassium-Sparing Diuretics

  • Include Amiloride, Triamterene, Spironolactone.

  • Reduce potassium loss and may help in cardiac remodeling in heart failure.

Aldosterone Antagonists

  • Spironolactone reduces salt retention and myocardial hypertrophy. Used in advanced heart failure cases.

  • Eplerenone has less endocrine side effects and reduces mortality post-myocardial infarction.

Renin-Angiotensin System Overview

  • ACE Inhibitors (ACEI): First-line agents when diuretics or β-blockers are not viable.

  • Mechanism: Reduce vascular resistance without increasing cardiac output.

  • Indications: Beneficial for diabetic nephropathy, post-myocardial infarction, chronic heart failure.

Adverse Effects of ACE Inhibitors

  • Potential side effects include dizziness, hypotension, GI distress, and cough.

Angiotensin II Receptor Blockers (ARBs)

  • Block AT1 receptors, leading to arterial and venous dilation.

  • Favorable for hypertensive patients with low tolerance for ACE inhibitors.

  • Lower risk of cough and angioedema compared to ACE inhibitors.

Renin Inhibitors: Aliskiren

  • Directly inhibits renin, lowers blood pressure effectively.

  • Can be combined with other antihypertensives.

  • Adverse effects include diarrhea, cough, and hyperkalemia, especially with ARBs.

Common Fixed-Combination Medications

  • Examples include:

    • Hydrochlorothiazide with Lisinopril or Losartan, among others.