Diuretics Overview and Mechanisms

Study Notes

Mannitol
- Freely filtered and not reabsorbed; increases osmolarity, drawing water into urine.
- Uses: Reduces cerebrospinal fluid volume; aids in excretion of toxic substances.
- Adverse effects: Can induce pulmonary edema, particularly in patients with congestive heart failure.
- Administered intravenously.

Acetazolamide
- Inhibits carbonic anhydrase, leading to increased bicarbonate excretion and more alkaline urine.
- Uses: Effective in treating metabolic alkalosis; creates alkaline urine for excreting acidic drugs.
- Adverse effects: Risk of inducing metabolic acidosis.

Furosemide
- Inhibits Na-K-2Cl transporter in the loop of Henle, decreasing sodium absorption.
- Uses: Efficiently removes edema; manages hypertension.
- Adverse effects: Can cause hypokalemia (low potassium levels), ototoxicity (hearing damage), and activation of the renin-angiotensin-aldosterone system.
- Drug interactions: Increased risk of ototoxicity when combined with aminoglycosides.

Hydrochlorothiazide, Chlorothiazide, Chlorthalidone
- Block sodium and chloride reabsorption via NaCl cotransporter in the early distal tubule, retaining these ions in urine and attracting water.

Mannitol is freely filtered by the kidneys and not reabsorbed, increasing osmolarity to draw water into urine.
Primary uses include reducing cerebrospinal fluid volume and facilitating the excretion of toxic substances.
In patients with congestive heart failure, mannitol can cause pulmonary edema.
Administration route is intravenous (I.V.).

Acetazolamide inhibits carbonic anhydrase, leading to increased bicarbonate excretion and more alkaline urine.
Useful for treating metabolic alkalosis and for creating alkaline urine to enhance urinary excretion of acidic drugs.
Can induce metabolic acidosis as an adverse effect.

Furosemide functions by inhibiting the Na-K-2Cl transporter in the loop of Henle, resulting in decreased sodium absorption.
Key applications include removing edema and treating hypertension.
Potential adverse effects include hypokalemia, ototoxicity (ear damage), and activation of the renin-angiotensin-aldosterone system.
Loop diuretics may interact adversely with aminoglycosides, increasing the risk of ototoxicity.

Hydrochlorothiazide, Chlorothiazide, and Chlorthalidone block the sodium-chloride cotransporter in the early distal tubule, preventing sodium and chloride reabsorption.
They are primarily used for managing hypertension and for removing edema and ascites.
Adverse effects include hypokalemia and activation of the renin-angiotensin-aldosterone system.

Epithelial Sodium Channel (ENaC) antagonists, such as Amiloride, inhibit sodium reabsorption, which leads to reduced potassium secretion.
These are commonly administered alongside loop or thiazide diuretics to mitigate diuretic-induced hypokalemia.
Aldosterone receptor antagonists like Spironolactone block aldosterone receptors, counteracting elevated blood sodium levels.
Both Amiloride and Spironolactone can cause hyperkalemia as an adverse effect.