Diuretics: Mechanism of Action, Indications, and Side Effects

Diuretics: Mechanism of Action, Indications, and Side Effects

Diuretics are a group of medications that help increase urine output, regulating fluid levels in the body. This article provides information about various diuretics, their mechanisms of action, indications, side effects, and related issues.

1. Classification of Diuretics:

• Potassium-depleting Diuretics:

• Exception: Triamterene

• Potassium-sparing Diuretics:

• Exception: Chronexan

• Loop Diuretics:

• Exception: Amiloride

• Osmotic Diuretics:

• Indications: Prevention of post-operative oliguria, increased intracranial pressure, diuresis for detoxification

• Contraindications: Intracellular dehydration, heart failure

• Characteristics: Freely filtered through the glomerulus, limited absorption in the renal tubules, almost no pharmacological activity

2. General Mechanism of Action of Diuretics:

• Increase the excretion of Na+ and water from extracellular fluid

• Effective in individuals without edema

• Direct or indirect influence on the excretion of K+, Cl-, HCO3-, and uric acid

3. Potassium-sparing Diuretics:

• Characteristics: Make urine alkaline; often used with potassium-depleting diuretics

4. Furosemide:

• Characteristics: Rapid and potent diuretic effect, lasting for 4-6 hours

5. Thiazide Diuretics:

• Characteristics: Strong diuretics, inhibiting Na+ reabsorption in the diluting segment of the renal tubule, inhibiting carbonic anhydrase, effective in both acidic and alkaline environments, excreting Na+ and Cl- in roughly equal amounts, reducing uric acid excretion through the renal tubules, locally inhibiting the effect of vasoconstrictor hormones

• Indications: Heart, liver, and kidney edema, unexplained hypercalciuria, hypertension

• Side Effects: Hypokalemia, hypokalemia, exacerbating gout, increasing cholesterol and LDL-C levels

6. Loop Diuretics:

• Characteristics: Increase Ca++ and Mg++ excretion, acting on the ascending limb of the loop of Henle

• Indications: Inhibit the co-transport mechanism of 1Na+, 1K+, and 2Cl- in the ascending limb of the loop of Henle, moderately inhibit carbonic anhydrase, potentially inhibit Na+ reabsorption in the proximal tubule

• Side Effects: Increased uric acid levels, arrhythmias due to hypomagnesemia, ototoxicity

7. Spironolactone:

• Characteristics: Acts on the distal convoluted tubule, inhibiting Na+ reabsorption through exchange with K+ excretion

• Side Effects: Gynecomastia in men, hirsutism and menstrual irregularities in women

8. Triamterene:

• Characteristics: Competes with aldosterone at the receptor in the distal convoluted tubule, does not compete with aldosterone, increases Na+ and Cl- excretion due to reduced permeability of the distal convoluted tubule to Na+, enhanced effect when combined with spironolactone

9. Combining Diuretics:

• Diuretics within the same chemical group can be combined.

• Combining loop and thiazide diuretics when one of these agents has become less effective.

• Combining potassium-sparing diuretics with loop or thiazide diuretics when hypokalemia cannot be managed by diet or KCl supplementation.

• Combining spironolactone with triamterene.

10. Strategies for Diuretic Resistance:

• Bed rest for the patient

• Increase the dose of loop diuretics

• Combine diuretics with different sites of action

11. Possible Metabolic Disturbances Associated with Diuretic Use:

• Hyperglycemia

• Hyperuricemia

• Calcium metabolism disorders

12. Factors Reducing the Effectiveness of Loop Diuretics:

• NSAIDs reduce renal blood flow when combined with diuretics

• Chronic kidney disease leads to accumulation of endogenous organic acids, competing with loop diuretics in the proximal tubule

• In nephrotic syndrome, proteinuria binds to loop diuretics, reducing the concentration of the drug bound to the receptor

• In cirrhosis and heart failure, the renal tubule becomes less responsive to the drug.

13. Detailed Information on Specific Diuretics:

• Acetazolamide:

• Site of action: Proximal convoluted tubule

• Drug class: Carbonic anhydrase inhibitors

• Characteristics: Causes metabolic acidosis

• Hydrochlorothiazide:

• Site of action: Diluting segment

• Furosemide:

• Site of action: Thick ascending limb of the loop of Henle

• Drug class: Loop diuretics

• Characteristics: Ototoxic

• Spironolactone:

• Aldosterone antagonist

• Causes gynecomastia in men

• Aldactone:

• Site of action: Distal convoluted tubule

• Mannitol:

• Site of action: Entire renal tubule

• Drug class: Osmotic diuretic

• Characteristics: Does not increase Na+ excretion

• Hydrochlorothiazide:

• Thiazide group

• Decreases urinary Ca++

• Hydrochlorothiazide effects:

• Inhibition of Na+, Cl- reabsorption in the diluting segment

• Hydrochlorothiazide undesirable effects:

• Hypokalemia, hyperuricemia, exacerbation of diabetes mellitus

• Potent diuretics:

• Furosemide, ethacrinic acid, bumetanide

• The rapid and potent diuretic effect of furosemide is due to:

• Inhibition of Na+ reabsorption in the thick ascending limb of the loop of Henle

• Undesirable effects of furosemide:

• Ototoxicity and may cause irreversible deafness

• Aldosterone antagonist diuretics:

• Spironolactone

• Osmotic diuretics:

• All of the above: Mannitol

• Contraindications for furosemide and ethacrinic acid:

• Combination with aminoglycoside antibiotics: streptomycin, gentamicin

Note:

• The information above is for reference only and should not replace the advice of a physician.

• Always consult a doctor before using any medications, including diuretics.

• Use diuretics as directed by your physician to avoid undesirable side effects.

We hope this article provides helpful information about diuretics.