Diuretics - Classification And Adverse Effects

Cornerstone of edema treatment. Travels via the proximal tubule to reach the luminal side through secretion. It cannot be filtered due to its protein binding. Diuretics with high protein binding inhibit tubular secretion.  Prevents the reabsorption of salt and chloride. Natriuresis: Reduced volume of ECF.

Adaptation to Action of Diuretics

• Post-diuretic sodium retention

Short half-life for loop diuretics; every dosage is followed by anti-natriuresis and natriuresis.

• Braking phenomenon

Only occurs with long-term diuretic use. Each dose reduces the natriuretic response's magnitude. Salt excretion equals salt intake.
RAAS and SNS activation. Lower renal and systemic arterial blood pressure.  A rise in ENaC expression. ANP (abnormal natriuretic peptide) resistance.

Classification of Diuretics

• Acting on PCT - Acetazolamide 
• Acting on the loop of Henle - Loop diuretics. 
• Acting on distal tubule - Thiazides.
• Acting on collecting duct - triamterene, spironolactone.
• Osmotic diuretics - Mannitol

Loop Diuretics

The strongest. Medication: Bumetanide, Torsemide, and Furosemide.
Blocks the sodium-potassium 2 chloride channel, or NK2CC, at the thick ascending limb of the Loop of Henle's apical membrane. 50% oral bioavailability of furosemide. Torsemide has an oral bioavailability of 80%.  Short half-life of elimination.

Need for short dosage intervals. To keep the luminosity at appropriate levels. Extended dose interval - increased sodium retention following diuretics. Need to be taken twice a day. Alternatively known as threshold medicines (doesn't work over threshold). Ethacrynic acid: Harmful to ears.

Distal Convoluted Tubule Diuretics

Metolazone and indapamide;  Thiazide and thiazide-like diuretics (chlorothiazide, hydrochlorothiazide, chlorthalidone). In the distal tubule, inhibit NaCl.  Reabsorbed sodium, 59% of it. Extended half-life. 

Also Read: Haemodialysis Apparatus : Dialysis System, Dialysis Machine

Hypertension Management

Edema: Loop diuretics work in concert with it. When NK2CC is inhibited, tubule Na levels rise.  Reabsorbed through the distal tube's sodium channel. You should take thiazide half an hour before taking a loop diuretic. Boosts the excretion of salt. Less useful if GFR is less than 30.

Collecting Duct Diuretics

Medications: amiloride, trimeterene. Spironolactone and eplerenone are examples of aldosterone antagonists. Act on ENaC: Amiloride and triamterene. Eplerenone and spirolactone: They bind to aldosterone receptors. Weak diuretic agent. Just 3% of sodium is obstructed.  Spironolactone is the DOC for edema related with cirrhosis. Amiloride is the DOC for Lindenfels syndrome.

Proximal Tubule Diuretics

Acetazolamide: this drug inhibits the enzyme carbonic anhydrase.
Inhibits the Na-H exchanger indirectly. Using carbonic anhydrase, carbonic acid is formed in the lumen by H+ and bicarbonate.
breaks down into water and CO2 -Water enters the cell -Divides into H+ and HCO3 -.In the lumen, H+ is once more reabsorbed and exchanged for Na+.  Employed in edematous metabolic alkalosis.

Osmotic Diuretics

Mannitol is poorly absorbed due to its free filtration at the glomerulus.
IV - diuresis is produced. Used as a treatment for cerebral edema
Syndrome of dialysis disequilibrium.

Adverse Effects

Mostly the drugs are sulfanilamide groups - allergy most common.

Diuretic Resistance  

Edema resistant to loop diuretics at maximal dosage. NSAID resistance that appears inhibits PG, or decreased blood flow to the kidneys; stops natriuresis. Proximal tubular reabsorption has increased
Water and sodium,  Greater tubular reabsorption at the distal end. The ENaC channel. NK2CC.

Prevention

• Stop NSAIDs.Combine with Thiazide diuretics.

Also Read: High-Yield NEET SS Medicine Nephrology Questions

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