The Kidney is one of the vital organs of the body and an important part of the Urinary system. Various drugs show their prominent pharmacological actions on kidney.
Diuretics: -
- “The drugs which increase formation, as well as excretion of urine & used mainly in the treatment of edema & hypertension, are called as diuretics.”
- e.g. Furosemide (Lasix.)
Classification:-
| Sr. No. | Category | Examples |
| 1 | Osmotic Diuretics | Mannitol Sorbitol. |
| 2 | Xanthine Diuretics | Caffeine Theophylline Theobromine. |
| 3 | Thiazide Derivatives | Chlorothiazide Hydrochlorothiazide Clopamide |
| 4 | Potassium Sparing Diuretics | Amiloride Spironolactone Triamterene |
| 5 | Loop Diuretics | Furosemide Torsemide Ethacrynic acid Bumetanide |
| 6 | Carbonic Anhydrase Inhibitors | Acetazolamide Dorzolamide. |
| 7 | Mercurial Diuretics. | Mersalyl Mercaptopurine |
| 8 | Saline Diuretics | Ammonium Chloride Sodium bi Carbonate |
Mechanisms of Action:
Osmotic Diuretics: (Inhibit reabsorption of Na ions act at Proximal convoluted tubule.)
- These drugs don't get metabolized and are get filtered as such at the glomerulus.
- They did not get reabsorbed by "Selective reabsorption process" and hence remain in tubules to get excreted.
- They prevent selective reabsorption of Na ions at proximal tubule.
- As sodium ions get excreted they also carry equal osmotic water with them resulting in diuresis.
- e.g. Sorbitol, Mannitol, Urea etc.
2. Xanthine Diuretics: (Act by increasing renal blood flow.)
- Xanthine derivatives are indirect diuretics.
- They did not interfere with urine formation process in the kidney.
- Xanthine derivatives act as a diuretic by increasing blood flow towards the kidneys.
- As blood flow entering kidney gets increased, the formation of urine gets increased hence resulting in diuresis.
- e.g. Theophylline, Theobromine, Caffeine.
3. Thiazide and Thiazide-like Derivatives: (At distal convoluted tubule by inhibiting reabsorption of Na and Cl ions.).
- The drugs which have a "Thiazide" chemical nucleus are called as Thiazides.
- While those who don't have "Thiazide" nucleus but shows actions like thiazides are called as Thiazide-like drugs.
- Thiazide derivatives inhibit reabsorption of Na and Cl ions at Distal convolution tubule by inhibiting"sodium-chloride symporter".
- As sodium ions get excreted they also carry equal osmotic water with them resulting in diuresis.
- e.g. Chlorothiazide, Hydrochlorothiazide. etc.
- Metabolic disturbances:
- Hypokalemia: They cause an increase in potassium excretion.
- Hyperglycemia: Thiazides decrease insulin secretion.
- Hypercalcemia: They increases reabsorption of Calcium ions.
- Hyperuricaemia: They decreases reabsorption of uric acid.
- Contraindications:
- Diabetes mellitus.
- Gout.
- With Digitalis therapy.
- Kidney failure.
- Nursing Mothers. (Known to pass in the milk and to reduce milk secretion.)
- Therapeutic Indications:
- all types of edemas.
- hypertension.
4. Potassium Sparing Diuretics: (Aldosterone antagonism @ distal convoluted tubule)
- Aldosterone acts on distal convoluted tubule to increase reabsorption of Na ions and excretion of K ions.
- Potassium-sparing diuretics antagonize the actions of Aldosterone and cause increased excretion of Na ions and spares K ions.
- As they spare K ions they are called as Potassium-sparing diuretics.
- Potassium-sparing diuretics act by inhibition Na-K ATPase pumps @ distal convolution and collecting ducts hence increasing Na ion excretion.
- As sodium ions get excreted they also carry equal osmotic water with them resulting in diuresis.
- As these parts of nephron deals with less amount of Na reabsorption, these diuretics are weak in nature.
- e.g. Spironolactone, Amiloride, Triamterene etc.
5. Loop Diuretics: (Loop of Henle)
- Loop Diuretics acts on the Loop of Henle, hence called as Loop Diuretics.
- The loop of Henle constitutes a large part of the nephron and hence these diuretics are called as Potent Diuretics or High ceiling Diuretics.
- Loop diuretics inhibits functions of Na+-K+-2Cl− symporter an enzyme responsible for reabsorption of Na, K, and Cl ions at the loop of Henle.
- The loop of Henle deals with a large portion of sodium reabsorption, as a large portion of sodium, is gets excreted along with equal osmotic water, the loop diuretics are called as potent diuretics.
- e.g. Furosemide, Torsemide, Ethacrynic Acid, Bumetanide etc.
- They are useful in hypertension and edema treatment.
- Loop diuretics are useful in impaired kidney and known to cause hypokalemia.
6. Carbonic Anhydrase Inhibitors: (Proximal Convolution).
- Water and carbon dioxide reacts to form Carbonic acid.
- H2O+CO2----->H2CO3.
- The enzyme carbonic anhydrase is present in tubular cells of the nephron is responsible for the formation of Hydrogen ions and Bicarbonate ions from carbonic acid.
- H2CO3-----Carbonic anhydrase----------> H+HCO3.
- The formed hydrogen ions are replaced for reabsorption of Na ions.
- The drugs like Acetazolamide inhibit carbonic anhydrase and hence stops the formation of H ions.
- Due to deficiency of H ions, the tubular cells are not able to reabsorb the Na ions.
- Na ions remain in the tubule and get excreted with the equal osmotic amount of water causing diuresis.
- The carbonic anhydrase thus produces diuresis by increasing excretion of sodium, potassium and bicarbonate ions.
- Due to increased excretion of bicarbonate ions these drugs produce systemic acidosis, which in turns reduces their effect. Hence their action is self-limiting.
- Examples of carbonic anhydrase inhibitors are Acetazolamide, Dorzolamide etc.
- They are useful as diuretic and also in the treatment of glaucoma.
- These Diuretics contain mercury in their chemical structure.
- They cause irritation to the kidney which results into diuresis.
- However, these Diuretics are not used nowadays due to their toxic profile.
- e.g. Mersalyl, Mercaptomerine.