10/04/2017

Drugs Acting On Kidney.

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.
CategoryExamples
1Osmotic DiureticsMannitol
Sorbitol.
2Xanthine DiureticsCaffeine
Theophylline
Theobromine.
3Thiazide DerivativesChlorothiazide
Hydrochlorothiazide
Clopamide
4Potassium Sparing DiureticsAmiloride
Spironolactone
Triamterene
5Loop DiureticsFurosemide
Torsemide
Ethacrynic acid
Bumetanide
6Carbonic Anhydrase InhibitorsAcetazolamide
Dorzolamide.
7Mercurial Diuretics.Mersalyl
Mercaptopurine
8Saline DiureticsAmmonium Chloride
Sodium bi Carbonate

Mechanisms of Action:

  1. 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.
7. Mercurial Diuretics:
  • 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.