Diuretics

Diuretics are drugs, which increase renal excretion of salt and water: are principally used to
remove excessive extracellular fluid from the body.
In order to understand the action of diuretics it is important to have some knowledge of the basic
processes that take place in the nephron (unit structure of kidney.
Approximately 180 liters of fluid is filtered from the glomerulus into the nephron per day. The
normal urine out put is 1-5 liters per day. The remaining is reabsorbed in different areas of
nephron. There are three mechanisms involved in urine formation

a) glomerular filtration
b) tubular reabsorption
c) Tubular secretion. These processes normally maintain the fluid volume, electrolyte
concentration and PH of the body fluids.
Classification of diuretics:-
Most of the diuretics used therapeutically act by interfering with sodium reabsorption by the
tubules. The major groups are:
I. Thiazides and related diuretics: e.g. Hydrochlorothiazide chlorthalidone, bendrofluazide,
etc.
II. Loop diuretics: e.g. furosemide, ethacrynic acid, etc.
III. Potassium sparing diuretics e.g. triamterene, amiloride, spironolactone, etc.
IV. Carbonic anhydrase inhibitors e.g. acetazolamide
V. Osmotic diuretics e.g. mannitol, glycerol
I. Thiazide diuretics act by inhibiting NaCl symport at the distal convoluted tubule. They are
used in hypertension, edema of hepatic, renal and cardiac origin.
Adverse effects: epigastric distress, nausea, vomiting, weakness, fatigue, dizziness,
impotence, jaundice, skin rash, hypokalemia, hyperuricemia, hyperglycaemia and visual
disturbance.
II. Loop diuretics: Loop diuretics like frusemde inhibit Na+

• K – 2Cl symporter in the ascending
  limb.
  Adverse effects: Hypokalemia, nausea, anorexia, vomiting epigastric distress, fatigue
  weakness muscle cramps, drowsiness. Dizziness, hearing impairment and deafness
  are usually reversible. Therapeutic uses: acute pulmonary edema, edema of cardiac,
  hepatic and renal disease. Hypertension, cerebral edema, in drug overdose it can be
  used to produce forced diuresis to facilitate more rapid elimination of drug.
  III. Potassium sparing diuretics mechanism of action: Potassium sparing diuretics
  (spironolactone, triamterene, amiloride) are mild diuretics causing diuresis by increasing the
  excretion of sodium, calcium and bicarbonate but decrease the excretion of potassium.
  Adverse effects: G.I. disturbances, dry mouth, rashes confusion, orthostatic hypotension,
  hyperkalaemia. Hyponatraemia
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  Therapeutic uses: used with conjunction with thiazides or loop diuretics in edema due to,
  cardiac failure nephrotic syndrome and hepatic disease.
  IV. Carbonic anhydrase inhibitors: these drugs like acetazolamide inhibit the enzyme carbonic
  anhydrase in renal tubular cells and lead to increased excretion of bicarbonate, sodium
  and potassium ions in urine. In eye it results in decrease information of aqueous humor.
  Therefore these are used in treatment of acute angle glaucoma. Main adverse effects of
  these agents are drowsiness, hypokalemia, metabolic acidosis and epigastric distress.
  V. Osmotic diuretics: these drugs like mannitol and glycerine (glycerol) are freely filtered at the
  glomerulus and are relatively inert pharmacologically and undergo limited reabsorption by
  renal tubule. These are administered to increase significantly the osmolality of plasma and
  tubular fluid. Some times they produce nausea, vomiting, electrolyte imbalances. They are
  used in cerebral edema and management of poisoning.