This document discusses the classification and mechanisms of different types of diuretic drugs. It describes high efficacy diuretics that inhibit sodium-potassium-chloride cotransport, medium efficacy diuretics that inhibit sodium-chloride symport like thiazide diuretics, and weak diuretics including carbonic anhydrase inhibitors, potassium sparing diuretics, and osmotic diuretics. It also covers the sites of action and transport mechanisms affected by these diuretic classes in different parts of the nephron like the thick ascending limb of Henle's loop and distal convoluted tubule.

1. Joydeep Ganguly
AND
THEIR MECHANISM

2. Diuretics
 These are the drugs which cause a net loss of Na+ and
water in urine.
 Diuretics are among the most widely prescribed drugs.
 Application of diuretics to the management of
hypertension & in edema.
CLASSIFICATION
1. High efficacy diuretics (lnhibitors of Na+-K+-2Cl-
cotransport)
 a) Sulphamoyl derivatives: Furosemide, Bumetanide,
Torasemide
 b) Phenoxyacetic acid derivatives: Ethacrynic acid
 c) Organomercurials: Mersalyl

3. Cont………
 2. Medium efficacy diuretics (lnhibitors of Na+ -Cl-
symport)
(a) Benzothiadiazines (thiazides): Hydrochlorothiazide, Benzthiazide,
Hydroflumethiazide, Clopamide
(b) Thiazide like (related heterocyclics): Chiorthalidone, Metolazone,
Xipamide, Indaoamide.
 3. Weak or adjunctive diuretics
 (a) Carbonic anhydrase inhibitors: Acetazolamide
 (b) Potassium sparing diuretics:
 (i) Aldosterone antagonist: spironolactone
 (ii) Inhibitors of renal epithelial Na+ channel: Triamterene,
Amiloride.
 (c) Osmotic diuretics: Mannitol, Isosorbide, Glycerol
 (d) Xanthines: Theophylline

4. High Ceiling Loop Diuretics (lnhibitors of Na+-K+-2Cl-
Cotransport)
Ion transport in the thick ascending limb of Henle's
loop, showing the site of action of loop diuretics

5. Cont……
 The sodium pump (P) is the main primary active transport
mechanism, and Na+, K+ and Cl- enter by a cotransport system
(C1). Chloride leaves the cell both through basolateral chloride
channels and by an electroneutral K+/Cl- cotransport system
(C2). Some K+ returns to the lumen via potassium channels in the
apical membrane, and some Na+ is absorbed paracellularly
through the zonula occludens.
Furosemide (Frusemide) Prototype drug
•The development of this orally and rapidly acting highly efficacious
diuretic
•Its maximal natriuretic effect is much greater than that of other
classes. The diuretic response goes on increasing with increasing
dose: upto 10 L of urine may be produced in a day.

6. THIAZIDE AIID RELATED DIURETICS (lnhibitors of Na+-Cl-
symport)
Salt transport in the distal convoluted tubule, showing the site of action of
thiazide diuretics. The sodium pump (P) in the basolateral membrane is the
primary active transport mechanism. Sodium and chloride ions enter by an
electroneutral cotransport carrier (C1). Exm- Chlorthiazide.

7. CARBONIC ANHYDRASE INHIBITORS
 1. Carbonic anhydrase (CAse) is an enzyme which catalyses the
reversible reaction. H2O + CO2 ↔ H2CO3.
 2. Carbonic acid spontaneously ionises.
 H2CO3 ↔ H+ + HCO3
 3. The enzyme is present in renal tubular cell (specially PT)
gastric mucosa, exocrine pancreas, ciliary body of eye, brain and
RBC. Eg: Acetazolamide.
Sodium is absorbed and hydrogen ion secreted at the luminal
surface by an antiport mechanism. Mostbicarbonate in the filtrate
is reabsorbed in this way in the proximal tubule. In the distal
tubule bicarobonate is added to the plasma and monobasic
phosphate or ammonium chloride is added to the urine. Primary
active transport mechanism is the sodium pump (P). Dashed line
with K+ indicative passive diffusion.

8. Cont…….

9. POTASSIUM SPARING DIURETICS
These are either aldosterone antagonist or directly inhibit Na+ channels in DT and
CD cells
to indirectly conserve K+. Eg: Spironolactone (Aldosterone antagonist)

10. OSMOTIC DIURETICS
1. Mannitol is a nonelectrolyte of low molecular weight (182) that is
pharmacologically inert
2. Given in large quantities sufficient to raise osmolarity of plasma
and tubular fluid.
Mannitol appears to limit tubular water and electrolyte
reabsorption in a variety of ways:
a. Retains water iso-osmotically in PT, dilutes luminal fluid which
opposes NaCl reabsorption
b. Inhibits transport processes in the thick AscLH by an unknown
mechanism. Quantitatively this appears to be the most important cause
of diuresis.
c. Expands extracellular fluid volume (because it does not enter cells,
mannitol draws water from the intracellular compartment)-increases
g.f.r. and inhibits renin release

11. Applications of Diuretics:
Diuretics are very effective in the treatment of conditions like:-
 Chronic heart failure
 Nephrotic syndrome
 Chronic hepatic diseases
 Hypertension
 Pregnancy associated oedema
 Cirrhosis of the liver
 Edema.