ADINA INSTITUTE OF PHARMACEUTICAL SCIENCES BY ASSO.PROF. IMRAN KHAN

1. ADINA INSTITUTE OF PHARMACEUTICALSCIENCES SAGAR
ASSO.PROF. IMRAN KHAN
imrankhanaips@gmail.com

2. • A diuretic is defined as a chemical that increase the rate
of urine formation. The diuretics are particularly useful in
the treatment of congestive failure, edema of lungs,
kidneys and liver. In these conditions fluid abnormally
accumulates in the body.
•
• Diuretics are the drugs that increase the excretion of Na+
and water from the body by an action on the kidney. Their
primary effect is to decrease the absorbance of Na+ and
Cl- from the filtrate, increased water loss being secondary
to the increased excretion of NaCl.

4. • CA inhibitors block the action of the enzyme in the renal
tubules, the secretion of hydrogen ions for exchange with
sodium ions of the fluid in the tubules inhibited and increase
excretion of Na+ and bicarbonate ions.
• Uses: Adverse effects:
• CCF hypokalaemia
• Petitmal epilepsy metabolic acidosis
• Edema of pregnancy hypersensitivity reactions
•
• Miscellanious class
• Xanthine alkaloids
• osmotic diuretics e.g. dextrose, mannitol, urea
• Mercurial diuretics e.g. mercaptomerin, meralluride,
merthoxylline

5. •
M/A: CA inhibitors block the action of the
enzyme in the renal tubules, the
secretion of hydrogen ions for exchange
with sodium ions of the fluid in the
tubules inhibited and increase excretion
of Na+ and bicarbonate ions.

6. •
Methazolamide is a potent inhibitor of
carbonic anhydrase. Inhibition of carbonic
anhydrase in the ciliary processes of the
eye decreases aqueous humor secretion,
presumably by slowing the formation of
bicarbonate ions with subsequent
reduction in sodium and fluid transport.

7. • Carbonic anhydrase inhibitors reduce
intraocular pressure by partially
suppressing the secretion of aqueous
humor (inflow), although the mechanism by
which they do this is not fully understood.
Evidence suggests that HCO3- ions are
produced in the ciliary body by hydration of
carbon dioxide under the influence of
carbonic anhydrase and diffuse into the
posterior chamber which contains more
Na+ and HCO3- ions than does plasma
and consequently is hypertonic. Water is
then attracted to the posterior chamber by
osmosis, resulting in a drop in pressure.

8. •
As a diuretic, chlorothiazide inhibits active
chloride reabsorption at the early distal
tubule via the Na-Cl cotransporter,
resulting in an increase in the excretion of
sodium, chloride, and water. Thiazides like
chlorothiazide also inhibit sodium ion
transport across the renal tubular
epithelium through binding to the thiazide
sensitive sodium-chloride transporter. This
results in an increase in potassium
excretion via the sodium-potassium
exchange mechanism. The
antihypertensive mechanism of
chlorothiazide is less well understood
although it may be mediated through its
action on carbonic anhydrases in the
smooth muscle or through its action on the
large-conductance calcium-activated

9. • 2nd position can tolerate the presence of relatively small
alkyl groups such as –CH3.
• 3rd position is an extremely important site and it
determine the potency and duration of action of thiazide
diuretics.
• Loss of C-C double bond at 3rd and 4th position increases
the potency to 3-10 fold.
• Direct substitution at position 4,5 or 8 with alkyl groups
usually diminishes diuretic activity.
• Substitution at position 6 with –Cl, -Br, -CF3 and –NO2
increases the activity.
• The sulfamoyl group should be as such at position 7 for
diuretic acivity.

10. •
Hydrochlorothiazide is transported from
the circulation into epithelial cells of the
distal convoluted tubule by the organic
anion transporters OAT1, OAT3, and
OAT4.6,3 From these cells,
hydrochlorothiazide is transported to the
lumen of the tubule by multidrug
resistance associated protein 4 (MRP4)
Normally, sodium is reabsorbed into
epithelial cells of the distal convoluted
tubule and pumped into the basolateral
interstitium by a sodium-potassium
ATPase, creating a concentration
gradient between the epithelial cell and
the distal convoluted tubule that
promotes the reabsorption of water

11. •
Hydroflumethiazide is a thiazide diuretic
that inhibits water reabsorption in the
nephron by inhibiting the sodium-chloride
symporter (SLC12A3) in the distal
convoluted tubule, which is responsible for
5% of total sodium reabsorption. Normally,
the sodium-chloride symporter transports
sodium and chloride from the lumen into
the epithelial cell lining the distal
convoluted tubule. The energy for this is
provided by a sodium gradient established
by sodium-potassium ATPase on the
basolateral membrane. Once sodium has
entered the cell, it is transported out into
the basolateral interstitium via the sodium-
potassium ATPase, causing an increase in
the osmolarity of the interstitium, thereby
establishing an osmotic gradient for water

12. • Hydrochlorothiazide, a thiazide diuretic,
inhibits water reabsorption in the nephron
by inhibiting the sodium-chloride symporter
(SLC12A3) in the distal convoluted tubule,
which is responsible for 5% of total sodium
reabsorption. Normally, the sodium-
chloride symporter transports sodium and
chloride from the lumen into the epithelial
cell lining the distal convoluted tubule. The
energy for this is provided by a sodium
gradient established by sodium-potassium
ATPases on the basolateral membrane.

13. • Furosemide promotes diuresis by blocking
tubular reabsorption of sodium and
chloride in the proximal and distal tubules,
as well as in the thick ascending loop of
Henle. This diuretic effect is achieved
through the competitive inhibition of
sodium-potassium-chloride transporters
(NKCC2) expressed along these tubules in
the nephron, preventing the transport of
sodium ions from the lumenal side into the
basolateral side for reabsorption. This
inhibition results in increased excretion of
water along with sodium, chloride,
magnesium, calcium, hydrogen, and
potassium ions.10 As with other loop
diuretics, furosemide decreases the
excretion of uric acid

14. •
Bumetanide interferes with renal cAMP
and/or inhibits the sodium-potassium
ATPase pump. Bumetanide appears to
block the active reabsorption of chloride
and possibly sodium in the ascending loop
of Henle, altering electrolyte transfer in the
proximal tubule. This results in excretion of
sodium, chloride, and water and, hence,
diuresis.

15. •
Ethacrynic acid inhibits symport of sodium,
potassium, and chloride primarily in the
ascending limb of Henle, but also in the
proximal and distal tubules. This
pharmacological action results in excretion
of these ions, increased urinary output, and
reduction in extracellular fluid. Diuretics
also lower blood pressure initially by
reducing plasma and extracellular fluid
volume; cardiac output also decreases,
explaining its antihypertensive action.
Eventually, cardiac output returns to
normal with an accompanying decrease in
peripheral resistance. Its mode of action
does not involve carbonic anhydrase
inhibition.

16. • Spironolactone competitively inhibits
aldosterone dependant sodium potassium
exchange channels in the distal convoluted
tubule. This action leads to increased
sodium and water excretion, but more
potassium retention.Label The increased
excretion of water leads to diuretic and
also antihypertensive effects.

17. •
As a diuretic, chlorothiazide inhibits active
chloride reabsorption at the early distal
tubule via the Na-Cl cotransporter,
resulting in an increase in the excretion of
sodium, chloride, and water. Thiazides like
chlorothiazide also inhibit sodium ion
transport across the renal tubular
epithelium through binding to the thiazide
sensitive sodium-chloride transporter. This
results in an increase in potassium
excretion via the sodium-potassium
exchange mechanism. The
antihypertensive mechanism of
chlorothiazide is less well understood
although it may be mediated through its
action on carbonic anhydrases in the
smooth muscle or through its action on the
large-conductance calcium-activated
potassium (KCa) channel, also found in the

18. • Mannitol is an osmotic diuretic that is
metabolically inert in humans and occurs
naturally, as a sugar or sugar alcohol, in
fruits and vegetables. Mannitol elevates
blood plasma osmolality, resulting in
enhanced flow of water from tissues,
including the brain and cerebrospinal fluid,
into interstitial fluid and plasma. As a result,
cerebral edema, elevated intracranial
pressure, and cerebrospinal fluid volume
and pressure may be reduced. As a
diurectic mannitol induces diuresis
because it is not reabsorbed in the renal
tubule, thereby increasing the osmolality of
the glomerular filtrate, facilitating excretion
of water, and inhibiting the renal tubular
reabsorption of sodium, chloride, and other
solutes. Mannitol promotes the urinary
excretion of toxic materials and protects