Diuretics, also called water pills, are medications designed to increase the amount of water and salt expelled from the body as urine. There are three types of prescription diuretics. They're often prescribed to help treat high blood pressure, but they're used for other conditions as well.

1. Site -II Diuretics
Md. Saiful Islam
B.Pharm, M.Pharm (PCP)
North South University
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2. Mechanism of Action ofSite-
II Diuretics
The loop diuretics inhibit Na+/Cl-/K+ cotransport system
located in the luminal membrane of the cells in the limb of
loop of Henle.
These drugs inhibit the re absorption of (20-25)% of the
filtered load sodium within minutes.
Loop diuretics block the re absorption of K+ at site-II by
inhibiting Na+/Cl-/K+ co transport complex.
 Loop diuretics induce synthesis of renal prostaglandins.

3. Loop Diuretics
(Site- II Diuretics)
Loop diuretics inhibit the sodium-potassium-chloride
cotransporter in the thick ascending limb (see above figure).
This transporter normally reabsorbs about 25% of the
sodium load; therefore, inhibition of this pump can lead to a
significant increase in the distal tubular concentration of
sodium, reduced hypertonicity of the surrounding
interstitium, and less water reabsorption in the collecting
duct.

4. Loop diuretics are mostefficacious
Loop diuretics selectively inhibit NaCl reabsorption
in TAL (thick ascending limb) of Loop of Henle. Due
to the large NaCl absorptive capacity of this
segment and the fact that the diuretic action of
these drugs is not limited by development of
acidosis, as is the case with the CA inhibitors,loop
diuretics are among the most efficacious diuretic
agents available

5. Classification of site-IIDiuretics
Site-II Diuretics Examples
 Organo mercurials Meralluride,
Mercaptomerin,
Merethoxylline
5-Sulphamoyl-2-Amino Benzoic
acid derivatives
Furosemide, Azosemide
5-Sulphamoyl-3-Amino Benzoic
acid derivatives
Bumetanide, Piretamide
4-Amino-3-pyridine sulphamoyl
urea
Torsemide, Triflocin.
 Phenoxy acetic acid derivatives Ethacrynic acid

6. Structure Activity Relationship
Structure-activity relationships (SAR) are the
established practices of medicinal chemistry which try to
transform the effect or the potency (i.e. activity) of
bioactive chemical compounds by modifying their
chemical structure. Medical chemists use the chemical
techniques of synthesis to introduce new chemical groups
into the biomedical compound and test the modifications
in their biological effect.

7. SAR of Site-II Diuretics
Among five kinds of site –II diuretics,5-
Sulphamoyl-2-Amino Benzoic acid derivatives
and 5-Sulphamoyl-3-Amino Benzoic acid
derivatives are the most common diuretics.
There are some prerequisites for optimal activity
of diuretics:
 Presence of acidic substituent.
 Presence of sulfamoyl group.
 Presence of activating group.
 Presence of aromatic ring.

8. SAR of Site-IIDiuretics

9. SAR of 5-Sulfamoyl-2-Amino Benzoicacid
derivatives
Presence of an aromatic ring is essential
for optimum diuretic activity and reduction
of aromatic ring causes decrease of diuretic
activity.
Substitution at C1 must be acidic for
optimum diuretic activity. Other acidic
groups also give optimum diuretic activity.
Substitution at C2 position must be by
furfuryl, benzyl, methyl group to get
maximal diuretic activity.
 Sulfamoyl group at C5 position is very
essential for maximal diuretic activity.
The activating group at C4 position can
be chloride group increases the activity.
Furosamide

10. SAR of 5-Sulfamoyl-3-Amino Benzoicacid
derivatives
Presence of aromatic ring is essential
for maximal diuretic activity.
Substitution at C1 position must be
acidic for maximum diuretic activity.
Substitution at C3 position by wide
variety of alkyl group gives optimum
diuretic activity. Such as, Bumetanide.
Substitution at C4 position by
phenoxy, anilino, alcoxy gives better
diuretic activity.
Bumetanide

11. Indications and Contraindication
Indication
 Hyperkalemia
 Acute renal failure
 Anion overdose
 Congestive heart failure
Contraindication
 Anuria
Hepatic coma or in states of severe
electrolyte depletion until the condition is
improved or corrected.

12. Toxicity
 Hypokalemic metabolic alkalosis
 Hypomagnesemia
 Allergic reactions
 Hyponatremia
 Hyperuricemia

13.  Muscle cramp
 Hypotension
 Dizziness
 Encephalopathy (Preexisting liver disease)
 Rashes and itching of skin
 Hypovolemia & Hypokalemia
Adverse effects