Introduction to diuretics. Therapeutic approaches. Normal physiology of urine formation. Classification of drugs . Mechanism of action of Acetazolamide. Mechanism of action of Thiazides. Mechanism of action of Loop diuretics. Mechanism of action of potassium sparing diuretics &aldosterone antagonists.

1. Presented by
B.RAVALI
Reg.no:11AB1R0008
Under the guidance of
Mr. P.RAVI SANKAR M. Pharm
Department of Pharmaceutical chemistry
Vadlamudi, Guntur Dt, A.P, INDIA.
PIN:522213
9/13/2014 1

2. CONTENTS
 Introduction to diuretics.
 Therapeutic approaches.
 Normal physiology of urine formation.
 Classification of drugs .
 Mechanism of action of Acetazolamide.
 Mechanism of action of Thiazides.
 Mechanism of action of Loop diuretics.
 Mechanism of action of potassium sparing diuretics &aldosterone
antagonists.

3. Diuretics (“water pills”) are the drugs which
increase the urine out put (or) urine volume .
What is natreuretic agent ?
Any drug when introduce into the body
increases the out put of sodium
ie., loss of sodium in urine.

4. Therapeutic approaches
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.

5.  Two important functions of the kidney are:-
 To maintain a homeostatis balance of electrolytes and water.
 To excrete water soluble end products of metabolites.
 Each kidney contains approximately one million nephrons and is
capable of forming urine independently.
 The nephrons are composed of glomerulus, proximal tubule, loop of
henle, distal tubule.

6.  Approximately 1200 ml of blood per minute flows through both
kidneys.
 Ions such as sodium, chloride,calcium are reabsorbed.
 Total amount of glucose, amino acids, vitamins, proteins are
reabsorbed.
 If the urine contains above it represents the disorders.
 For example proteins such as albumin in higher amounts causes
albuminaria.

7. Types of
urine
Normal Polyuria

8. CLASSIFICATION OF
DRUGS
LOOP DIURETICS
Furosemide
Cl
O
H2N S
COOH
O
NH
O
CARBONIC ACID INHIBITORS
Acetazolamide CH3
C NH
N N
S
O
S
O
N
H
H
O

9. POTASSIUM SPARING DIURETICS
Aldosterone antagonist
O
O
H3C
H3C
O
O
S C CH3
N
N
O NH
N
H NH2
Cl
H2N NH2
Spironolactone
Amiloride

10. THIAZIDE DIURETICS
Hydrochlor thaizide
H2NO2S
Cl
O O
N
H
NH
S
H2NO2S
Cl
O O
N
NH
S
Chlorothiazide

11. THIAZIDE LIKE DIURETICS
Chlor thalidone
OH
NH
Cl
SO2NH2
O
N
H
N
CH3
CH3
Cl
H2NO2S
O
Metolazone

12.  1 cardiac output -5 lit/min.
 Out of that 20% goes to kidneys i.e.1 lit/min.
 1 lit of blood of has 40%of cells and 60%of plasma.
 600 ml of plasma is not entered into glomerulus only a part of plasma
can enter into it and the rest pass through the efferent arteriole.
 Only 20% can enter into glomerelus that is 120 ml.
 This 120 ml/min makes glomerular filtrate.

16.  It is a sulfonamide derivative which is a non competitive
reversible inhibitor of “carbonic anhydrase enzyme”.
 This enzyme is responsible for catalytic reversible hydration of
carbon dioxide and dehydration of carbonic acid.
 ADVERSE EFFECTS:
 Hypo kalaemia.
 Renal calculi.
 Nausea,loss of hearing,loss of apetite.

17.  These drugs compete for the chloride binding site of the
sodium/chloride symporter and inhibit the re-absorption of
sodium &chloride.

18. Uses
 Treatment of glaucoma.
 Reduces the intra occular pressure.
 Alkalizing the urine.
 These are given in combination with
amiloride,allopurinol to prevent the formation of calcium stones
in hyper calciuric patients.

19. ADVERSE EFFECTS
 GI effects -Anorexia
 CNS effects -Dizziness, vertigo.
 CVS effects-Ortho static hypotension.

20. 6
The position 2 can tolerate the presence of small alkyl
groups such as methyl.
Substituents in 3 position determines the potency,duration
of action.
S
N
R N 1
SO2NH
2
R
O
O
4
3
2
1
8
7
5

21. Loss of c-c double bond between 3&4 positions of nucleus
increases diuretic potency approximately three to ten fold.
Direct substitution of the 4,5 or 8 position with an alkyl group
usually results in diminished diuretic activity.
Substitution of the 6-position with an activating group is
essential for diuretic activity . The best substituent's include
Cl,Br,CF3 and No2 groups.
The sulphamoyl group in the7-position is a prerequisite for
diuretic activity.

22. DRUGS SUBSTITUEN
TS
chlorothiazide R1 =H
hydrochlorothiazide R1=H,R=Cl
trichlormethiazide R1=CHCl2,R=Cl
methyclothiazide R1=CH2Cl,R=Cl
hydroflumethiazide R1=H,R=CF3

23. MECHANISM OF ACTION OF LOOP DIURETICS
 These agents produce a peak diuresis much greater than observed
with other commonly used diuretics.
 They act by inhibiting the luminal Na/K/2Cl symporter.

24. Furosemide is preferred usually to ethacrynic acid for a
number of reasons:
 It is less ototoxic.
 It has broader dose response curve.
 It is more convenient for i.v. use.
 It causes fewer git side effects.

25. SYNTHESIS OF FUROSEMIDE

26. LOOP DIURETICS THIAZIDE DIURETICS
 They inhibit Na/K/2Cl symporetr.
 Acts at thick ascending loop of
henle.
 These are Ca wasting drugs.
 They cause heavy diuresis.
 Para thyroid hormone
independent Ca absorption.
 It can reabsorb 25%to 30% of Na.
 They act by inhibiting Na/Cl
symporter.
 Acts at distal convoluted tubule.
 These are Ca retaining drugs.
 They cause mild diuresis.
 Para thyroid hormone dependent
Ca absorption.
 It can reabsorb 8% of Na.

27. MECHANISM OF ACTION OF OSMOTIC
DIURETICS.
 Osmotic agents such as Mannitol are low molecular weight
compounds that are freely filtered through bowmans capsule.
 They have limited reabsorption because of high water solubility.
 Osmotic diuretics increase the volume of water and almost all of
the electrolytes.

28. They act by inhibiting sodium reabsorption in the late distal tubule and thus
indirectly spare potassium excretion.
USES:-
Liddle’s syndrome(pseudo-hyper aldosteronism).
Amiloride is used to treat lithium induced nephrogenic diabetes insipidus.

29.  Aldosterone,by binding to its receptor in the cytoplasm increases
expression &function of Na channel and sodium pump.
 Spironolactone competitively inhibits the binding of aldosterone and
abolishes its biological effect.

30. O
O
H3C
CH3
O
O
S C CH3
Spironolactone-
17-hydroxy-7-α-mercapto-3-oxo-17αpreg-4-ene-21-carboxlic acid-ϒ-lactone
acetate

31. Generic name Trade name
Chlorothiazide Diuril
Metalazone Zaroxylon
Furosemide Lasix
Chlorthalidone Thalitone
Indapamide Lozol
Hydroflumethiazide Saluron

32. CONCLUSION
Diuretics are the first line agents to treat hypertension. When it
is not controlled it can be given in the form of combinations
with other anti hypertensive's.
Some of these agents has the capacity to reabsorb more
calcium so they can be prescribed for the patients suffering
from osteoporosis.

33. REFERENCES
Thomas L Lemke /David A Williams –Foye’s principles of
Medicinal chemistry 6th edition pg.no:722-735.
Lippincott Williams & Wilkins – Remington The science &practice
of pharmacy 21st edition pg.no:1422-1431.
D. Sriram, P.Yogeeswari –Medicinal chemistry pg.no:171-181.

34. REFERENCES
 Wilson & Gisvold’s Text book of Organic Medicinal &
Pharmaceutical chemistry 11th edition pg. no:596-621.
 Bertram G.Katzung –Basic & Clinical pharmacology 12th
edition pg.no:251-269.

35. ACKNOWLEDGEMENTS
I oblige to pay my deep gratitude for the patience hearing
of my presentation delivered by me with reference to
power point.
I thank one and all.
 I would like to thank my guide Mr. P.RAVI SANKAR for his
extreme support & guidance.
 I would like to thank our principal Dr.P.SRINIVAS BABU
I also would like to thank our organizing committee.

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