B.Pharm Subject Detailed about Diuretic drugs

1. DIURETICS
By,
Dr.P.Dheen Kumar,M.Pharm,Ph.D.,

2. 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.

3. 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.
Therapeutic approaches

4.  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.

5.  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.

6. Furosemide
C l
O
O
H 2 N S C O O H
N H
O
CARBONIC ACID INHIBITORS
Acetazolamide CH3 C NH
NN
S
S
O
O
N
H
H
O
CLASSIFICATION
LOOP DIURETICS

7. POTASSIUM SPARING DIURETICS
Aldosterone antagonist
O
O
H 3 C
H 3 C
O
S C C H 3
O
N
N
N
H N H2
N H2H 2N
Cl
O N H
Amiloride
Spironolactone

8. H 2 N O 2 S
Hydrochlor thaizide
C l
N
H
N H
S
O O
H 2 N O 2 S
C l
N
N H
S
O O
Chlorothiazide
THIAZIDE DIURETICS

9. Chlor thalidone
N H
O H
C l
S O 2 N H 2
O
N
H
N
C H 3
C H 3
C l
H 2 N O 2 S
O
Metolazone
THIAZIDE LIKE DIURETICS

10.  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.

12.  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.

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

14. 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.

15. 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
R 1
S O 2 N H
2
R
O
O
N
4
3
2
N1
8
7
6
5

16. 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'sinclude
Cl,Br,CF3 and No2 groups.
The sulphamoyl group in the7-position is a prerequisite for
diuretic activity.

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

18. SYNTHESIS OF FUROSEMIDE

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

20. 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.

21. 36