The document discusses diuretics, which are drugs that increase urine production. It defines diuretics and describes their primary mechanism of action as inhibiting sodium reabsorption along the nephron. This leads to increased sodium and water excretion, reducing extracellular fluid volume and edema. The document classifies major types of diuretics, including carbonic anhydrase inhibitors, loop diuretics, thiazides, and potassium-sparing diuretics. It provides examples of drugs for each class, along with their uses, mechanisms, and side effects. Structure-activity relationships that determine diuretic activity are also summarized.

1. DIURETICS
Prepared By:- Miss Anamika Singh

2. A Diuretic Is Define As Drug That Increase The Rate Of Urine
Formation. The Primary Action Of Most Diuretic Is The Direct
Inhibition Of Na+ Reabsorption (Increased Excretion)at One Or
More Of The Four Major Side Along The Nephron.An Increased
Na+ Excretion Accompanied By Anion Like Since Nacl Is The
Major Determinant Of Extracellular Fluid Volume. Diuretic
Reduce Extracellular Fluid Volume (Decrease In Edema) By
Decreasing Total Body Nacl Content.
Introduction

3. Site 1:-Proximal Convoluted Tubule(PCT)
Site2:-Ascending Loop Of Henle
Site 3:-Distal Convoluted Tubule (DCT)
Site4:- Late Distal Tubule And And Collecting Duct.
Four Major Sites Along Nephrone That Are
Responsible For Reabsorbtion

4. These Are Drug Which Cause A Net Loss Of Na+ And
Water In Urine .
There Are Several Categories Of Diuretic. All Diuretic
Increase The Excretion Of Water From Body.
DEFINATION

6. RISK FACTOR
There Are Certain Risk Factor Which Must Be Monitored In Patient Post
Obstruction Which Can Lead To Post Obstructive Diuresis .
Edema
Congestive Heart Failure
Hypertension
Azotemia (High Level Of Nitrogen –Containing Compound Such As
Urea And Creatinine .

7. COMPLICATION
Volume Depletion
Azotemia
Hypokalemia
Metabolic Alkalosis
Hyponatremia
Hyperuricemia
Hypomagnesaemia

8. THERAPEUTIC APPROACH
Diuretic are very effective in the treatment of condition like :-
Chronic heart failure
Nephrotic syndrome
Chronic hepatic disease
Hypertension
Pregnancy associated oedema
Cirrhosis of the liver

9. CLASSIFICATION
1) CARBONIC ANHYDRASE INHIBITOR :-
Acetazolamide, Methazolamide,
Dichlorphenamide ,Chloramphenamide
2) LOOP DIURETIC (HIGH CELLING DIURETIC) :-
Furosemide, Ethacrynic Acid ,
Bumetanide
3) THIAZIDE :-
Chlorothiazide, Hydrochlorothiazide ,Benzthiazide,
Hydroflumethazide, Bendroflumethiazide.
4) POTASSIUM SPARING DIURETIC:-
Triamterene ,Amiloride,spironalactone.
5) OSMOTIC DIURETIC:-
Mannintol

10. DIAGRAM BASIS CLASSIFICATION

11. CARBONIC ANHYDRASE INHIBITOR :-
Although the available CA inhibitor are used infrequently as diuretic. They not only
played an important role in the development of other major classes of diuretic that
are currently in widespread use but also aided in our understanding of basis renal
physiology .shortly after its introduction for the treatment of bacterial infection .it
was a relatively weak inhibitor of renal CA. and the dose needed to exert adequate
diuresis was associated with severe adverse effect . To improve on the CA-
inhibitory property of sulfanilamide ,many sulphonyl containing compound
(SO2.NH2,) were synthesized and screened for their diuretic cavity in vivo and their
ability to inhibit CA in vitro . Two pups of CA inhibitor emerged : simple
heterocyclic sulfonamide and into meta- disulfamoylbenzene derivatives.

12. ACETAZOLAMIDE
Route of administration :- mouth, intravenous
Metabolism:- none
Execration :-Urine (90%)
Protein binding:- 70-90%
Use:-Acetazolamide is used to treat glaucoma, a condition in which
increased pressure in the eye can lead to gradual loss
vision. Acetazolamide decreases the pressure in the eye.

13. SYNTHESIS OF ACETAZOLAMIDE

14. METHAZOLAMIDE
Use:- Methazolamide is used to treat glaucoma (a condition in
which increased pressure in the eye can lead to gradual loss of
vision). Methazolamide is in a class of medications called
carbonic anhydrase inhibitors. It works by decreasing the pressure
in the eye.
Route of administration :-oral
Metabolism:- none
Execration :-Urine (90%)
Protein binding:- 55%

15. DICHLORPHENAMIDE
Use:- Dichlorphenamide is used to treat inherited muscle disorders, such
as primary hyperkalemic periodic paralysis, primary hypokalemic periodic
paralysis, and related variants. This medicine is a carbonic anhydrase
inhibitor.
Route of administration :-oral
Metabolism:- none
Execration :-Urine (90%)
Protein binding:- 55%

16. STRUCTURE ACTIVITY
RELATIONSHIP
SAR Studies Involving The Simple Hetrocyclic Sulphonamides Yielded
The Prototypic Ca Inhibitor, Acetazolamide .
The Sulfamoyl Group Is Essential For In Vitro Ca Inhibitory Activity
And For Diuresis Production In Vivo.
The Sulfamoyl Nitrogen Atom Must Remain Unsubstituted To Retain
Both In Vivo And In Vitro Activities . This Features Explain Why All
Antibacterial Sulphonamide Except Sulfanilamide Are Capable Of
Inhibiting Ca Or Extering Diuresis.
In Contrast ,Substitution Of A Methyl group One Of Acetazolamide
Ring Nitrogen Yields Methazolamide A Product The Retains Ca Inhibitor
Activity.
The Moiety To Which Are Sulphonyl Group Is Attached Must Posses
Aromatic Character .

17. In Addition ,Within A Given Series Of Heterocyclic Sulphonamides The
Derivative With The Highest Lipid / Water Partition Coefficients And The
Lowest Pka Value Have The Greatest CA Inhibitory And Diuretic
Activities.
The Sar Studies Involving The Meta- Disulfamoylbenzene Lacked
Diuretic Activity ,But Key Substitutions Led To Compound With Diuretic
Activities .
The First Commercially Available Analogue Dichlorphenamide ,Is
Similar To Acetazolamide In Its Ca-inhibitory Activity, But It Is Also A
Chloruretic Agent .Subsequently ,Chloraminophenamide When Given By
The Intravenous Route Was Shown To Possess Less Ca Inhibitory Activity
Bu More Chloruretic Activity . Poor Diuretic Following The Oral
Administration Of Chloraminophenamide Precluded Its Marketing.

18. LOOP DIURETIC
Act By Inhibition Of Na+,k+, And Cl- Absorption From The Ascending
Limb Of The Loop Of Henle In Renal Tuble .
They Also Tend To Reduce Renal Ca+reabsobtion Thus They Are Used
Treatment Of Hypercalcimia.
High Efficiency Diuretic .

19. FUROSEMIDE
Use:- Furosemide Is Used To Treat Edema (Fluid Retention; Excess
Fluid Held In Body Tissues) Caused By Various Medical Problems,
Including Heart, Kidney, And Liver Disease. Furosemide Is In A Class
Of Medications Called Diuretics ('Water Pills').
Route Of Administration :- IV,IM ,MOUTH
Metabolism:- Hepatic
Execration :-Urine
Bioavailability :-43-69%

20. SYNTHESIS OF FUROSEMIDE

21. ETHACRYNIC ACID
Use:- Ethacrynic Acid Is A Diuretic That Is Used To Treat Edema When A
Stronger Agent Is Required. It Is Available As A Pill Or Injected Form. The
Pill Is Used To Treat Edema Associated With Congestive Heart
Failure, Cirrhosis And Renal Disease, Accumulation Of Liquid In The
Belly Associated With Cancer Or Edema, And Management Of Hospitalized
Children With Congenital Heart Disease Or Nephrotic Syndrom
Route Of Administration :- IV,oral
Metabolism:- Hepatic
Execration :-Urine
Protein binding : 98%

22. BUMETANIDE
Use:- It Used To Treat Swelling And High Blood Pressure.[1] This Include
Swelling As A Result Of Heart Failure, Liver Failure, Or Kidney
Problems.[1] For High Blood Pressure It Is Not A Preferred Treatment.[1] It
Is Taken By Mouth, Or By Injection Into A Vein Or Muscle.[1]
Route Of Administration :- IV,IM,Mouth
Metabolism:- Hepatic
Execration :-Urine
Protein binding : 98%
Bioavailability:- 80%

23. SAR OF LOOP DIURETIC
They Are Either 5- Sulphamoyl -2-amino Benzoic Acid Or 5 Sulphamoyl 3-
amino Benzoic Acid Derivatives.
The Carbonyl Group At C:1 Provide Optimal Diuretic Activity
The Substitution Of Activating Group (X) In The Position 4 By Cl ,Alkoxy,
Aniline, Benzyl, Or Benzyl Group, At 4 Th Position Increase The Diuretic
Activity .
 The Presence Of Sulphanomyl Group In The 5th Position Is Essential For
Activity
The Two Series Of 5-sulphamoyl Benzoic Acid Differ In The Nature Of The
Functional Group That Substituted In 2nd And 3 Rd Position.
The Presence Of Furfuryl,phenyl,and Thienyl Methyl Group At 2nd Amino
Group Of 5- Sulphomoyl.
2 Amino Benzoic Acid Gives Maximum Diuretic Activity.
The Wide Range Of Alkyl Group Can Be Substituted At 3rd Amino Group
At 5 Sulphomoyl 3-amino Benzoic Acid Without Modifying The Optimal
Diuretic Activity .

24. THIAZIDE :-
Secreted Into The Tubular Lumen By The Organic Acid Transport
Mechanism In The Proximal Tubule.
Act On The Distal Tubule To Inhibit Sodium And Chloride Transport And
Result In A Modest Diuresis.
Increase Renal Excretion Of Potassium Magnesium.
Reduce Calcium And Urate Excretion .
Not Effective At Low Glomerular Filtration Rates.
Impair Maximal Diluting But Not Maximal Concentrating Ability .

25. CHLOROTHIAZIDE,
Use:- Chlorothiazide Is A "Water Pill" (Diuretic) That Causes You To
Make More Urine. This Helps Your Body Get Rid Of Extra Salt And
Water. This Medication Is Also Used To Decrease Swelling (Edema)
Caused By Conditions Such As Cancer, Congestive Heart Failure, Liver
Disease, And Kidney Disease.
Route Of Administration :- IV,Mouth
Metabolism:- Nill
Execration :-Renal
Protein binding : 28%
Bioavailability:-Low

26. SYNTHESIS OF CHLORTHIAZIDE

27. HYDROCHLOROTHIAZIDE
Use:- Hydrochlorothiazide Is Used To Treat Edema (Fluid Retention;
Excess Fluid Held In Body Tissues) Caused By Various Medical
Problems, Including Heart, Kidney, And Liver Disease And To
Treat Edema Caused By Using Certain Medications Including Estrogen
And Corticosteroids
Route Of Administration :- Mouth
Metabolism:- Nill
Execration :-Kidney
Protein binding : 88%
Bioavailability:-70%

28. BENZTHIAZIDE
Use:- Benzthiazide Is Used To Treat Hypertension And Edema. Like
Other Thiazides, Benzthiazide Promotes Water Loss From The Body
(Diuretics). They Inhibit Na+/Cl- Reabsorption From The Distal
Convoluted Tubules In The Kidneys
Route Of Administration :-Oral
Metabolism:- Nill
Execration :-Renal
Protein binding : 30%
Bioavailability:-70%

29. HYDROFLUMETHAZIDE
Use:- Hydroflumethiazide Is An Oral Thiazide Used To
Treat Hypertension And Edema. High Blood Pressure Adds To The
Workload Of The Heart And Arteries
Route Of Administration :-Nill
Metabolism:- Essentially unchanged
Execration :-Renal
Protein binding : 74%
Bioavailability:-52%

30. BENDROFLUMETHIAZIDE.
Use:- Bendroflumethiazide Is A Type Of Medicine Called A Diuretic. It's
Used To Treat High Blood Pressure (Hypertension) And The Build-up Of
Fluid In Your Body (Oedema). Diuretics Are Sometimes Called
'Water Pills' Because They Make You Pee More. This Helps Get Rid Of
Extra Fluid In Your Body.
Route Of Administration :-Oral
Metabolism:- Exensive
Execration :-Renal
Protein binding : 96%
Bioavailability:-100%

31. SAR OF THIAZIDE
The 2- Position Can Tolerate Small Alkyl Group Are Ch3 .
Substitution At The 3- Position Determine The Potency And Duration Of
Action Of The Thiazide .
Saturation Of C-C Bond Between The 3 And 4 Position Of The
Benzothiadiazine 1,1 Dioxide Nucleus Increase The Potency Of His Class
Of Diuretic Approximately 3-10fold.
Direct Substitution Of The 4,5 Or 8 Position With An Alkyl Group Usually
Result In Diminished Diuretic Activity.
Substitution Of The 6- Position With An Activating Group Is Essential For
Diuretic Activity .The Best Substituent Include Cl-,br-,cf3-,and No2
Group.
 The Sulfamoyl Group In The 7 Position Is Essential For Diuretic Activity .

32. POTASSIUM SPARING DIURETIC
Potassium-sparing Diuretics Are Medicines That Increase Diuresis
(Urination) Without The Loss Of Potassium. They Are Generally Weak
Diuretics And Work By Interfering With The Sodium-potassium
Exchange In The Distal Convoluted Tubule Of The Kidneys Or As An
Antagonist At The Aldosterone Receptor.

33. TRIAMTERENE
Use:- Triamterene Is Used Alone Or With Other Medications To
Treat Edema (Fluid Retention; Excess Fluid Held In Body Tissues)
Caused By Various Conditions, Including Liver And Heart Disease.
Triamterene Is In A Class Of Medications Called Diuretics
Route Of Administration :-Oral
Metabolism:-Nill
Execration :-Renal
Protein binding : 60%
Bioavailability:-70%

34. AMILORIDE
Use:- Amiloride is used in combination with other medicines to
treat high blood pressure (hypertension). High blood pressure adds to the
workload of the heart and arteries. If it continues for a long time, the heart
and arteries may not function properly.
Route Of Administration :- Mouth
Metabolism:- Nill
Execration :-Urine
Protein binding : 23%
Bioavailability:-25%

35. SPIRONALACTONE
Use:- Spironolactone is used to treat certain patients with hyperaldosteronism
(the body produces too much aldosterone, a naturally occurring
hormone); low potassium levels; heart failure; and in patients with edema
(fluid retention) caused by various conditions, including liver, or kidney
disease
Route Of Administration :- Mouth, Topical
Metabolism:-Liver
Execration :-Urine
Protein binding : 88%
Bioavailability:-60-90%

36. OSMOTIC DIURETIC
Osmotic diuretics are substances that are freely filtered at the glomerulus
but are poorly reabsorbed. Mannitol is the prototype of these diuretics.
The mechanism by which mannitol produces diuresis is that it increases
the osmotic pressure within the lumen of the proximal tubule and the loop
of Henle.

37. MANINTOL
Use:- Mannitol is a diuretic used to force urine production in people with
acute (sudden) kidney failure. Mannitol injection is also used to reduce
swelling and pressure inside the eye or around the brain. Mannitol is
available under the following different brand names: Osmitrol.
Route Of Administration :- Mouth, Intravenous
Metabolism:-Liver
Execration :-Kidney
Protein binding : 8%
Bioavailability:-7%

39. THANK YOU…