III PHARM.D

1. Mrs. VARSHA JAIN BA
Asst. Professor
Dept. of Pharmacology
Sri Adichunchanagiri
College of Pharmacy, BG
Nagar

2.  Definition
Adverse effect
Mechanism of action
Pharmacokinetics
Therapeutic uses
Classification

3. Definition
Greek - "dia-", thoroughly +
"ourein", to urinate = to urinate thoroughly
Diuretics are the drugs which increase the rate
of urine formation causing a net loss of
solute (mainly NaCl) along with equivalent
volume of water, by interfering with
transport mechanism responsible for the
reabsorption of solutes from various
segments of the nephron.

4. *
These are drugs which cause a net loss of
Na+ and water in urine
There are several categories of diuretics.
All diuretics increases the excretion of
water from body
NATRIURETICS: Substance that promotes
the renal excretion of Na+

5. a. Edema, CHF, pregnancy & nutritional
b. Nephrotic syndrome
c. Diabetes insipidus
d. Hypertension
e. Cirrhosis of liver
f. And also lower the intracellular and CSF
pressure.
Diuretics are very effective in the treatment
of :

6. •KIDNEY:
>Weight-0.5% of body,
>Receive 25% of cardiac output (50 times)
>Each kidney contain 1.3 million nephron
• KIDNEY FUNCTIONS:
>Balance of electrolytes,Plasma volume, Acid
–base
>Activation of vitamin D
>Synthesis of Erythropoietin,Urokinase
>Excretion of Urea, Uric acid, Creatinine etc.

7. •Tubular reaborption:
>Reabsorption of 99% of glomerular filtrate-
only ±1 ml/min excreted as urine
>1.5L/day of urine
• Glomerular filtration:
>Receive 25% of cardiac output
>Filtration rate: 100-120 ml/minute
>180 L of glomerular filtrate/day
• Tubular secretion

11. • Proximal tubules:
>Reabsorption of 60-70% Na+
>Permeable to water– isotonic urine
>Active absorption of Nacl,NaHCO3,glucose,amino
acids, organic solutes
• Loop of Henle:
>Thin descending limb: most active water
reabsorption
>Thick ascending limb: reabsorption of Na+,
impermeable to water

12. • Distal Tubule:
>Na+ reabsorption
>Calcium excretion is regulated
• Collecting duct:
>Selectively water permeable

13. DIURETICS ARE CLASSIFIED AS:
1.High ceiling/Loop diuretics
2.Thiazides
3.Carbonic anhydrase inhibitors
4.Potassium—sparing diuretics
5.Osmatic diuretics
6.Low ceiling diuretics

14. * Classification…
According to Site of Action
(A) Proximal Tubule
Osmotic Diuretics (Loop of Henle, collecting duct )
Carbonic anhydrous Inhibitors
Xanthine Diuretics
(B) Ascending Limb of Loop of Henle
Loop Diuretics
(C) Distal Tubule
Thiazide Diuretics
(D) Collecting Tubule
K+ - Sparing Diuretics
ADH Antagonist

15. DIURETICS ARE CLASSIFIED ON THE BASIS
OF EFFICACY:
1.HIGH EFFICACY DIURETICS:
(Inhibitors of Na+,K+,2Cl- cotransport)
(a) Sulphamoyl derivatives:
Furosemide
Bumetanide
Torasemide
(b) Phenoxyacetic acid derivative:
Ethacrynic acid

16. 2.MEDIUM EFFICACY DIURETICS:
(Inhibitors of Na+,Cl- symport)
(a)Benzothiadiazines(Thiazides):
Hydrochlorothiazide
Benzthiazide
Hydroflumethiazide
Clopamide
(b) Thiazide like diuretics:
Chlorthalidone
Metolazone
Xipamide
Indapamide

17. (a)Carbonic anhydrase inhibitors:
3.WEAK 0R ADJUNCTIVE DIURETICS:
Acetazolamide
(b)Potassium sparing diuretics:
i. Aldosterone antagonist:
Spironolacton
Eplerenone
ii. Inhibitors of renal epithial Na+
channel:
Triametrene
Amiloride

18. (C)Osmotic diuretics:
Mannitol
Glycerol
Isosorbide
(d)Xanthines:
Theophlline

21. Loop diuretics are active on loop of henle(thick
ascending limb)
FUROSEMIDE(FRUSEMIDE)
It is a prototype drug
It is a sulfonamide derivative
It is the most powerful diuretics

22. Mechanism of action
FUROSEMIDE
Enter proximal tubule via organic acid
transporter
It blocks the Na+ K+ 2Cl- cotransport in the
thick asending limb
Competes with Cl- binding site
Enhances the Mg2+,Ca2+,K+&H+ excretion

23. It inhibits NaCl- reabsorption in the thick
ascending limb
It inhibits reabsorption of ~25% of glomerular
filtrate

24. Pharmacokinetics
• Furosemide are administered orally
• Furosemide and other loop diuretics are
rapidly and almost completely absorbed
• They are extensively bound to plasma
proteins
• They are partly metabolized in the liver and
the metabolites are excreted by urine
Adverse effects
• Hypokalaemia
• Metabolic alkalosis
• Hyponatraemia
• Hyperuricaemia

25. • Ototoxicity
• Hypomagnesaemia
• Hypocalcaemia
Therapeutic uses
• They are highly effective for the relief of
oedema of all origins like cardiac, hepatic or
renal oedema
• Used for the treatment of acute renal failure
• Furosemide is used as an alternative to or in
combination with osmotic diuretics
• Used for the treatment of hypertension,
hypercalcaemia and hyperkalaemia

26. Drug interactions
• It may increase the ototoxic potential of
aminoglycoside antibiotics, especially in
the presence of impaired renal function
• Furosemide combined with angiotensin
converting enzyme inhibitor thus may
lead to severe hypotention
Contraindication
• Pronounced hyponatremia and anuria

27. Thiazide diuretics are active in distal
convoluted tubule
Thiazide are medium efficacy diuretics
Chlorothiazide was the first thiazide to be
synthesized
All thiazide have a sulfonamide group

28. Mechanism of action
THIAZIDES
Reach distal convoluted tubule
Bind to and block Na+ Cl- symport system
Increase the excretion of Na+ Cl-
Also increase the excretion of K+ and Mg2+
Decrease the excretion of Ca2+ and uric acid

30. Pharmacokinetics
 Thiazide are well absorbed after oral
administration
 Rapid acting with in 60 minutes
 Duration of action varies from 6-48 hours
 They are excreted in urine
Adverse effects
 Hypokalaemia
 Hyperglycaemia
 Metabolic alkalosis
 Hyperuricaemia
 Hyponatraemia

31.  Hypercalcaemiae
 Fatigue
 Anorexia
 GI disturbances
 Allergic reactions
Therapeutic uses
 Thiazides are the first line drugs for
treatment of hypertension
 They are used for treatment of CHF
 Hypercalciuria with renal stones can be
treated with thiazides which reduce calcium
excretion
 Treatment of nephrogenic diabetes insipidus

32. Drug interaction
• It combine with digitalis glycosides ,they
induce the hypokalemia and hypomagnesemia
and cause digitalis toxicity
• It combines with lithium and decrease the
lithium clearance and cause lithium toxicity
Contraindication
• It is contraindicated in pregnancy, they may
reduce the maternal uterine blood flow
• It is also contraindicated in diabetes
pregnant women

33. They are active in proximal tubule
They are limited uses of diuretics
ACETAZOLAMIDE
It is a prototype drug
It is a sulfonamide
derivative

34. Mechanism of action
ACETAZOLAMIDE
Bind to and inhibits enzymes carbonic anhydrase
Blocks NaHCO3- reabsorption
Increases the excretion of Na+, K+, HCO3- and
water

36. Pharmacokinetics
 Acetazolamide is well absorbed orally
 Onset of action is with in 60-90 minutes
 Duration of action is 8-12 hour
 It is excreted in unchanged urine
Adverse effects
 Metabolic acidosis
 Hypokalaemia
 Drowsiness
 Paraesthesia(pain due to pins & needles
under the skin)
 Skin rashes

37. Therapeutic uses
 Acetazolamide decrease the intraocular
pressure, hence used to treat glaucoma
 Used to alkalinize the urine
 Acetazolamide is used mainly as
prophylactic agent in acute mountain
sickness
 Acetazolamide is used as an adjuvant in
epilepsy

38. Drug interaction
• It combined with warfarin which
decrease the metabolism rate
• It combined with 2,4 thiazolidinedione
which decrease the excretion rate
Contraindication
• It is contraindicated in situation in which
sodium or potassium blood serum levels
are depressed ,in cases of liver disease

39. Potassium sparing diuretics may act by two
ways
Aldosterone antagonists
Spironolactone
Inhibitors of renal epithial Na+
channel
Triamterene
Amiloride

40. Mechanism of action
SPIRONOLACTONE
Enter the cell and bind to specific
mineralocorticoid receptor(MR) in DT and CD
cells
Inhibit action of aldosterone
Increases the Na+ and water excretion,
decreases the K+ loss

41. AMILORIDE/TRIAMTERENE
They block the Na+ transport through the
sodium channels in the luminal membrane
Increases the Na+ and water excretion ,
decreases the K+ loss

43. Pharmacokinetics
spironolactone
 Orally administered
 It is highly bound to plasma proteins
 Completely metabolized in liver, converted
to active metabolites
Amiloride
 Oral administration, 50% effective
 not metabolized
 not bound to plasma proteins

44. Triamterene
 It is incompletely absorbed orally
 Partly bound to plasma proteins
 Largely metabolized in liver to an active
metabolite and excreted in urine
Adverse effects
Spironolactone
 Hyperkalaemia
 Drowsiness
 Confusion
 Gynaecomastia
 Hirsutism

45. Triamterene
 Nausea
 Dizziness
 Muscle cramps
 Photosensitivity
Amiloride
 Nausea
 Diarrhoea
 Headache
 Hyperkalaemia

46. Therapeutic uses
 Potassium sparing diuretics are used with
thiazides/loop diuretics for treatment of
hypertension
 The combination therapy increases the
diuretics and antihypertensive effect
 They are used to treat cirrhosis and CHF
 To counteract K+ loss due to thiazide and
loop diuretics

47. Drug interaction
• It interact with lithium , that may increase
the level of potassium in the blood
• It also interact with ACE inhibitor, digoxin
and steroids like prednisone
Contraindications
• It contraindicated in the patients with
hyperkalemia, Addison's disease

48. Osmotic diuretics are not interact with receptors
or directly block the renal transport
Activity dependent on development of osmotic
pressure
MANNITOL
 It is a prototype drug
It is pharmacologically inert ,so
can be given in large quantities
sufficient to rise osmolarity of
plasma and tubular fluid

49. Mechanism of action
MANNITOL
Increases osmolarity of plasma
Shift of fluid(osmotic effect) from the
intracellular compartment(ICC) to extracellular
fluid(ECF)
Expansion of ECF volume
Increases glomerular filtration rate, mannitol
is freely filtered at the glomerulus

50. Increases osmolarity of tubular fluid
Inhibits reabsorption of water and
NaCl-
The net effect is increased urinary excretion of
Na+, K+, Ca2+, Mg2+, and CL-

51. Pharmacokinetics
 Mannitol is administered intravenously
 It is neither metabolized in the body nor
reabsorbed from the renal tubules
 It is pharmacologically inert and is freely
filtered at the glomerulus
Adverse effects
 Hyponatraemia
 Pulmonary oedema
 Headache
 Nausea
 vomiting

52. Therapeutic uses
 It is used to reduce the elevated intracranial
tension following head injury or tumour
 It is used both pre and post-operatively to
reduce the elevated IOP in acute congestive
glaucoma
 Mannitol is used to produce diuresis in case
of poisoning
 Mannitol is used to prevent acute renal
shutdown in shock, cardiovascular surgery,
haemolytic transfusion reactions ect..

53. Drug interaction
• It interact with depression medications like
Effexor and Lexapro
• It also interact with diabetes drug like
TANZEUM
Contraindications
• Anuria
• Pulmonary edema
• Severe dehydration
• Intracranial haemorrhage

54. Essential of medical pharmacology by KD
Tripathi 7th edition.
Text book Pharmacology by padmaja
udaykumar.

 https://youtu.be/NzdvoGZquIk
https://youtu.be/oh0nAyW5r5Y