The lecture includes basic physiology of urine formation, classification of diuretics and detail of individual diuretics.

1. Dr. Kiran G. Piparva
Assistant professor, Pharmacology department,
AIIMS Rajkot.
Date: 7/03/2022

2. • Diuretic: substance that
promotes the excretion of
urine (net loss of Na and
water)
• caffeine, yerba mate, nettles,
cranberry juice, alcohol…
• Natriuretic: substance that
promotes the renal excretion
of Na+

3. Physiology of Urine Formation
• Volume and Composition of Urine formed is determined
by: (Kidney receives 25% of cardiac output at rest)
• 1. Glomerular Filtration: 180L/day
Filter blood soluble solute, protein, lipids
 2. Tubular Reabsorption: 99% filtrate reabsorbed- 1.5L
urine/ 24 hrs produced
 3. Active Tubular Secretion:
 Hormonal control: by antidiuretic hormone (ADH, Post. Pit.)
and aldosterone (adrenal cortex)

4. Urine excretion = filtration rate –reabsorption rate(2)+
secretion rate (3)
1 3
2
2
1
3

5. Glomerular Filtration Rate: GFR
 Amount of filtrate formed by both kidneys together in unit
time is called GFR.
 Average adult GFR is about 125 ml/min or 180 L/day
 Entire plasma volume: 3 ltrs -filtered and processed
about 60 times each day.
 High GFR allows the kidneys to precisely and rapidly
control the volume and composition of the body fluids,
so also the toxic products in the body.

6.  GFR is 180 liters per day and the urine output is only
1.5 to 2 ltrs. That clearly shows that Reabsorption is a
major quantitative activity that is taking place.
 Here Diuretics act as mainly Inhibiting the
reabsorption of water.
 Most of the diuretics are Natriuretics and Kaliuretics.

7. •180 Liters
•1.5 to 2 Liters
MORE URINE
DIURETIC

8. • Juxtamedullary nephron functions
• Bowman's capsule: filtering
• Proximal tubule: recovery of nutrients
• Loop of Henle: generation of a salt gradient
• Distal tubule: further ion recovery
• Collecting duct: generation of hypoosmotic or
hyperosmotic urine

9. Tubular Reabsorption & Secretion in different
parts of Nephron

10. • Site 1: PCT- proximal convoluted tubule
• Site 2: Loop of henle :
– Descending part of loop of henle
– Ascending part of loop of henle
• Site 3: Distal convoluted tubule
• Site 4: Collecting duct

11. 70%
20%
4.5%
0.5%
Volume 1.5 L/day
100%
GFR 180 L/day
Plasma Na 145 mEq/L
Filtered Load 26,100 mEq/day
5%

12. • Na+
• HCO3-
• K+ H2O
• Glucose
• Amino acids
• Chlorides
65 to 70 %: TUBULAR REABSORPTION
Site: 1: PCT

13. TUBULAR SECRETION
• H+
• Metabolic wastes
Urea creatinine
• Drugs:Penicillin,Salicylates
H+ + HCO3- H2CO3
H2CO3 CO2 + H2O
( Carbonic Anhydrase Enzyme )
PCT
Isotonic fluid

14. Loop of Henle: Descending part of LOH
• Only Permeable to Water leaves
tubule by osmosis
• Na+ and urea concentrations
outside the tubule (medullary
interstitium)
• So it increase medulary tonicity
from 400 to 1200 mOsmol from
the top to then bottom of the loop
respectively.
Pharmacology department
urea

15. Site 2: Loop of Henle: Ascending part of LOH:
• Active Na+ reabsorption (25%
of filtered load) by Na+/K+/2Cl-
cotransporter
• Reabsorption of Ca++ &Mg++
(via a paracellular pathway)
• Dilution of the tubular fluid
(hypotonic)
• Counter current multiplier -
medullary tonicity
• √ Free water clearance
Pharmacology department

16. Na-Cl-2K

19. Site 3: Distal tubule
• Na+ reabsorption (10% of filtered
load) by Na-Cl̄ symporter
• Ca++ is reabsorbed (by Na-Ca
exchanger regulated by PTH)
• Water relatively impermeable,
therefore further dilutes the
tubular fluid referred to as the
diluting segment
• Na+ Remaining: 5%
Pharmacology department

20. Site 4: Collecting duct:
Final site for determining Na+ concentration of the urine
• Active Na+ reabsorption (2-5%
of filtered load)
• K+ secret- into the tubular
luman through K+ channels
• Aldosterone:
• Increases activity of membrane
Na+ (re-absorption) and K+
(excretion) channels
• Antidiuretic hormone (ADH):
• increases permeability of water
- concentrated urine passed.
Pharmacology department

21. Late Distal Tubule & Cortical Collecting Tubule
• Reabsorb Na+ (through
Na+ channels) and Water
from Lumen
• Specific renal epithelial Na
channel (ADH action)
• Secrete K+ into Lumen.
• Site for action of K Sparing
diuretics
• Secrete H+ (Produced by
H2 + H2O H+ + HCO3- )
• Reabsorb HCO3
• It is in exchange for
HCO3-(ONE FOR ONE)
PRINCIPAL CELLS INTERCALATED CELLS

23. Late DCT: Cortical CT
PRINCIPAL CELLS INTERCALATED CELLS
Na
+
K+
Na + K+ ATPase
Pump
H2O
Na+
K+
Cl-
POTASSIUM
SPARING DIURETICS
Na+ CHANNEL BLOCKERS
ALDOSTERONE
Stimulation of’
Na+ reabsorption
K+ Secretion ECgradient

24. Medullary Collecting Duct
• Reabsorb <10 % of the filtered water and Na
• it is the final site for processing the urine -
determining the final urine output of water
and solutes.
1.Action of ADH
2.Permeability to Urea.
3.Has a role in Acid-Base regulation as it secretes H+ ions

25. • Juxtamedullary nephron functions
• Bowman's capsule: filtering
• Proximal tubule: recovery of nutrients
• Loop of Henle: generation of a salt gradient
• Distal tubule: further ion recovery
• Collecting duct: generation of hypoosmotic or
hyperosmotic urine

27. Classification of Diuretics
High celing
diuretic

28. • High Ceiling ( loop) diuretics:
frusemide, torsemide, bumetenide…
• Medium Ceiling Diuretics:
Benzothiazide, thiazide like
• Minimal Ceiling Diuretics
• A: CA inhibitors B: Osmotic
• C: K+ sparing : Aldosterone antagonists.
2. renal epithelial Na channel inhibitors

29. sites of action of diuretics
Pharmacology department

30. • active in “loop” of Henle….
• Furosemide (prototype)
• Bumetanide
• Torsemide
• Ethacrynic acid
1. Loop Diuretics/ High ceiling
diuretic

31. Ceiling Effect
• Ceiling effect of a drug refers…
• The dose beyond which there is no
additional effect - Higher doses do not
provide any additional effect but may
increase the likelihood of side effects as
well as the cost of treatment.

32. Exceeding Ceiling Dose Yields:
No Additional
Effect
Possible Adverse
Effects
CONCEPT OF CEILING DOSE

33. Furosemide: Site of Action

34. Loop diuretics: mechanism of action….
Pharmacology department
urea
↑↑ Na+ excretion (+)
↑ K+ excretion (+)
↑ Ca2+ + excretion
↑ Mg2+ excretion(+)
↑ Cl- excretion
↓ urate excretion

36. a. Renal action (Effect on urinary excretion)
• Effects on Urinary
Excretion(Renal action)
• ↑↑ Na+ Cl- excretion
• ↑ K+ excretion
• ↑ Ca2+ Mg2+ excretion
• ↓ H+ excretion
• Weak CA inhibition ↑ HCO3
excretion – alkalosis
• ↓ urate secretion
• If excess/ continuous than….
Electrolyte disturbance: (ADR)
Hyponatremia,hypotension,
dehydration
• Hypokalemia
• Hypocalcemia, hypomagnesemia
• Hypokalemic Metabolic Alkalosis
• Hyperuricemia
Pharmacology department

37. • Impairs the generation of a Medullary gradient
• Thus…
– Impairs dilution of tubular fluid
– Increased free water
excretion
Impairs urine concentration
Acute change in renal and systemic hemodynemics
on intravenous infusion:
↑ Renal blood flow and GFR

38. b. Extra renal effect.....
I/V infusion
• Extra renal effect:
• Direct vascular effects –acutely
increase systemic venous
capacitance (venodilation) and
thereby decrease left ventricular
filling pressure -- rapidly relieves
pulmonary edema ... May be
mediated by PGs
Afford quick
relief in LVF and
pulmonary odema
Pharmacology department

39. Dose: 20-80mg once a daily in morning
Onset of action: roughly 30 minutes with PO, 5
minutes with IV
Plasma half life – 1-2 hrs but it is prolonged in
pulmonary odema , renal and hepatic insufficiency
Duration: 6 hours
Lasts Six Hours = LASIX
Furosemide :P/K
(Most Popular Commercial Name)
.

40. Therapeutic uses….
1. Edema irrespective of origin (nephrotic, cardiac, renal)
chronic kidney disease- For rapid mobilization of fluid
in chronic renal failure it is continue to be effective
2. Acute Pulmonary Edema :rapid increase in venous
capacitance + brisk natriuresis -reduces left ventricular
filling pressures and thereby rapidly relieves
pulmonaryedema ------- IV furosemide
3. Hypertension
Only used in presence of renal insufficiency or
hypertensive emergencies
• Otherwise less useful than Thiazides because of ↑ ADR and
frequent dosing
Pharmacology department

41. 4. Congestive Heart Failure :
- ↓preload & circulating volume
- removal of peripheral edema & pulmonary
congestion
5. Rx of Hypercalcemia of malignancy- medical
emergency
- Rapid and large volume of Normal saline +Loop
diuretic
6. Along with blood transfusion: To prevent
volume overload Pharmacology department

42. Diuretics
• LASIX
– Quick onset of diuresis
• Good for acute volume overload
– Increases urinary calcium excretion
• Used to treat hypercalcemia (Malignancy,
Hyperparathyroidism)
– Increases urinary excretion of potassium and
hydrogen ions
• Used to treat acute hyperkalemia
3 Reasons to like your loop diuretic

43. Diuretics
• LASIX
– Excessive diuresis can lead to volume
depletion and ARF/hypotension/CV collapse
– Can exacerbate calcium based kidney stones
– Can cause hypokalemia, metabolic alkalosis
3 Reasons to think twice

44. • active in distal convoluted tubule
• Chlorothiazide (prototype)
• Hydrochlorothiazide
• Chlorthalidone
• Metolazone
2. Thiazide Diuretics

46. Distal convoluted tubule
Lumen Interstitial
space
Na+
Cl−
3Na+
2K+
Cl−
Cl−
NCC1
Na+K+ATPas
e
NCC1 inhibited
by Thiazides
Ca2+ Ca2+
Distal convoluted tubule
Distal convoluted tubule
Ca2+
3Na+
Na+Ca2+ exchanger
Basolateral
membrane
Apical membrane
↑↑ Na+ excretion (++)
↑ K+ excretion (++)
↓ Ca2+ + secretion
↑ Mg2+ excretion(+)
↓ urate excretion(+++)
THAIZIDE : Mechanism of action :
Pharmacology department

47. Loop Diuretic: Acts on early part of distal
tubules Inhibit Na+-Cl- symporter and reabsorption
• ↑↑ Na+ excretion (+++)
• ↑ K+ excretion (+++)
• ↓Ca2+ Reabsorption
• ↑ Mg2+ excretion
• Change
intrarenalhemodynamic,
may reduce GFR further
Hypokalemia (parallal to
natriuresis) (+++)
• Hypercalcemia
• Hypomagnesemia
• -Not effective in very low
GFR of < 30ml/min
No Significant alteration in acid base balance of body

48. Renal action
• Change in electrolyte-
moderately efficacious
• No loss of counter current
mechanism
• Positive free water
clearance is reduced
Other action
• Reduces in blood volume
• Reduces GFR

49. Nephrology Dialysis Transplantation, Volume 15, Issue 12, December 2000, Pages 1903–1905,
https://doi.org/10.1093/ndt/15.12.1903
The content of this slide may be subject to copyright: please see the slide notes for details.
Fig. 1. Mechanism of action of the paradoxical effect of thiazide
diuretics on NDI.

50. ADR: (Loop diuretic and thiazide)
1. Hypokalemia: Rare at low dose.
Only when with brisk diuresis or prolonged therapy
- Dietary intake low
- Manifestation: fatigue, weakness, muscle cramps
Serious complication: Cardiac arrythmias
- Management: High dietary intake
Concurrent use of k+ sparing diuretic
(best option)
Supplement KCL (don’t combine with
diurteic+KCL together)
Pharmacology department

51. 2. General ADR: GI upset- N/V/D
CNS- headache, giddiness, paresthesia
3. Hyperuricemia: long term higher doses
4. Hypocalcemia (high ceiling diuretic)
hypercalcemia (thiazide diuretic)
5. Magnesium depletion (after prolonged use): Risk of
ventricular arrythmia especially in MI and CHF patients
treated with Digitalis
6. Acute saline depletion: vigorous diuresis with high
ceiling agents
7. Dilutional hypernatremia in CHF patients
Pharmacology department

52. 8. Metabolic – Hyperglycemia - Hyperlipidemia (chronic
use in hypertension)
9. Agent specific ADR: Ototoxicity (in renal
insufficiency, increased salt concentration into
endolymph- direct damage to hair cells.
10. Allergic manifestation: Rash- photosensitivity
11. Avoided in – renal insufficiency(↓GFR), cirrhotic
patient(mental disturbance), toxemia of pregnancy
(compromise placental circulation)

53. ADR…
General ADR:
GIT, CNS
ADR due to
pharmacological action
Acute ADR/ ADR due to
High dose use:
1. Acute saline depletion
2. Dilutional
hyponatremia
3. Hearing loss
ADR due to chronic use:
1. Electrolyte disturbance
Other ADR:
Metabolic, Allergic

54. Furosemide Thiazide
Renal action:
Site II : Na+-K+ 2cl- block
Renal action:
↑ Na+, K+, Mg2+ , Cl- excretion
↑ H+ excretion , ↓urate excretion
↑ Ca2excretion, corticomedulary
Extra renal effect: Direct vascular
effects – (I/V infusion) acutely
increase systemic venous
capacitance (venodilation) and
thereby decrease left ventricular
filling pressure -- rapidly relieves
pulmonary oedema May be
mediated by PGs
Renal Action: Site III : NA+ cl- block
Renal action
↑ Na+, K+, Mg2+ , Cl- excretion
↑ H+ excretion – alkalosis
↓ urate excretion
↓ Ca2+ + &
Change intrarenal, may reduce GFR
further- Not effective in very low
GFR of < 30ml/min
• Extra renal effect:
• Persistent sodium deficient-
reduces pressure response of CA,
Ag2- fall in BP- antihypertensive
Pharmacology department

55. • Other effect:
• Hyperglycemia, ↑ LDL & TG
• Ototoxicity – hearing impairment
,tinnitus
• Uses:
1.Edema with hepatic cirrhosis,
congestive heart failure and
associated with renal disease
3. Ascites due to malignancy,
lymphedema, idiopathic edema
4. Hypertensive emergency
5. ALVF and pulmonary edema
6. Along with blood transfusion
• Other effect:
• Hyperglycemia & precipitation
of diabetes
• ↑ LDL & TG
• Uses:
1. Hypertension (Hydrochlorothiazide,
Indapamide)
2. Edema : Cardiac, Hepatic,Renal
• Less efficacious than loop diuretic
• Useful for maintenance therapy
3. Diabetes Insipidus (DI)
(Nephrogenic responds better)
Paradoxical. More complete
reabsorption in PT Convenient,
Cheaper than Desmopressin in
Neurogenic DI
4. Hypercalciuria and renal Ca
stones
Pharmacology department

56. Furosemide Thiazide
• ADR:
Electrolyte disturbance
• Hypokalaemia (+)
• Hypomagnesemia (Rare, low
intake, prolonged use related)
• Hyperuricemia (+)
• Hypocalcemia
• Acute saline depletion
• Dilutional hyponatremia
• Hypchloremic alkalosis
ADR:
Electrolyte disturbance:
Hypokalaemia (++)
• Hypomagnesemia (Rare, low
intake, prolonged use related)
• Hyperuricemia (++)
• Hypercalcemia
• Acute saline depletion
• Dilutional hyponatremia
• Hypchloremic alkalosis
Pharmacology department

57. • 2. Metabolic :
• Hyperglycemia (+)
(↓insulin release probably a
consequences of
hypkalaemia)
• Hyperlipidemia
• Hyperuricemia
• 3. Others:
• Reversible hearing lose
• Plasma t1/2: 1-2hr
• C/I pregnancy
• 2. Metabolic :
• Hyperglycemia(+++)
(↓insulin release probably a
consequences of
hypkalaemia)
• Hyperlipidemia
• Hyperuricemia
• 3. Others:
• Allergic reaction
• Aggravate renal
insufficiency
• Plasma t1/2: 6-12hr
• C/I pregnancy
Pharmacology department

58. Drug interaction……
1) Thiazide/high ceiling + Antihypertensive=
potentiate action
2) Diuretic: Hypokalaemia–
- enhances digitalis toxicity
- Increases incidence of antiarrhymics
- potentiate action of neuromuscular blocker
- potentiate action of sulfonylurea action

59. 3. Additional Ototoxic/ Nephrotoxic drugs:
Aminoglycosides…
4. Diuretic+Cotromoxazole= throbocytopenia
5. NSAID diminish action of diuretics
6.Probenecid decrease transport of diuretic in tubular
fluid--- so decrease their action
7. Increases serum lithium level

61. 3. Weak diuretics…
A) CA inhibitors
B) K+ sparing diuretics
C) Osmotic diuretics

62. A. CA inhibitors: Acetazolamide
• Prototype: Developed from sulfanilamide, Weak diuretic: As
diuretic limited use:
• CA catalyses reversible reaction of H+ + HCO3≈ H2O +CO2, and
as well back reaction into proximal tubule as well in brush
border.
• Acetazolamide Inhibit CA (non-competitive- reversible) in renal
proximal tubule cells.

63. • Inhibition of CA-
• Decreases [H+] formation in
tubular cell
• Less H+ available for Na+/H+
exchange
• Increased lumen Na+, decreased
H2O reabsorption
• Net effect: ↓Na+ water, HCO3-
reabsorption
• Secretion in DT & CD is also
inhibited but lesser extent
Acidosis

65. • When CA inhibitors given: Distal Na exchange take
place with K+ which lost in excess–
 when same degree of natriuresis: CAI causes
 Marked kaliuresis among all diuretic
Extrarenal action: CA enzyme present in
• Ciliary body of eye:↓Intraocular tension by ↓aqueous humour
• Gastric mucosa: ↓Gastric HCL high dose
• Exocrine gland of pancreases:↓Pancreatic NaHCO3
(clinically not significant)
• Raised level of CO
2
and lowering of Ph brain: sedation and
elevate seizure threshold.

66. Uses and adverse drug reaction
As diuretics: Not used…….??????
1. Glaucoma : reduce aqueous humour formation- adjuvant
2. Epilepsy: adjunctive agent; retards abnormal, excessive
discharge of CNS neurons: adjuvant
3. Reversal of metabolic alkalosis
4. To alkalize urine: for UTI and promote excretion of acidic
drugs
5. Nausea and vomiting associated with acute mountain
sickness : symptomatic as well prophylaxis- ↓ CSF
formation & change in brain PH..
Pharmacology department

67. Rapid ascent to high attitude: Pulmonary/ cerebra odema:
headache, nausea, vomiting, giddiness, weakness, insomnia.
Start acetazolamide 1-2 days before start.
Acetazolamide works by altering transport of CO2 in lung,
brain and tissue and lower Ph.

68. Potential adverse effect:
• S/E: Hypokalemia (most marked kaliuresis among all
diuretics)
• Metabolic acidosis (↓H+ secretion)
• ADR: Hypersensitivity reaction
• Drowsiness, fatigue, abdominal discomfort
• Rare but serious- Bone marrow depression
• C/I-
• liver disease (precipitate coma)- may precipitate coma by
interfering elimination of NH3 (due to alkaline urine)
• COPD: acidosis

69. B. Potassium sparing diuretics
1. Aldosterone
antagonist:
Spironolactone
Eplerenone
2: Direct Epithelial NA
channel in DT/CD
cells:
Triamterene
Amiloride

70. Aldosterone
Collecting Duct
Na Na
Na
Na
K
Aldosterone is the mineralocorticoid
At late DT, CD cells
Bind to Mineralocorticoid receptor (MR)
by increasing the number AIP- on the
luminal surface and the number of Na-K
pumps on the basolateral surface
which promotes Na reabsorption, K
excretion
Aldo

71. A) Spironolactone : Mechanism of action
Collecting Duct
Na Na
Na
Na
Aldosterone act from interstitial site of
cell
Bind to MR-competitive antagonist
Inhibit formation of AIP
which promotes Na reabsorption, K
excretion
Mild saluretics -3-4 days onset
 Reverse resistant to other diuretics-
secondary hyperaldosteronism
Aldo
 Spironolactone has no effect in absence of ADH
K

72. P/K: Dose : 100mg/day
Given orally microfine powder tab.
Bioavailability 75%
Converted to active metabolite canrenone (18hrs)
Onset of action is very slow (steroid receptors)
Pharmacology department
Seldom used alone (low potency), used in combination with
K+ depleting agents; esp. in antihypertensive therapy.

73. ADR of spironolactone
General ADR
Abdominal upset,
drowsiness 2. S/E
Electrolyte
disturbance
Hyperkalemia
Acidosis
3. Androgenic
side effect..

74. • 1. Electrolyte disturbance
a) Hyperkalemia
- particularly in renal insufficiency
-Avoid excessive K supplementation/drug causing
hyperkalamia when patient is on Spironolactone.
b) Acidosis: in cirrhotic patients
2. GI disturbance: Abdominal upset, drowsiness, mental
confusion, epigastric distress, loose motion.
ADR…

75. 3. Androgen like effects:
• Dose and duration related hormonal
side effect:
• Due to it steroid structure: it interact with
progestin and androgen receptor….
• so increases testosterone clearance and
hasten its conversion to estradiol:
• Male: Gynecomastia, loss of libido,
erectly dysfunction
• Female: menstrual irregularities, breast
tenderness
• C/I : Peptic ulcer

76. Elperenone
• More selective to steroid receptor
• Less hormonal side effect
• Suitable for long term use in HT and CHF
• Can be used as alternative to spironolactone

77. Spironolactone : therapeutic uses……
• Prevent K loss caused by other diuretics in: breaks
resistance to thiazides or frusemide in ….
– Hypertension
– Refractory edema (especially edema in Cirrhotics)
– Heart failure
• Primary aldosteronism
• Hirsutism due to P C O D
•CHF: as a adjunctive therapy it retards disease
progression and reduces mortality

78. Therapeutic uses of spironolactone
1. Edema more useful in cirrhotic and nephrotic syndrome
 breaks resistance to thiazides or frusemide in refractory
edema – refractory edema
 To counteract K loss due to thiazides, frusemide
3. Hypertension: combined with thiazide (to potentiate effect and
counteract k+ loss)
 Eplerenone is a new drug approved for HT, No
gynaecomastia
4. CHF: as a adjunctive therapy it retards disease progression and
reduces mortality in moderate- severe CHF.
5. Primary Hyperaldosteronism (Conn’s syndrome)
Pharmacology department

79. K Sparing Diuretics
– Aldosterone antagonists have a
greater effect in cirrhotics than
lasix!
– Cirrhotic patients- low albumin state
and reduced tubular secretion- poor
response to lasix
– Aldosterone antagonists do not require
secretion into the tubular lumen, and
thus may remain effective despite
marginal renal perfusion in the
context of cirrhosis

80. • Non-steroid in structure.
(It is not a Aldosterone Antagonists)
• Action is independent of
aldosterone…
• Decreases K+ excretion
accompanied by only small
increase Na excretion
2: Triamterene and Amiloride

81. 2. Amiloride/ Triameterene
Collecting Duct
Na Na
Na
Na
Amiloride and Triamterene directly
block the distinct renal epithelial
ENaC channel at late DT and CD
Na entry- operate transepithelial
gradient- driving force for K+
secretion- Indirect inhibit
K+secretion
Amiloride reduces negative potential
–decreses H secretion- acidosis.
K K

82. 2. Triamterene /Amiloride
Pharmacology department

83. • Hyperkalemia: Avoid K+ supplementation
• Gi disturbance: Nausea, diarrhoea, heaache
Drug interaction –
 Do not use in combination with spironolactone:
additive action
 Caution with ACE inhibitors/B blockers/ NSAIDS…
Toxicity

84. • Eliminate K wasting effects of other
diuretics in:
– Edema
– Hypertension: along with thiazide/ frusemide
– Amiloride – Lithium induced Diabetes
Insipidus.
Therapeutic uses

85. Thank You

86. c. Osmotic diuretics:
Ideal properties
1. Orally effective
2. Well absorbed
3. Not metabolized
4. Freely filtered at glomeruli
5. Not reabsorbed
6. Inert
7. Cheap
Drugs used
• Mannitol
• Glycerol
• Isosorbide
Pharmacology department

87. • Do not interact with receptors or directly block renal
transport
• Activity dependent on development of osmotic
pressure
• Mannitol (prototype/ intravenous)
• Glycerol
• Isosorbide (oral)
Osmotic Diuretics

88. Mannitol
• Nonelectrolyte of LMW
• Pharmacologically inert
• Given in large quantity to raise
plasma osmolarity
• Only given I.V.
• Freely filtered: limited
reabsorption
• Limit tubular water and electrolyte
reabsorption in a variety of
ways….

89. • Freely filter through glomerulus
osmotic diuretics are not reabsorbed
• increases osmotic pressure specifically in the proximal
tubule and loop of Henle
• prevents passive reabsorption of H2O and electrolyte
• osmotic force solute in lumen > osmotic force of
reabsorbed Na+
• increased H2O and Na+ excretion
• Expand ECF but don’t enter inside cell-, increases
GFR, increase renin release
Mannitol: Mechanism of Action

91. • Mannitol :Drug of choice: non-toxic, freely filtered, non-
reabsorbable and non-metabolized – Never use for chronic
edema
1. Prophylactic : administered prophylatically for
impedining /acute renal failure secondary to
trauma, CVS disease, surgery or nephrotoxic
drugs (C/I: renal failure)
2. Acute glaucoma :Short-term treatment: before
and after ocular surgery
Therapeutic Uses : given intravenously

92. 3. infused to lower intracranial pressure :
• Due to head injury or brain stroke- by osmotic
action it encourges movement of water from brain
parnechym,CSF.
• 1-1.5g/kg is infused over 1 hour as 20%
intravenous solution.
• Also used before and after brain surgery
• 4. To counteract low osmolarity of plasma or ECF
due to rapid haemodialysis/ peritoneal dialysis…

93. Adverse drug reaction:
1) Most common side effect is Headache (due to
hyponatremia)
2) Nausea, Vomiting
3) Hypersensitivity-rare
4) Acute Intravascular volume expansion
• Before diuresis starts it exerts osmotic effect in the blood
• Contraindicated in pulmonary edema, Cardiac edema (CHF)
and intracranial hemorrage, established renal failure
Pharmacology department

94. Non Diuretic Uses of Diuretic Drugs
• HTN (hydrochlorothiazide)
• Idiopathic calcium urolilthiasis
(hydrochlorothiazide)
• Diabetes insipidus (hydrochlorothiazide)
• Glaucoma (Acetazolamide)
• Mountain sickness (Acetazolamide)
• Hirsutism (Spironolactone)

96. MCQ….
• Which of the following diuretic causes
maximum kaliuresis???
a) Furosemide
b) Thiazide
c) Acetazolamide
d) spironolactone

97. • Electrolyte disturbance is more with
which of the following…….
a) Regular dose of furosemide in emergency
b) Regular dose of thiazide in emergency
c) Chronic use of regular dose of thiazide than
furosemide
d) Chronic use of higher dose of thiazide as
compared to furosemide

98. • All of the following drug having drug drug
interaction with diuretics.. EXCEPT…..
a) Aminoglycoside
b) NSAIDS
c) Digoxine
d) penicillin

99. • Diuretic precipitate hepatic coma in
liver disease patients because….
a) Due to alkaline Ph & Interfering with
elimination of NH3
b) Hypokalamia
c) Alkalosis
d) All of the above

100. Rapid fire questions…
• Which drug reduces action of diuretics?
• Which diuretic causes maximum
natriuresis?
• Which diuretic causes metabolic acidosis?
• Which diuretic is used in renal ca stone
management?
• Which diuretic causes hypercalcemia?
• Which diuretic is used in glaucoma?

101. Drug of choice….diuretics..
• Drug of choice for lithium induced
diabetis insipidus?
• Drug of choice for cerebral edema?
• Drug of choice for hypertensive
emergency?
• Drug of choice for resistant edema?
• Drug of choice for nephrogenic diabetes
insipidus?

102. Thank you