This document discusses diuretics and their classification and mechanisms of action. It begins by classifying diuretics as high ceiling, medium efficacy, or weak/adjunctive. It then focuses on weak diuretics, describing their subclasses including carbonic anhydrase inhibitors, osmotic diuretics, and potassium sparing diuretics. Specific drugs like spironolactone, eplerenone, amiloride, and mannitol are discussed in depth, outlining their mechanisms of action, uses, and potential adverse effects or drug interactions. Key points are summarized at the end, differentiating how potassium sparing diuretics work by antagonizing aldosterone or inhibiting epithelial sodium channels.

1. Diuretics-II
Dr. Pravin Prasad
M.B.B.S., MD Clinical Pharmacology
Assistant Professor, Maharajgunj Medical Campus
26 November 2021 (10 Mangsir 2078), Friday

2. Answer the following…
Classify diuretics
Why loop diuretics are also known as high ceiling
diuretics?
Mechanism of action of thiazide diuretics?
Which class diuretic is preferred in essential
hypertension?
Any two important drug interaction of diuretics.

3. By the end of this class, BDS 2nd
year students will be able to:
Explain the mechanism of action of weak diuretics
Discuss the salient pharmacological aspects of
weak diuretics
Differentiate between the two types of potassium
sparing diuretics

4. Diuretics: Classification
High ceiling
Medium efficacy
Weak / adjunctive

5. Weak/ Adjunctive Diuretics:
Classification
Carbonic Anhydrase
Inhibitors
• Acetazolamide
Osmotic Diuretics
• Mannitol
• Isosorbide, Glycerol
Potassium sparing diuretics
Renal epithelial Na+
channel blockers
• Amiloride,
Triamterene
Aldosterone antagonists
• Spironolactone,
Eplerenone

6. Aldosterone antagonists
Spironolactone, Eplerenone
Conserve K+ indirectly, produces mild natriuresis
Potassium sparing diuretics
No effect in the absence of aldosterone
Useful in states related to high aldosterone
activity
Spironolactone has hormonal side effects
Eplerenone is safer in this regard

7. ECF
Luminal
Fluid
Spironolactone: Mechanism of
Action
Aldosterone
Mineralocorticoi
d receptor
Nucleus
AIP
ATP
Na+
K+
K+
Spironolactone

8. Spironolactone: Mechanism of
Action
Binds to Mineralocorticoid receptors
Blocks aldosterone activity
• Competitive antagonist
Aldosterone Induced Protein / Na+ channels not
expressed
Decreased absorption of Na+ and water and
secretion of K+
• K+ loss in urine is decreased

9. Spironolactone: Uses
Hypertension
Adjuvant to thiazide, loop diuretics
• Counteracts K+ loss
• Attenuates hypertensive nephropathy
Oedema
Cirrhotic/ nephrotic patients
Refractory
Congestive Heart Failure
Primary hyperaldosteronism

10. Spironolactone in congestive
heart failure
Blocks the effects of aldosterone, which are:
Expansion of e.c.f. volume
• Increased cardiac preload
Fibroblast proliferation and fibrotic change in
myocardium
• Worsening systolic dysfunction and pathological
remodelling
Hypokalemia and hypomagnesemia
• Increased risk of ventricular arrhythmias, sudden
cardiac death

11. Spironolactone in hypertension
Slight decrease in blood pressure when used alone
Augment the antihypertensive action of thiazide
diuretics
Inhibits aldosterone induced pathological changes
in the body:
Ventricular and vascular hypertrophy
Renal fibrosis

12. Spironolactone: Adverse effects
Drowsiness, mental confusion, ataxia, epigastric
discomfort, loose motions
Interacts with progestin and androgen receptors:
Gynaecomastia, erectile dysfunction, loss of
libido
Breast tenderness, menstrual irregularities
Hyperkalaemia in renal impaired patients
Acidosis in cirrhotics
Peptic ulcer: CONTRAINDICATION

13. Eplerenone
Lower affinity for androgen and progestin receptors
Inactivated by CYP3A4 enzyme
Indications:
Moderate to severe CHF
Post infarct left ventricular dysfunction
Hypertension

14. Renal epithelial Na+ Channel
inhibitors
Triamterene, Amiloride
Decreases K+ excretion, accompanied with small
increase in Na+ loss
Potassium sparing diuretics
Alkaline urine produced
Cl-, HCO3
-
Reduces Ca2+ and Mg2+ excretion

15. Amiloride: Mechanism of Action
ECF
Luminal
Fluid
Principal cells of late DT and CD
• Rich in K+, Low Na+
• Activity of Na+-K+ ATPase at
basolateral membrane
Na+
K+
K+
Amiloride
Na+ Na+
K+
K+
K+
K+
K+
K+
Na+
Na+

16. Amiloride: Mechanism of Action
Blocks luminal amiloride sensitive renal epithelial
Na+ channels
Decrease reabsorption of Na+ in DT and CD
Luminal negative charge not developed
Less secretion of K+ from principal cells
Less secretion of H+ from intercalated cells

17. Amiloride: Uses
Hypertension
As adjuvant
• Prevents hypokalaemia
• Increase natriuretic response
More likely to develop hyperkalaemia if given
along with ACEI/ARBs, NSAIDs, β blockers
Cystic fibrosis

18. Adverse effects
Amiloride:
Nausea, diarrhoea, headache
Decreases entry of lithium in CD cells
• Lithium induced diabetes insipidus
Triamterene:
Impaired glucose tolerance, photosensitivity
Rise in blood urea

19. Osmotic diuretics
Mannitol, glycerol, isosorbide
Non-electrolyte, low molecular weight
Pharmacologically inert
Acts by:
• Raising osmolarity of plasma and tubular fluid
• Gets freely filtered at glomerulus
• Limits tubular water and electrolyte
reabsorption (cations as well as anions)

20. Mannitol
Tubular water and electrolyte reabsorption action of
mannitol mediated by:
Retaining water isosmotically in PT and
Descending limb of LoH
Inhibit transport process in TAL
Expands extracellular fluid volume
Increases renal blood flow
• Corticomedullary osmotic gradient lost

21. Mannitol
Given intravenously
Uses:
Increased intracranial pressure
Increased intraocular pressure
Counteract low osmolarity of plasma and ECF
due to rapid haemodialysis or peritoneal dialysis
(dialysis disequilibrium)

22. Mannitol
CONTRAINDICATIONS:
Renal insufficiency
Acute tubular necrosis
Anuria
Pulmonary oedema
Acute left ventricular failure
CHF
Cerebral haemorrhage
• Side Effects
• Headache
• Nausea/
vomiting
• Hypersensitiv
e reactions

23. Post Test
All of the following are a potassium sparing
diuretics EXCEPT:
? Acetazolamide
? Triamterene
? Eplerenone
? Spironolactone

24. Conclusion
Weak diuretics either act early in PT or in late DT
and CD
Spironolactone has activity on progestin and
androgen receptors
Eplerenone safer in this regard
Potassium sparing diuretics acts either by
antagonising the activity of aldosterone or by
directly inhibiting action of epithelial Na+ channels

25. Any queries?
Revise the topics from
BOOK
Thank you.