thiazide,potassium sparing diuretics and osmotic diuretics

1. Pokhara University
School of Health and Allied Sciences
Diuretics
Nirmal Raj Marasine
First Semester, M Pharm(Clinical Pharmacy)
School of health and allied Sciences
Pokhara University, Dhungepatan, Lekhnath-12, Kaski, Nepal

2. Pokhara University
School of Health and Allied Sciences
Thiazide diuretics
MOA
The thiazide derivatives act mainly in the distal tubule to
decrease the reabsorption of Na+
by inhibition of a Na+
/ Cl-
co-
transporter on the luminal membrane .
As a result these drugs increase the concentration of Na and
Cl in the tubular fluid and increase its excretion.
some have carbonic anhydrase inhibitory action in PT
Reduce blood volume decrease G.F.R
Decrease B.P. in hypertensives.
January 9, 2018 2

3. Pokhara University
School of Health and Allied Sciences
Fig:Mechanism of salt reabsorption in early distal tubular cell and site
of action of thiazide diuretics on Na+Cl¯ symporter(source :essential
of pharmacology ,by K.D tripathi 7th
edition).
January 9, 2018 INS 591: Presentation 3

4. Pokhara University
School of Health and Allied Sciences
Thiazides in edema
 Thiazides are considered better for maintenance therapy .
They act best in cardiac edema,less effective in hepatic or
renal edema, cirrhotics develop refractoriness to thiazides
due to development of hyperaldosteronism.
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5. Pokhara University
School of Health and Allied Sciences
Thiazides in CHF
They can be the diuretic of choice in reducing extracelluar
volume in mild to moderate CHF.They decrease the cardiac
workload and oxygen demand by decreasing plasma volume
and subsequently venous return to the heart(preload).they
also decrease afterload .
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6. Pokhara University
School of Health and Allied Sciences
Thiazides in hypertension
• Initially diuresis reduces plasma and E.C.F.volume by about
15% decreased the cardiac output
• Compensating mechanisms operate to regain Na+
balance and
plasma volume cardiac output is restored, but fall in B.P.
maintained by slowly developing reduction in t.p.r.
• About 5% persisting Na+
and volume deficit decrease in
intracellular Na+ concentration in vascular smooth muscles may
decrease stiffness of vessel wall and increase their compliance
reduction
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7. Pokhara University
School of Health and Allied Sciences
• In .T.P.R .
• This is the reason why antihypertensive action of diuretics is
lost when salt intake in high.
January 9, 2018 INS 591: Presentation 7

8. Pokhara University
School of Health and Allied Sciences
Nephrogenic diabetes insipidus
• Plasma volume reduction by thiazides fall in GFR
enhanced proximal reabsorption of NacL andwater decreased
delivery of fluid to diluting segment volume of dilute urine is
lowered.
January 9, 2018 8

9. Pokhara University
School of Health and Allied Sciences
Thiazides in Nephrolithiasis
• Thiazides diuretics enhance Ca2+
reabsorption in DCT and
thus reducing urinary Ca2+
concentration,
• As a result chances of formation of calcium oxalate stones
can be minimized.
January 9, 2018 9

10. Pokhara University
School of Health and Allied Sciences
Adverse effects of thiazide diuretics
• Potassium depletion
• Hyperuricemia
• Hypotension
• Hypercalcemia and hypomagnesemia
• Hyperglycemia
• Hyperlipidemia
• Hypersensitivity
• Nausea, vomiting ,diarrhea
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11. Pokhara University
School of Health and Allied Sciences
• If used in toxaemia of pregnancy compromise placental
circulation miscarriage foetal death.
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12. Pokhara University
School of Health and Allied Sciences
Potassium sparing diuretics
MOA
Competitive and reversible inhibition of the aldeosterone
present in the cytoplasm of principal cells(located in late DCT
and cortical CT)
Formation of inactive spironoloactone-receptor complex which
cannot get traslocated into the nucleus to bind to DNA.
January 9, 2018 12

13. Pokhara University
School of Health and Allied Sciences
failure to produce “aldosterone-induced proteins” which
normally promote Na+
reabsorption via ENac and as a result of
which K+
secretion via K+
channel is facillated.
Loss of ENac activity
Decreased Na+
reabsorption and decreased K+
secretion
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14. Pokhara University
School of Health and Allied Sciences
Net loss of Na+ and water in urine
January 9, 2018 14

15. Pokhara University
School of Health and Allied Sciences
USES
Fluid retention of hyperaldosteronism
Resistant HTN
To counteract K+
loss due to thiazide and loop diuretics
Hypokalemia and hypomagnesemia
Heart failure
January 9, 2018 15

16. Pokhara University
School of Health and Allied Sciences
ADR
I. Oestrogenic S/E
- Gynaecomastia and impotence in male
-breast discomfort and menstrual irregularities in
female.
II. GI upset –can cause peptic ulcer
III. Hyperkalemia
IV. Lethargy and mental confusion
January 9, 2018 16

17. Pokhara University
School of Health and Allied Sciences
Inhibitors of Renal ENac
• Direct inhibition of Enac present in the luminal membrane
of the principal
• Decreased transport function of ENac which normally
promotes Na+
reabsorption and as a result of which K+
secretion via K+
channels is facilitated
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18. Pokhara University
School of Health and Allied Sciences
Loss of ENac activity
Decreased Na+
reabsorption and decreased K+
secretion
Net loss of Na+
and water in urine
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19. Pokhara University
School of Health and Allied Sciences
Uses
To counteract K+
loss due to thiazide and loop diuretics.
Hypokalemia and hypomagnesemia
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20. Pokhara University
School of Health and Allied Sciences
ADR
Hyperkalemia
Nausea ,diarrhea
Lethargy and mental confusion
January 9, 2018 20

21. Pokhara University
School of Health and Allied Sciences
Osmotic diuretics
• Osmotic diurectics act on proximal tubule and also at loop of
henle .where they prevent water reabsorption by increasing
osmolarity of tubular fluid
increase urine volume
flow rate
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22. Pokhara University
School of Health and Allied Sciences
contact time between fluid and tubular
epithelium
Na absorption
 Increase water excretion rather than Na+
excretion
January 9, 2018 22

23. Pokhara University
School of Health and Allied Sciences
USES
Increased intracranial or intraocular tension(acute congestive
glaucoma,head injury,storke,etc.)
To maintain g.f.r.and urine flow in impending acute renal
failure
To counteract low osmolarity of plasma/e.c.f.due to rapid
haemodialysis
January 9, 2018 23

24. Pokhara University
School of Health and Allied Sciences
References
1. Bruton LL.,Chabner BA,Knollman BC(Eds):Goodman
and Gilman’s The Pathological Basis of Therapeutics:12th
edition:McGraw-Hill,New York,2011.
2. Katzung BG,Masters SB,Trevor AJ(Eds):Basic and
clinical Pharmacology:12th
edn:Lang Medical Book, Tata
McGraw-Hill, New delhi,2012
3. Tripathi KD:Essential of medical pharmacology:7th
edn:Jaypee Brothers,New Delhi,2013
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