2. Physiology of urine formation
• Urine formation starts from glomerular filtration.
• Normally 180 lts of fluid is filtered everyday.
• More than 99% of glomerular filtrate is
reabsorbed in the tubules.
• About 1.5 lts of urine is produced in 24 hrs.
3.
4. Diuretics
• Classification
1. High efficacy diuretics/ Loop diuretics
(inhibitors of Na-K-2Cl cotransport)
E.g Frusemide, Bumetanide, Ethacrynic acid
2. Medium efficacy diuretics
(inhibitors of Na- Cl symport)
E.g Hydrochlorothiazide, Chlorothiazide,
Indapamide, Metolazone, Xipamide
5. Contd…….
3. Weak or adjunctive diuretics
a)Carbonic anhydrase inhibitors : Acetazolamide,
Dorzolamide
b) Potassium sparing diuretics:
i) Aldosterone antagonist: Spironolactone,
Eplerenone
ii) Directly acting ( inhibitors of renal epithelial Na
channel): Triamterene, Amiloride
c) Osmotic diuretics: Mannitol, Glycerol
6. Loop diuretics
• M.A :- Acts at thick ascending loop of Henle
where it inhibits Na-K-2CL cotransport.
• K excretion is increased ( hypokalemia)
• I.v Furosemide causes increase in systemic
venous capacitance and decreases left ventricular
filling pressure so used in LVF and pulmonary
edema.
7. Pharmacokinetics
• Rapidly absorbed orally but bioavailability is
about 60%.
• Lipid solubility low and highly bound to
plasma proteins.
• Partly conjugated in liver and excreted by
kidney. Some excretion in bile and directly in
intestine also occurs.
8. Bumetanide
• About 40 times more potent than Furosemide
more lipid soluble, extensively bound to
plasma proteins.
• It may act in resistant cases of Furosemide.
• Side effects less than Furosemide but rarely
causes myopathy.
9. Uses
• Edema
• Cerebral edema
• Forced diuresis
• Hypertension
• Along with blood transfusion
• Hypercalcemia and renal stones
• Pulmonary edema
11. Thiazides
• The site of action is early DCT.
• M.A :- Na/Cl transport inhibitor resulting in
increased Na and Cl in DCT
increased diuresis
• Moderately efficacious because 90% of the
glomerular filtrate is already absorbed before
it reaches the site of action.
12. Contd……..
• They decrease renal Calcium excretion and
urate excretion( hyperuricaemia).
• Increase magnesium excretion.
• Decreases insulin release( hyperglycaemia)
• The extrarenal actions of Thiazides consists of
slowly developing fall in BP in hypertensive.
14. Carbonic anhydrase inhibitors
• H2O + CO2 H2CO3
• H2CO3 H+ and HCO3-
• This reaction can’t occur in PT cells and H+ is
not available to exchange with luminal Na+
resulting in natriuresis.
17. Spironolactone
• Aldosterone antagonist acting on late DCT and CD
cells.
• Acts from basolateral side of the tubular cell
combines with mineralocorticoid receptor and
inhibits formation of AIP(aldosterone induced
protein).
• AIP activate Na+ channel, translocate Na+ channel
from cytosolic site to luminal memberane.
18. Contd…
• Mild saluretic because most of sodium has
already been reabsorbed.
• Increases calcium excretion.
19. Uses
• Weak diuretic and is used only in combination
with other diuretics.
• Edema
• To counteract potassium loss due to Thiazide
and loop diuretics.
• Hypertension
• CHF
20. Adverse effects
• Drowsiness
• Confusion
• Abdominal upset
• Gynaecomastia
• Impotence
• Menstrual irregularities
• Most serious is Hyperkalemia
• Acidosis mostly in cirrhotics
21. Directly acting agents
• The luminal membrane of late DCT and CD
expresses amiloride sensitive or renal
epithelial Na channel.
• By these channels Na enters cell down its
electro-chemical gradient which is generated
by Na-K ATPase.
• This Na entry partially depolarizes the luminal
membrane creating a transepithelial potential
difference which promotes K excretion.
22. Contd..
• Amiloride and Triamterene block luminal Na
channel and indirectly inhibit K excretion.
• USES: along with Thiazides and loop diuretics
Lithium induced Diabetes insipidus
(Amiloride)
• S/E : Hyperkalemia, nausea, headache
23. Osmotic Diuretics
• Given Intravenously, Mannitol is filtered at
glomerulus and limit water and electrolytes
reabsorption resulting in diuresis.
Uses- Increased intra-cranial and intra-ocular
pressure
Forced diuresis in poisonings
C/I : anuria, Pulmonary edema, Acute LVF
