1. DIURETICS
BYBY
MR. V P PATILMR. V P PATIL
ASST. PROF.ASST. PROF.
DEPT. OF PHARMACOLOGYDEPT. OF PHARMACOLOGY
BLDEA’SBLDEA’S
SSM COLLEGE OF PHARMACY AND RESEARCHSSM COLLEGE OF PHARMACY AND RESEARCH
CENTRE.CENTRE.
VIJAYAPUR.VIJAYAPUR.
3. 1. Major Functions of The Kidney
• Regulation of osmolarity of the body fluid
• Regulating the volume of the extracellular fluid
• Regulating concentrations of electrolytes of the
extracellular fluid
• Regulation of acid-base balance
• Clearance of metabolic waste products (urea, uric acid,
creatinine)
• Production of special substances (erythropoietin, renin,
prostaglandins, and thromboxane)
4.
5. Diuretics are the drugs which causes net loss
of Na + and water in urine by inhibiting
reabsorption of Na+ & water.
Normally sodium is reabsorbed ---
~ 65 % in PCT
~ 20 % in As Loop of Henle
~ 10 % in DCT
~ 5 % in CD
9. Diuretics
High ceiling loop diuretics : Furosemide
(Inhibitors of Na+ K+ 2Cl Co-transport) :
-- Major action on thick Ascending loop of
Henle
-- Diuretic response can be increased to 10 L of
urine
-- It is active in patients with severe renal
failure
11. Diuretics
Furosemide :
Minor action on PCT – weak carbonic
anhydrase activity – excretion of HCO3-
I.V cause increase in systemic venous
capacitance and decrease left ventricular filling
pressure.
12. Diuretics
Furosemide
Furosemide increases calcium excretion
{thiazides decrease calcium excretion}
It increase the plasma uric acid levels by
decreasing renal excretion – interference with
tubular secretion and reabsorption.
Hyperglycemia is seen with loop diuretics.
13. Furosemide
Hypokalemia, Hearing loss, Hyperuricemia, Hyperglycemia
Hypocalcemia
Interactions:
1.Furosemide + ACE-I ---Antihypertensive action potentiated
2. - + NSAIDS --- Loss of diuretic effect
3. - + Aminoglycosides --- ototoxicity
4. - + Li --- Li toxicity
Dose: Furosemide – 20-80mg once daily in morning
Diuretics
14. Diuretics
High ceiling loop diuretics :
(Inhibitors of Na+ K+ 2Cl Co-transport) :
Bumetanide : It is 40 times more potent than
furosemide .
Ethacrynic acid : similar to furosemide
It is an irritant – orally it produces diarrhea.
It is toxic and can cause hearing loss and
hepatotoxicity.
16. Diuretics
Inhibitors of Na+ / Cl - symport :
Hydrochlorothiazide , Metazolone, Indapamide
The primary site of action is cortical diluting
segment or early distal tubule.
Secondary action is CA inhibition in PCT.
17. Diuretics
Inhibitors of Na+ /Cl - symport : Thiazides :
Increased urinary Na+, Cl-, K+
and Mg++
excretion
Weak CAase inhibition – excretion of HCO3
Uric acid excretion, Ca++
Moderately efficacy as 90% of Na+ is reabsorbed before it
reaches DCT
They decrease blood pressure and increase blood sugar.
They are not effective in low GFR.
21. Diuretics
Carbonic anhydrase inhibitors :
CA is an enzyme which catalyzes the reversible
reaction
H20 +CO2 «-------------» H2CO3.
Carbonic acid ionizes into HCO3 and H+, thus
helps in the transport of CO2 and H+
secretion.
The CA enzyme is present in the renal tubular
cells, gastric mucosa, pancreas, ciliary body
and RBC.
22.
23. Diuretics
Carbonic anhydrase inhibitors : Acetazolamide
The net effect is inhibition of HCO3
reabsorption in PCT.
The secretion of H+ is inhibited.
The urine produced is rich in bicarbonate --
alkaline urine – depletes body of HCO3----
producing acidosis.
24. Diuretics
Carbonic anhydrase inhibitors :
Extra – renal actions :
Lowering of intraocular tension due to
decreased formation of aqueous humor.
Decreased gastric acid and bicarbonate
secretion.
28. Diuretics
Potassium Sparing Diuretics :
Spironolactone : Aldosterone antagonists
Aldosterone acts by combining with
intracellular receptors --- induces formation
of proteins – which promotes reabsorption
of Na+ and secretion of K+
It increases calcium excretion by direct
action on the tubules
Action is dependent on aldosterone
30. Diuretics
Potassium Sparing Diuretics :
Spironolactone :
adverse effects
Gynaecomastia, menstrual irregularities,
impotence, hyperkalemia.
Uses
It is a weak diuretic – more useful in cirrhotic,
nephrotic and refractory edema
It is used to counteract the K+ loss due to
thiazides and loop diuretics
31. Diuretics
Renal epithelial Na+ channel inhibitors :
Triamterene, Amiloride
Non-steroidal in nature
Action is similar to spironolactone – but
independent of aldosterone
Acts by inhibiting Na channels of the DT and
CD
32. Diuretics
Renal epithelial Na+ channel inhibitors :
Triamterene, Amiloride
Both are used in conjunction with thiazides
and loop diuretics
Hyperkalemia occurs when used with ACE
inhibitors.
33. Diuretics
Renal epithelial Na+ channel inhibitors :
Amiloride :
10 times more potent than the triamterene
It decreases calcium excretion and increases
urate excretion
Half life ~ 15 hrs
Blocks entry of lithium into renal cells and
mitigate DI caused by lithium
34.
35. Diuretics
Mannitol: Osmotic diuretics :
It is a non-electrolyte – pharmacologically
inert
Not metabolized, freely filtered in the
glomerulus, undergoes limited reabsorption
Inhibits water and electrolyte reabsorption
36. Diuretics
Mannitol: Osmotic diuretics :
Expands extracellular fluid and increases GFR
Increases renal blood flow - salt reabsorption is
reduced
Primary action is to increase urinary volume
Not absorbed orally – given I.V
37. Diuretics
Mannitol: Osmotic diuretics : Uses
To maintain GFR and urine flow in renal
failure
Forced diuresis in poisoning
To reduced IOT – by its osmotic activity
Editor's Notes
Furosemide : Pharmacokinetics :
It is rapidly absorbed orally
Highly bound to plasma proteins
Conjugated with glucuronic acid
Excreted in urine and bile