This document discusses different classes of diuretic drugs, including their mechanisms of action and sites of action in the kidney. It covers carbonic anhydrase inhibitors which act in the proximal convoluted tubule, loop diuretics which act in the loop of Henle, thiazide diuretics which act in the distal convoluted tubule, and potassium-sparing diuretics which act in the cortical collecting duct. Adverse effects are discussed for each class. The key functions of the kidney in filtration, reabsorption and regulation of water and electrolytes are also summarized.

1. DIURETICS
PRESENTED BY:-
PRASHANT N. AMALE
M.PHARM- (PHARMACOLOGY)
DEPARTMENT OF PHARMACEUTICAL SCIENCES
RTMNU.

2. KIDNEY
• Kidney
– Excretion of wastes
– Acid-base homeostasis
– Osmolality regulation
– Blood pressure regulation
– Hormone secretion
• Functional Unit
– Nephron

3. RENAL PHYSIOLOGY
• Renal processes
– Filtration
• At glomerulus (GFR)
– Reabsorption
• Water, electrolytes
– Active tubular secretion
• Organic acids
and bases

5. 3/5/2016 Free Template from www.brainybetty.com 5
= GLOMERULAR
HYDROSTATIC
PRESSURE (60 mmHg)
= BLOOD COLLOID
OSMOTIC PRESSURE
(32 mmHg)
=CAPSULAR
HYDROSTATIC
PRESSURE (18 mmHg)
NET OUTWARD = 60-18-32
PRESSURE = +10 mmHg

6. FLOW OF GLOMERULAR FILTRATE
GLOMERULUS BOWMAN’S SPACE IN BOWMAN’S CAPSULE
PROXIMAL CONVOLUTED TUBULE (PCT)
DISCENDING LIMB OF LOOP OF HENLE (DCT)
ASCENDING LIMB OF HENLE’S LOOP (AscLH)
. DISTAL CONVOLUTED TUBULE
RENAL PELVIS COLLECTING DUCT

7. TUBULAR REABSORPTION & SITE OF DRUG ACTION

8. From Knauf & Mutschler Klin. Wochenschr. 1991 69:239-250
70%
20%
5%
4.5%
0.5%
Volume 1.5 L/day
Urine Na 100 mEq/L
Na Excretion 155 mEq/day
100%
GFR 180 L/day
Plasma Na 145 mEq/L
Filtered Load 26,100 mEq/day
CA Inhibitors
Proximal tubule
Loop Diuretics
Loop of Henle
Thiazides
Distal tubule
Antikaliuretics
Collecting
duct
Thick
Ascending
Limb

9. Diuretics
Classification of Diuretics
Site 1
Proximal Convoluted Tubule (PCT)-Carbonic Anhydrase
Inhibitors
Site 2
Loop of Henle (LH )- Loop diuretics
Site 3
Distal convoluted tubule (DCT)- Thiazide
Site 4
Collecting Duct (CD)- Potassium sparing diuretics

10. CARBONIC ANHYDRASE INHIBITORS (Acetazolamide
(Oral) ; Dorzolamide (Ocular) ; Brinzolamide (Ocular)
Mechanism of action :-Simply inhibit reabsorption of sodium
and bicarbonate.
It prevents the
reabsorption of
HCO3 and Na
•Inhibition of HCO3 reabsorption  metabolic acidosis.
•HCO3 depletion  enhance reabsorption of Na and Cl  hyperchloremia.
•Reabsorption of Na  ↑ negative charge inside the lumen  ↑K secretion

11. SIDE EFFECTS OF ACETAZOLAMIDE:
Sedation and drowsiness; Hypersensitivity
reaction (because it contains sulfur)Acidosis
(because of decreased absorption of HCO3)
Renal stone (because of alkaline urine);
Hyperchloremia, hyponatremia and
hypokalemia

12. 1. OSMOTIC DIURETICS (E.G.: MANNITOL)
Mechanism of action: They are hydrophilic, that are
easily filtered through the glomerulus with little re-
absorption and thus increase urinary output via osmosis.
PK: Given parentrally. If given orally it will cause
osmotic diarrhea.
Adverse Reactions:
- Extracellular water expansion may complicate heart
failure & produce pulmonary edema.
- Dehydration
- Hypernatremia due to loss more water than sodium

13. B. Loop Diuretics :- Furosemide,Torsemide,Bumetanide

14. Dosage of loop diuretics:
Furosemide 20-80 mg
Torsemide 2.5-20 mg
Bumetanide 0.5-2.0 mg
Loop
diuretics
Furosemide:
Taken orally or i.v
If taken orally only 50 % is
absorbed
Torsemide:
Taken orally.
Better absorption
Fast onset of action
2/1t↑
Bumetanide (Bumex®)
Taken orally
40 times potent than
furosemide.
Fast onset
Short duration of action

15. Hypokalemia, metabolic alkalosis,
hypercholesterolemia, hyperuricemia, hyperglycemia,
hyponatremia
Dehydration and postural hypotension
Hypocalcemia (in contrast to thiazides)
Hypersensitivity
OTOTOXICITY (especially if given by rapid IV bolus)
ADVERSE EFFECTS OF LOOP DIURETICS

16. C. THIAZIDES :- Hydrochlorthiazide

17. THIAZIDES - PHARMACOKINETICS
• Rapid GI absorption
• Distribution in extracellular space
• Elimination unchanged in kidney
• Variable elimination kinetics and therefore
variable half-lives of elimination ranging from
hours to days.

18. SIDE EFFECTS OF THIAZIDES
• HYPERLIPIDEMIA; mechanism unknown but
cholesterol increases usually 1% increase
• IMPOTENCE
• HYPONATREMIA due to thirst, sodium loss,
inappropriate ADH secretion (can cause confusion in
the elderly),
• HYPERSENSITIVITY

19. D. DIURETICS THAT INHIBIT TRANSPORT IN THE
CORTICAL COLLECTING TUBULE (e.g. potassium
sparing diuretics).
Classification of Potassium Sparing Diuretics:
A) Direct antagonist of mineralocorticoid receptors
(Aldosterone Antagonists e.g spironolactone
(AldactoneR) or
B) Indirect via inhibition of Na+ influx in the luminal
membrane (e.g. Amiloride, Triametrene)

20. Spironolactone (AldactoneR)
►Synthetic steroid acts as a competitive antagonist of
aldosterone with a slow onset of action.
► Mechanism of action:
►Aldosterone cause ↑K and H+ secretion and ↑Na
reabsorption.
►The action of spironolactone is the opposite

21. SIDE EFFECTS
►Hyperkalemia (some times it’s useful other wise it’s
a side effect).
► Hyperchloremic (it has nothing to do with Cl)
metabolic acidosis
► Antiandrognic effects (e.g. gynecomastia: breast
enlargement in males, impotence) by
spironolactone.
►Triametrene causes kidney stones.
Clinical Uses of K+ sparing Diuretics:
-In states of primary aldosteronism (e.g. Conn’s
syndrome, ectopic ACTH production) of secondary
aldosteronism (e.g. heart failure, hepatic cirrhosis,
nephrotic syndrome)
– To overcome the hypokalemic action of diuretics
– Hirsutism (the condensation and elongation of female
facial hair) because it is an antiandrogenic drug