Principles of

Diuretic Therapy
Dr. Rania Magadmi, MBBS, PhD
Assistant Professor, Pharmacology
department, Faculty of Medicine,
KAU

1
Objectives:
1. Review the structure and function of the nephron.
2. Classify the major classes of diuretics.
3. Discuss the main site of action ,mechanisms, indications and
adverse effects of each class of diuretics.
• Urine is formed in 3 processes:

t ly
os
m

Filtration + Secretion – Reabsorption = Urine

 65% 5%

CT
+
a
-
N DCT
l
C

Na+
PCT 1%

DL TAL 25%

Diuretics interfere with reabsorption of Na+ at different

segments of Nephrone
Diuretics

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 PT 1. Carbonic anhydrase inhibitors: Acetazolamide

Carbonic
anhydrase
inhibitors PT
Lumen blood

Na+
Na+ ATP

K+
HCO3- + H+ H+ HCO3-

H2CO3
H2CO3
CA CA
H2O +CO2 H2O +CO2

Acetazolamide
 PT 1. Carbonic anhydrase inhibitors: Acetazolamide
Mechanism of action
Carbonic
anhydrase Inhibits carbonic anhydrase enzyme in PCT à interferes
inhibitors with NaHCO3 reabsorption .
- Increase excretion of Na+, HCO3-, H2O, K+ “Alkaline diuresis”
- Metabolic acidosis.
- Weak diuretics.
Therapeutic uses:
- Glaucoma (reduce formation of aqueous humor by
blocking carbonic anhydrase in ciliary body of eye).
- Mountain sickness
- Epilepsy (decrease cerebrospinal fluid volume-CSF).
Adverse effects
- Ca and Phosphate renal stones (due to alkaline urine).
- Metabolic acidosis (drowsiness)
- Hypokalemia (potassium loss).
 TAL 2. Loop diuretics:
Furosemide, Torsemide, Bumetanide

Loop diuretic

Loop Diuretics

Na+/K+/2CI- Na+/K+ ATPase

Co-transporter
 TAL 2. Loop diuretics:
Furosemide, Torsemide, Bumetanide

Loop diuretic Mechanism of action

- Act on Thick ascending loop of Henle (TAL).

- Inhibit Na+ / K+ / 2 Cl- co-transporter àreducing NaCl reabsorption.
(~ 25-30% of Na+ reabsorption).
- Inhibit Ca++ and Mg++ reabsorption
- The most effective diuretics.
- Given orally or parenterally.

Therapeutic uses:
- Are widely used drugs (drug of choice) for emergency:
- Acute pulmonary edema of heart failure
- Acute hypertensive encephalopathy.
- The major application is in the treatment of edematous states (e.g
heart failure, ascites, liver faliure, acute renal failure).
 TAL 2. Loop diuretics:
Furosemide, Torsemide, Bumetanide

Loop diuretic
Adverse effects
1. Metabolic alkalosis.
2. Acute hypovolemia: hypotension and collapse.
3. Hyponatremia, Hypomagnesaemia, Hypocalcemia.
4. Hypokalemia .
5. Hyperuricemia: competes with transport of uric acidà
block uric acid secretion.
6. Osteoporosis (Chronic use)
7. Ototoxicity; altered electrolyte handling in the endolymph
(particularly when used together with aminoglycoside
antibiotics).
 DT 3. THIAZIDE DIURETICS

THIAZIDE
DIURETICS

Thiazide
diuretics

Na+/Cl- co-
transporter
Na+/K+ ATPase

Na+/Ca++ exchanger
 DT 3. THIAZIDE DIURETICS
• Hydrochlorothiazide
• Chlorthalidone (Taken once daily)
THIAZIDE • Indapamide " Thiazide-like diuretics“
DIURETICS • Metolazone Less renal toxicity

Mechanism of action
- Decrease NaCl reabsorption via inhibition of Na+/Cl- in DCT (~ 5-8% of
Na+ reabsorption)àModerate diuretics..
- Ca++ is reabsorbed. Thus patients on thiazides have a reduced risk for
osteoporosis (so preferred in elderly hypertensive patients).
Therapeutic uses:
1. The major application is in hypertension.
2. Heart failure ( loop diuretics are drug of choice in reducing
extracellular volume, thiazide may be added if needed).
 DT 3. THIAZIDE DIURETICS

THIAZIDE
DIURETICS Adverse effects

1. Metabolic alkalosis
2. Electrolytes imbalance: Hypokalemia, Hyperuricemia,
Hypercalcemia.
3. Hyperglycemia (chronic use)
(if the patient is diabetic monitor his blood glucose)
4. Hyperlipidemia: - Decreased insulin levels and high glucose
levels being converted to fat instead of going through
metabolism.

THIAZIDE = dar Zaid

Loop/ Thiazide Diuretics

• Both produced diuresis

• Both produce natriuresis
• Both produce kaliuesis (hypokalemia)
• Both cause metabolic alkalosis
• But; loop diuretics waste Ca++ (hypocalcemia),Thiazide
retain Ca++
• Loop working on T.A.L (strong diuretics)
• Thiazide working on D.C.T (moderate to mild diuretics)

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 • Now:
1. Carbonic anhydrase inhibitors
2. Loop Diuretics (Furosemide,)
3. Thiazide diuretics

K + wasters

(avoid the hypokalemia by adding: dietary K+

supplementation or K+- sparing diuretics).
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 CT 4. K+-SPARING DIURETICS

K+-SPARING
DIURETICS CT Interstitium/
Lumen
Cl- blood
Triamterene Na+
Amiloride Na+ ATP

K+
K+
Spironlactone

Aldosterone

Principal cell

Intercalated
cell
 CT 4. K+-SPARING DIURETICS (Spironolactone,
Amiloride, Triamterene)
K+-SPARING Mechanism of action
DIURETICS
- Spironolactone is a competitive antagonist to aldosterone.
- Triamterene and Amiloride inhibit Na+ reabsorption from
collecting ducts (K-sparing effect).

Therapeutic uses:
- Drug of choice for patient with hepatic cirrhosis due to elevated serum
aldosterone levels (aldosteronism).
- Diuretics in combination with thiazide or loop diuretics (to correct for
hypokalemia).

Adverse effects
- Hyperkalemia.
- Metabolic acidosis.
- Gynecomastia in male and menstrual irregularities in females.
PT, LH, CT 5. OSMOTIC DIURETICS
MANNITOL
OSMOTIC
DIURETICS
PT, LH, CT 5. OSMOTIC DIURETICS
MANNITOL
OSMOTIC
Mechanism of action
DIURETICS Freely filtered at the glomerulus but not reabsorbed or
secreted, mannitol remains in the lumen and ‘‘holds’’ water by
its osmotic effect.
Pharmacokinetics
Not absorbed orally - Given only I.V.
- Acts in proximal convoluted tubules; descending
loop of Henle and collecting tubule

Therapeutic uses: MANnitol

1. Cerebral edema (DOC); increased intracranial pressure.
2. Glaucoma

Adverse effects
- Dehydration, Adequate water replacement is required.
Nursing notes
• Weight the patient each morning
(indicator of the patient’s response to
diuretics).
• Watch the patient at risk for injury
related to postural hypotension and
dizziness.
• Give the diuretic in the morning to
prevent nocturia from disturbing the
patient’s sleep.
• Ask the patient taking loop and thiazide
diuretics to consume plenty of
potassium-rich foods.

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Osmotic diuretics
(Mannitol)
Therapeutic uses:
Increased ICP, Cerebral
edema, Acute renal failure.
Adverse effects:
Dehydration.
Carbonic anhydrase Thiazide diuretic (Hydrochlorothiazide)
inhibitors (Acetazolamide) Therapeutic uses: diuretic of choice in treatment of
Therapeutic uses: for glaucoma & Hypertension.
Mountain sickness. Adverse effects: hypokalemia, Hypercalcemia,
Adverse effects: hypokalemia & Hyperuricemia, hyperglycemia, hyperlipidemia.
metabolic acidosis.
-
- +
a
N
PCT
-
l DCT
C

TAL
CT
-
Loop diuretic -
(Furosemide) K+-Sparing Diuretics
Therapeutic uses: The diuretic (Spironolactone)
of choice in treatment of acute Therapeutic uses: used in combination
pulmonary edema of HF & with other diuretics. It is the diuretic of
edematous states. choice for patient with hepatic cirrhosis.
Adverse effects: hypokalemia, Adverse effects: Hyperkalemia, Metabolic
Hyperuricemia, osteoporosis & acidosis & Gynecomastia.
ototoxicity.
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Thank you
rmagadmi@kau.edu.sa

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References
 https://kahoot.it

https://kahoot.it/challenge/07636057?challenge-id=75f175e6-4003-
4fac-b012-75f890f90143_1602535842572