Diuretics

Basic Pharmacology Block

PDNT/PMED.PMSC/PPHR -213
1
 Objectives

1. Explain actions of major classes of diuretics.

2. Describe how pharmacokinetic/Pharmacodynamic differences
between diuretic agents affect their use in clinical practice.
3. List the adverse effects of diuretics.

2
 Diuretics

• Drugs that aid in removing excess extracellular fluid and

electrolytes and increased urine flow.

• These agents are ion transport inhibitors that decrease the

reabsorption of Na+ at different sites in the nephron. As a
result, Na+ and other ions such as Cl- enter the urine in greater
amounts than normal along with water.

3
4
 Summary of diuretic drugs

Diuretic Drugs

Carbonic Loop Thiazide Diuretics Potassium- Osmotic

Anhydrase Diuretics Sparing Diuretics
Inhibitor

1. Acetazolamide 1. Bumetanide 1.Hydrochlorothiazide 1. Amiloride 1. Mannitol

2. methazolamide 2. Furosemide 2. Metolazone 2. Spironolactone 2. Urea

3. Ethacrynic 3. chlorthiazide 3. Triamterene

acid 4. Eplerenone

4. Torsemide 4. Indapamide
5. Chlorthalidone

5
 Thiazides
(Hydrochlorothiazide, Metolazone)
• Thiazides (Frontline, 1st of equals): Hydrochlorothiazide,
Metolazone
• The prototypical thiazide is hydrochlorothiazide

Major locations of ion and water exchange in the nephron, showing sites of action of the
6
diuretic drugs
 Thiazides action
Mechanism of action:
1. The thiazide derivatives act mainly in early distal tubule to inhibit
Na-Cl cotransporter à inhibit water/Na+ reabsorption.

2. Increased excretion of Na+ and Cl-

¯ BP by depletion body of Na+ → ↓ blood volume (BV)/plasma
volume (PV)

3. Loss of K+

4. Loss of Mg2+

5. Decreased urinary calcium excretion

7
 Therapeutic uses

• High clinical value as antihypertensive & combination therapy

- Inexpensive, effective, retain effectiveness with elderly.
- Convenient to administer, and well tolerated.

• Hypercalciuria
– Patients with calcium oxalate stones in the urinary

8
 Adverse effects

• Hypokalemia
• ↑ uric acid retention → hyperuricemia in
70% of patients
• Hyperglycemia
• Hypercalcemia: The thiazides inhibit the
secretion of Ca2+, sometimes leading to
elevated levels of Ca2+ in the blood.
• Erectile dysfunction (less common in the
low doses used and its reversible).

9
 Loop diuretics
(Bumetanide, furosemide)
• Loop diuretics drugs have the highest
efficacy in mobilizing Na+ and Cl– from
the body (the most efficacious diuretic),
capable of the excretion of 15-25% of
filtered Na+.

• Inhibit the cotransport of Na+/K+/2Cl– in

the luminal membrane in the ascending
limb of the loop of Henle.

10
Major locations of ion and water exchange in the nephron, showing
sites of action of the diuretic drugs
11
 Adverse effects

• Ototoxicity (ethacrynic acid>furosemide>bumetanide)

– Particularly when used in conjunction with the
aminoglycoside antibiotics.
• Hyperuricemia
• Hyperglycemia
• Acute hypovolemia
– Hypotension, shock, and cardiac arrhythmias.
• Hypokalemia
• Hypomagnesemia.
• Hypocalcemia
• Metabolic alkalosis (Due to increase HCO3) 12
 Therapeutic uses

• Generally not used in hypertension pharmacotherapy

• Mainly used to decrease edema
• The loop diuretics are the drugs of choice for reducing the
acute pulmonary edema of heart failure.

13
 Potassium-sparing diuretics
• Potassium-sparing diuretics act in the
collecting tubule to inhibit Na+ reabsorption
and K+ excretion.
1. Aldosterone antagonists:
Spironolactone, Eplerenone
2. Epithelial sodium channel blockers
Amiloride, Triamterene
• Used as adjunct therapy (usually with
thiazide & loop), least potent
• Act at collecting tubule and duct, can cause
hyperkalemia
• Used also in heart failure
14
Major locations of ion and water exchange in the nephron, showing
sites of action of the diuretic drugs

Adverse effects:
Gynecomastia in males and menstrual irregularities in females,
hyperkalemia, nausea and hyponatremia.
15
 Carbonic anhydrase inhibitor
(Acetazolamide)

• Inhibits the enzyme carbonic

anhydrase in the proximal tubular
epithelial cells.

16
 Carbonic anhydrase inhibitor
• Carbonic anhydrase inhibitors are more
often used for their other
pharmacologic actions rather than for
their diuretic effect, because they are
much less efficacious than the thiazides
or loop diuretics
– Treatment of glaucoma
– Mountain sickness
• Adverse effects: Metabolic acidosis
(mild), Hypokalemia, renal stone
formation

17
 Osmotic diuretics
• The primary effect involves an increased fluid loss caused by the
osmotically active diuretics molecules, this result in reduced Na+
and water reabsorption from the proximal tubule.
• An additional contribution to the diuresis induced by that osmotic
diuretic is the increase in renal blood flow that follows their
administration.
Mannitol: -
Therapeutic uses:
Treatment of patients with increased intracranial pressure or acute
renal failure.
Adverse effects:
Dehydration and hyponatremia.
* Can only be given intravenously because it is not absorbed when given orally.18
19