Module 2: Drugs Affecting Fluid & Elec. Balance (Diuretics)

Types of Diuretics:

1. Osmotic

2. Carbonic Anhydrase Inhibitors

3. Benzothiazides/Thiazides

4. Aldosterone antagonist

5. Xanthine/Aminouracils

6. Potassium-Retaining Agent

7. Loop of Henle Diuretics

8. Aquretics

9. Neural Endopeptidase Inhibitor (NEP)

10. Dopamine (D1) Receptor agonist

Examples of Osmotic Diuretics:

• Mannitol

• Sorbitol

• Inositol

• Glycerin

• Isosorbide

MOA of Osmotic Diuretics:

Increases osmotic pressure within the lumen of the proximal tubule & Loop of Henle

Clinical Uses of Osmotic Diuretics:

1. Tx of nephritis

2. Tx of renal failure

3. Regulation of CSF

4. Reg. of intra-ocular fluid

5. Induction of polyuria to eliminate toxin

6. Tx of urolithiasis

7. Tx of cystitis

Examples of Carbonic Anhydrase Inhibitors:

• Acetazolamide

• Dichlorphenamide

• Methazolamide

• Ethoxzolamide

MOA Carbonic Anhydrase Inhibitors:

Inhibition of resorption of bicarbonate by the tubular cells, leading to retention of bicarbonate in tubular lumen.

Clinical Uses Carbonic Anhydrase Inhibitors:

1. Tx of chronic glaucoma

2. Tx of udder edema

3. Reduces intra-ocular pressure

4. Adjunct to tx of epilepsy

5. Acute mountain (high-altitude) sickness

Examples Benzothiazides:

• Chlorothiazide

• Cyclothiazide

• Hydrochlorothiazide

• Polythiazide

Clinical Uses Benzothiazides:

1. Tx of edema associated w/ CHF

2. Tx of edema w/ renal, cardiac, hepatic origin

3. Tx of nephrogenic diabetes insipidus

Clinical Uses Benzothiazides:

1. Tx of edema associated w/ CHF

2. Tx of edema w/ renal, cardiac, hepatic origin

3. Tx of nephrogenic diabetes insipidus

Examples Aldosterone Antagonist:

• Eplerenone

• Canrenone

• Potassium canrenoate

• Spironolactone (true competitive antagonist)

Not an aldosterone antagonist but prevents release of aldosterone

Heparin

MOA Aldosterone Antagonist:

Blocks the effect of aldosterone, preventing the reabsorption of sodium, which encourages water loss.

Clinical Uses Aldosterone Antagonist:

1. Tx of hypokalemia

2. Tx of edema associated w/ renal, liver, cardiac failure

3. Tx of severe ascites

True competitive antagonist of aldosterone that may be under Potassium Retaining Diuretics and has some estrogen-like activity.

Spironolactone

Examples Xanthine/Aminouracils:

• Theophylline/Aminophylline

• Theobromine

• Caffeine

• Chlorazanil hydrochloride

MOA Xanthine/Aminouracils:

Promotes renal vascular vasodilation.

Clinical Uses Xanthine/Aminouracils:

1. Increase heart function

2. Increase pressure

3. Increase filtration

4. Increase water release

Examples Potassium-Retaining Agent:

• Triamterene

• Amiloride

• Spironolactone (Potassium-sparing)

• Eplerenone (Potassium-sparing)

These potassium-sparing agents inhibit aldosterone receptors and prevent excess excretion of potassium.

Spironolactone and Eplerenone.

MOA Potassium-Retaining Agents:

Prevent sodium reabsorption in the collecting tubule.

Clinical Uses Potassium-Retaining Agent:

1. Tx of edema associated w/ CHF

2. Tx of edema with liver cirrhosis

3. Tx of edema with nephrotic symptoms

Examples Loop of Henle Diuretics:

• Furosemide

• Ethacrynic acid

• Bumetanide

• Torsemide

MOA Loop of Henle Diuretics:

Inhibits sodium, potassium, chloride transport in Loop of Henle.

Clinical Uses Loop of Henle Diuretics:

1. Tx or edema

2. Tx of pulmonary congestion

3. Tx of ascites

4. Tx of hydrothorax

5. Tx of renal failure

6. Tx of CHF

7. Exercise-induced pulmonary hemorrhage (EIPH) in horse

8. Have ototoxic effect

Contraindications of Loop of Henle Diuretics:

1. Anuria

2. NSAID

3. Aminoglycoside

Examples Aquretics:

• Arginine vasopressin

• Lixivaptan

• Tolvaptan

• Conivaptan

MOA Aquretics:

Inhibit V2 receptors which mediate anti-diuretic hormone (ADH)

Clinical Uses Aquretics:

Tx of edema associated w/ cirrhosis, heart failure, nephrogenic syndrome, and inappropriate secretion of ADH.

Example Dopamine (D1) Receptors Agonist:

Fenoldopam

Clinical Uses Dopamine Receptors Agonist:

1. Increase renal blood flow

2. Increase filtration

3. Induce natriuresis