Module 7: Diuretics

Question 1

Introduction to Diuretics

Answer 1

How diuretics work: Mechanism of action
 Blockade of sodium and chloride reabsorption
Site of action
 Proximal tubule produces greatest diuresis
Adverse effects
 Hypovolemia
 Acid-base imbalance
 Electrolyte imbalances

Question 2

Classification of Diuretics

Answer 2

Classification of diuretics
 Four major categories
* Loop: Furosemide
* Thiazide: Hydrochlorothiazide
* Osmotic: Mannitol
* Potassium-sparing: Two subcategories
 Aldosterone antagonists (spironolactone)
 Nonaldosterone antagonists (triamterene)

Fifth group
 Carbonic anhydrase inhibitors

Question 3

Loop Diuretics

Answer 3

Furosemide (Lasix): Most frequently prescribed
loop diuretic
 Mechanism of action
* Acts on ascending loop of Henle to block reabsorption
 Pharmacokinetics
* Rapid onset (PO 60 minutes; IV 5 minutes)
 Therapeutic uses
* Pulmonary edema
* Edematous states
* Hypertension

Adverse effects
 Hyponatremia, hypochloremia, and dehydration
 Hypotension
* Loss of volume
* Relaxation of venous smooth muscle
 Hypokalemia
 Ototoxicity
 Hyperglycemia
 Hyperuricemia
 Use in pregnancy
 Impact on lipids, calcium, and magnesium

Drug interactions
 Digoxin
 Ototoxic drugs
 Potassium-sparing diuretics
 Lithium
 Antihypertensive agents
 Nonsteroidal anti-inflammatory drugs

Preparations, dosage, and administration
 Oral
 Parenteral

Question 4

Other High-Ceiling (Loop) Diuretics

Answer 4

Ethacrynic acid [Edecrin]
 Bumetanide [Bumex]
 Torsemide [Demadex]

All can cause:
 Ototoxicity, hypovolemia, hypotension, hypokalemia,
hyperuricemia, hyperglycemia, and disruption of lipid
metabolism

Question 5

Thiazides and Related Diuretics

Answer 5

Effects similar to those of loop diuretics
 Increase renal excretion of sodium, chloride,
potassium, and water
 Elevate levels of uric acid and glucose
 Maximum diuresis is considerably lower than
with loop diuretics
 Not effective when urine flow is scant (unlike
with loop diuretics)

Question 6

Hydrochlorothiazide

Answer 6

Hydrochlorothiazide [HydroDIURIL]
 Most widely used
 Action: Early segment distal convoluted tubule
 Peaks in 4 to 6 hours

Therapeutic uses
* Essential hypertension
* Edema
* Diabetes insipidus

Adverse effects
 Hyponatremia, hypochloremia, and dehydration
 Hypokalemia
 Use in pregnancy and lactation
 Hyperglycemia
 Hyperuricemia
 Impact on lipids, calcium, and magnesium

Drug interactions
 Digoxin
 Augments effects of hypertensive medications
 Can reduce renal excretion of lithium (leading to
accumulation)
 NSAIDs may blunt diuretic effect
 Can be combined with ototoxic agents without
increased risk of hearing loss

Question 7

Potassium-Sparing Diuretics

Answer 7

Useful responses
 Modest increase in urine production
 Substantial decrease in potassium excretion
Rarely used alone for therapy
 Aldosterone antagonist
Spironolactone
 Nonaldosterone antagonists
Triamterene
Amiloride

Question 8

Spironolactone [Aldactone]

Answer 8

Mechanism of action
 Blocks aldosterone in the distal nephron
 Retention of potassium
 Increased excretion of sodium

Therapeutic uses
 Hypertension
 Edematous states
 Heart failure (decreases mortality in severe failure)
 Primary hyperaldosteronism
 Premenstrual syndrome
 Polycystic ovary syndrome
 Acne in young women

Adverse effects
 Hyperkalemia
 Benign and malignant tumors
 Endocrine effects
Drug interactions
 Thiazide and loop diuretics
 Agents that raise potassium levels

Question 9

Triamterene [Dyrenium]

Answer 9

Mechanism of action
 Disrupts sodium-potassium exchange in the distal
nephron
 Direct inhibitor of the exchange mechanism
 Decreases sodium reuptake
 Inhibits ion transport

Therapeutic uses
 Hypertension
 Edema

Adverse effects
 Hyperkalemia
 Leg cramps
 Nausea
 Vomiting
 Dizziness
 Blood dyscrasias (rare)

Question 10

Amiloride [Midamor]

Answer 10

Mechanism of action
 Blocks sodium-potassium exchange in the distal
nephron
 Therapeutic use
Counteract potassium loss caused by more powerful
diuretics
 Adverse effects
Hyperkalemia
 Drug interaction
ACE inhibitors; other drugs with hyperkalemia