CVS - Diuretics - Drugs affecting fluid & electrolytes

Question 1

Classes of diuretics & examples

Answer 1

1. Caffeine
2. Carbonic Anhydrase Inhibitors (Acetazolamide)
3. Loop Diuretics (Furosemide, Ethacrynic Acid)
4. Thiazide Diuretics (Hydrochlorothiazide)
5. Potassium Sparing Diuretics (Spironolactone, Triamterene)
6. ADH/Vasopressin Antagonists (Lithium, Vaptans)

Question 2

Uses of diuretics (3+4)

Answer 2

Edematous States

1. Heart Failure
2. Renal Disease & Renal Failure (due to Na retention by kidney)
3. Hepatic Cirrhosis (often resistant to loops, use spirono)

Non-edematous States

1. Hypertension
2. Nephrolithiasis
3. Hypercalcemia
4. Diabetes Insipidus

Question 3

Mechanism of action of caffeine

Answer 3

Weak antagonist of adenosine receptors - A1 receptor antagonist - blocks PT reabsorption of Na+

Question 4

Mechanism of action of CAI

Answer 4

Blocks NaHCO3 reabsorption

Question 5

Uses of CAI (4)

Answer 5

1. Glaucoma - reduces aq humour formation & intraocular pressure
2. Acute Mountain Sickness - reduces CSF production & pH - increases ventilation - decreases pulmonary/cerebral edema
3. Metabolic Alkalosis
4. Urinary Alkalinization - enhances excretion of weak acids

Question 6

Mechanism of action of loop diuretics

Answer 6

1. Inhibits NKCC2 co transporter - selectively inhibits NaCl reabsorption - decreased lumen positive potential - increased cation secretion
2. Increased expression of COX-2 - catalyses PGE2 production from arachidonic acid - PGE2 inhibits NaCl transport in TAL

Question 7

Uses of loop diuretics (6)

Answer 7

1. Acute Pulmonary Edema
2. Other edematous conditions
3. Acute Hypercalcemia
4. Mild Hyperkalemia
5. Acute Renal Failure - enhances urine flow & K+ excretion, flushes intratubular casts
6. Anion Overdose

Question 8

Toxicity of loop diuretics (5)

Answer 8

1. Hypomagnesemia - prolonged use, reversible with oral Mg
2. Hypokalemic Metabolic Alkalosis - reversible by K+ replacement & rehydration
3. Ototoxicity - esp with poor renal function
4. Hyperuricemia, precipitate gout attacks - due to hypovolemic associated enhanced reabsorption of uric acid
5. Allergic Reactions

Question 9

Mechanism of action of thiazide diuretics

Answer 9

1. Inhibits NaCl reabsorption by blocking Na/Cl cotransporter
2. Enhances Ca reabsorption (A) passively in PCT due to hypovolemia (B) Na/Ca exchanger on basolat membrane in DCT by decreasing intracellular Na

Question 10

Uses of thiazide diuretics (4)

Answer 10

1. Hypertension
2. Heart Failure
3. Nephrolithiasis - due to idiopathic hypercalciuria
4. Nephrogenic Diabetes Insipidus

Question 11

Toxicity of thiazide diuretics (6)

Answer 11

1. Hypokalemic Metabolic Alkalosis
2. Hyperuricemia (Gout)
3. Impaired Carbohydrate Tolerance - impaired insulin release & impaired tissue glucose utilization
4. Hyperlipidemia
5. Hyponatremia - reduce dose and limit H2O intake
6. Allergic Reactions

Question 12

Mechanism of action of K+ sparing diuretics

Answer 12

Antagonizes effects of aldosterone in CCT - prevents K+ secretion

1. Direct antagonism of mineralocorticoid receptors (spironolactone, eplerenone)
2. Inhibits Na+ influx through ENaC (amiloride, triamterene)

Question 13

Uses of K+ sparing diuretics (2)

Answer 13

1. Primary Hyperaldosteronism

2. Secondary Hyperaldosteronism

Question 14

Toxicity of K+ sparing diuretics (5)

Answer 14

1. Hyperkalemia
2. Hyperchloremic Metabolic Acidosis
3. Gynecomastia
4. Acute Renal Failure
5. Kidney Stones

Question 15

Mechanism of action of ADH antagonists

Answer 15

Lithium: anti-ADH
Vaptans: non-peptide V1a & V2 receptors antagonist

Question 16

Toxicity of ADH antagonists (1)

Answer 16

1. Nephrogenic Diabetes Insipidus