Diuretics

Question 1

Drug class: Acetazolamide

Answer 1

Carbonic Anhydrase Inhibitor

Question 2

Drug class: Mannitol

Answer 2

Osmotic diuretic

Question 3

Drug class: Furosemide

Answer 3

Na+/K+/2Cl- Transporter inhibitor (Loop diuretic)

Question 4

Drug class: Hydrochlorothiazide

Answer 4

Na+/Cl- transporter inhibitor (Thiazide diuretics)

Question 5

Drug class: Amiloride

Answer 5

Inhibitor of ENaC (“K-sparing” diuretics)

Question 6

Drug class: Spironolactone

Answer 6

Antagonists of mineralocorticoid receptor (Aldosterone antagonist)

Question 7

Drug class: Tolvaptan

Answer 7

Antagonists to vasopressin (ADH)

Question 8

What is diuretic braking?

Answer 8

Diuretics cause a temporal increase in excretion of Na+ and H2O. Compensatory mechanisms then diminish excretion, so that excretion is again equal with sodium and water intake, and a new steady state is achieved (lower fluid volume).

Question 9

What are the two indications of diuretics?

Answer 9

1. Edematous states (CHF, pulmonary edema, nephrotic syndrome, hepatic cirrhosis)
2. Hypertension (essential and secondary).

Question 10

Describe the mechanism of Acetazolamide:

Answer 10

Secreted into the PCT by organic anion transporter. By reducing the effect of CA, there is increased HCO3- and H+ in the lumen (H2CO3) and therefore reduced activity of the H+/Na+ antiporter in the PCT, and therefore reduced Na+ uptake in the PCT.

In addition, HCO3- trapped in the lumen increases electronegativity causing increased Na+ and K+ secretion in the CD, and increased Cl- reabsorption in the CD.

Question 11

What are some side effects of Acetazolamide?

Answer 11

Increased HCO3- secretion causes increased urine pH (8). Increased solute delivery to macula densaa causes reduced gloemrular flow (lower GFR).

Potential electrolyte disturbances: metabolic acidosis due to HCO3- wasting and H+ retention. Hypokalemia and hyperchloridemia.

Question 12

Acetazolamide: indication

Answer 12

Reducing intraocular pressure (topical preps); Urinary alkalinization (improved excretion of weak acids); to correct metabolic alkalosis.

Question 13

Furosemide: mechanism

Answer 13

1. Secreted into lumen by OATs at PCT
2. Blocks activity of Na/K/2Cl- cotransporter
   Result is more excretion of Na, K+, Cl-, Mg2+, H+, Ca2+. Abolishes corticomedullary osmotic gradient

Question 14

Furosemide: side effects

Answer 14

Hypokalemia; Hypotension; also hypochloremia, metabolic alkalosis

Question 15

HCTZ: mechanism

Answer 15

1. Secreted into lumen by OATs
2. Blocks activity of Na+/Cl- symporter in DCT
3. Increased distal sodium delivery increases secretion of K+, H+

Question 16

HCTZ: indications

Answer 16

Aside from usual (HTN, CHF), used to prevent renal stones (hypercalciuria) and as treatment for nephrogenenic diabetes insipidus (renal insensitivity to ADH- provide for fluid retention).

Question 17

HCTZ: adverse

Answer 17

1. Hypokalemia, metabolic alkalosis, hypercalcemia, hyperuricemia.
2. Hyperglycemia in pts with diabetes/abnormal glucose tolerance
3. Hyperlipidemia

Question 18

Amiloride: mechanism

Answer 18

1. Secreted into tubule by OCT in PCT
2. Blocks ENaC channel in CD.
3. Less Na+ in cells of the CD leads to K+ retention
   * Independent of effect of Aldosterone on ENaC channels

Question 19

Amiloride: Adverse

Answer 19

Hyperkalemia

Question 20

Spironolactone: Mechanism

Answer 20

*NOT secreted into tuble. Active metabolite is Instead blocks the action of aldosterone on the CD by entering the basolateral side, binding to mineralocorticoid receptor in the cells of the CD. The result is less expression of ENaC channels, and less activity/expressoin of Na/K ATPase. Less Na is reabsorbed in the CD, and less K+ is wasted.

**Ineffective w/o circulating aldosterone

Question 21

Spironolactone: Adverse

Answer 21

Hyperkalemia, gynecomastia in males, menstrual irregularities in females

Question 22

Mannitol: mechanism

Answer 22

Pharmocologically inert. Filtered in glomerulus, not reabsorbable. Increases filtrate osmolality and decreases the osmotic gradient. Increases renal blood flow, further reducing corticomedullary gradient.

Question 23

Mannitol: route, adverse

Answer 23

IV only (not absorbed orally).

Acute: hyponatremia (moving fluid into extracellular compartment)

Later: Hypernatremia since relatively more water is excreted. Hypomagnesemia due to increased Mg excretion. Hyperkalemia.

Question 24

Mannitol: indication

Answer 24

Rapid reduction in intracranial and intraocular pressure before and after surgery.

Question 25

Tolvaptan: mechanism

Answer 25

Acts as antagonist of ADH on V2 ADH receptors in basolateral membrane of the collecting duct. Result is increased urine volume and decreased osmolality.

Question 26

Tolvaptan: Indication

Answer 26

Syndrome of inappropriate ADH.

Question 27

Describe how diuretics can be used in combination for CHF:

Answer 27

1. Give thiazide diuretic, if inadequate response…
2. Switch to loop diuretic. If inadequate response…
3. Increase dosage of loop. If inadequate response…
4. Add thiazide diuretic to Loop. If inadequate response…
5. Add K+ sparing diuretic

Question 28

Describe yow to manage K+ in patients on loop diuretics

Answer 28

1. Advise patients that Na restriction and K supplementation can help with low K levels.
2. When conservative management is unsuccessfule, the patient can be placed on a K+ sparing diuretic.