Diuretics

Question 1

In general, how do diuretics increase urinary output?

Answer 1

Diuretics increase urinary output by reducing the amount of
sodium and water reabsorbed by the nephron.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 645.

Question 2

How do all loop diuretics exert their action?

Answer 2

All loop diuretics work by inhibiting sodium and chloride
reabsorption in the thick ascending limb of the loop of Henle.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 646.

Question 3

What are potential adverse side effects of loop

diuretics?

Answer 3

Loop diuretics cause an increase in sodium delivery to the distal
tubule and collecting tubule eliciting an increase in potassium
and hydrogen ion secretion at these locations. This can result
in hypokalemia and metabolic alkalosis. The increased urinary
excretion of calcium can result in urinary calculi and possibly
hypocalcemia. Hypomagnesemia may also result due to
increased magnesium excretion. Reversible hearing loss has
also been reported with the use of furosemide and ethacrynic
acid.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 647.

Question 4

How do loop diuretics affect electrolyte balance?

Answer 4

Loop diuretics increase the excretion of sodium, chloride,
calcium, and magnesium and can potentially result in symptoms
related to low serum levels of these electrolytes in addition to
the signs and symptoms of hypovolemia due to increased water
excretion.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 646.

Question 5

Where do carbonic anhydrase inhibiting diuretics

exert their effect?

Answer 5

Carbonic anhydrase inhibitors such as acetazolamide decrease
sodium reabsorption and H+ secretion in the proximal tubules.
They can result in a mild hyperchloremic metabolic acidosis.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 648.

Question 6

How do thiazide-type diuretics exert their action?

Answer 6

Thiazide-type diuretics such as thiazides (obviously),
chlorthalidone, quinethazone, metolazone, and indapamide act
on the distal tubule and connecting segment. The inhibit
sodium reabsorption which results in impaired dilutional
capability. In contrast to loop diuretics, thiazide-type diuretics
enhance the reabsorption of calcium in the distal tubule. Of
interest is indapamide which has intrinsic vasodilating
capabilities and is the only thiazide-type diuretic that undergoes
significant hepatic excretion.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 647.

Question 7

What are the potentially adverse side effects of

thiazide-type diuretics?

Answer 7

Thiazide diuretics can impair renal diluting capacity resulting in
hyponatremia. They can also result in hyperglycemia,
hyperuricemia, hypercalcemia, and hyperlipidemia.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 647.

Question 8

Do both thiazide-type diuretics and loop diuretics

result in hypokalemia?

Answer 8

Yes. Thiazide diuretics do not inhibit sodium reabsorption to
the degree that loop diuretics do, thus the amount of sodium
delivered to the collecting tubules is less. This results in less
potassium secretion than occurs with loop diuretics, but is still
sufficient to produce hypokalemia and metabolic alkalosis.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 647.

Question 9

How do bumetanide and triamterene differ in their

effect on potassium levels?

Answer 9

Bumetanide is a loop diuretic associated with decreased serum
potassium levels. Drugs such as triamterene, spironolactone,
NSAIDs, ACE inhibitors, and beta blockers are associated with
increased potassium levels.
Stoelting RK, Hillier SC. Pharmacology and Physiology in
Anesthetic Practice. Philadelphia, PA: Lippincott Williams and
Wilkins; 2006: 488.

Question 10

How do the noncompetitive potassium-sparing

diuretics exert their action?

Answer 10

Unlike spironolactone, triamterene and amiloride do not rely on
aldosterone activity. They inhibit sodium reabsorption and
potassium secretion by limiting the number of open sodium
channels in the lumen of the collecting tubules.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 648.

Question 11

What is the chief indication for the administration of

the potassium-sparing diuretic spironolactone?

Answer 11

Spironolactone is a direct aldosterone receptor antagonist that
acts to inhibit aldosterone-mediated sodium reabsorption and
potassium secretion in the collecting tubules. As a result, it is
only indicated for patients with hyperaldosteronism.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 648.

Question 12

How does the efficacy of potassium-sparing diuretics
compare with that of loop diuretics and thiazide
diuretics?

Answer 12

Potassium sparing diuretics are relatively weak agents that
inhibit sodium reabsorption in the collecting tubules. They
excrete about 10% of the amount of sodium (and subsequently
water) that loop diuretics do and about 30% of the sodium that
thiazide diuretics secrete.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 647.

Question 13

How do the potential adverse effects of
noncompetitive potassium-sparing diuretics differ
from that of loop and thiazide diuretics?

Answer 13

Amiloride and triamterene can result in hyperkalemia and
metabolic acidosis whereas loop diuretics and thiazide diuretics
can result in hypokalemia and metabolic alkalosis.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 648.

Question 14

What accounts for the resistance to diuretics seen in

patients with impaired renal function?

Answer 14

Diuretics are highly protein bound which mean that very little of
the drug enters the tubules by filtration. Because diuretics exert
their action within the lumen of the tubule, most of them must be
secreted into the lumen by the proximal tubule via an organic
anion pump. In patients with decreased renal function, this
mechanism is not effective, therefore less drug is able to cross
into the tubule to exert an effect.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 736.

Question 15

How do osmotic diuretics such as mannitol increase

urinary output?

Answer 15

Osmotic diuretics are filtered at the glomerulus and undergo
little to no reabsorption in the proximal tubule. These large
molecules exert a strong attraction to water and thereby limit the
reabsorption of water that normally follows sodium
reabsorption. As a result, water excretion is increased.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 736.

Question 16

What are the potential adverse effects that could be

attributed to the administration of mannitol?

Answer 16

Because the administration of mannitol results in an acute
increase in plasma and extracellular osmolality, fluid shifts from
the intracellular space into the extracellular space and
eventually the intravascular compartment resulting in
congestive heart failure. Additionally, the increase in plasma
volume results in hemodilution which can present as transient
hyponatremia and a drop in hematocrit.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 737.

Question 17

What results would you expect from the
administration of mannitol in patients with
hypovolemia or severe, renal parenchymal injury?

Answer 17

In patients with hypovolemia, mannitol will augment urinary
output. In patients with severe glomerular or tubular injury,
however, mannitol will have little effect on urinary output.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: 736.

Question 18

A patient exhibits hyponatremia with a high serum
osmolarity. What diuretic would most likely cause
this phenomenon?

Answer 18

Hyponatremia with a normal or high serum osmolarity result
from the presence of non-sodium solutes such as mannitol.
Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC,
Ortega R. Clinical Anesthesia. 7th ed. Philadelphia, PA:
Lippincott Williams and Wilkins; 2013: 342.

Question 19

What diuretic would be most appropriate for a patient

allergic to sulfonamide drugs?

Answer 19

The only diuretic (other than osmotic diuretics such as mannitol)
that is not derived from sulfonamides is ethacrynic acid which
may make it the drug least likely to result in an allergic reaction
in patient with sulfa allergies.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s
Clinical Anesthesiology. 5th ed. New York, NY: McGraw-Hill;
2013: .