Diuretics

Question 1

Which class of diuretics acts on the PCT?

Answer 1

carbonic anhydrase inhibitors

Question 2

Explain the mechanism of action of diuretics that reduce potassium loss during sodium diuresis and provide two examples.

Answer 2

Potassium-sparing diuretics work in the collecting duct. They block sodium uniport channels that exclusively reabsorb sodium. Usually, this sodium reabsorption is coupled with excretion of a potassium ion to maintain charge balance. So, blocking sodium reabsorption here will reduce potassium secretion, but still cause diuresis. Two examples are amiloride and triamterene.

Question 3

How do loop diuretics cause diuresis?

Answer 3

inhibition of the Na/K/2Cl transporter in the loop of Henle

Question 4

What are the three thiazide-like diuretics?

Answer 4

(1) Indapamide (Lozol)
(2) Chlorthalidone (Hygroton)
(3) Metolazone (Diulo, Zaroxolyn)

Question 5

Which class of diuretics is the most effective?

Answer 5

loop diuretics

Question 6

Which loop diuretic can be used in patients with a sulfa allergy?

Answer 6

ethacrynic acid (Edecrin)

Question 7

Describe how osmotic diuretics work and provide an example.

Answer 7

Osmotic diuretics provide an osmotic force that keeps water in the urine despite sodium reabsorption.

Question 8

What are the toxicities associated with aldosterone antagonists?

Answer 8

(1) hyperkalemia
(2) hyperchloremic metabolic acidosis
(3) BPH
(4) gynecomastia
(5) impotence

Question 9

What are the indications for osmotic diuretics?

Answer 9

reduction of intracranial/intraocular pressure, increase urine volume

Question 10

What are the toxicities associated with loop diuretics?

Answer 10

(1) hypocalcemia/hypomagnesemia
(2) dehydration
(3) saline-responsive metabolic alkalosis
(4) ototoxicity
(5) hyperuricemia

Question 11

Which diuretic is administered as a prodrug?

Answer 11

ethacrynic acid (Edecrin)

Question 12

What are the indications/contraindications of CA inhibitors?

Answer 12

indications:
(1) acute mountain sickness
(2) glaucoma
(3) metabolic alkalosis
(4) urinary alkalinization (drug trapping)

contraindications:

(1) metabolic acidosis
(2) sulfa allergies

Question 13

Because they increase renal blood flow, this class of diuretics can be used in cases of acute renal failure.

Answer 13

loop diuretics

Question 14

These diuretics block sodium chloride reabsorption in the DCT.

Answer 14

thiazides and thiazide-like

Question 15

Describe the characteristic structure of thiazide diuretics.

Answer 15

two connected rings, sulfa moiety, chlorine substituent

Question 16

What are the toxicities associated with thiazide diuretics?

Answer 16

(1) decreased carbohydrate tolerance
(2) hypokalemic metabolic alkalosis
(3) hyperuricemia (same as loops)
(4) hyperlipidemia
(5) hyponatremia

Question 17

What are the indications of ADH antagonists, and one example?

Answer 17

SIADH, or any situation in which ADH levels are acutely elevated

example provided is Demeclocycline (Declomycin)

Question 18

Both amiloride and triamterene share two common contraindications (which are?), but triamterene has an additional one, which is ________.

Answer 18

They share K supplements and ACE inhibitors because they both increase serum potassium, but triamterene is also contraindicated in patients with kidney stones due to poor solubility.

Question 19

Which toxic effects can occur with excessive administration of ADH antagonists?

Answer 19

(1) nephrogenic diabetes insipidus

(2) renal failure

Question 20

Which aldosterone antagonist can be used for hypertension or CHF in combination with other diuretics?

Answer 20

spironolactone (Aldactone)

There is some evidence of chronically elevated aldosterone levels and damage to cardiac tissue involved in CHF.

Question 21

Which two structural modifications will increase natriuretic/diuretic activity of CA inhibitors, but decrease their CA inhibiting effect?

Answer 21

(1) amine substitution

2) substitution of sulfamoyl with another electrophilic group (carboxylic acid, etc.

Question 22

Which structural motif is required for CA inhibitor activity?

Answer 22

unsubstituted sulfamoyl group

Question 23

What toxicities are associated with carbonic anhydrase inhibitors?

Answer 23

(1) renal potassium wasting
(2) renal stones
(3) drowsiness/paresthesia
(4) hyperchloremic metabolic acidosis

Question 24

Explain how thiazide diuretics cause increased calcium reabsorption.

Answer 24

As less sodium is brought into tubular cells and eventually into peritubular capillaries, sodium-calcium antiporters are activated and bring some of that sodium back into the cell while pumping calcium out. This lowers intracellular calcium levels, so more is brought in from the urine.

Question 25

What are some clinical uses of loop diuretics?

Answer 25

(1) edematous conditions, specifically pulmonary edema
(2) decrease calcium/mag reabsorption
(3) increase renal blood flow