(2) CV & Renal: Diuretics (2.1-2.4)

Question 1

What part of the nephron do Acetazolamide and Mannitol act on?

Answer 1

PCT

Question 2

Is the renal tubule Na+/K+ ATPase located on the apical or basolateral membrane?

Answer 2

Basolateral

(Yellow tract is tubular lumen, gray track is intracellular compartment)

Question 3

Is the renal tubule Na+/H+ exchanger located on the apical or basolateral membrane?

Answer 3

Apical

Question 4

What reaction does carbonic anhydrase in the renal tubule catalyze?

Answer 4

HCO3^- + H⁺ → H₂O + CO₂

Question 5

What reaction does intracellular carbonic anhydrase catalyze in the renal tubule?

Answer 5

H₂O + CO₂ → H+ + HCO₃^-

Question 6

MOA: Acetazolamide

Answer 6

Inhibits carbonic anhydrase

Question 7

Name 3 effects Acetazolamide has on renal electrolyte concentrations

Answer 7

(1) ↑ HCO3-
(2) ↑ Na+
(3) ↑ K+
* (↓ CA ⇒ ↓ Intracellular H+ ⇒ Inhibition of Na+/H+ exchanger ⇒ ↑ lumenal [Na+])*

Question 8

What acid/base disorder does Acetazolamide cause?

Answer 8

Normal anion gap metabolic acidosis

(Remember, anion gap acidosis is due to the production of volatile organic acids such as in diabetic ketoacidosis)

Question 9

Indications - Non-diuretic (3) : Acetazolamide

Answer 9

(1) Glaucoma
(2) Idiopathic intracranial hypertension
(3) Mountain sickness
* (Alkalinization of urine also treats gout and cystinuria by ↑ crystal solubility)*

Question 10

What type of renal tubular acidosis does Acetazolamide cause?

Answer 10

Type II

Question 11

Acetazolamide promotes the precipitation of what type of kidney stone?

Answer 11

Calcium phosphate

(Tubular alkalinization shifts the HPO₄^2- ↔ PO₄^3- + H⁺ to the right ∴ ↑ [PO₄^3-] ∴ ↑ Ca₃(PO₄)₂ solubility product ⇒ Precipitation)

Question 12

Which diuretics are Sulfa drugs?

Answer 12

(1) Acetazolamide
(2) Loop diuretics
(3) Thiazide diuretics
* (Note: Ethacrynic acid is a loop diuretic but NOT a Sulfa drug)*

Question 13

MOA: Mannitol

Answer 13

Osmotic diuretic

Question 14

Indications (2) : Mannitol

Answer 14

(1) ↑ Intracranial pressure
(2) ↑ Intraocular pressure

Question 15

Adverse Effects (3) : Mannitol

Answer 15

(1) Pulmonary edema
(2) Exacerbate heart failure
(3) Altered Na+ levels
* (↑ Serum osmolarity draws fluid from CSF/eyes, but this can dilute serum sodium and increase cardiac afterload)*

Question 16

Does Mannitol cause hyper or hyponatremia?

Answer 16

Either, depending on the situation

• (↑ Solute in serum ⇒ ↑ Osmotic draw from ECF ⇒ Dilution and hyponatremia)*
• (↑ Solute in urine ⇒ ↑ Osmotic draw in tubular fluid ⇒ ↑ Water excretion ⇒ Concentration and hypernatremia)*

Question 17

Which segment of the nephron is most impermeable to water?

Answer 17

Thick ascending loop of Henle

(Note: DCT is relatively impermeable to water as well)

Question 18

What transporter do loop diuretics inhibit?

Answer 18

Na+/K+/2Cl- Cotransporter

(On the lumenal membrane)

Question 19

MOA: Furosemide

Answer 19

Inhibits Na+/K+/2Cl- Cotransporter

Question 20

MOA: Ethacrynic acid

Answer 20

Inhibits Na+/K+/2Cl- Cotransporter

Question 21

What ions do loop diuretics promote excretion of indirectly?

Answer 21

(1) Mg2+
(2) Ca2+

Question 22

Do loop diuretics have a larger effect on serum Mg2+ or Ca2+?

Answer 22

Mg2+

(Ca2+ levels are corrected by ↑ intestinal absorption due to Vitamin D, ↑ renal absorption due to PTH)

Question 23

Which class of diuretics induce the expression of COX-2?

Answer 23

Loop diuretics

Question 24

Which class of pain medication can interfere with loop diuretics?

Answer 24

NSAIDs

Question 25

**Indications** (3) : Loop diuretics

Answer 25

(1) Pulmonary edema/CHF (2) Ascites (3) Hypertension * (Also useful in hypercalcemia)*

Question 26

Which class of diuretics are the first-line treatment for pulmonary edema secondary to heart failure?

Answer 26

Loop diuretics *(∵ They are the most efficacious. Also note the #1 on the balloon)*

Question 27

Are loop diuretics potassium wasting?

Answer 27

Yes *(Inhibition of Na+/K+/2Cl- cotransporter ⇒ ↑ lumenal Na+ concentration and ∴ increased activity of Na+/K+ ATPase)*

Question 28

**Adverse Effects** (5) : Loop diuretics

Answer 28

(1) Ototoxicity (2) Sulfa allergy (3) Interstitial nephritis (4) Hyperuricemia (5) Contraction alkalosis

Question 29

Name a loop diuretic that is NOT a Sulfa drug

Answer 29

Ethacrynic acid

Question 30

Where do thiazide diuretics act?

Answer 30

Distal convoluted tubule

Question 31

**MOA**: Thiazide diuretics

Answer 31

Inhibits NaCl cotransporter *(In DCT)*

Question 32

What is the difference in the mechanism of Ca²⁺ reabsorption in DCT vs. TAL?

Answer 32

(1) _DCT_: Active transport (2) _TAL_: Driven by (+) lumenal voltage

Question 33

What effect do thiazide diuretics have on Ca²⁺ reabsorption?

Answer 33

Increase *(Contrast with loop diuretics)*

Question 34

**Indications** (5) : Thiazides

Answer 34

(1) Hypertension (2) Heart failure (3) _Nephrogenic diabetes insipidus_ (4) Ca2+ stones (5) Osteoporosis

Question 35

**Adverse Effects** (7) : Thiazides

Answer 35

(1) Hyper**calc**emia (2) Hyper**_glyc_**emia (3) Hyper**lipid**emia (4) Hyper**uric**emia (5) ↑ Serum Li⁺ (6) Hypo**nat**remia (7) Hypokalemia * ("Hydrochlorothiazide at the high dive makes a lot of labs high!")*

Question 36

Which part of the renal tubule do K+ sparing diuretics act on?

Answer 36

Collecting duct

Question 37

What part of the renal tubule does Aldosterone act on?

Answer 37

Collecting duct

Question 38

Which cell regulates Na+/K+/H2O reabsorption in the collecting duct?

Answer 38

Principal cell

Question 39

Where is ENaC located?

Answer 39

Apical collecting duct membrane

Question 40

What drives K+ secretion in the collecting duct?

Answer 40

(-) Lumenal voltage *(Na+ reabsorption ⇒ (-) Lumenal voltage ⇒ Pulls K+ through channels)*

Question 41

What cell is responsible for H+ secretion in the collecting duct?

Answer 41

α-intercalated cells *(**α** for **α**cid)*

Question 42

Name 4 ion transporters in the collecting duct upregulated by Aldosterone

Answer 42

(1) K+ channels (2) ENaC (3) Na+/K+ ATPase (4) H+ ATPase

Question 43

Which K+ sparing diuretics _directly_ inhibit Na+ channels?

Answer 43

(1) Amiloride (2) Triamterene

Question 44

MOA (2) : K+ sparing diuretics

Answer 44

(1) Inhibit ENaC (2) Antagonize aldosterone receptor * (∴ Prevents generation of negative lumenal potential and ∴ K+ wasting)*

Question 45

What ENZYME does Spironolactone inhibit?

Answer 45

17α-hydroxylase

Question 46

Name 2 mineralcorticoid receptor antagonists

Answer 46

(1) Eplerenone (2) Spironolactone

Question 47

Other than Spironolactone, what can be used to treat the symptoms of Conn's syndrome?

Answer 47

Eplerenone

Question 48

What are two classes of diuretics which prevent cardiac remodeling and improve outcomes in heart failure?

Answer 48

(1) Aldosterone receptor antagonists (2) ACE Inhibitors * (Theme: ↓ Aldosterone Fx ⇒ ↑ Survival)*

Question 49

Which class of antidiuretics are useful in **Liddle's** syndrome?

Answer 49

K+ sparing diuretics * (Specifically, ones that target ENaC)* * Recall: Liddle's syndrome is overactive ENaCs*

Question 50

**Adverse Effects** (2) : K+ sparing diuretics

Answer 50

(1) Hyperkalemia (2) Normal anion gap metabolic acidosis

Question 51

What type of renal tubular acidosis do K+ sparing diuretics cause?

Answer 51

Type 4

Question 52

What is the only cause of type 4 renal tubular acidosis associated with hyperkalemia?

Answer 52

K+ sparing diuretics

Question 53

Name 4 side effects of Spironolactone which distinguish it from other K+ sparing diuretics

Answer 53

(1) Inhibits 17α-hydroxylase (2) Inhibits androgen receptor (3) ⇒ Gynecomastia (4) ⇒ Impotence

Question 54

What diuretic can be used to treat polycystic ovarian syndrome (PCOS)?

Answer 54

Spironolactone