Diuretic

Question 1

Name a carbonic anhydrase inhibitor

Answer 1

acetazolamide

Question 2

Name an osmotic diuretic

Answer 2

mannitol

Question 3

Name a “loop” diuretic

Answer 3

Furosemide

Question 4

Name a Thiazide and Thiazide-like diuretic

inhibit Na/Cl transport

Answer 4

Hydrochlorothiazide

Question 5

Name a “K sparing” diuretic

ENAC inhibitor

Answer 5

amiloride

Question 6

Name an aldosterone/”K sparin” diuretic

mieralocorticoid antagonist

Answer 6

spironolactone

Question 7

Name an ADH antagonist

Answer 7

Tolvaptan

Question 8

What does it mean to have “diuretic braking?”

Answer 8

Diuretics cause temporal increase in excretion of Na+ and H2O.

Compensatory mechanisms then diminish excretion, so that excretion is again equal with sodium and water intake

**new steady state is thus achieved when **

in = out

Question 9

How does diuretic braking occur?

Answer 9

body adapts to diuretic effects

↑ sympathetic activity

↑ RAA system activity

↑ ADH

During diuretic use, a new steady state is reached at a lower fluid volume

Question 10

Where do the diuretics work on the nephron?

Answer 10

Question 11

What is the MOA of carbonic anhydrase inhibitors?

Answer 11

Acetazolamide is secreted into proximal tubule by the anion transporter, therefore less Na and H2O reabsorbed.

HCO3 trapped in lumen increases negative charge: Na+ and K+ are attracted, Cl- is repelled from lumen

Question 12

What are the results of the carbonic anhydrase inhibitors?

Answer 12

Creates:

Alkaline urine (pH 8)

TGF: GFR & RBF ↓ due to ↑ solutes to macula densa

Cl- secretion is ↓ due to ↑ of negatively charged HCO3- in CD lumen that repels Cl- but attracts Na+ & K+ as well as ↓ activity of basolateral HCO3/Cl exchanger
Plasma - ↓HCO3-, ↓K+, ↑Cl-, ↑H+

Question 13

What are the sites of action of carbonic anhydrase inhibitors?

Answer 13

PT (secondary site = CD intercalated cells); eye
(aqueous humor), RBC and gastric mucosa.

Question 14

What are adverse reactions from carbonic anhydrase inhibitors?

Answer 14

• *Hyperchloremic metabolic acidosis**
• *Renal stones** – calcium salts are less soluble at alkaline pH

Cross-hypersensitivity with other sulfonamides

Question 15

Loop diuretic MOA?

Answer 15

*INHIBIT Na/K/2Cl SYMPORTER

therefore abolishes medullary osmotic gradient

Question 16

What is the main effect on urine by loop diuretics?

Answer 16

increased excretion of all ions: Na+, Cl-, K+, H+, Mg2+, Ca2+, as well as HCO3- in case of furosemide

Question 17

What are the main adverse effects of loop diuretics?

Answer 17

• hypochloremic alkalosis and hypokalemia
• hypotension
• ototoxicity (ethacrynic acid)

Question 18

Where do thiazide diuretics work in the nephron?

Answer 18

INHIBITORS OF NA/CL SYMPORTERS

in the DCT

*do NOT abolish the medullary gradient

Question 19

What is the main effect on urine by thiazide diuretics?

Answer 19

• ↑ Na+, Cl- and K+, ↓ excretion of
  Ca2+

calcium-sparing

Question 20

What are major adverse effects of hydrochlorothiazide?

List 5 hyper and 1 hypo

Answer 20

*hypokalemic metabolic alkalosis
hypercalcemia

hyperuricemia

*hyperglycemia- in patients with diabetes or abnormal glucose tolerance tests.

hyperlipidemia

hypersensitivity reaction when allergic to sulfonamides

Question 21

Where do K sparing diuretics work?

Answer 21

DCT and CD

Question 22

What is the MOA of amiloride?

Answer 22

Block Na+ channels. Effects are independent of the
presence of aldosterone.

Question 23

What is the main effect of amiloride and spironolactone on urine?

Answer 23

Decrease excretion of K+

Question 24

What is the MOA of spironolactone?

Answer 24

Canrenone, the active metabolite of spironolactone, forms
an inactive receptor complex, blocking the action of aldosterone**. W/o circulating aldosterone, spironolactone has no effect. **

Question 25

What are the main adverse effects of spironolactone?

Answer 25

hyperkalemia - \*Contraindicated in chronic renal insufficiency gynecomastia

Question 26

How does mannitol work?

Answer 26

Question 27

What are the main effects of mannitol on urine and plasma?

Answer 27

Urine - **Mg++↑** Plasma – Acute phase: mannitol draws fluid into vasculature -\> **hyponatremia.** Later, **hypernatremia**, since relatively more water is excreted

Question 28

What are the effects of mannitol with chronic use?

Answer 28

Chronic: dehydration, hypernatremia, **hyperkalemia** | (when cells shrink, their K+ ↑, which favors passive K+ exit to plasma)

Question 29

Which diuretic induces cytochrome P-450?

Answer 29

spironolactone

Question 30

Which diuretic is metabolized by CYP3A4?

Answer 30

tolvaptan

Question 31

Major diuretic effects

Answer 31

Question 32

Which drug is characterized by ## Footnote *Loss of plasma bicarb, alkaline urine, hyperchloremic acidosis, TGF, mountain sickness*

Answer 32

CAIs

Question 33

Which drug is characterized by ## Footnote *Powerful diuretics, loss of all ions, ototoxicity, hyperuremia, loss of osmotic gradient, RBF up*

Answer 33

loop diuretics

Question 34

Which drug is characterized by ## Footnote *Calcium sparing, alkalosis, hypokalemia, hyperuremia, synergize with loops, antidiuretics in Diabetes insipidus*

Answer 34

Thiazide diuretics

Question 35

Which drug is characterized by *K(and other cations) sparing, work in absence of aldosterone, triamterene can cause stones*

Answer 35

``` Na Ch (ENaC) Blockers ```

Question 36

Which drug is characterized by *K(and other cations) sparing, work only in presence of aldosterone, gynecomastia, p450 induction*

Answer 36

Aldosterone antagonists

Question 37

Which drug is characterized by *increase in RBF, indiscriminate loss of ions and water, acute hyponatremia, followed by hypernatremia*

Answer 37

osmotic diuretics

Question 38

Sites of action of diuretics

Answer 38

Question 39

True/false: Giving a **loop** (Na/K/2Cl at TALH, 25%) + **thiazide** (Na/Cl at DCT, 4%) together blocks two major sites of sodium reabsorption = **_synergistic effects_**

Answer 39

true

Question 40

What is the main determinant of extracellular fluid volume?

Answer 40

Total body **_NaCl_**

Question 41

What is the MOA of most diuretics?

Answer 41

Most are aimed at **_decreasing**_ extracellular fluid volume by _**decreasing_** total body NaCl

Question 42

Why does altering sodium excretion change H2O excretion?

Answer 42

water follows Na

Question 43

Which diuretic abolishes the corticomedullary osmotic gradient?

Answer 43

Loop diuretics \*vs. thiazide diuretics DO NOT

Question 44

Which diuretic does not require a transporter and crosses the basolateral membrane to bind with a mineralocorticoid receptor?

Answer 44

Aldosterone

Question 45

What drug does not use a transporter and works on the aquaporins on the basolateral membrane?

Answer 45

tolvaptan