Pharmacology Review of Renal Physiology & Diuretics - III and IV - Grassl

Question 1

What drugs decrease the ability of ADH to increase the water permeability of the late distal tubule and the collecting duct?

Answer 1

Aquaretics

Question 2

What drugs decrease the solute reabsorption in one or more segments of the nephron?

Answer 2

Saluretics

Question 3

Loop diuretics, thiazide diuretics and potassium-sparing diuretics are what kinds of drugs?

Answer 3

Saluretics

decrease the solute reabsorption in one or more segments of the nephron

Question 4

Lithium is what kind of drug with respect to the kidney?

Answer 4

Aquaretic

decrease the ability of ADH to increase the water permeability of the late distal tubule and the collecting duct

Question 5

Fluoride is what kind of drug with respect to the kidney?

Answer 5

Aquaretic

decrease the ability of ADH to increase the water permeability of the late distal tubule and the collecting duct

Question 6

Demeclocycline is what kind of drug with respect to the kidney?

Answer 6

Aquaretic

decrease the ability of ADH to increase the water permeability of the late distal tubule and the collecting duct

Question 7

Use: Demeclocycline

Answer 7

Aquaretic

To reverse the effect of inappropriate ADH secretion arising from ADH-secreting oat-cell carcinomas of the lung

Question 8

Use: vaptan family of ADH receptot antagonists, ie Lixivaptan

Answer 8

Treat euvolemic hyponatremia

Question 9

In what segment of the nephron do carbonic anhydrase inhibitors act?

Answer 9

Carbonic anhydrase inhibitors act in the proximal tubule by decreasing sodium and bicarbonate reabsorption –> decrease tubular reabsorption

Question 10

Why do carbonic anhydrase inhibitors yield urine that has increased amounts of potassium?

Answer 10

Because the increase in sodium reabsorption in the late distal tubule and collecting duct is coupled to potassium secretion

Question 11

Where do high-ceiling or loop diuretics exert their effects?

Answer 11

thick ascending limb of the loop of Henle (medullary portion)

Question 12

Where do thiazide diuretics exert their effects?

Answer 12

thick ascending limb of the loop of Henle (cortical portion), (early distal tubule)

Question 13

T/F: High-ceiling, loop and thiazide diuretics all significantly increase the amount of potassium in the urine.

Answer 13

True, because of the sodium reabsorption in the late distal tubule.

Question 14

MOA: Potassium-sparing diuretics

Answer 14

Act in the late distal tubule and collecting duct to decrease sodium reabsorption (and potassium secretion)

Question 15

Which diuretics induce the smallest diuresis?

Answer 15

Potassium-sparing diuretics

Question 16

Which diuretics induce the largest diuresis?

Answer 16

Loop diuretics

Question 17

T/F: When a patient is volume CONTRACTED, loop diuretics increase free water clearance by causing a decrease in osmotic clearance.

Answer 17

True
The result is a less negative free water clearance than in the absence of diuretic and an impaired ability to defend against dehydration and ECF volume contraction

Question 18

T/F: When a patient is volume EXPANDED, loop diuretics decrease free water clearance (C-H2O) by causing an increase in osmolar clearance (C-osm)

Answer 18

True

The result is less positive free water clearance and an increase in the time necessary to return ECF volume to normal.

Question 19

Where a patient is volume expanded, thiazide diuretics decrease the magnitude of positive free water clearance by causing:

Answer 19

Where a patient is volume expanded, thiazide diuretics decrease the magnitude of positive free water clearance by causing an increase in osmolar clearance –> increases the time necessary for the kidney to correct ECF volume expansion –> risk of hyponatremia

Question 20

Class: Acetazolamide

Answer 20

Carbonic anhydrase inhibitor

Sulfonamide

Question 21

Class: Methazolamide

Answer 21

Carbonic anhydrase inhibitor

Sulfonamide

Question 22

Class: Dichlorphenamide

Answer 22

Carbonic anhydrase inhibitor

Sulfonamide

Question 23

Class: Hydrochlorothiazide

Answer 23

Thiazide

Question 24

Class: Dihydrochlorothiazide

Answer 24

Thiazide

Question 25

Class: Ethacrynic acid

Answer 25

High-ceiling diuretic

Question 26

Class: Furosemide

Answer 26

High-ceiling diuretic

Question 27

Class: Torsemide

Answer 27

High-ceiling diuretic

Question 28

Class: Bumetanide

Answer 28

Loop diuretic

Question 29

Class: Spironolactone

Answer 29

Potassium-sparing diuretic

Question 30

Class: Triamterene

Answer 30

Potassium-sparing diuretic

Question 31

Class: Amiloride

Answer 31

Potassium-sparing diuretic

Question 32

What diuretics are inhibitors of Na/Cl symport?

Answer 32

Thiazide diuretics | Act in the Early distal tubule

Question 33

What diuretics are inhibitors of Na/K/2Cl symport?

Answer 33

Loop diuretics and high-ceiling diuretics | Act in loop of Henle

Question 34

What diuretics are inhibitors of renal epithelial sodium channels OR antagonists of mineralcorticoid receptors?

Answer 34

Potassium-sparing diuretics | Act in the late distal tubule and collecting duct

Question 35

Main uses: carbonic anhydrase inhibitors

Answer 35

Decrease intraocular volume and pressure; | Prevention and treatment of acute mountain sickness

Question 36

Complications: Carbonic anhydrase inhibitors

Answer 36

Hypokalemia resulting from loss of potassium in the urine; | Toxicity can be caused by metabolic acidosis, bone marrow depression, skin toxicity, allergic reactions

Question 37

Use: Aminophylline

Answer 37

To prevent and relieve inflammation and bronchospasm in patients with asthma

Question 38

MOA: Aminophylline

Answer 38

Aminophylline = methylxanthine theophylline + ethylene diamine Increases GFR; Inhibits phosphodiesterase --> increases intracellular cAMP --> decreased sodium reabsorption in the proximal tubule

Question 39

What is osmotic diuresis?

Answer 39

An increase in the rate and volume of urine elimination due to the filtration and presence of a nonreabsorbable solute in the tubular fluid. ie Mannitol, excess glucose

Question 40

Class: Mannitol

Answer 40

Osmotic diuretic

Question 41

Use: Mannitol

Answer 41

Treatment of drug overdoses ie barbituates, to hasten the clearance of the drug; Used in shock or major surgery to minimize acute renal failure; To reduce intraocular and intracranial pressure

Question 42

Risk: Mannitol

Answer 42

Pulmonary edema, because of transient increase in ECF volume and intravascular pressure

Question 43

MOA: Mannitol

Answer 43

Opposes water and sodium reabsorption at proximal tubule --> increased osmolarity of tubular fluid

Question 44

MOA: Acetazolamide Methazolamide Dichlorphenamide

Answer 44

Inhibits luminal carbonic anhydrase at proximal tubule --> less activity of Na/H antiporter, decreased HCO3 and Na+ (and water) reabsorption

Question 45

Are carbonic anhydrase inhibitors contraindicated for some patients?

Answer 45

Yes, cirrhotics

Question 46

``` MOA: Furosemide Bumetanide Torsemide Ethacrynic acid ```

Answer 46

Loop diuretics Inhibits Cl portion of Na-K-2Cl cotransporter in luminal membrane at medullary and cortical (proximal) talH --> decreased K+, Ca++ and Na+ reabsorption, resultant K+ loss

Question 47

``` Use: Furosemide Bumetanide Torsemide Ethacrynic acid ```

Answer 47

Loop diuretics Crisis edema (pulmonary, CHF, cirrhosis), hypercalcemia, drug toxicity/OD; severe hypertension in setting of CHF or cirrhosis

Question 48

``` Side effects: Furosemide Bumetanide Torsemide Ethacrynic acid ```

Answer 48

Hypokalemia/hypocalcemia/hypomagnesemia (--> arrhythmia), contraction alkalosis, increased BUN & creatinine, ototoxicity (esp. w/aminoglycoside) Other side effects: Hyper -glycemia, -lipidemia, -uricemia; hypo -magnesia, -natremia; gout, photosensitivity, nephrocalcinosis, drug interactions; erectile dysfunction

Question 49

MOA: Chlorothiazide Hydrochlorothiazide

Answer 49

Thiazide diuretics Inhibits the Cl portion of the Na-Cl cotransporter in the luminal membrane at the early distal tubule --> decreased Na+ (and water) reabsorption, increased Ca++ reabsorption, resultant K+ loss

Question 50

Uses: Chlorothiazide Hydrochlorothiazide

Answer 50

``` Thiazide diuretics HTN (intravascular contraction), chronic edema (cardiac insufficiency), idiopathic hypercalciuria (stones), nephrogenic diabetes insipidus ```

Question 51

Side Effects: Chlorothiazide Hydrochlorothiazide

Answer 51

Thiazide diuretics Hypokalemia/hypercalcemia, contraction alkalosis, increased BUN & creatinine

Question 52

``` READ: Contraindications for thiazide AND thiazide like diuretics: Chlorothiazide Hydrochlorothiazide Chlothalidone Quinethazone Metolazone Indapamide ```

Answer 52

FeNa = 8%; lethal interaction w/quinidine (v. tach --> fib, may be due to hyperkalemia); avoid NSAIDs, bile sequestrants; increased risk of hypokalemia w/anti-inflammatory steroids or Amphotericin B; decreases positive free water clearance

Question 53

``` Class: Chlothalidone Quinethazone Metolazone Indapamide ```

Answer 53

Thiazide-like diuretic

Question 54

``` MOA: Chlothalidone Quinethazone Metolazone Indapamide ```

Answer 54

Thiazide-like diuretic Inhibits the Cl portion of the Na-Cl cotransporter in the luminal membrane at the early distal tubule --> decreased Na+ (and water) reabsorption, increased Ca++ reabsorption, resultant K+ loss

Question 55

``` Use: Chlothalidone Quinethazone Metolazone Indapamide ```

Answer 55

``` Thiazide-like diuretic HTN (intravascular contraction), chronic edema (cardiac insufficiency), idiopathic hypercalciuria (stones), nephrogenic diabetes insipidus ```

Question 56

``` Side Effects: Chlothalidone Quinethazone Metolazone Indapamide ```

Answer 56

Thiazide-like diuretic Hypokalemia/hypercalcemia, contraction alkalosis, increased BUN & creatinine

Question 57

Class: Amiloride Triamterene

Answer 57

K+-sparing diuretic; renal ENaC inhibitor (+ charge)

Question 58

MOA: Amiloride Triamterene

Answer 58

K+-sparing diuretic; renal ENaC inhibitor (+ charge) Blocks Na channel and Na/H antiporter in lumenal membrane at the late distal tubule and collecting duct --> decreased K+ secretion and distal tubule acid secretion, increased Ca++ absorption

Question 59

Use: Amiloride

Answer 59

Combination with other diuretics to prevent hypokalemia; edema, idiopathic hypercalciuria (stones); lithium-induced polyuria & toxicity, Liddle syndrome, mucocilliary clearance

Question 60

Use: Triamterene

Answer 60

Combination with other diuretics to prevent hypokalemia; | edema

Question 61

Side effects: Amiloride and Triamterene

Answer 61

Hyperkalemia in patients with renal failure or on ACE inhibitors

Question 62

Important side effect: Triamterene

Answer 62

Megaloblastic anemia in patients with liver cirrhosis

Question 63

Amiloride and Triamterene are contraindicated in what patient population?

Answer 63

Renal failure

Question 64

Spironolactone is contraindicated in what patient population?

Answer 64

Renal failure Contraindicated in patients with renal failure (hyperkalemia); FeNa = 2%; requires a salt-restricted diet; only drug not requiring tubular lumen access

Question 65

Use: Spironolactone

Answer 65

K+-sparing diuretic; aldosterone receptor antagonist Reduction in CHF mortality (30% in NYHA class III and IV); combination with other diuretics to prevent hypokalemia; edema; primary and secondary aldosteronism; hypertension; anti-testosterone agent

Question 66

MOA: Sprionolactone

Answer 66

Competes for aldosterone receptor, inhibiting mRNA transcription and translation --> decreased Na and K channels, decreased number and activity of Na-K-ATPase pumps in the late distal tubule and collecting duct --> decreased K+ secretion, distal tubule acid secretion

Question 67

Class: Conivaptan Tolvaptan

Answer 67

Aquaretic

Question 68

Use: Conivaptan Tolvaptan

Answer 68

Hyponatremia (SIADH, CHF)

Question 69

MOA: Conivaptan Tolvaptan

Answer 69

Vasopressin (ADH) receptor antagonist working at collecting duct --> increased free water excretion

Question 70

Aldosterone-dependent regulation of Na+ reabsorption occurs in the:

Answer 70

Aldosterone-dependent regulation of Na+ reabsorption occurs in the late distal tubule.

Question 71

T/F: the hypocalciuric effect of the thiazide and thiazide-like diuretics is greater than the hypocalciuric effect of amiloride

Answer 71

True

Question 72

Thiazide diuretics may be used to control the polyuria resulting from nephrogenic diabetes insipidus by an indirect effect on:

Answer 72

Glomerular filtration Thiazide diuretics may be used to control the polyuria resulting from nephrogenic diabetes insipidus by further decreasing the ECF volume which induces a decrease in GFR. Any reduction in GFR, when dehydrated, will decrease urine excretion.

Question 73

How does hydrochlorothiazide work?

Answer 73

Hydrochlorothiazide inhibits solute reabsorption in the diluting segment of the nephron which raises the osmolality of the tubular fluid and urine. This effect decreases the positive free water clearance in response to ECF volume expansion which puts the patient at risk for hyponatremia.