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

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Flashcards in Pharmacology Review of Renal Physiology & Diuretics - III and IV - Grassl Deck (73)
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1
Q

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

A

Aquaretics

2
Q

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

A

Saluretics

3
Q

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

A

Saluretics

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

4
Q

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

A

Aquaretic

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

5
Q

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

A

Aquaretic

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

6
Q

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

A

Aquaretic

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

7
Q

Use: Demeclocycline

A

Aquaretic

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

8
Q

Use: vaptan family of ADH receptot antagonists, ie Lixivaptan

A

Treat euvolemic hyponatremia

9
Q

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

A

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

10
Q

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

A

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

11
Q

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

A

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

12
Q

Where do thiazide diuretics exert their effects?

A

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

13
Q

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

A

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

14
Q

MOA: Potassium-sparing diuretics

A

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

15
Q

Which diuretics induce the smallest diuresis?

A

Potassium-sparing diuretics

16
Q

Which diuretics induce the largest diuresis?

A

Loop diuretics

17
Q

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

A

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

18
Q

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)

A

True

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

19
Q

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

A

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

20
Q

Class: Acetazolamide

A

Carbonic anhydrase inhibitor

Sulfonamide

21
Q

Class: Methazolamide

A

Carbonic anhydrase inhibitor

Sulfonamide

22
Q

Class: Dichlorphenamide

A

Carbonic anhydrase inhibitor

Sulfonamide

23
Q

Class: Hydrochlorothiazide

A

Thiazide

24
Q

Class: Dihydrochlorothiazide

A

Thiazide

25
Q

Class: Ethacrynic acid

A

High-ceiling diuretic

26
Q

Class: Furosemide

A

High-ceiling diuretic

27
Q

Class: Torsemide

A

High-ceiling diuretic

28
Q

Class: Bumetanide

A

Loop diuretic

29
Q

Class: Spironolactone

A

Potassium-sparing diuretic

30
Q

Class: Triamterene

A

Potassium-sparing diuretic

31
Q

Class: Amiloride

A

Potassium-sparing diuretic

32
Q

What diuretics are inhibitors of Na/Cl symport?

A

Thiazide diuretics

Act in the Early distal tubule

33
Q

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

A

Loop diuretics and high-ceiling diuretics

Act in loop of Henle

34
Q

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

A

Potassium-sparing diuretics

Act in the late distal tubule and collecting duct

35
Q

Main uses: carbonic anhydrase inhibitors

A

Decrease intraocular volume and pressure;

Prevention and treatment of acute mountain sickness

36
Q

Complications: Carbonic anhydrase inhibitors

A

Hypokalemia resulting from loss of potassium in the urine;

Toxicity can be caused by metabolic acidosis, bone marrow depression, skin toxicity, allergic reactions

37
Q

Use: Aminophylline

A

To prevent and relieve inflammation and bronchospasm in patients with asthma

38
Q

MOA: Aminophylline

A

Aminophylline = methylxanthine theophylline + ethylene diamine

Increases GFR;
Inhibits phosphodiesterase –> increases intracellular cAMP –> decreased sodium reabsorption in the proximal tubule

39
Q

What is osmotic diuresis?

A

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

40
Q

Class: Mannitol

A

Osmotic diuretic

41
Q

Use: Mannitol

A

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

42
Q

Risk: Mannitol

A

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

43
Q

MOA: Mannitol

A

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

44
Q

MOA:
Acetazolamide
Methazolamide
Dichlorphenamide

A

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

45
Q

Are carbonic anhydrase inhibitors contraindicated for some patients?

A

Yes, cirrhotics

46
Q
MOA:
Furosemide
Bumetanide
Torsemide
Ethacrynic acid
A

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

47
Q
Use: 
Furosemide
Bumetanide
Torsemide
Ethacrynic acid
A

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

48
Q
Side effects:
Furosemide
Bumetanide
Torsemide
Ethacrynic acid
A

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

49
Q

MOA:
Chlorothiazide
Hydrochlorothiazide

A

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

50
Q

Uses:
Chlorothiazide
Hydrochlorothiazide

A
Thiazide diuretics
HTN (intravascular contraction), 
chronic edema (cardiac insufficiency), 
idiopathic hypercalciuria (stones), 
nephrogenic diabetes insipidus
51
Q

Side Effects:
Chlorothiazide
Hydrochlorothiazide

A

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

52
Q
READ: Contraindications for thiazide AND thiazide like diuretics:
Chlorothiazide
Hydrochlorothiazide
Chlothalidone
Quinethazone
Metolazone
Indapamide
A

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

53
Q
Class:
Chlothalidone
Quinethazone
Metolazone
Indapamide
A

Thiazide-like diuretic

54
Q
MOA:
Chlothalidone
Quinethazone
Metolazone
Indapamide
A

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

55
Q
Use:
Chlothalidone
Quinethazone
Metolazone
Indapamide
A
Thiazide-like diuretic
HTN (intravascular contraction), 
chronic edema (cardiac insufficiency), 
idiopathic hypercalciuria (stones), 
nephrogenic diabetes insipidus
56
Q
Side Effects:
Chlothalidone
Quinethazone
Metolazone
Indapamide
A

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

57
Q

Class:
Amiloride
Triamterene

A

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

58
Q

MOA:
Amiloride
Triamterene

A

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

59
Q

Use: Amiloride

A

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

60
Q

Use: Triamterene

A

Combination with other diuretics to prevent hypokalemia;

edema

61
Q

Side effects: Amiloride and Triamterene

A

Hyperkalemia in patients with renal failure or on ACE inhibitors

62
Q

Important side effect: Triamterene

A

Megaloblastic anemia in patients with liver cirrhosis

63
Q

Amiloride and Triamterene are contraindicated in what patient population?

A

Renal failure

64
Q

Spironolactone is contraindicated in what patient population?

A

Renal failure

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

65
Q

Use: Spironolactone

A

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

66
Q

MOA: Sprionolactone

A

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

67
Q

Class:
Conivaptan
Tolvaptan

A

Aquaretic

68
Q

Use:
Conivaptan
Tolvaptan

A

Hyponatremia (SIADH, CHF)

69
Q

MOA:
Conivaptan
Tolvaptan

A

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

70
Q

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

A

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

71
Q

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

A

True

72
Q

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

A

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.

73
Q

How does hydrochlorothiazide work?

A

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.