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Pharmacology Block 2 > 11 Diuretics > Flashcards

11 Diuretics Flashcards

1
Q

Where is most sodium and chloride reabsorbed in the nephron?

A

Proximal Tubule

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2
Q

Function of proximal tubule

A

Reabsorption!

  • Na+ and Cl- (50-75%)
  • K+
  • HCO3- (80-90%)
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3
Q

On what part of the nephron is chloride actively reabsorbed?

A

Ascending Limb of Loop of Henle

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4
Q

On what part of the nephron is water impermeable?

A

Ascending Limb of Loop of Henle

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5
Q

Function of Ascending Limb of Loop of Henle

A
  • Na+ and Cl- reabsorbed (20-30%)
    • active chloride reabsorbed
  • impermeable to H2O: no reabsorption
  • compensates for inc Na+ delivery from proximal tubule by increasing reabsorption
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6
Q

On what part of the nephron is K+ secreted?

A

Distal Tubule and Collecting Duct

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7
Q

On what part of the nephron does regulation of Na+ and K+ exchange by aldosterone occur?

A

Distal Tubule and Collecting Duct

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8
Q

On what part of the nephron is water permeability regulated by ADH (Vasopressin)?

A

Distal Tubule and Collecting Duct

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9
Q

Function of Distal Tubule and Collecting Duct

A
  • Na+ reabsorbed (8-9%)
  • K+ secreted from blood to tubule lumen to urine
  • Aldosterone regulation of Na+/K+ exchange
  • Water permeability regulated by ADH
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10
Q

What drugs are renal vasodilators?

A

Dopamine
Fenoldapam
Atriopeptins

Work at glomerulus

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11
Q

Where do renal vasodilators such as dopamine, fenoldapam, and atriopeptins exert their action?

A

Glomerulus

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12
Q

What group of drugs selectively dilates the renal vasculature that modifies the proximal tubular function?

A

Renal Vasodilators: Dopamine, Fenoldapam, Atriopeptins

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13
Q

What group of drugs decrease filtration fraction?

A

Renal Vasodilators: Dopamine, Fenoldapam, Atriopeptins

Inc renal blood flow without changing GFR

FF = GFR / RBF

Dec FF reduces protein concentration and hydroosmotic forces in peritubular capillaries

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14
Q

Renal Vasodilator Characterisitcs

A

Dopamine, Fenoldapam, Atriopeptins

Mech:

  • inc RBF w/o reducing GFR, which dec FF, which reduces protein conc and hydroosmotic forces in the peritubular capillaries
  • Na+ and H2O leak back into tubule for excretion

Weak as diuretic due to compensatory Na+ reabsorption in distal nephron

Use:
- Limited clinically– hypertensive crisis and shock

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15
Q

What type of drug is mannitol?

A

Osmotic Diuretic

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16
Q

Where on the nephron does mannitol exert effect?

A

Whole nephron but mostly proximal tubule

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17
Q

What drug acts in the tubular lumen as a non-reabsorbable solute to increase urinary excretion of Na+, Cl+, K+, and H2O?

A

Mannitol

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18
Q

What is mannitol used for?

A

Edema
Glaucoma–reduce intraocular pressure
Acute renal failure

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19
Q

Characteristics of Mannitol

A
  • freely filtered at glomerulus
  • not reabsorbed by tubule
  • metabolically inert

Mech:
- act in tubular lumen as non-reabsorbable solute to limit reabsorption of water from tubule

  • urine volume and Na+ excretion proportional to osmotic load
  • increases urinary excretion of Na+, K+, Cl-, H2O, and mannitol

Tx:

  • edema
  • Glaucoma
  • Acute renal failure
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20
Q

What type of drug is acetazolamide?

A

Carbonic Anhydrase Inhibitor

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21
Q

What drug inhibits carbonic anhydrase in the proximal and distal tubule?

A

Acetazolamide–carbonic anhydrase inhibitor

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22
Q

What does acetazolamide do to the pH of urine?

A

Alkalinizes the urine

Prevents carbonic anhydrase from providing H+ ions to the lumen in exchange for Na+ for the reabsorption of HCO3-

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23
Q

What are the side effects of acetazolamide?

A

Metabolic acidosis

Hypokalemia

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24
Q

What drug can be used to alkalinize the urine (ex. to decrease drug toxicity)?

A

Acetazolamide

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25
Q

What drug can be used to treat mountain or altitude sickness?

A

Acetazolamide

26
Q

What can acetazolamide be used to treat?

A

Glaucoma
Akalinize the urine
Mountain or altitude sickness
Anticonvulsant

27
Q

Characteristics of Acetazolamide

A

Carbonic Anhydrase Inhibitor

  • weak diuretic
  • inhibited by acidosis (limited clinical use)

Mech:

  • filtered and secreted by OAT on tubular lumen
  • inhibit CA in proximal and distal tubule
      • CA provides H+ ions for bicarb reabsorption
  • increases excretion of Na+, K+, HCO3-, and H2O (less excretion of Cl-)

AEs:

  • metabolic acidosis (reduces renal response to drug)
  • hypokalemia

Tx:

  • glaucoma
  • alkaline the urine
  • mountain or altitude sickness
  • anticonvulsant
28
Q

What type of drugs are furosemide, bumetanide, and ethacrynic acid?

A

Loop Diuretics

29
Q

What drug inhibits the Na+/K+/2Cl- symporter?

A

Loop Diuretics: furosemide, bumetanide, ethacrynic acid

30
Q

Where on the nephron do furosemide, bumetanide, and ethacrynic acid exert action?

A

Cortical and medullary segments of ascending limb of Loop of Henle

31
Q

What are disadvantages to using loop diuretics such as furosemide, bumetanide, ethacrynic acid?

A 
Hypokalemia
Alkalosis
Hypovolemia
Hyperuricemia
Hyperglycemia (furosemide only)
Ototoxicity
32
Q

Characteristics of furosemide, bumetanide, and ethacrynic acid

A

Loop Diuretics

  • high efficacy (20-30% filtered Na+ load excreted)
  • rapid onset/short duration

Mech:

  • filtered and secreted by OAT
  • inhibits Na+/K+/2Cl- symporter
  • act on cortical and medullary segments of ascending limb of loop of Henle
  • increases excretion of Na+, K+, Cl-, and H2O (also Ca2+)
  • inc RBF and GFR
  • large urine volume

AEs:

  • hypokalemia
  • alkalosis
  • hypovolemia
  • hyperuricemia (inc urate reabsorption @PT)
  • hyperglycemia (furosemide only)
  • ototoxicity

Tx:

  • edema of cardiac, hepatic, or renal origin
  • acute pulmonary edema
  • hypertension
33
Q

What type of drugs are hydrochlorothiazide and metolazone?

A

Thiazide and Thiazide-like Diuretics

34
Q

Where do thiazide and thiazide-like diuretics exert action on the nephron?

A

Cortical segments of distal tubule

35
Q

What drugs inhibit the Na+/Cl- symporter?

A

Hydrochlorothiazide and Metolazone: Thiazide and Thiazide-like Diuretics

36
Q

What drug exerts effect on cortical segment of the distal tubule to create a hypertonic urine?

A

Hydrochlorothiazide and Metolazone: Thiazide and Thiazide-like Diuretics

37
Q

What are the disadvantages to using hydrochlorothiazide or metolazone?

A 
Hypokalemia
Alkalosis
Hyperuricemia
Hyperglycemia
Dec in GFR
38
Q

What can hydrochlorothiazide or metolazone be used to treat?

A

Edema due to CHF
Hypertension
Hypercalciuria

39
Q

Characteristics of Hydrochlorothiazide and Metolazone

A

Thiazide or Thiazide-like

  • intermediate efficacy (8-10% of filtered Na+ load excreted)
  • moderate onset/long duration

Mech:

  • filtered and secreted by OAT
  • inhibits Na+/Cl- symporter
  • acts on cortical segment of distal tubule
  • increases excretion of Na+, K+, Cl-, and H2O
  • urine is hypertonic
  • enhances urate reabsorption (PT)
  • dec renal Ca2+ excretion

AEs:

  • hypokalemia
  • alkalosis
  • hyperuricemia
  • hyperglycemia
  • dec in GFR

Tx:

  • edema due to CHF (chronic disease)
  • hypertension
  • hypercalciuria
40
Q

What is used for hypercalciuria?

A

Hydrochlorothiazide or Metolazone

41
Q

What are the 2 classes of K+ sparing diuretics?

A

Aldosterone Antagonists: Spironolactone, Eplerenone

Sodium Channel Inhibitors: Amiloride, Triamterene

42
Q

What drugs are Na+ channel inhibitors?

A

Amiloride and Triamterene

43
Q

What drugs are aldosterone antagonists?

A

Spirinolactone and Eplerenone

44
Q

What drugs can be used to increase Na+ excretion without K+ loss?

A

K+ sparing diuretics:

Aldosterone antagonists: Spirinolactone, Eplerenone

Sodium channel inhibitors: amiloride and triamterene

45
Q

Why are K+ sparking drugs used in combination with loop diuretics?

A

K+ sparing can cause hyperkalemia

Loop diuretics can result in hypokalemia

46
Q

Where on the nephron do K+ sparing diuretics exert its effect?

A

Distal tubule Cortical Collecting Duct

47
Q

Characteristics of Spironolactone and Eplerenone

A

K+ sparing: Aldosterone Antagonist

  • weak diuretic (2-3%)
  • act on distal tubule as competitive antagonist of aldosterone
  • urine volume inc
  • inc Na+ / dec K+ excretion

AEs:

  • hyperkalemia
  • gynecomastia (spirinolactone is weak progesterone agonist)

Uses:

  • hypertension
  • refractory edema
  • primary aldosteronism
  • use with thiazide or loop diuretic to enhance diuretic effect and reduce potassium loss
48
Q

Characteristics of amiloride and triamterene

A

K+ sparing: Na+ channel inhibitor

  • weak diuretic (2-3%)
  • inhibit entry of Na+ into principal cells (prevents Na+/K+ exchange on basolateral membrane)
  • urine volume inc
  • inc Na+/ dec K+ excretion

AEs:

  • hyperkalemia
  • mild azotemia (high Nitrogen levels)
  • Triamterene dec RBF and GFR (high dose)

Tx:

  • edema or hypertension
  • use with thiazide or loop diuretic to enhance diuretic effect and reduce potassium loss
49
Q

Which what drugs can mild azotemia (high levels of Nitrogen) occur?

A

Potassium sparing diuretic:

  • Sodium channel inhibitors: amiloride and triamterene
50
Q

What is often the cause of edema?

A

Edema is often secondary to cardiac or hepatic disease. Treat primary condition

51
Q

Which diuretic has greatest intrinsic activity?

A

loop > thiazides > potassium-sparing

52
Q

Which diuretic is cheapest to prescribe?

A

thiazides < loop < potassium sparing

53
Q

Which diuretic has a faster onset of action?

A

Loop > Thiazide

54
Q

Diuresis derives fluid from what fluid compartments first?

A

Intravascular Space Edematous tissue (ECF) Body compartments (peritoneal or pleural space)

55
Q

Which diuretic has the greatest ceiling effect? Diseased conditions that exhibit ceiling effect?

A

Loop > Thiazide > K+ sparing

Diminished nephron response in nephrotic syndrome, cirrhosis, and heart failure

Exceeding ceiling dose yields possible adverse effects

56
Q

What does K+ loss parallel? How can this be corrected? Is this fatal?

A
  • K+ loss parallels Na+ excretion
  • can inc intake of K+ supplements or dec output with K+ sparing diuretics
  • hyperkalemia = fatal; hypokalemia is rarely life-threatening
57
Q

Foundation of Diuretic Antihypertensive therapy

A

Reduce renal tubular Na+ and H2O reabsorption

  1. Lower BP
  2. Prevent Na+ and H2O retention and enhance BP lowering by other antihypertensive drugs

Drugs: hydrochlorothiazide, furosemide

58
Q

How do diuretics decrease BP?

A

=> Deceases vascular volume
=> Decreases venous return (preload)
=> Decreases Cardiac output
=> Decreases BP

Also relaxes arteriolar smooth muscle

59
Q

Diuretics in Chronic Heart Failure

A
  • inc salt and water excretion. reduce ECF volume and preload
  • reduce symptoms of CHF and improve exercise capacity

Furosemide and thiazides:

  • reduce symptoms of CHF
  • do not improve survival from CHF so used in combo with ACE inhibitors, etc.

Spironolactone and Eplerenone:

  • inhibit renal and cardiac effects of aldosterone
  • weak diuretics so small effect on salt and water excretion and CHF symptoms
  • act on heart to inhibit hypertrophy and fibrosis caused by aldosterone
  • proven to improve survival from CHF
60
Q

Drugs used in chronic heart failure target compensatory reflexes. What types of drugs are these?

A

Sympathetic nervous system:
- Beta blockers

Renin/angiotensin/aldosterone activation:

  • ACE inhibitors
  • ARBs
  • Spironolactone, Eplerenone
61
Q

What Starling Forces are imbalanced by disease that results in edema?

A

Edema = fluid entering interstitial space

Decreased oncotic pressure due to:

  • malabsorption
  • nephrotic syndrome
  • liver failure
  • malnutrition

Increased capillary hydrostatic pressure due to:

  • venous obstruction
  • cirrhosis
  • CHF
  • constriction/restriction
  • renal failure
  • pregnancy
62
Q

Foundation of diuretic edema therapy

A

Increase salt and water excretion by reducing renal tubular sodium and water reabsorption

  1. Reduce intravascular volume
  2. Reduce ECF and edema

Drugs: hydrochlorothiazide, furosemide

Pharmacology Block 2 (12 decks)

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