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Pharmacology 2 > Diuretics > Flashcards

Diuretics Flashcards

0
Q

What is the definition of a diuretic?

How do they do this?

A
  • Drugs that increase the rate of urine flow.

- Increase the rate of sodium excretion usually as sodium chloride.

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1
Q

What are 7 classifications of diuretics?

A
  • Osmotic diuretics
  • Loop or high ceiling diuretics
  • Thiazide diuretics
  • Potassium-sparing diuretics
  • Carbonic anhydrase inhibitors
  • Cardiovascular diuretics
  • Physiological diuretics
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2
Q

What are examples of cardiovascular diuretics?

A
  • Digitalis (digoxin)

- Phosphodiesterase Inhibitors: Aminophylline, Inamrinone , Milrinone

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3
Q

What is the therapeutic use of cardiovascular diuretics?

A

Treatment of edema associated with congestive heart failure.

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4
Q

Water as a physiological diuretic is used for what?

A

Used in compensated chronic interstitial nephritis of dogs.

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5
Q

Sodium chloride as a physiological diuretic is used for what?

A

Used in urolithiasis in sheep, calves and cats.

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6
Q

Name 4 examples of osmotic diuretics.

A
  • Mannitol
  • Urea
  • Glycerin
  • Isosorbide
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7
Q

Where do osmotic diuretics act in the nephron?

A

Proximal convoluted tubule and thick ascending loop of henle

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8
Q

What is the mechanism of action for osmotic diuretics?

Where do they act?

A
  • May interfere with transport mechanisms in the thick ascending limb increasing the urinary excretion of NA+, K+, Ca2+, Mg2+, Cl-, HCO3- and phosphate.
  • Act in both the thick ascending loop of Henle (primary site) and proximal convoluted tubule (secondary site).
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9
Q

Do osmotic diuretics increase renal blood flow and renal medullary blood flow?

A

Yes

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10
Q

Do osmotic diuretics increase or reduce medullary tonicity?

How do they do this?

A
  • Reduce

- By an osmotic effect in the tubule.

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11
Q

What are 5 therapeutic uses of osmotic diuretics?

A
  • Treatment of cerebral edema
  • Treatment of glaucoma
  • Treatment of acute renal failure
  • Mobilization of edema fluid
  • Used in patients with drug overdose
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12
Q

How are urea and Mannitol administered?

A

IV

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13
Q

How are glycerin and isosorbide administered?

A

Orally

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14
Q

Is Mannitol metabolized?

How is it eliminated?

A
  • No

- Rapidly by the kidney

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15
Q

What are 3 examples of Loop or High Ceiling diuretics?

A
  • Furosemide
  • Bumetanide
  • Ethacrynic acid
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16
Q

What is the mechanism of action of loop or high ceiling diuretics?

A
  • Inhibit Na2+/K+/2Cl- symporter at the luminal membrane in teh thick ascending loop of Henle.
  • This also results in inhibiting paracellular reabsorption of Na+, Ca2+, Mg2+.
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17
Q

You don’t use mannitol with what condition?

A

Generalized edema

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18
Q

Which are the most effective diuretics?

Why?

A
  • Loop diuretics

- Approximately 25% of the filtered Na+ is reabsorbed in the thick ascending loop.

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19
Q

With loop or high ceiling diuretics, increasing Na+ delivery to the late distal tubule and collecting duct has what effect?

A

Increases depolarization of the luminal membrane creating a lumen-negative transmembrane potential difference.

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20
Q

Can you see allergies with loop or high ceiling diuretics?

Is there cross-hypersensitivity among the different drugs in this category?

A
  • Yes

- Yes

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21
Q

What is the result of loop or high ceiling diuretics facilitating K+ excretion through K+ channels in the luminal membrane of the principal cells and H+ secretion in type A intercalated cells into the lumen?

A

Hypokalemia and systemic alkalosis

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22
Q

What also contributes to hypokalemia and systemic alkalosis that can be seen with loop or high ceiling diuretics?

A

Stimulating the renin-angiotensin-aldosterone system.

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23
Q

Do loop or high ceiling diuretics increase or decrease total renal blood flow?
What might this mechanism involve?

A
  • Increase

- Prostaglandins

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24
Q

Do loop or high ceiling diuretics increase or decrease systemic venous capacitance?
This may be mediated by what?

A
  • Increase

- Prostaglandins

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25
Q

What are 3 therapeutic uses of loop or high ceiling diuretics?

A
  • Treatment of acute pulmonary edema and pulmonary congestion.
  • Treatment of generalized edema associated with congestive heart failure, chronic renal failure and liver cirrhosis.
  • Combined with isotonic saline to treat hypercalcemia and to prevent volume depletion.
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26
Q

Loop or high ceiling diuretics may be useful in treating what condition?

A

Acute renal failure

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27
Q

What can be used to treat intracranial pressure and udder edema?

A

Loop or high ceiling diuretics

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28
Q

What is used for the treatment of exercise-induced pulmonary hemorrhage in horses?
What type of a diuretic is this?

A
  • Furosemide

- Loop or high ceiling diuretic

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29
Q

Can loop and high ceiling diuretics be used in patients with drug overdose?

A

Yes

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30
Q

What do you combine loop or high ceiling diuretics with for the treatment of life-threatening hyponatremia?
Why?

A
  • Hypertonic saline

- Loop diuretics inhibit the kidney from producing concentrated urine.

31
Q

What can you use to treat edema of nephrotic syndrome which is usually refractory to other diuretics?

A

Loop or high ceiling diuretics

32
Q

What are 5 adverse effects of loop or high ceiling diuretics?

A
  • Ototoxicity
  • Hypokalemia
  • Hypomagnesemia
  • Acute Hypovolemia
  • Hypotension
33
Q

What are 5 more adverse effects of loop or high ceiling diuretics?

A
  • Cardiac arrhythmias
  • Hyperglycemia
  • Hyperuricemia
  • Systemic alkalosis
  • Hypersensitivity reactions in patients allergic to sulfonamides
34
Q

How is furosemide administered?

A

Oral and IV

35
Q

T/F: With furosemide, onset of action is rapid and duration of action is long.

A

False - onset of action is rapid, but duration of action is short.

36
Q

How is furosemide metabolized?
How is it excreted?
How is it secreted?

A
  • Partially by conjugation.
  • Partially unchanged in urine.
  • Actively secreted in urine by the organic acid secretory mechanism.
37
Q

What are 2 examples of Thiazide diuretics?

A

Hydrochlorothiazide and chlorothiazide

38
Q

What is the mechanism of action of thiazide diuretics?

A
  • Inhibit Na+/Cl- symporter in the distal convoluted tubule resulting in inhibition of tubular reabsorption of Na+, Cl- and diuresis.
  • Diuretic efficacy is moderate because 5% of Na+ occurs in the early distal tubule.
  • Also inhibit K+ and Mg2+ reabsorption but increase reabsorption of Ca2+.
39
Q

What are 2 adverse effects of thiazide diuretics?

A
  • Hypokalemia

- Systemic alkalosis

40
Q

What are 3 therapeutic uses of thiazide diuretics?

A
  • Treatment of edema of CHF, liver cirrhosis, nephrotic syndrome and acute glomerular nephritis.
  • Treatment of hypertension alone or combined with other antihypersensitive drugs.
  • Treatment of nephrogenic diabetes insipidus and useful in central diabetes insipidus.
41
Q

What are 2 other uses of thiazide diuretics?

A
  • Treatment of calcium nephrolithiasis and may be useful for the treatment of osteoporosis.
  • Treatment of udder edema of cows.
42
Q

What are 3 adverse effects of thiazide diuretics?

A
  • Electrolyte imbalances (hyponatremia, kypokalemia, hypomagnesemia) are less than with loop diuretics.
  • Hyperglycemia
  • Hypersensitivity reactions in patients allergic to sulfonamides.
43
Q

How are thiazide diuretics administered?

A

Oral

44
Q

T/F: Thiazide absorption is slow and incomplete.

A

True

45
Q

Do thiazide diuretics bind to plasma proteins?

A

Yes, extensively.

46
Q

How are thiazide diuretics excreted?

How are they secreted?

A
  • Mainly by the kidneys.

- Actively secreted in urine by the organic acid secretory mechanism.

47
Q

What effect does decreased renal blood flow have on thiazide diuretics?

A

Decreases their effectiveness.

48
Q

What are 3 examples of potassium-sparing diuretics?

A
  • Spironolactone
  • Triamterene
  • Amiloride
49
Q

What is the mechanism of action of spironolactone?

A
  • Competitively blocks aldosterone binding to aldosterone-receptor in the late distal tubule and collecting duct.
  • This results in excretion of NaCl and diuresis as well as retention of K+ and H+.
50
Q

Aldosterone receptors are also called what?

A

Mineralocorticoid receptor (MR)

51
Q

What does the diuretic efficacy of spironolactone depend on?

A

The levels of endogenous aldosterone.

52
Q

Why is the diuretic efficacy of spironolactone mild?

A

Only 2% of Na+ reabsorption occurs in the late distal tubule and collecting duct.

53
Q

What are 2 therapeutic uses of spironolactone?

A
  • Diuretic

- Treatment of primary and secondary hyperaldosteronism.

54
Q

What are 3 adverse effects of spironolactone?

A
  • Hyperkalemia
  • Systemic acidosis
  • Adverse effects on reproduction because it acts on progesterone and androgen receptors.
55
Q

How is spironolactone administered?

A

Oral

56
Q

T/F: Spironolactone is slowly absorbed and highly bound to plasma proteins.

A

False - Readily absorbed and highly bound to plasma proteins.

57
Q

How is spironolactone metabolized?

A

Extensively by the liver and is converted to an active metabolite.

58
Q

Is the onset of action for spironolactone slow or fast?

How long does it take?

A
  • Slow

- 2 to 3 days

59
Q

Is the duration of action for spironolactone short or long?

A

Long

60
Q

What is the mechanism of action for triamterene and amiloride?

A
  • Block epithelial Na+ channels in the luminal membrane of the principal cells in the late distal tubule and collecting duct.
  • This results in excretion of Na+ and diuresis as well as retention of K+ and H+.
61
Q

Is the diuretic effect of triamterene and amiloride strong or mild?

A

Mild

62
Q

What are 2 therapeutic uses for triamterene and amiloride?

A
  • Treatment of hypokalemia and hypomagnesemia.

- Occasionally used in edematous disorders and hypertension.

63
Q

What are 2 adverse effects of triamterene and amiloride?

A
  • Hyperkalemia

- Systemic acidosis

64
Q

How are triamterene and amiloride administered?

A

Orally

65
Q

How is amiloride excreted?

A

By the kidneys.

66
Q

How does triamterene leave the body?

A

Converted to an active metabolite in the liver which is actively secreted in urine.

67
Q

What are 4 examples of carbonic anhydrase inhibitors (CAIs)?

A
  • Acetazolamide
  • Methazolamide
  • Dorzolamide and brinzolamide (ophthalmic)
68
Q

What is the mechanism of action for carbonic anhydrase inhibitors?

A
  • Reversible inhibition of carbonic anhydrase which inhibits the exchange of hydrogen for sodium in the proximal tubule which is the primary site.
  • Secondary site of carbonic anhydrase is the collecting duct.
  • Carbonic anhydrase inhibitors lower intraocular pressure (IOP) by inhibition of carbonic anhydrase in the eye decreasing formation of aqueous humor.
69
Q

What are 2 therapeutic uses of carbonic anhydrase inhibitors?

A
  • Treatment of open-angle glaucoma.

- Acetazolamide has been used in udder edema.

70
Q

What are 7 adverse effects of carbonic anhydrase inhibitors?

A
  • Mild systemic acidosis
  • Hypokalemia
  • Hyperglycemia
  • Signs in dogs (vomiting, diarrhea, hyperventilation)
  • Polyuria and polydipsia
  • Pruritus of paws
71
Q

How is acetazolamide administered?

A

Orally

72
Q

What is the onset of action and duration of action for carbonic anhydrase inhibitors?

A

Onset of action - about 30 mins; Duration of action - 4 to 6 hours in small animals

73
Q

How is acetazolamide eliminated?

How is it secreted?

A
  • Mainly by the kidneys.

- Actively in urine by the organic acid secretory mechanism.

74
Q

How are Dorzolamide and Brinzolamide administered?

A

Topically on the eye.

Pharmacology 2 (10 decks)

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