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Renal I > Pharmacology: Diuretics > Flashcards

Pharmacology: Diuretics Flashcards

1
Q

What are the 4 classes of natriuretic diuretics?

A
  1. Carbonic anydrase inhibitors
  2. Loop Diuretics
  3. Thiazide Diuretics
  4. K+ Sparing Diuretics
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2
Q

What are osmotic diuretics?

A

Aquaretics

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3
Q

Where do carbonic anydrase inhibitors act?

A

Proximal tubule

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4
Q

Where do osmotic diuretics act?

A

Proximal tubule and thin descending limb of henle

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5
Q

Where do loop diuretics act?

A

Thick ascending limb of henle

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6
Q

Where to thiazide diuretics act?

A

Distal convoluted tubule

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7
Q

Wherre do K sparing diuretics act?

A

Collecting duct

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8
Q

What is acetazolamide?

A

Carbonic anhydrase inhibitor

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9
Q

What type of transporters excrete acetazolamide and where?

A

Organic acid transporters

S2 segment of the proximal tubule

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10
Q

What does acetazolamide inhibit?

A

Lumenal and intracellular carbonic anhydrases

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11
Q

What is the efficacy of acetazolamide and why?

A

It has limited efficacy (2-3 days) because of bicarb depletion and eventual increased reabsorption distal to the proximal tubule

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12
Q

What are the 6 features cellularly associated with acetazolamide?

A
  1. Bicarbonaturia
  2. Natriuresis
  3. Diuresis
  4. Metabolic acidosis
  5. Hyperchloremia
  6. Hypokalemia
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13
Q

What are the 5 adverse effects of acetazolamide?

A
  1. Hyperchloremic metabolic acidosis
  2. Hypokalemia
  3. Alkalinization of urine
  4. Allergic reactions
  5. Paresthesia, nervous system toxicity
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14
Q

What causes hypokalemia associated with acetazolamide?

A

The upregulation of Na reabsorption (and thus K excretion) in the distal convoluted tubules

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15
Q

With acetazolamide, the AE of urine alkalinization can lead to what 2 things?

A
  1. Calcium stone pecipitation

2. Hyperammonemia

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16
Q

What can hperammonemia lead to in patients with cirrhosis?

A

Hepatic encephalopathy (AKA be careful giving acetazolamide to patients with cirrhosis)

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17
Q

What component of acetazolamide can cause allergic reactions?

A

The sulfonamide moiety

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18
Q

What are the 4 clinical indications for acetazolamide?

A
  1. Glaucoma
  2. Prophylactic for altitude sickness
  3. Urinary alkalinaztion
  4. Metabolic alkalosis
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19
Q

Why is acetazolamide used in glaucoma?

A

It reduces aqueous humor formation

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20
Q

How does acetazolamide work to reduce altitude sickness?

A

It reduces CSF formation and decreases pH of CSF and brain, which leads to increased ventilation and reduced ICP at high altitudes

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21
Q

What is the osmotic diuretic we discussed?

A

Mannitol

22
Q

When referring to the primary mechanism of action for mannitol, how is the drug given?

A

IV, it is poorly absorbed by GI and not metabolized

23
Q

What are the 4 actions mannitol has orimarily?

A
  1. Increases extracellular osmolarity
  2. Expands ECF volume
  3. Decreases renin release
  4. Increases renal blood flow
24
Q

Is renal medullary tonicity increased or reduced due to the primary effects of mannitol?

A

Reduced

25
Q

What does mannitol do primarily in the thin descending limb of Henle and what is the result of this?

A

It reduces the gradient for water reabsorption and reduces NaCl concentration

26
Q

Because of the effect that mannitol has of reducing NaCl concentration in the thin descending limb of Henle, what happens in the thick ascending limb of henle?

A

The thick ascending limb detects less NaCl and feeds back to inhibit proximal tubular reabsorption of Na

27
Q

If the proximal tubular reabsorption of Na is blocked by mannitol, what else is a consequence of this?

A

The loss of ability to reabsorb water in the proximal tubule

28
Q

When referring to the secondary MOA of mannitol, what route is the drug given by?

A

IV, because it is poorly absorbed by GI and not metabolized and freely filtered

29
Q

What are the 2 features of the secondary MOA of mannitol?

A
  1. Increases lumenal osmolality in the proximal tubule and descending limb of Henle
  2. Reduce water reabsorption in the proximal tubule and thin descending limb of Henle
30
Q

What is the major AE of mannitol?

A

Extracellular volume expansion…results in hyponatremia

31
Q

What can result if you don’t give water replacement for patients taking mannitol?

A

Dehydration, hyperkalemia, and hypernatremia

32
Q

What are the clinical indications for mannitol?

A
  1. Reduce ICP in neurologic conditions
  2. Reduce intraocular pressure before opthalmologic surgery
  3. Increase urine volume
33
Q

What are the 3 ADH antagonists we discussed?

A
  1. Conivaptan
  2. Tolvaptan
  3. Demeclocycline
34
Q

Where do ADH antagonists act?

A

In the collecting ducts

35
Q

What type of ADH receptors to conivaptan and tolvaptan act at?

A

V2 receptors

36
Q

How is conivaptan given?

A

IV

37
Q

Is tolvaptan given IV?

A

No, tolvaptan is orally bioavailable

38
Q

Which V2 receptor antagonist is selective for V2?

A

Tolvaptan

39
Q

What other receptor can conivaptan bind besides V2?

A

V1a

40
Q

What is the adverse effect of V2 receptor antagonists?

A

Nephrogenic diabetes insipidus

41
Q

What are the clinical indications for V2 receptor antagonists?

A

Hyponatremia associated with syndrome of inappropriate ADH secretion (SIADH)

42
Q

What is demeclocycline?

A

A post-receptor ADH antagonist

43
Q

How is demeclocycline given?

A

It is orally bioavailable

44
Q

How does demeclocycline

A

It blocks the insertion of aquaporin 2 into the collecting duct by an unknown mechanism

45
Q

What is the propsed mechanism of how demeclocycline blocks insertion of AQP-2 into the collecting duct?

A

Interferes with adenylate cyclase bloccking the formation of cAMP

46
Q

What adverse effects are associated the demeclocycline?

A
  1. Nephrogenic diabetes insipidus

2. Acute renal failure

47
Q

What are the clinical indications for demeclocycline?

A

Persistent chronic SIADH

48
Q

How do osmotic diuretics initially work?

A

They expand extracelular fluid volume

49
Q

What can the expansion of extracellular fluid volume due to osmotic diuretics result in?

A

Exacerbation of heart failure

-Osmotic diuretics are contraindicated in patients with heart failure

50
Q

What other condition do you have to be careful with in giving osmotic diuretics to due to the inability to handle the expansion of extracellular fluid volume?

A

Impaired renal function

Renal I (8 decks)

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