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Pharmacology II > Diuretic > Flashcards

Diuretic Flashcards

1
Q

Name a carbonic anhydrase inhibitor

A

acetazolamide

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2
Q

Name an osmotic diuretic

A

mannitol

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3
Q

Name a “loop” diuretic

A

Furosemide

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4
Q

Name a Thiazide and Thiazide-like diuretic

inhibit Na/Cl transport

A

Hydrochlorothiazide

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5
Q

Name a “K sparing” diuretic

ENAC inhibitor

A

amiloride

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6
Q

Name an aldosterone/”K sparin” diuretic

mieralocorticoid antagonist

A

spironolactone

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7
Q

Name an ADH antagonist

A

Tolvaptan

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8
Q

What does it mean to have “diuretic braking?”

A

Diuretics cause temporal increase in excretion of Na+ and H2O.

Compensatory mechanisms then diminish excretion, so that excretion is again equal with sodium and water intake

**new steady state is thus achieved when **

in = out

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9
Q

How does diuretic braking occur?

A

body adapts to diuretic effects

↑ sympathetic activity

↑ RAA system activity

↑ ADH

During diuretic use, a new steady state is reached at a lower fluid volume

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10
Q

Where do the diuretics work on the nephron?

A
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11
Q

What is the MOA of carbonic anhydrase inhibitors?

A

Acetazolamide is secreted into proximal tubule by the anion transporter, therefore less Na and H2O reabsorbed.

HCO3 trapped in lumen increases negative charge: Na+ and K+ are attracted, Cl- is repelled from lumen

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12
Q

What are the results of the carbonic anhydrase inhibitors?

A

Creates:

Alkaline urine (pH 8)

TGF: GFR & RBF ↓ due to ↑ solutes to macula densa

Cl- secretion is ↓ due to ↑ of negatively charged HCO3- in CD lumen that repels Cl- but attracts Na+ & K+ as well as ↓ activity of basolateral HCO3/Cl exchanger
Plasma - ↓HCO3-, ↓K+, ↑Cl-, ↑H+

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13
Q

What are the sites of action of carbonic anhydrase inhibitors?

A

PT (secondary site = CD intercalated cells); eye
(aqueous humor), RBC and gastric mucosa.

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14
Q

What are adverse reactions from carbonic anhydrase inhibitors?

A
  • *Hyperchloremic metabolic acidosis**
  • *Renal stones** – calcium salts are less soluble at alkaline pH

Cross-hypersensitivity with other sulfonamides

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15
Q

Loop diuretic MOA?

A

*INHIBIT Na/K/2Cl SYMPORTER

therefore abolishes medullary osmotic gradient

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16
Q

What is the main effect on urine by loop diuretics?

A

increased excretion of all ions: Na+, Cl-, K+, H+, Mg2+, Ca2+, as well as HCO3- in case of furosemide

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17
Q

What are the main adverse effects of loop diuretics?

A
  • hypochloremic alkalosis and hypokalemia
  • hypotension
  • ototoxicity (ethacrynic acid)
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18
Q

Where do thiazide diuretics work in the nephron?

A

INHIBITORS OF NA/CL SYMPORTERS

in the DCT

*do NOT abolish the medullary gradient

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19
Q

What is the main effect on urine by thiazide diuretics?

A
  • ↑ Na+, Cl- and K+, ↓ excretion of
    Ca2+

calcium-sparing

20
Q

What are major adverse effects of hydrochlorothiazide?

List 5 hyper and 1 hypo

A

*hypokalemic metabolic alkalosis
hypercalcemia

hyperuricemia

*hyperglycemia- in patients with diabetes or abnormal glucose tolerance tests.

hyperlipidemia

hypersensitivity reaction when allergic to sulfonamides

21
Q

Where do K sparing diuretics work?

A

DCT and CD

22
Q

What is the MOA of amiloride?

A

Block Na+ channels. Effects are independent of the
presence of aldosterone.

23
Q

What is the main effect of amiloride and spironolactone on urine?

A

Decrease excretion of K+

24
Q

What is the MOA of spironolactone?

A

Canrenone, the active metabolite of spironolactone, forms
an inactive receptor complex, blocking the action of aldosterone**. W/o circulating aldosterone, spironolactone has no effect. **

25
Q

What are the main adverse effects of spironolactone?

A

hyperkalemia - *Contraindicated in chronic renal insufficiency

gynecomastia

26
Q

How does mannitol work?

A
27
Q

What are the main effects of mannitol on urine and plasma?

A

Urine - Mg++↑

Plasma – Acute phase: mannitol draws fluid into vasculature -> hyponatremia.
Later, hypernatremia, since relatively more water is excreted

28
Q

What are the effects of mannitol with chronic use?

A

Chronic: dehydration, hypernatremia, hyperkalemia

(when cells shrink, their K+ ↑, which favors passive K+ exit to plasma)

29
Q

Which diuretic induces
cytochrome P-450?

A

spironolactone

30
Q

Which diuretic is metabolized by CYP3A4?

A

tolvaptan

31
Q

Major diuretic effects

A
32
Q

Which drug is characterized by

Loss of plasma bicarb, alkaline urine, hyperchloremic
acidosis, TGF, mountain sickness

A

CAIs

33
Q

Which drug is characterized by

Powerful diuretics, loss of all ions, ototoxicity,
hyperuremia, loss of osmotic gradient, RBF up

A

loop diuretics

34
Q

Which drug is characterized by

Calcium sparing, alkalosis, hypokalemia, hyperuremia,
synergize with loops, antidiuretics in Diabetes insipidus

A

Thiazide diuretics

35
Q

Which drug is characterized by

K(and other cations) sparing, work in absence of
aldosterone, triamterene can cause stones

A 
Na Ch (ENaC)
Blockers
36
Q

Which drug is characterized by

K(and other cations) sparing, work only in presence of
aldosterone, gynecomastia, p450 induction

A

Aldosterone antagonists

37
Q

Which drug is characterized by

increase in RBF, indiscriminate loss of ions and water,
acute hyponatremia, followed by hypernatremia

A

osmotic diuretics

38
Q

Sites of action of diuretics

A
39
Q

True/false: Giving a loop (Na/K/2Cl at TALH, 25%) + thiazide (Na/Cl at DCT, 4%) together blocks two major sites of sodium reabsorption = synergistic effects

A

true

40
Q

What is the main determinant of extracellular fluid volume?

A

Total body NaCl

41
Q

What is the MOA of most diuretics?

A

Most are aimed at decreasing** extracellular fluid volume by **decreasing total body NaCl

42
Q

Why does altering sodium excretion change H2O excretion?

A

water follows Na

43
Q

Which diuretic abolishes the corticomedullary osmotic gradient?

A

Loop diuretics

*vs. thiazide diuretics DO NOT

44
Q

Which diuretic does not require a transporter and crosses the basolateral membrane to bind with a mineralocorticoid receptor?

A

Aldosterone

45
Q

What drug does not use a transporter and works on the aquaporins on the basolateral membrane?

A

tolvaptan

Pharmacology II (7 decks)

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