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Pharmacology > Diuretics > Flashcards

Diuretics Flashcards

1
Q

Most diuretics exert effects at ___ of renal tubule cells

A

luminal (urine) surface

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2
Q

Mechanisms of actions for diuretics include

A
  1. Interactions with membrane transport proteins–(thiazides, furosemide, triamterene)
  2. Interactions with enzymes– (acetazolamide) or hormone receptors– (spironolactone)
  3. Osmotic effects preventing water reabsorption– (mannitol)
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3
Q

___ is the major extracellular cation and its movement is controlled by ___

A

Na+

regulated activated transport via Na-K ATPase

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4
Q

how do diuretics affect Na+

A

decrease Na+ reabsorption at various sites in the nephron

*increased amounts of Na+ (and other ions) enter urine with H2O passively to maintain osmotic equilibrium

***THEY DO NOT INHIBIT NA/K ATPase!!!!

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5
Q

What are the diuretics of choice to treat hypercalcemia

A

saline infusion +/- loop diuretics

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6
Q

The most
useful diuretic agent in the treatment of recurrent
calcium stones (hypercalcuria) is

A

hydrocholorthiazide

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7
Q

What are the diuretics of choice to treat Edema from HF

A

loop of henle agents

osmotic agents-mannitol, ADH antagonists

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8
Q

What are the diuretics of choice to treat HTN

A

thiazides

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9
Q

What are the diuretics of choice to treat refractory edema

A

loop + thiazide

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10
Q

What are the diuretics of choice to treat alkalosis

A

Carbonic anhydrase inhibitors (acetazolamide)

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11
Q

What diuretics can have a side effect of causing arrhythmias

A
  1. loop of henle agents
  2. thiazides
  3. loop + thiazides
    (–1-3 decrease K+)
  4. aldosteron antagonists and Na channel blockers (increase K+
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12
Q

What diuretics have a side effect of causing gout?

A
  1. loop of henle agents
  2. thiazides

*increase uric acid

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13
Q

What diuretics can cause high K+

A

Aldosterone antagonist (spironolactone)

**K+ sparing

(lisinopril can also cause high K+)

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14
Q

what is reabsorbed in the proximal convoluted tubule

A

Almost all of

  1. glucose,
  2. amino acids,
  3. NaHCO3, and
  4. other metabolites are reabsorbed here.
  5. 60-70% of Na+ reabsorbed
  6. (Cl- and H2O follow passively)
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15
Q

Where/how do Carbonic anhydrase inhibitors work?

A

inhibit carbonic anhydrase (CA) enzyme in the proximal convoluted tubule, which results in retention of HCO3- in urine (Lumen) with mild alkaline diuresis

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16
Q

What kind of diuresis do carbonic anhydrase inhibitors create?

A

alkaline diuresis (retained HCO3- in urine)

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17
Q

What diuretics are carbonic anhydrase inhibitors

A

“-amides”

  1. Acetazolamide
  2. Dorzolamide*
  3. Brinzolamide*

*available topically to avoid systemic complications

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18
Q

What are the clinical uses of carbonic anhydrase inhibitors

A
  1. chronic management of open angel glaucoma (decrease aqueous humor production and IOP)
  2. urinary alkalinization
  3. chronic metabolic alkalosis
  4. acute mountain sickness

*infrequent use as a diuretic agent (NOT USED IN HF!!)

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19
Q

What diuretic inhibits formation of aqueous humor and CSF that is dependent on HCO3- transport?

A

carbonic anhydrase inhibitors

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20
Q

What diuretics are commonly used for chronic open angel glaucoma

A
  1. Dorzolamide
  2. Brinzolamide

*available topically to avoid systemic complications

(carbonic anhydrase inhibitors)

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21
Q

how do CA inhibitors tx acute mountain sickness

A

slows progression of pulmonary or cerebral edema (via decrease in formation of CSF and pH of CSF)

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22
Q

What are adverse drug reactions of CA inhibitors

A

Minor

  1. loss of appetite
  2. drowsiness
  3. confusion
  4. tingling in extremities
  5. hypersensitivity rxns
  6. hyperchloremic metabolic acidosis
  7. renal stones (via increase in urinary pH)
  8. K+ wasting
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23
Q

What are the loop diuretics

A
  1. Furosimide
  2. Bumetanide
  3. Torsemide
  4. ethacrynic Acid
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24
Q

What are osmotic diuretics

A

Mannitol

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25
Q

Where/How do osmotic diuretics work?

A

diuretic osmotic action limits H20 reabsorption renal segments permeable to water:

  1. Proximal tubule
  2.   Descending loop of Henle 3.  Collecting tubule

**Does not affect Na+ reabsorption

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26
Q

Describe the transport of ions and water in the loop of henle (descending and ascending limbs)

A
  1. Descending limb: water removal as a result of hypertonic osmotic forces (HCO3-, glucose, osmotic diuretics)
  2. Ascending limb: impermeable to H20, but active NaCl reabsorption via Na/K/2Cl cotransport
  3. leads to excessive intracellular K+ which then diffuses back into urine which drives the reabsorption of Mg2+ and Ca2+ back into the blood
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27
Q

Where/how do loop diuretics work?

A

inhibit NaCl transport (Na/K/2Cl transporter) in the thick ascending loop

  • this increase Mg and Ca excretion and
  • increased renal blood flow via RA and prostaglandin system
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28
Q

What effect to loop diuretics have on electrolytes?

A

Decrease K+, H+, Ca2+, Mg2+

increase: uric acid

29
Q

a decrease in Na+ reabsorption at the thick ascending loop by loop diuretics means more Na+ at collect tubule, ultimately this results in _____

A

more K+ and H+ loss –> hypokalemic metabolic alkalosis

30
Q

What effect to CA inhibitor diuretics have on electrolytes?

A

decrease: K+ (a little), and HCO3- (A LOT)

31
Q

what diuretic works extremely fast with IV

A

furosemide

32
Q

What loop diuretics have the following duration of effects:
2-3 hrs:
4-6 hrs:
6 hrs:

A

2-3 hrs: furosemide
4-6 hrs: torsemide
6 hrs: bumetanide

33
Q

What are the uses of loop diuretics

A
  1. CHF** (enhanced w/ salt restriction, less than 2g/day)
  2. acute pulmonary edema
  3. refractory edema
  4. hypercalcemia
34
Q

Patients with HF have reduced diuretic response (ie. to loop diuretics) related to:

A
  1. decreased drug delivery to kidney due to
  2. decreased RBF and
  3. hypoperfusion activation of RAAS and SNS
35
Q

What is the preferred diuretic class because of greater efficacy

A

loop diuretics

36
Q

how do loop diuretics help treat acute pulmonary edema

A
  1. rapid reduction in ECF and venous return

2. hemodynamic response via decrease in RV output and pulmonary vascular pressure

37
Q

what diuretic is used for refractory edema. Used if no response to Na+ restriction or thiazide diuretic - especially useful if renal disease and fluid overload present.

A

loop diuretic

38
Q

Why are loop diuretics given with a saline infusion when treating hypercalcemia?

A

to prevent ECF volume depletion

39
Q

describe the use of low vs high ceiling diuretics

A

High-ceiling (loop): higher dose for severe CHF and oliguria

low-ceiling (low dose thiazides): lower dose for HTN and mild CHF

40
Q

What are adverse reactions of loop diuretics

A
  1. hypokalemic metabolic alkalosis (due to increased K+ and H+ loss)
  2. hyperuricemia– may precipitate a gout attack
  3. hypomagnesemia
  4. hypocalcemia
  5. Ototoxicity (ethacrynic acid)
  6. OD- rapid blood volume depletion- dizziness, HA, orthostatic hypotension
41
Q

there is a higher incidence for ototoxicity with ethacrynic acid (loop diuretic) with:

A

diminished renal fxn and concomitant aminoglycoside (AG) Abx

42
Q

hypokalemic metabolic alkalosis (often seen with loop diuretics) predisposes a patient to

A
  1. ectopic pacemakers and arrhythmias
  2. weakness
  3. paretheasias
43
Q

describe the transport of ions and water in the distal convoluted tubule

A
  1. relatively impermeable to H20
  2. NaCl reabsorption via Na/Cl cotransporter
  3. active Ca2_ reabsorption via Na/Ca exchanger (regulated by PTH)
44
Q

Where/how do thiazide diuretics work?

A

inhibits NaCl cotransporter in the distal convoluted tubule which increases urinary excretion of NaCl
*INCREASE reabsorption of Ca2+ (unlike loop diuretics which decrease it)

45
Q

a decrease in Na+ reabsorption at the distal convoluted tubule with thiazide diuretics means more Na+ at collect tubule, ultimately this results in _____

A

more K+ and H+ loss –> hypokalemic metabolic alkalosis

46
Q

What are thiazide diuretics

A
  1. hydrochlorithiazide

2. chlorthalidone

47
Q

What effect do thiazide diuretics have on electrolytes?

A
  1. decrease K+
  2. decrease H+
  3. INCREASE ca2+
  4. increase uric acid
48
Q

describe the PK of thiazide diuretics

A

best to take early in day

HCTZ: 2x/day
chlorthalidone: 1x/day

49
Q

Uses of thiazide diuretics

A
  1. Hypertension
  2. CHF
  3. Hypercalciuria (renal stones)
  4. refractory edema
50
Q

how do thiazides work to treat hypertension?

A

counters Na/H20 retention seen with vasodilator use

-moderate reduction in circulatory volume-possible vasodilating effect on vascular smooth muscle

51
Q

Reduced urinary excretion of Ca++ decreases incidence of kidney stones

A

hypercalciuria

52
Q

adverse reactions for thiazide diuretics

A
  1. hypokalemia (ectopic pacemakers)
  2. hyperglycemia (impaired carb tolerance)
  3. hyperuricemia (gout)
  4. hyperlipidemia (if used to long-term for HTN)
  5. volume contraction may lead to secondary hyperaldosteronism
  6. allergic rxns: skin rashes (sulfonamide structure)
53
Q

What are sodium channel blockers diuretics

A

Amiloride

Triamterene

54
Q

What are aldosterone receptor antagonist diuretics

A

Spironolactone

Eplerenone

55
Q

describe the movement of ions in the collecting tubule

A
  1. Na+ is driven into the cell exceeds that of K+ leaving
  2. Cl- is driven into cells
  3. K+ is driven out of cells

*K+ excretion is coupled to Na+ reabsorption

56
Q

____, through effects on gene transcription, increases the number and activity of both Na+ (ENaC) and K+ membrane channels and the Na+-K+-ATPase in the collecting tubule

A

Aldosterone

57
Q

How/where do sodium channel blockers and aldosterone receptor antagonist diuretics work?

A

decrease Na+ reabsorption and decrease K+ excretion in the collecting tubule:

  • by being a competitive antagonist at aldosterone recepto–> blocks synthesis of Na and K channels- Na/K ATPase
    and
    -blocking the Na channels on collecting duct lumen to decrease Na reabsorption
58
Q

Direct effect to block the Na+-channels on collecting duct lumen to decrease Na+ reabsorption (and thus decreases coupled K+ secretion)

A

Triamterene / Amiloride

59
Q

K+ excretion is loosely coupled to Na+ reabsorption, describe how this affects K+ with different diuretics

A

loop-thiazide: blocks proximal Na reabsorption–> increase K+ excretion (HYPOkalemia- K+ wasting)

Diuretics that block collecting tubule (aldosterone antagonists/Na channel blockers) Na reabsorption receptor–> decrease K excretion (HYPERkalemia- K sparing)

60
Q

No utility in HF - do not block pro-fibrotic actions of

aldosterone

A

Triamterene / Amiloride

61
Q

Uses of Spironolactone

A
  1. CHF (blocks aldosterone receptors on heart rather than kidney)
  2. block anti-remodeling action in CHF caused by alderosterone on the heart (hypertrophy and fibrosis)
  3. primary hyperaldosteronism, hypokalemia
  4. HTN (in combo w/ thiazides)
  5. Hirsutisim of PCOS (block androgen receptor)
62
Q

Uses of Eplerenone

A
  1. CHF if spironolactone not tolerated,

2. HTN

63
Q

Uses of Triamterene/Amiloride

A
  1. edema of secondary hyperaldosteronism

2. HTN (with thiazides)

64
Q

What are the adverse reactions of K+ sparing diuretics?

A
  1. Hyperkalemia–> conduction abnormalities, arrhythmias
  2. Gynecomastia (not w/ eplerenone)
  3. mild: GI upset, drowisness
65
Q

the risk of hyperkalemia w/ K+ sparing diuretics are increased by:

A
  1. increasing age
  2. underlying renal dysfunction
  3. higher doses
  4. combo use of ACEI or ARB
  5. use of NSAID analgesics
66
Q

Uses of Mannitol

A
  1. increase urine volume in ACUTE renal failure
  2. reduce ICP rapidly in acute head injury
  3. reduce intraocular pressure acutely in glaucoma
67
Q

How does mannitol reduce ICP rapidly in acute head injury

A

via decrease in extracellular volume

-can’t cross BBB–> edema fluid moves into plasma compartment via osmotic action of mannitol

68
Q

adverse reactions of mannitol

A
  1. expansion of ECF in periphery leading to initial HYPOnatremia as acute effect
  2. HA
  3. N/V
  4. Dehydration and hypernatremia w/ chronic excessive use w/o water replacement
69
Q

-Rapid distribution of mannitol to ECF moves H
ICF diluting extracellular Na+ -Additionally this in ECF volume can complicate CHF
and produce pulmonary edema

A

mannitol

Pharmacology (31 decks)

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