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Renal Week 1 > Diuretics > Flashcards

Diuretics Flashcards

1
Q

What is a carbonic anhydrase inhibitor that acts in the PT?

A

Acetazolamide [Diamox], PO 500 mg BID.

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2
Q

What is the mechanism of CAIs?

A

Inhibit C.A., resulting in bicarbonate and Na+ loss in the urine with more alkaloid urine

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3
Q

Net effect of CAIs?

A

Alkaline urine, due to Na+-bicarbonate loss in the urine.

Enhanced chloride reabsorption resulting in acidosis.

The extra Cl- in the mood neutralizes the HCO3- in the blood, limiting the effectiveness as a diuretic

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4
Q

Clinical uses of CAIs?

A
  • Diuretics: limited use.
  • Alkalinize urine (Cystinuria).
  • Reduce intra ocular pressure after cataract surgery
  • Given prophylactically for mountain sickness.
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5
Q

Side effects of CAIs?

A
  • Metabolic acidosis.
  • Markedly increases K+ loss in the urine (acute effect)-think why.

• Acetazolamide should be avoided in advanced renal failure (can cause a wasting syndrome).

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6
Q

FAS of osmotic diuretics?

A

Small molecules that are filtered, but not reabsorbed by the kidney.

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7
Q

Where do osmotic diuretics work?

A
  • LOH (major)

- PCT (minor)

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8
Q

What do osmotic diuretics stimulate in the PCT?

A

Osmotically inhibit Na+ & H2O reabsorption

Produces the larges volume of urine but it is Na poor (hypo-osmolar urine)

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9
Q

What do osmotic diuretics stimulate in the LOH?

A

•Given in large doses, they increase the osmolarity of plasma.

  • Extract water from peripheral tissues and decrease blood viscosity.
  • Increase medullary renal blood flow and reduce its tonicity.
  • Impair water reabsorption in the thin descending limb
  • Impair NaCL & urea extraction in thin ascending limb of Henle’s loop.
  • Interfere with transport processes in the TALH.
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10
Q

Net effects of osmotic diuretics?

A

Significantly increase urine with small increments of NaCl and other ions.

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11
Q

Clinical uses of Osmotic diuretics?

A
  • Treatment of dialysis disequilibrium syndrome.
  • Reduce intra cranial pressure (it’s main use at this time)-if given 0.5g
  • Reduce intraocular pressure .

not really used anymore as a diuretic

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12
Q

Example of an osmotic diuretic?

A

Mannitol: Injection [50 mL of a 25% solution], usual dose 1-5 g.

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13
Q

Side effects of osmotic diuretics?

A
  • Volume overload.
  • High doses are toxic in renal failure.
  • Contraindicated in cardiac failure.
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14
Q

What is the mechanism of loop diuretics?

A
  • Inhibit Na-K-2Cl symporter in ThickALH.
  • Inhibit the ability of the macula densa to “sense” NaCl.
  • Stimulates biosynthesis of prostaglandins.
  • Increase total renal blood flow.
  • Maintain GFR, by increasing % of the extraction fraction.
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15
Q

What does the biosynthesis of prostaglandins stimulated by loop diuretics promote?

A
  • Reduce Na+ reabsorption in the distal nephron, and Antagonize ADH
  • Redistribute renal blood from cortex to juxtaglomerulus.
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16
Q

Loop diuretics can potentially increase renin release how?

A
  • inhibiting the macula densa.
  • reflexely activating the sympathetic NS.
  • stimulating intrarenal baroreceptor mechanisms.
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17
Q

Net effects of loop diuretics?

A
  • Most potent class of diuretics in mobilizing NaCl.
  • Copious diuresis and significant NaCl loss.
  • Increase urinary excretion of K+/H+ .
  • Increase excretion of Ca2+ and Mg2+.
  • Impair the ability of the kidney to concentrate urine.
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18
Q

What are some clinical uses of loop diuretics?

A
  • edema of cardiac, hepatic, or renal origin (oral)
  • pulmonary edema (IV)
  • hypercalcemia
  • washout of toxins by increasing urine flow

-Anti-HTN

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19
Q

How do loop diuretics abate pulmonary edema?

A
  • Decrease pulmonary wedge pressure.
  • Increase compliance of pulmonary vessels. Secondary to decreasing venous return
  • Increase peripheral venous capacitance.
  • Reduce left ventricular filling pressure.
  • Cause brisk diuresis.
20
Q

Examples of loop diuretics

A

-Furosemide (inhibits NaCl reabsorption in TALH)

  • Bumetanide
  • Torsemide
21
Q

How is Furosemide given?

A

PO or IV/IM- wide margin of safety.

22
Q

a

A

a

23
Q

Effects of Furosemide?

A

• copious diuresis with significant NaCl losses.

  • more urinary excretion of K+/H+
  • more urinary excretion of Ca2+ and Mg2+
  • more renal prostaglandins.
  • more venous capacitance.
24
Q

How is Furosemide given?

A

20-40 mg daily or BID

25
Q

Does Furosemide act quickly? Duration?

A

Diuretic response in 30 min, lasting ~8hr (Short half-life (1.5 hr), but extensively protein bound)

Excreted in the urine 65%.

26
Q

Metabolic side effects of furosemide?

A

Abnormalities of fluid and electrolytes:
— volume and Na+ depletion
—hypokalemia and disorders in pH (metabolic alkalosis).
—requires initial monitoring.

27
Q

Other side effects of furosemide?

A

Elevated BUN, hyperglycemia, hyperuricemia.

Ototoxicity, sialadenitis (inflammation of salivary glands).

28
Q

What are some possible drug interactions of furosemide?

A
  • interactions with Li+
  • indomethacin,
  • probenecid
  • warfarin
29
Q

Is Bumetanide more or less effective than Furosemide?

A

40x more potent. May be substituted for furosemide in patients receiving
warfarin.

30
Q

How is Bumetanide given?

A

1 mg once or twice daily

31
Q

What are the advantages of Torsemide?

A

• Loop diuretic that also lowers blood pressure.
• Has a longer half-life than other loop diuretics, given
once daily.

32
Q

What is the mechanism of thiazide diuretics?

A

Bind to the chloride site of the NACl symporter in the Na+-K+
aldosterone-independent segment of the distal tubule.

33
Q

Effects of thiazides?

A

• moderate loss of Na+, K+ and Cl-, cause 3X increase in
urine flow.

  • sodium loss and volume contraction reduced GFR (chronic).
  • elevation of excreted urinary potassium (Hypokalemia).

• Increase excretion of titratable acid, due to increased
delivery of Na+ to the distal tubule.

  • Decrease the urinary excretion of Ca2+.
  • Increase the urinary excretion of Mg2+.
34
Q

Therapeutic uses of thiazides?

A

• Diuretic to reduce edema associated with:
CHF, cirrhosis and nephrotic syndrome
• Hypercalcuria and renal calcium stones.
• Antihypertenssive: To reduce blood pressure in essential
hypertension (alone).
• To augment the action of other antihypertensives.
• Osteoporosis
• Nephrogenic Diabetes insipidus.

35
Q

Note: like loop diuretics, thiazides require secretion into the tubular fluid to exert their effect.

A

Note: like loop diuretics, thiazides require secretion into the tubular fluid to exert their effect.

36
Q

When do thiazides become ineffective?

A

With possible exceptions of metolazone and indapamide,

most thiazides are ineffective when GFR

37
Q

What are the class I thiazides?

A

Preferably used when GFR > 50 mL/min.

  • Hydrochlorothiazide: (T1/2 = 2.5 h). Oral, 25-50 mg BID.
  • Chlorthalidone: [Hygroton] (T1/2 = 47h). Oral, 50 mg once daily.
38
Q

What are the class II thiazides?

A

More potent, might be effective in some patients with GFR 30
mL/min.

  • Metolazone [Zaroxolyn]: 10X more potent than HCTZ.
  • Indapamide [Lozol]: 20X more potent than HCTZ.
39
Q

The antiHTN effect of thiazides plateaus where?

A

at 25mg of HCTZ.- Higher doses only result in more side effects

40
Q

When is the only time increasing thiazide dose above 25mg is appropriate?

A

ONLY when treating for calcium kidney stones.

41
Q

What are the actions of aldosterone/

A
  • Aldosterone binds to a mineralocorticoid receptor in DCT.
  • Translocates to nucleus and binds to hormone-sensitive elements.
  • Regulate the expression Aldosterone-induced EnaC Na+ channels.
  • Consequently transepithelial NaCl transport is enhanced.
  • Lumen-negative transepithelial voltage in increased.
  • The latter effect increases the secretion of K+ and H+.
42
Q

So what is the net effect of aldosterone inhibitors?

A

—Increase Urinary excretion of Na+ (Natriuretic effect)

—inhibit the secretion of K+ and H+ (K-sparing)

43
Q

What are some aldosterone inhibitors?

A
  • spironolactone

- eplenerone

44
Q

T or F. Spironolactone is a pro-drug that is extensively metabolized.

A

T. Canrenone is an active metabolite with a longer T1/2.

45
Q

Side effects of Spirolactone?

A

Hyperkalemia (combine with a thiazide)

Gynecomastia, hirsutism (due to specificity for androgen receptors as well, uterine bleeding.

46
Q

T or F. Eplenerone is expected to have less side effects because it has very low affinity
for androgen receptors compared to spironolactone.

A

T.

47
Q

What are the clinical uses of aldosterone antagonists?

A
  • Diuretic, usually in combination with HCTZ.
  • Treatment of CHF
  • Management of cirrhosis.

Renal Week 1 (20 decks)

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