Renal Week 1 > Diuretics > Flashcards

Diuretics Flashcards

(47 cards)

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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?

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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

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A

-Furosemide (inhibits NaCl reabsorption in TALH)

  • Bumetanide
  • Torsemide
21
Q

How is Furosemide given?

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A

PO or IV/IM- wide margin of safety.

23
Q

Effects of Furosemide?

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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?

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A

20-40 mg daily or BID

25
Does Furosemide act quickly? Duration?
Diuretic response in 30 min, lasting ~8hr (Short half-life (1.5 hr), but extensively protein bound) Excreted in the urine 65%.
26
Metabolic side effects of furosemide?
Abnormalities of fluid and electrolytes: — volume and Na+ depletion —hypokalemia and disorders in pH (metabolic alkalosis). —requires initial monitoring.
27
Other side effects of furosemide?
Elevated BUN, hyperglycemia, hyperuricemia. Ototoxicity, sialadenitis (inflammation of salivary glands).
28
What are some possible drug interactions of furosemide?
* interactions with Li+ * indomethacin, * probenecid * warfarin
29
Is Bumetanide more or less effective than Furosemide?
40x more potent. May be substituted for furosemide in patients receiving warfarin.
30
How is Bumetanide given?
1 mg once or twice daily
31
What are the advantages of Torsemide?
• Loop diuretic that also lowers blood pressure. • Has a longer half-life than other loop diuretics, given once daily.
32
What is the mechanism of thiazide diuretics?
Bind to the chloride site of the NACl symporter in the Na+-K+ aldosterone-independent segment of the distal tubule.
33
Effects of thiazides?
• 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
Therapeutic uses of thiazides?
• 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
Note: like loop diuretics, thiazides require secretion into the tubular fluid to exert their effect.
Note: like loop diuretics, thiazides require secretion into the tubular fluid to exert their effect.
36
When do thiazides become ineffective?
With possible exceptions of metolazone and indapamide, | most thiazides are ineffective when GFR
37
What are the class I thiazides?
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
What are the class II thiazides?
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
The antiHTN effect of thiazides plateaus where?
at 25mg of HCTZ.- Higher doses only result in more side effects
40
When is the only time increasing thiazide dose above 25mg is appropriate?
ONLY when treating for calcium kidney stones.
41
What are the actions of aldosterone/
* 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
So what is the net effect of aldosterone inhibitors?
—Increase Urinary excretion of Na+ (Natriuretic effect) —inhibit the secretion of K+ and H+ (K-sparing)
43
What are some aldosterone inhibitors?
- spironolactone | - eplenerone
44
T or F. Spironolactone is a pro-drug that is extensively metabolized.
T. Canrenone is an active metabolite with a longer T1/2.
45
Side effects of Spirolactone?
Hyperkalemia (combine with a thiazide) Gynecomastia, hirsutism (due to specificity for androgen receptors as well, uterine bleeding.
46
T or F. Eplenerone is expected to have less side effects because it has very low affinity for androgen receptors compared to spironolactone.
T.
47
What are the clinical uses of aldosterone antagonists?
* Diuretic, usually in combination with HCTZ. * Treatment of CHF * Management of cirrhosis.
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