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CPR Exam 2 > Lecture 2: Diuretics Pharm > Flashcards

Lecture 2: Diuretics Pharm Flashcards

1
Q

What’s a diuretic vs. natriuretic vs. aquaretic?

A
  • Diuretic = substance that promotes excretion of urine
  • Natriuretic = substance that promotes renal excretions of sodium
  • Aquaretic = substance that produces free water clearance = Vaptans
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2
Q

What 2 types of diuretics act at the proximal tubule?

A
  1. Osmotic diuretics
  2. Carbonic anhydrase inhibitors
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3
Q

Which class of diuretics act at the Thin descending limb of Henle?

A

Osmotic diuretics

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4
Q

What are the 4 classes of K+-losing diuretics?

A
  1. Thiazides
  2. Loop diuretics
  3. Carbonic anhydrase inhibitors
  4. Osmotic diuretics
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5
Q

Major effects of hyperkalemia on the heart?

A
  • Tall T waves
  • Arrhythmias including bradycardia
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6
Q

Major effects of Hypokalemia on the heart?

A
  • Tall U waves
  • Atrial arrhythmias
  • VTAC or VFIB
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7
Q

Explain why some diuretics are potassium-losing and others are potassium-sparing?

A
  • K+-losing diuretics block Na+ reabsorption causing an increased delivery to the distal segments of the nephron, which activates aldosterone-sensitive Na+ pumps, which exchange Na+ for K+
  • K+-sparing either block Na+ channels or the aldosterone sensitive pumps in the distal segments form working so that no Na+ is exchanged for K+
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8
Q

Where do Loop Diuretics exert their effects in the nephron?

MOA?

A
  • Thick ascending limb of Henle
  • Block the Na+-K+-2Cl- co-transporter = inhibit reabsorption of Na+ and Cl-
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9
Q

What is the prototypical loop diuretic?

Others in this class?

A
  • Furosemide = most frequently prescribed
  • Torsemide
  • Bumetanide
  • Ethacrynic acid
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10
Q

What are loop diuretics used for?

A
  • Use when rapid and massive fluid removal is needed
  • Management of edema in HF, hepatic and renal dz
  • Acute pulmonary edema, by decreasing preload
  • Tx of HTN that is unresponsive to other diuretics
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11
Q

If a patient has a sulfa allergey, which loop diuretic can you use?

A

Ethacrynic acid

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12
Q

What distinguishes the loop diuretics torsemide and bumetanide?

A
  • Torsemide = longer t1/2, better oral absorption, and may work better in HF
  • Bumetanide = has more predictable oral absorption
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13
Q

Which diuretic class can work in patients with low GFR and RBF?

A

Loop diuretics

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14
Q

Major adverse effects of Loop Diuretics?

Which toxicity?

A
  • HYPOmagnesemia
  • HYPOcalcemia –> increased kidney stone risk (opposite of thiazides!)
  • Ototoxicity
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15
Q

How powerful are Loop Diuretics and what kind of urine is produced?

A
  • Greatest amount of diuresis
  • Max doses –> Larg volume of isotonic urine; irrespective of whether urine was dilute or concentrated
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16
Q

What are 3 drug interactions you must be aware of when using Loop Diuretics?

A
  1. Digoxin
  2. Ototoxic drugs
  3. K+-sparing diuretics
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17
Q

What is the most commonly used Thiazide diuretic?

A

Hydrochlorothiazide (HCTZ)

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18
Q

Where is the site of action for Thiazides in the nephron?

MOA?

A
  • Distal convoluted tubule (DCT)
  • Block Na+-Cl- cotransporter
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19
Q

What are the major therapeutic uses of Thiazide diuretics?

Decreases risk of?

A
  • Primary HTN (often in combo w/ other drugs) and edema
  • Nephrogenic diabetes insipidus (if NOT due to lithium toxicity)
  • Decreases Ca2+ excretion, can decrease risk of kidney stones (opposite of loop diuretics)
20
Q

What are 4 major adverse effects of Thiazides?

A
  • HYPOvolemia
  • K+-losing diuretic
  • Hypochloremic metabolic alkalosis
  • HYPOmagnesemia (may be severe!)
21
Q

What are some drug interactions (good/bad) of Thiazides?

A
  • Often combined w/ antihypertensive meds from other classes to potentiate BP lowering effects
  • Increased risk of digoxin and lithium toxicity!
22
Q

What are the 2 classes of K+ sparing diuretics and drugs in each?

A
  1. Na+ channel blockers –> amiloride and triamterene
  2. Aldosterone antagonists –> spironolactone and eplerenone
23
Q

Where do the K+-sparing diuretics, amiloride and triamterene, exert their effects?

MOA?

A
  • Directly block the Na+ channels (ENaC) in the collecting ducts and adjacent upstream nephron region known as “connecting tubule”
  • ↑ urinary Na+ excretion
  • ↓ urinary K+ excretion
24
Q

What are the therapeutic uses of the K+-sparing diuretics (amiloride and triamterene)?

Off label uses?

A
  • HTN and edema, often in combo w/ loop or thiazide diuretics
  • Counteracts K+ loss induced by the other diuretics
  • Sometimes used off label: ascites and pediatric HTN
25
Q

Adverse effects associated with the K+-sparing diuretics: amiloride and triamterene?

A
  • Hyperkalemia (boxed warning)
  • N/V, leg cramps, and dizziness are common
26
Q

Where do the K+-sparing diuretics, spironolactone and eplerenone, exert their effects and what is their MOA?

Which 2 receptors do they act on?

A
  • Competitive antagonists of aldosterone receptors in the collecting duct —> ↑ Na+ excretion and ↓ K+ excretion
  • Also partial agonists at andogen receptors
27
Q

Why is the pharmacokinetics of the K+-sparing diuretics, spironolactone and eplerenone, significant?

A

Can take 48 hours to work!

28
Q

What are the therapeutic used for the K+-sparing diuretics, spironolactone and eplerenone?

Known to greatly reduce mortality rate in which pts?

A
  • Tx of HTN and edema, often in combo w/ loop or thiazide diuretics
  • Primary hyperaldosteronism
  • Also known to greatly reduce mortality rate in pts w/ severe heart failure… decrease myocardial fibrosis, reduced early morning rise in HR
29
Q

What are 2 major adverse effects associated with the K+-sparing diuretics, spironolactone and eplerenone?

A
  • HYPERkalemia
  • Endocrine effects –> gynecomastia, impotence, menstrual irregularites, hirsutism, and deeping voice
30
Q

What is the MOA and site of action for the Vaptans?

A

- Block the ADH receptor in the collecting duct

  • Prevent ADH-mediated insertion of the aquaporin H2O channels into luminal membrane of principle cells of collecting duct
  • Increases H2O excretion –> ↓ plasma volume and ↑ plasma osmolality
31
Q

What is special about the aquaretic, Tolvaptan?

When is it used for hyponatremia and what must you be careful about?

A
  • Selective V2 recpetor antagonist administered orally
  • Only used in hospital and MUST use ≤ 30 days for hyponatremia, due to potential for fatal hepatotoxicitiy
32
Q

What are the therapeutic uses for the Vaptans?

A
  • Hypervolemic or Euvolemic HYPOnatremia in pts who are hostpitalized, symptomatic, or not responsive to fluid restriction
  • Autosomal dominant polycystic kidney dz (slows progression)
33
Q

What are the adverse effects associated with the Vaptans?

A
  • Orthostatic HTN
  • Fatigure
  • Thirst
  • Polyuria, bedwetting
34
Q

Vaptans are metabolized by what, so there is potential for drug interactions?

A
  • CYP3A4
  • Inhibitors and inducers of this enzyme can alter its 1/2 life and potential for toxicity
35
Q

Which 2 diuretics are sulfonamide drugs so must be careful with people that have sulfa allergies?

A
  • Thiazides
  • Loop diuretics (except ethacrynic acid)
36
Q

What is the prototypical carbonic anhydrase inhibtor of the diuretic class?

A

Acetazolamide

37
Q

What are the pharmacologic effects of the carbonic anhydrase inhibitor, acetazolamide?

Acts where?

A
  • Acts at proximal tubule
  • Sodium bicarbonate diuresis
  • Hyperchloremic acidosis
38
Q

Use of carbonic anhydrase inhibitors is now quite limited, but what are 4 things its still used for?

A
  • Urinary alkalinization
  • Metabolic alkalosis
  • Glaucoma
  • Acute mountain sickness
39
Q

What is the prototype osmotic diuretic and what is its MOA both in the kidney and throughout the body?

Net effect?

A
  • Mannitol
  • Minimally reabsorbed and the inability to reabsorb this solute keeps H2O in the prox. tubule lumen –> excreted
  • Mannitol acts throughout body to pull H2O out of cells
  • Net effect = excrete total body water in excess of plasma electrolytes
40
Q

Adverse effects of Osmotic Diuretics?

A
  • Extracellular volume is acutely increased, which can exacerbate heart failure
  • HA, N/V, and fluid/electrolyte imbalances can occur
41
Q

What are/were 3 therapeutic uses of osmotic diuretics?

A
  • Prophylaxis of renal failure –> prevents renal tubule collapse when GFR is low
  • Reduction of ICP (no longer the best choice)
  • Reduction of intraolcular pressure –> Tx of glaucoma when pts haven’t responded to other therapy
42
Q

The loss of what ion tends to be greater with thiazides than loop diuretics?

A

Mg2+

43
Q

Drug of choice for treating central/neurogenic diabetes insipidus?

A

Desmopressin (synthetic V2 agonist)

44
Q

Drug of choice for treating nephrogenic diabetes insipidus?

A

Thiazide diuretic (unless caused by Li+)

45
Q

Treatment of choice for Li-induced Diabetes Insipidus?

A

Amiloride —> blocks Li+ influx into principal cells, allowing ADH to work

46
Q

Appearance of what 3 clinical findings is suggestive of bilateral renovascular HTN rather than primary HTN?

A
  • Flash pulmonary edema
  • Progressive renal failure
  • Refractory congestive cardiac failure

CPR Exam 2 (21 decks)

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