Diuretics Flashcards

1
Q

What is the target response of diuretics?

A

Increase urine volume by increasing excretion of Na+ (solutes) and H2O (inhibiting reabsorption)

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2
Q

What is Natriuresis?

A

Increasing excretion of Na+ from the body.

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3
Q

What are the principle uses of diuretics?

A
  • Treatment of Edema (excreting water)

- Treatment of Mild Essential Hypertension

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4
Q

Where is the main site of Na+/ H20 reabsorption in the nephron?

A

-The Proximal Convoluted Tubule (65%)

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5
Q

Examples of Carbonic Anhydrase Inhibitors and their mechanism of action?

A
  • Acetazolamide
  • Inhibits Carbonic Anhydrase enzyme action
  • ->Increases excretion of NaHCO3 and K+.
  • ->Retention of H+ ions.
  • ->Hypokalemia of PCT
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6
Q

What are the Therapeutic Uses of Carbonic Anhydrase Inhibitors?

A
  • Glaucoma, petit mal (absence/ small) seizures
  • *Acute high altitude mountain sickness
  • ->Promotes metabolic acidosis due to accumulation of H+ which increases respiration?
  • Can treat edema and metabolic alkalosis
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7
Q

What are the adverse effects of Carbonic Anhydrase Inhibitors?

A
  • Metabolic acidosis (due to the excretion of bicarbonate and retention of H+)
  • Hypokalemia (due to the excretion of K+)
  • Hypersensitivity reactions
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8
Q

True of False:

Osmolairty increases along the descending loop of Henle.

A

True.

–>At the bottom of the descending loop of Henle, Na+ concentration is 3x higher than the top portion.

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9
Q

Mannitol

A

Osmotic Diuretic
–>Causes a high amount of water excretion and minimal solute loss in the Thin Descending loop of Henle.
(Promotes diuresis and little natriuresis)

-Used to treat cerebral edema (decrease intracranial pressure) and acute renal failure (promote urine formation)

Adverse Affects: Dehydration in long term use.

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10
Q

What is characteristic of the Thin Descending loop of Henle?

A

-NO electrolyte loss.

Aquaporins channels allow for water movement only

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11
Q

What is characteristic of the Thick Ascending loop of Henle?

A
  • Impermeability to water
  • ->Electrolyte movement only.
  • Major site of salt reabsorption
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12
Q

Mechanism of Action of Loop Diuretics?

A

-Blocks the Na+/ K+/ 2Cl- Pump (Inhibits exchanger) in the Thick Ascending loop of Henle

  • Drugs include Furosemide, Bumetanide, Torsemide and Ethacrynic Acid
  • Rapid onsets
  • ->Increased secretion of Na+/ K+/ Cl- and Ca2+

Therapeutic uses?

  • Edema due to increased secretion of solutes and increased retention of H2O.
  • -Adverse Effects include hypokalemia, hyponatremia, hypovolemia, alkalosis, ototoxicity, hypotension and hyperuricemia.
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13
Q

What drugs affect the Distal Convoluted Tubule, and what is their mechanism of action?

A
  • ->Thiazides!
  • Inhibits Na+/ Cl- pump to increase SECRETION of Na+, Cl-, K+ and H+
  • ->Increases Ca2+ reabsorption

Examples of thiazides include:
-Hydrocholorthiazide (HCTZ)
(Chlorothalidone Indapamine)

Therapeutic uses include:

  • Essential hypertension
  • Treatment for hypocalcemia

Adverse Effects include: Hyperkalemia, hypercalcemia, hyperuricemia, alkalosis and impaired glucose tolerance.

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14
Q

What are the two mechanism’s of action of K+ Sparing Diuretics, where do they act on the nephron and what drugs are included in this category?

A

Act on the cortical collecting tubule.

1) Aldosterone receptor antagonists (blocks K+ excretion/ H+ excretion)
- Spironolactone and Eplerenone

2) ENa+C Inhibitors (Blocks H+/ Na+/K+ excretion)
- Triamerene and Amilorde

Therapeutic uses:
Spironolactone is frequently used in combination with Furosemide (Loop Diuretic) to reduce hypokalemia in patients with hypertension or heart disease.

Adverse Effects include hyperkalemia and acidosis.

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15
Q

Spironolactone:

A
  • K+ Sparing Diuretic
  • ->Aldosterone receptor antagonist
  • MILD androgen blocker (can cause gynecomastia) and menstrual irregularities.
  • Can be used to treat Hirsutism (hair growth on women’s faces)
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16
Q

What is the final site of urine concentration determination?

A

Medullary collecting tubule -Responsible for maintaining/ regulating bodily fluid volume.

17
Q

Describe the mechanism of ADH in the medullary collecting tubule.

A

ADH stimulates the V2 receptor (vasopressin receptor) which leads to the activation of cAMP and the movement of water through aquaporin channels.

18
Q

Tolvaptan:

A

An ADH antagonist.
-Competitive V2 antagonist.
(Leads to an INCREASE in water excretion)

Used to treat:

  1. SIADH (The syndrome of inappropriate ADH secretion)
  2. Heart Failure with low blood plasma (Hyponatremia)
19
Q

What are the adverse effects of ADH antagonists?

A
  • Hypernatremia

- Hypovolemia (Xerostomia (dry mouth and thirst)

20
Q

True or False:

Tolvaptan (ADH antagonist) should not be administered to patients with hypovolemia hyponatremia.

A

-True.

Low blood volume and low Na+ excretion

21
Q

List the correct order of Prescribing Diuretics?

A
  1. Loop Diuretics (Furosemide)
  2. Osmotic Diuretics (Mannitol)
  3. Thiazides (HCTZ)
  4. Carbonic Anhydrase Inhibitors (CAI’s)
  5. K+ Sparing Diuretics
  6. ADH Antagonists
22
Q

How does tolerance develop to diuretics?

A

By taking the first diuretic dose, there is a negative Na+ balance in the nephron. In this time, blood volume is reduced and edema disappears.
-Excretion of Na+ leads to compensatory increase in Na+ reabsorption. After a few days, Na+ balance is restored and edema may reoccur.

23
Q

Compensatory mechanisms of the nephron to restore Na+/ H20 levels:

A
  • Macula densa cells sense reduction in blood volume and increase the secretion of renin and leads to a release of aldosterone, increasing H2O retention.
  • Baroreceptors sense reduction in H2O levels and cause an increase in sympathetic activity on beta1 receptors, increasing renin release.
24
Q
True or false: 
If Furosemide (a loop diuretic) causes hypokalemia, a
K+ sparing diuretic (spironolactone) can be used to increase K+ levels.
A

True