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Pharma Recall - Pharmacology > Ch 23 - Diuretics - DONE > Flashcards

Ch 23 - Diuretics - DONE Flashcards

1
Q

What are diuretics?

A

Diuretics are drugs that increase the volume of urine flow

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2
Q

How do the diuretics work?

A

In general, they affect ion transport in the nephorne.

Clinically useful diuretics primarily inhibit Na+ reabsorption.

Water is then carried along passively in order to maintain an osmotic equilibrium.

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3
Q

What are the diuretics principal sites of action?

A
  • Proximal convoluted tubule (PCT)
  • Thick ascending limb of loop of Henle
  • Distal convoluted tubule (DCT)
  • Collecting tubule
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4
Q

Why is knowing the site of action of the diuretics important?

A

This knowledge helps predict:

  1. The magnitude and pattern of the diuresis
  2. The side effects of the medication
  3. The pattern of electrolyte loss
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5
Q

Name five major classes of diuretics:

A
  1. Carbonic anhydrase inhibitors
  2. Loop diuretics
  3. Thiazide diuretics
  4. Osmotic diuretics
  5. Potassium-sparing diuretics
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6
Q

What is the function of carbonic anhydrase?

A

Carbonic anhydrase is an enzyme that catalyzes the following reaction:

CO2 + H2O ↔ H2CO3

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7
Q

How does an carbonic anhydrase inhibitor produce diuresis?

A

The H+ ion produced by the spontaneous breakdown of H2CO3 is usually exchanged for Na+ and is also used to combine with HCO3- in the lumen of PCT.

Without the H+ there is decreased reabsorption of Na+ and HCO3-; this results in diuresis.

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8
Q

How efficient is the diuresis produced by carbonic anhydrase inhibitor?

A

They are weak diuretics properties because other sites further along in the nephrone can compensate for the increased Na+ load

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9
Q

Name the prototype carbonic anhydrase inhibitor:

A

Acetazolamide

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10
Q

What is the route of administration of carbonic anhydrase inhibitor?

A
  • Oral
  • IV
  • Acetazolamide analogues such as Dorzolamide can be given topically for use in the eye
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11
Q

What are the clinical use of Acetazolamide?

A
  • Glaucoma: Acetazolamide decreases production of aqueous humor
  • To correct a metabolic alkalosis
  • Mountain sickness: Acetazolamide is occasionally used as prophylaxis against mountain (altitude) sickness
  • Epilepsy: in combination with other antiepileptic drugs
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12
Q

Acetazolamide (carbonic anhydrase inhibitor) AE:

A
  • Paresthesias and drowsiness are fairly common
  • Hyperchloremic metabolic acidosis caused by loss of bicarbonate
  • Potassium depletion caused by the sodium load and increased flow rate past the DCT
  • Renal calculus: the alkalinaztion of the urine can cause the precipitation of calcium salts

Acetazolamide is a sulfonamide derivative and therefore can cause problems similar to those of other sulfonamides, such as allergic reaction.

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13
Q

Name the loop diuretics:

A
  • Furosemide
  • Ethacrynic acid
  • Bumetanide
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14
Q

What is the mechanism of action and the site of action of loop diuretics?

A

Loop diuretics work by blocking the Na+/K+/2Cl- cotransport system in the thick ascending limb of the loop of Henle

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15
Q

Why are the loop diuretics also called “high-ceiling diuretics”?

A

because they have the highest efficacy of all the diuretics

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16
Q

Why are the loop diuretics the most efficacious diruteics?

A

READ ON PAGE 197

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17
Q

How do loop diuretics affect Ca2+ metabolism?

A

Loop diuretics increase the Ca2+ content of the urine

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18
Q

What are the clinical use of loop diuretics?

A
  • Pulmonary edema, CHF, or other states that require a rapid reduction in blood volume
  • Acute hypercalcemia, hyperkalemia, and acute renal failure
19
Q

What is the route of administration of loop diuretics?

A
  • Oral

- IV

20
Q

Loop diuretics AE:

A
  • Volume depletion
  • Ototoxicity: especially when used in conjunction with an aminoglycoside
  • Hyperuricemia
  • Hypokalemia
  • Hypomagnesemia
  • Hypocalcemia
  • Hyperchloremic metabolic alkalosis
  • Interstitial nephritis: Loop diuretics are sulfonamide derivatives
21
Q

What are Thiazide diuretics?

A

Sulfonamide derivatives related structurally to carbonic anhydrase inhibitors

22
Q

Give some examples of Thiazide diuretics:

A
  • Chlorothiazide
  • Hydrochlorothiazide
  • Metolazone and Indapamide: are considered thiazide analogues because they differ slightly in structure but share a similar mechanism of action.
23
Q

Where does the Thiazide diuretics work?

A

All Thiazide diuretics work in the early segments of the distal convoluted tubule.

24
Q

Thiazide diuretics mechanism of action:

A

They block the Na+/Cl- cotransport of the luminal side of the distal covoluted tubule

25
Q

How effective are the Thiazide diuretics?

A

They are only moderately effective because most of the filtered Na+ is absorbed before it reaches the DCT.

26
Q

What are the uses of Thiazide diuretics?

A

They are used to treat:

  • Hypertention
  • CHF
  • Nephorsis
  • Hypercalciuria
  • Nephorgenic diabetes insipidus
27
Q

Nephorgenic diabetes insipidus:

Thiazide diuretics

A

Thiazides have the ability to produce a slightly hyperosmolar urine and thus diminish polyuria.

28
Q

Which Thiazides are the most effective?

A

All Thiazides are equally effective.

- They differ only in potency

29
Q

How do Thiazides affect plasma Ca2+ levels?

A

Thiazides, unlike loop diuretics, decrease Ca2+ levels in the urine, which results in increased Ca2+ levels in the blood.

30
Q

What are the side effects of Thiazides diuretics?

A
  • Hypokalemia (most common)
  • Hyponatremia
  • Hypochloremic metabolic alkalosis
  • Hyperuricemia
  • Hyperglycemia
  • Hyperlipidemia
  • Hypercalcemia
31
Q

What are the most commonly used osmotic diuretics?

A
  • Mannitol

- Urea

32
Q

What is the mechanism of action of osmotic diuretics?

A

Osmotic diuretics are freely filterable substances; once they become a component of the luminal fluid, they create an osmotic effect to pull in water along the entire nephrone but especially at the PCT and collecting duct.

These agents are not effective in excreting Na+ like other diuretics.

33
Q

What are the clinical use of osmotic diuretics?

A

They are mainly used in a hospital setting to treat increased intracranial and intraocular pressure and acute renal failure

34
Q

What is the route of administration of osmotic diuretics?

A

These drugs must be given IV; other modes of administration will cause cathartic diarrhea

35
Q

What are the toxicities associated with osmotic diuretics?

A
  • Hypovolemia
  • Hypernatremia
  • Can cause pulmonary edema because they rapidly enter the extracellular compartment and pull water out of cells
36
Q

Potassium-sparing diuretics examples:

A
  • Spironolactone
  • Amiloride
  • Triamteren
37
Q

What is the mechanism of action of Potassium-sparing diuretics?

A

They work by inhibiting the passage of sodium from the luminal fluid into the principal cells of the late distal convoluted tubule and cortical collecting tubule.

Sequently, this prevents the movement of K+ from these cells into the luminal fluid

38
Q

What is the efficacy of Potassium-sparing diuretics?

A
  • Weak

- They are used today primarily in conjunction with another diuretic such as a Thiazide in order to limit the K+ wasting

39
Q

What is Spironolactone?

A
  • synthetic steroid

- a competitive antagonist for the mineralocorticoid aldosterone

40
Q

What does the Spironolactone do?

A

binds to aldosterone receptor sites and prevents the formation of mediator proteins that stimulate the Na+/K+ pump

41
Q

What are the clinical indications for the use of Spironolactone?

A
  • Primary hyperaldosteronism (Conn´s syndrome)
  • Edematous states caused by:
    • secondary aldosteronism, especially cirrhosis
    • nephrotic syndrome
    • CHF
42
Q

How does Spironolactone differ from Triamterene and Amiloride?

A

Triamterene and Amiloride work independently of aldosterone by directly blocking Na+ channels; therefore, these agents can be used even in cases of hypoaldosteronism such as Addison´s disease.

In contrast, Spironolactone requires elevated levels of aldosterone to have an effect.

43
Q

Potassium-sparing diuretics AE:

A
  • Hyperkalemia: most important effect to watch for
  • Metabolic acidosis: because of an intracellular shift of H+ ions
  • Rarely, Triamterene cause leg cramps and forms renal stones

Pharma Recall - Pharmacology (14 decks)

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