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PHARMACOLOGY > Diuretics > Flashcards

Diuretics Flashcards

1
Q

What is a diuretic?

A

An agent used to increase urine volume

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2
Q

Differentiate between a naturetic and an aquaretic

A

Naturetics increase urine volume by increasing renal excretion of sodium while aquaretic increase solute free urine volume

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3
Q

Give four major locations and the transporters in which sodium is reabsorbed

A
  1. Proximal Convoluted tubule - Na/H+ Exhanger3 (NHE3)
  2. Thick ascending limb (25%) - Na/K/2Cl
    (NKCC2)
  3. Distal convoluted tubule (5%) - Na/Cl (NCC)
  4. Collecting tubule - Epithelial Sodium Channel (ENaC)
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4
Q

What type of diuretics inhibits the Thick ascending limb and the Distal convoluted tubules

A

Thick ascending limb - Loop Diuretics
Distal Convoluted tubules - Thiazide diuretics

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5
Q

Give three inhibitors of the ENaC at the collecting tubule

A
  1. Potassium sparing diuretics -
  2. Mineralocorticoid Antagonist Receptor
  3. Aldosterone antagonists
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6
Q

Give functional differences between the Potassium sparing diuretics and the Mineralocorticoids Antagonist Receptor

A

Potassium sparing diuretic inhibit ENaC directly while the Mineralocorticoids indirectly reduce expression of the receptor on the luminal membrane of the principal cells

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7
Q

The NHE3 on the proximal convoluted tubules are indirectly inhibited by

A

Carbonic anhydrase inhibitors

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8
Q

Give two types of inhibitors at the collecting tubule

A
  1. ENaC inhibitors
    a) Potassium sparing diuretics
    b) Mineralcorticoid receptor antagonists
    c) Aldosterone antagonists
  2. ADH antagonists
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9
Q

All diuretics except whoch one reach their targets from the tubular lumen

A

Spironolactone

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10
Q

Most diuretics excepts Spironolactone reach their targets in the kidney from ?

A

Tubular lumen

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11
Q

What percentage of most diuretics are protein bound and how does this affect the glomerular filtration

A

95%. It reduces the glomerular filtration

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12
Q

Most diuretics are secreted from the blood into the proximal tubules using two types of transporters.
Name them

A

Organic Anion Transporters
Organic Cation Transporters

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13
Q

Furosemide is a

A

Loop diuretic

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14
Q

Give drugs that use
1) Organic anion transporters
2) Organic cation Transporters

A

Organic anion transporters
- Loop diuretics , Thiazide diuretics and Acetazolamide
Organic Cation Transporters
Triamterene and Amiloride

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15
Q

Give drugs that use
1) Organic anion transporters
2) Organic cation Transporters

A

Organic anion transporters
- Loop diuretics , Thiazide diuretics and Acetazolamide
Organic Cation Transporters
Triamterene and Amiloride

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16
Q

Acetazolamide is a

A

Carbonic anhydrase inhibitor

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17
Q

Amiloride and Tiamterene are

A

Potassium sparing diuretics

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18
Q

Although most diuretics are secreted into the proximal convoluted tubules using the organic anion/cation transporters, two classes are not secreted. Name them

A

Mineralocorticoid receptor antagonists
Osmotic diuretics

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19
Q

Give the 6 major classes of Diuretics

A

Carbonic anhydrase inhibiotrs
Osmotic diuretics
Loop Diuretics
Thiazide diuretics
Mineralcorticoid antagonist receptor
Aldosterone antagonists
ADH antagonists

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20
Q

define Loop diuretics and Thiazide diuretics under
1) Efficacy
2) Potassium effect

A

Loop - High efficcacy while Thiazide - Moderate efficacy
Both are potassium depleting causing hypokalemia

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21
Q

Give 3 examples of Loop diuretics

A

BTF
Bumetanide
Torasemide
Furosemide

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22
Q

Thiazide examples
a) Thiazides
b) Thiazide related

A

Thiazide
1) Hydrochlorothiazide
2) Bendroflumethazide
Thiazide related
Metolazone
Chlorthalidone
Indapamide

23
Q

Give two examples of aldosterone antagonists

A

Spironolactone
Eplerone

24
Q

An example of an osmotic diuretic includes

25
Q

Two examples of Carbonic anhydrase inhibitors

A

Acetazolamide
Dorzolamide

26
Q

Give the classes of Drugs according to efficacy

A

High - Loop
Moderate - Thiazide
Low - Potassium sparing diuretics, Osmotic diuretics, Aldosterone antagonists and Carbonic anhydrase inhibitors

27
Q

Give the MOA of Osmotic diuretics

A

They increase the osmolality of renal tubular fluid thus reducing reabsorption of water

28
Q

Osmotic diuretics are said to be pharmacologically inert , tru or false

29
Q

Give four examples of Osmotic diuretics

A

Mannitol
Urea
Isosorbide
Glycerin

30
Q

How does Mannitol work

A

Mannitol is a noreabsorbable agent and thus increases the osmolality of renal tubular fluid.
This in turn reduces reabsorption of water and thus increasing the urine volume

30
Q

How does Mannitol work

A

–> Countervailing osmotic force
Mannitol is a noreabsorbable agent and thus increases the osmolality of renal tubular fluid.
This in turn reduces reabsorption of water and thus increasing the urine volume
–> It also causes increased sodium excretion due to reduce contact time between fluid and tubular epithelium due to increased fluid rate. This causes naturesis although less than the water diuresis causing hypernatremia
–> They also oppose the action of ADH in the collecting tubules

31
Q

Osmotic diuretics mainly work on which parts of the nephron

A

The proximal CT
The descending limb of the loop of Henle

32
Q

Osmotic diuretics increase renal blood flow by four main mechanisms

A

Dilating afferent arteriole
Reducing blood viscosity
Increasing ecf volume
Inhibiting renin release

33
Q

Give PK of Mannitol

A

Given IV for systemic effects ( also used to reduce intercranial pressure and intra-ocular pressure)
Poorly absorbed in GIT
Not metabolized
Filtered by glomerulus in 30min
Not reabsorbed nor secreted

34
Q

Give the ROA of
1) Mannitol -
Urea -
Glycerin -
Isosorbide -

A

1) Mannitol -IV
Urea - IV
Glycerin - orally
Isosorbide - orally

35
Q

Give the A/E of Osmotic diuretics

A

1)Exacerbate Pulmonary Edema due to increased ECF volume
2) Cause hyponatremia in the begining due to increased ECF volume
3) Later causes hypernatremia and dehydration due to increased urine volume and water loss
4) Extravasation of urea causes thrombosis
5) Metabolism of glycerin causes hyperglycemia

36
Q

give the C/I of osmotic diuretics

A

1) Anuria due to renal disease - passage of urine less than 100ml per day
2) Urea in impaired liver function which can cause uremia (increased urea plasma conc that can lead to encephalopathy and seizures)

37
Q

Give therapeutic uses of Osmotic diuretics

A

1) Dialysis disequilibrium syndrome
Ocurs during hemodialysis where ECF solutes are quickly removed from ECF thus causing movement of water into the ICF.
Osmotic diuretics help increase the ECF volume
2) Reduces intercranial pressure - cerebral edema ( due to traumatic head injury)
3) Reduces intra-ocular pressure like in acute glaucoma attacks

38
Q

Carbonic anhydrase inhibitors usually work at which part of the nephron?

A

The proximal convoluted tubules

39
Q

Give three examples of Carbonic anhydrase inhibitors

A

MAD
Acetazolamide, Dichlorphenamide, Methazolamide

40
Q

What is the mechanism of action of carbonic anhydrase inhibitors

A

Carbonic anhydrase inhibitors inhibit carbonic anhydrase which prevents dissociation of carbonic acid into hydrogen ions and bicarbonate within the PCT cell.
This indirectly inhibits the sodium hydrogen exchanger thus reduced reabsorption of sodium and water. It also inhibits the reabsorption of bicarbonate ions leading to metabolic acidosis

41
Q

Give effects of Carbonic anhydrase inhibitors in urine

A

1) Increase in bicarbonate ion secretion, which increases the urinary pH.
2) Development of metabolic acidosis
3) Increase in phosphate excretion
4. Inhibits excretion of titratable NH+4 in collecting duct

42
Q

Give four other extra renal effects of Carbonic anhydrase inhibitors

A

1) In the eye they are used to treat glaucoma as they decrease intraocular pressure due to reduced formation of aqueous humor.
2) They reduce gastric acid secretion in the GIT.
3) Increase levels of CO2 in the peripheral tissues
4) Have an anticonvulsant effect in the CNS

43
Q

What is the PK of Carbonic anydrase inhibitors

A

Well absorbed
Excreted in the PCT

44
Q

Give uses of Carbonic anhydrase inhibitors

A

1) Treatment of glaucoma due to reduce aqueous formation
2) They can be used to alkalinize urine in patients with uric acid stones and cystinuria as they increase solubilization and excretion of uric acid. Tho this can lead to formation of calcium stones
3) Used in treatment of metabolic alkalosis
4) Reducing symptoms of acute mountain sickness by reducing CSF formation and increasing cerebral and respiratory ventilation
5) Adjuvants in epilepsy
6) Hypokalemic periodic paralysis
7) Severe Hyperphosphatemia

45
Q

Give some Adverse effects of using Carbonic anhydrase inibitors

A

1) Hyperchloremic metabolic acidosis
2) Formation of renal calcium stones
3) Renal potassium wasting
4) Drowsiness
5) Parasthesia
6) Hypersensitivity reactions due to the sulfonamide moeity

46
Q

Give the C/I of carbonc anhydrase inhibitors

A

1) Hepatic encephalopathy due to hyperammonia - The drugs usually reduce excretion of ammonia due to urinary alkalinization by bicarbonate ions

47
Q

Loop diuretics work in the ?

A

Descending limb of the loop of Henle

48
Q

Which transporter do loop diuretics inhibits

A

Na/K/2Cl symporter

49
Q

Give four examples of Loop diuretics

A

Torsemide
Bumetanide
Furosemide
Ethacrynic acid
sulfonyl urea

50
Q

Loop diuretics increase the excretion of several ions, name them

A

Na and Cl (25% of filtered load)
Ca and Mg
HCO-3 and Phosphate (Furosemide has a weak carbonic anhydrase activity)
K+ and H+

51
Q

Loop diuretics act diferently in acute and chronic uric acid secretion, explain

A

Acutely they increase its excretion but in chronic use they reduce its excretion as they

52
Q

Give effects of Loop diuretics

A

1)The stimulate renin release by interfering with NaCl transport in macula densa
2) Acutely increase uric acid excretion
3) Cause drug induce ototoxicity as the Na/K/2Cl symporter also exists in the ear
4)

PHARMACOLOGY (17 decks)

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