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13 - Urinary > 3 Diuretics > Flashcards

3 Diuretics Flashcards

1
Q

What is diuresis?

A

Diuresis is the increased formation of urine by the kidney

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2
Q

What is a diuretic?

A

A diuretic is a substance/drug that promotes a diuresis by increasing the renal excretion of Na+/H2O, reducing ECF volume

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3
Q

When are diuretics used clinically?

A

Clinical use is in conditions where Na+ and H2O retention cause expansion of ECF volume and oedema eg. heart failure

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4
Q

Briefly, describe how diuretics act on the nephron/kidney

A

Diuretics act by blocking reabsorption of Na+ and H2O by the tubule and increase the fractional excretion (FE) of Na+

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5
Q

Describe the 4 pathways in which diuretics can act on the nephron

A
  • By blocking Na+ transporters in the luminal membrane
  • By antagonising the action of aldosterone
  • By modification of filtrate content (osmotic diuretics)
  • By inhibiting activity of enzyme carbonic anhydrase in the PCT
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6
Q

Identify the 3 types of diuretics which act on cells to block Na+ transporters in the luminal membrane

A
  • Thiazide diuretics
  • Loop diuretics
  • K+ sparing diuretics
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7
Q

Describe the action of loop diuretics

A
  • Drug is secreted into the lumen in the PCT
  • Acts on Loop of Henle
  • Blocks NaKCC co-transporter
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8
Q

Describe the action of thiazide diuretics

A
  • Drug is secreted into the lumen in the PCT
  • Acts on the early Distal Tubule
  • Blocks Na–Cl cotransporter
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9
Q

Describe the action of K+ sparing diuretics

A
  • Drug is secreted into the lumen in the PCT
  • Acts on Late DT & CD
  • Blocks Epithelial Na channels
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10
Q

Describe how aldosterone acts on the kidney nephron

A

Aldosterone acts on principal cells of Late DT & CD to increase Na+ reabsorption via ENaC

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11
Q

Identify and describe the mechanism of action of diuretics which antagonise the action of aldosterone

A
  • Aldosterone antagonists act through competitive inhibition of the aldosterone receptor, decreasing Na+ reabsorption
  • They also have a K+ sparing effect
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12
Q

Osmotic diuretics act by modifying the filtrate content.

Describe this

A

Small molecules are freely filtered at glomerulus but not reabsorbed:

  • Increased osmolarity of filtrate
  • Reduced water & Na+ reabsorption throughout the tubule
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13
Q

Describe the action of carbonic anhydrase inhibitors

A

Carbonic anhydrase has an inhibiting effect and interferes with Na+ & HCO3- reabsorption in PCT

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14
Q

Loop diuretics block apical Na-K-2 Cl transporter.

In 5 steps, explain how this leads to diuresis

A

⇒ Na+ and Cl- is not absorbed resulting in less H2O absorption

⇒ Result is: Na+ and H2O loss

⇒ K+ carried across apical membrane drifts back into lumen via K+ channels

⇒ Creates a (+) lumen potential

⇒ This decreases the absorption of Ca2+ and Mg2+

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15
Q

Provide 2 examples of loop diuretics

A
  • Furosemide
  • Bumetanide
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16
Q

Loop diuretics are very potent.

What is the impact of this?

A
  • Affects 25 - 30% of filtered sodium reabsorption
  • Segments beyond have limited capacity to reabsorb the resulting flood of Na+ & H2O
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17
Q

Describe the use of loop diuretics in heart failure

A
  • Treats of symptoms of breathlessness & oedema
  • Causes vaso and venodilatation (decreases after/preload)
  • No effect on reducing mortality
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18
Q

Describe the use of loop diuretics in treating acute pulmonary oedema

A

IV Furosemide given for rapid action

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19
Q

Loop diuretics are used to treat fluid retention & oedema in a number of clinical conditions.

Identify 3

A
  • Nephrotic syndrome
  • Renal failure
  • Cirrhosis of liver (spironolactone preferred)
20
Q

Loop diuretics are also used in treatment of hypercalcaemia.

Explain the benefit of this

A
  • Impairs calcium absorption in the Loop of Henle
  • Increases urinary excretion of calcium
  • Furosemide given together with IV fluids
21
Q

Thiazide diuretics block Na–Cl transporter in DCT.

In 4 steps, explain how this leads to diuresis

A

⇒ Diuretic secreted into lumen in PCT and travels to act on DCT

⇒ Blocks Na+ absorption and increases Ca2+ absorption

⇒ Increases Na+ (and H2O) loss in urine

⇒ Reduces Ca2+ loss in urine

22
Q

Provide an example of a thiazide diuretic

A

Bendroflumethiazide

23
Q

Thiazide diuretics are less potent diuretics than loop diuretics.

How does this manifest?

A
  • Only 5% of sodium reabsorption inhibited
  • Ineffective in renal failure
24
Q

Where are thiazide diuretics most commonly used?

A

Widely used in hypertension (vasodilatation)

25
Q

Two groups of drugs have potassium sparing diuretics.

Identify these groups and provide examples

A

Act on late distal tubule and collecting duct:

  • Inhibitors of ENaC e.g. Amiloride, triamterene
  • Aldosterone antagonist e.g. Spironolactone
26
Q

Identify 4 similarities between aldosterone antagonist diuretics and inhibitors of ENaC

A
  • Reduce ENaC activity (directly or indirectly)
  • Reduce the loss of K+
  • Can produce life threatening hyperkalaemia
  • Are mild diuretics (affects only 2% of Na+ reabsorption)
27
Q

Hyperkalaemia may occur with both groups of K+ sparing diuretics.

Illustrate this mechanism

28
Q

The 2 groups of drugs with potassium sparing effects are more likely to produce severe hyperkalaemia when used in certain circumstances.

Identify 3 of these

A
  • ACE Inhibitors
  • K+ supplements
  • Patients with renal impairment
29
Q

Describe 3 clinical uses of aldosterone antagonists

A
  • Reduces mortality in heart failure
  • Preferred drug for cirrhosis (ascites & oedema)
  • Additional therapy in hypertension caused by primary hyperaldosteronism
30
Q

Describe the clinical use of ENaC blockers

A

Usually used in combination with K+ losing diuretics such as Loop or Thiazide diuretics to minimise K+ loss

31
Q

In 5 steps, explain how diuretics may also contribute to hypokalaemia

A

⇒ Diuretics may lead to reduced circulatory volume

⇒ Activation of RAAS

⇒ Increased aldosterone secretion

⇒ Increased Na+ absorption & K+ secretion

⇒ Hypokalaemia

32
Q

Loop & Thiazide diuretics both block Na+ & H2O reabsorption in LoH or early DT.

Ilustrate how this might lead to hypokalaemia

33
Q

What is Nephrotic syndrome?

A

Nephrotic syndrome is a glomerular disease caused by an increase in the permeability of the glomerular basement membrane to protein

34
Q

In 5 steps, explain the biochemical basis of Nephrotic Syndrome

A

⇒ Proteins are filtered and lost in urine (proteinuria)

⇒ Results in low plasma albumin and thus, low plasma oncotic pressure

⇒ Peripheral oedema occurs

⇒ The reduced circulatory volume activates RAAS

⇒ Na & water retention causes more oedema

35
Q

What is oedema?

A

Oedema is the abnormal accumulation of fluid in the interstial spaces

36
Q

In 4 steps, explain how oedema results from liver cirrhosis

A

⇒ Reduced albumin synthesis in liver

⇒ Results in low plasma albumin

⇒ Leads to low plasma oncotic pressure

⇒ Peripheral oedema occurs

37
Q

What is ascites?

A

Ascites is free fluid in the peritoneal cavity

38
Q

In 4 steps, explain how ascites results from liver cirrhosis

A

⇒ Low oncotic pressure occurs

⇒ Portal hypertension causes increased venous pressure in GI circulation

⇒ Fluid moves into peritoneal cavity (transudate)

⇒ Ascites occurs

39
Q

Describe the action of carbonic anhydrase inhibitors and a consequence of such

A
  • Inhibits action of Carbonic anhydrase in brush border & PCT cell
  • Can cause metabolic acidosis due to loss of HCO3- in urine
40
Q

Identify an example of a carbonic anhydrase inhibitor

A

Acetazolamide

41
Q

Describe the clinical use of carbonic anhydrase inhibitors

A

Treatment of glaucoma – reduces formation of aqueous humor in eye by about 50%

42
Q

Osmotic diuretics act by increasing the osmolarity of the kidney filtrate.

In 4 steps, explain how this leads to diuresis

A

⇒ Small inert molecules increase plasma osmolarity

⇒ Fluid drawn out from tissues and cells

⇒ Increased osmolarity of filtrate

⇒ Causes loss of H2O, Na+ and K+ in the urine

43
Q

Identify an example of an osmotic diuretic

44
Q

Describe a clinical use of osmotic diuretics

A

IV mannitol used to treat cerebral oedema

45
Q

Identify 7 adverse effects of diuretic use

A
  • Potassium abnormalities
  • Hypovolaemia (mainly loop)
  • Hyponatraemia
  • Increased uric acid → gout (thiazides & loop)
  • Glucose intolerance (thiazides & loop)
  • Gynaecomastia (spirinolactone)
  • Erectile dysfunction (thiazides)
46
Q

Identify 3 other substances which have diuretic action

A
  • Alcohol which inhibits ADH release
  • Coffee which increases GFR and decreases tubular Na+ reabsorption
  • Drugs which inhibit action of ADH on CT e.g. Lithium
47
Q

Identify 4 conditions which cause diuresis and present as polyuria

A
  • Diabetes Mellitus
  • Diabetes Insipidus (cranial – decreased ADH release)
  • Diabetes Insipidus (nephrogenic – poor response of CT to ADH)
  • Polydypsia

13 - Urinary (24 decks)

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