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Kirstys Flashcards > CPT2: Renal diuretics > Flashcards

CPT2: Renal diuretics Flashcards

1
Q

What can diuretics be used for?

A
  • Hypertension
  • Heart failure
  • Tissue swelling (oedema)
  • Polycystic ovary syndrome
  • Certain kidney disorders e.g. kidney stones
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2
Q

How do diuretics work?

A
  • They increase excretion of Na+ and water
  • The decrease reabsorption of Na+, Cl- and water
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3
Q

What do the following mean?

  1. Diuresis
  2. Natriuresis
A
  1. Increased or excessive urine production
  2. Increased or excessive Na in the urine
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4
Q

What are the general mechanisms in which diurtics can work?

A
  • Directly by acting on cells of the nephron
  • Indirectly by action modifying content of filtrate
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5
Q

What are example of direct diuretics and their site of action?

A
  1. Proximal convoluted tubule - Carbonic anhydrase inhibitors
  2. Loop of henle - loop diutetics
  3. Distil convoluted tubule - thiazides
  4. Collecting tubules - aldosterone antagonists and amiloride
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6
Q

What is absorbed in the loop of henle, how?

A
  • 25-35% Na+ and Cl- is reabsorbed in the thick ascending loop of Henle (majority of Na+ absorbed here)
  • Mainly reabsorbed through luminal (apical) NCCK2 pump. 1 Na+ in, 1 K+ in, 2 Cl- in
  • Relatively impermeable to water
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7
Q

Where do loop diuretics target?

A

NKCC2 pump

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8
Q

Function of loop henle or loop diuretics???

A

reduction in the osmolality of tubular fluid

and

generation of hyperosmotic extracellular environment surrounding medullary loop, vasa recta and collecting duct

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9
Q

How do loop diuretics work?

What is the result and why is this useful?

A
  • Usually taken orally therefore:
    1. Swallowed and absorbed
    2. Binds to plasma proteins
    3. Is secreted into the proximal tubule by organic acid transporters (This means the drug can acess the apical membrane)
    4. Blocks NKCC2 by binding at the Cl- binding site and inhibiting it
    5. This reduces Na+ Cl- and K+ reabsorbetion
    6. Reduces Ca2+ and Mg reabsorption
    7. Promotes production of dilute urine as more Na+ in tubules therefore more water.
    8. Results in decreased blood volume. Ideal for hypertension or odema
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10
Q

What is the impact of loop diuretics?

A
  • Disruption of Na and Cl reabsorption in the loop of henle leads to more electrolytes in the tubule and less in the extracellular space and vasa recta
  • This rduces the osmotic force driving water reabsorption in the collecting ducts
  • As a result more water and Na passed out in urine and more dilute urine
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11
Q
A
  • Loop diuretics change the osmolarity of the tubular fluid sensed by the macula densa and juxtaglomerular apparatus which in turn modify the feedback control of renal blood flow
  • BUT

loop diuretics also block the NKCC2 transporter in the macula densa cells and have vasodilator effects on the afferent arterioles prior to any diuretic effect

AND there is a chronic adaption to diuretics by stimulation of the RAAS

  • Loop diuretics stimulate renin release:
    (i) via inhibition of macula densa NKCC2 leads to volume independent renin release
    (ii) via stimulation of renal prostacyclin and nNOS that in turn stimulate renin release
    (iii) Lowering ECF reduces stretch of juxtaglomerular cells which leads in turn stimulates renin release

Other effects may be via changes in cAMP, sympathetic innervation, ANP feedback etc…..

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12
Q

What is an example of a loop diuretic?

What are the adverse effects?

A

Furosemide

  • Hypokalemia (low plasma K+)
  • low electoryltes
  • Ototoxicity (deafness or vertigo) - only if dose too strong
  • MASSIVE DIURESIS OF 35% FILTRATE CAUSES RAPID REDUCTION IN BLOOD VOLUME
  • Hyperuricdaemia
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13
Q

What transporters are available in the disal tubules?

A
  • APICAL:
    • electroneutral Na/Cl co-transporters (1Na in and 1 CL in)
  • Basolateral
    • Cl- ion channels
    • Na/K pump
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14
Q

What is the function of the distal tubule?

A
  • Part of the tubule for further diluting luminal fluid
  • 5-10% of filtered Na+ reabsorbed
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15
Q

How do thiazides work?

What are there effects?

A
  • The block Na/Cl transporters on the distal apical membrane by binding to the Cl- binding site on the receptor
  • Reduced blood volume stimulates renin secretion therefore limited actions on blood pressure
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16
Q
  1. What is an example of a thaizidine?

What can be said about:

  1. It as a diuretic
  2. How it is taken
  3. Onset
  4. Half life
  5. Maximal around
  6. excretion
A
  1. Hydrochlorothiazidine
  2. weaker diuretic
  3. orally
  4. 1hr
  5. 8-12hr
  6. 4-6hr
  7. varies
17
Q

Uses of thiazidines

A
  • Heart failure
    • Loop diuretics preferred
  • Hypertension
  • Odemea
    • In conjuction with loop diuretics
  • Osteoperosis
    • Decreased Ca2+ excretion
18
Q

What are adverse effects of thiazides?

A
  • Hypokalaemia
    • Delivery of more Na+ to distal portions
    • Na+ reabsorbed and replaced with K+
  • Lowered excretion of uric acid
    • Incereased proximal reabsorption
    • Reduced tubular secretions
  • Hypocalciuria
    • Decreased Ca+ excretion
    • Benefical for bone metabolism
    • Reduction in stone formation
  • SIMILAR TO GITELMAN’S AND BARTTER’S SYNDROME
    • DISORDERS AFFECTING TRANSPORTERS
    • RENAL SALT LOSS and LOW BLOOD PRESSURE
19
Q

How does reabsorption occur in collecting tubules?

A
  • Na+ transported in by apical Na+ channels (e.g. ENaC)
  • K+ transported out by K+ channels
  • Voltage difference favours K+ secretion
  • High intracellular-to-lumen K+ gradient favours K+ secretion
  • Almost all K+ secretion occurs here
20
Q

What effect does aldosterone have on reabsorption in the collecting tubules?

A
  • Caues synthesis of new ptoreins and insertion of ENaC and K+ channels i the collectinf tubules by activation of receptors in principle cells
  • This causes increased absotpion
21
Q

What are target sites in collecting tubules

A

To block Na+ reabsorption:

  • BLock Na+ channel protines
  • Block synthesis of channels e.g. mineralocorticoid receptor
22
Q

What are examples of potassium sparing diuretics and there function

A
  1. Spironolactone (aldosterone antagonist)
    • Inhibits synthesis of channels
    • Reduced Na+ reabsorption and K+ sectretion
  2. Triamterene and Amiloride
    • Inhibits luminal ENaC
    • Reduced Na+ reabosrption and K+ secretion
23
Q

What are clinical uses for potassium sparing diuretics?

A
  • Heart failure
  • Mild to moderate hypertension
    • Effective at reducing BP
  • Hyperaldosteronism (conns sy drome)
  • Secondary hyperaldosternoism
24
Q

Adverse effects of potassuim sparing diureticd

A
  • Hyperkalemia
    *
25
Q

How do carbonic anhydrase inhibitors work?

What effects is there?

A
26
Q

What is an example of a carbonic anhydrase inhibitor?

What is it used for?

A
27
Q
A

Kirstys Flashcards (116 decks)

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