W26 Diuretics (SM)

Question 1

What is Diuresis?
What is the role of diuretic drugs?

Answer 1

• Excretion of water from the body in the form of urine
• They target to increase Na+ excretion

Question 1

How to increase diuresis?

Answer 1

• Natriuresis (Na+ excretion) as when Na+ is excreted, water follows.
• Osmotic (concentration) gradient system for water movement from artery to tubular lumen is provided by Sodium (Na+ excretion- Natriuresis)

Question 2

Sodium Reabsorption. How much % sodium is reabsorbed?

Answer 2

65% PCT
25% Loop of H
5% DCT
5% CD

Question 3

Diuretic drugs:
Where do… act?
1. Osmotic agents?
2. Loop Diuretics?
3. Thiazide diuretics?
4. Potassium-sparing diuretics?
Which is a potent diuretic?

Answer 3

PCT - highly potent
LH- potent
DCT- weak
CD- weak

Question 4

What are Osmotic agents?
What is an example?
Side effects?

Answer 4

• A non-reabsorbable solute, Inert (no pharmacological effect)
• Filtered through glomeruli but poorly reabsorbed
• Increase osmolarity of tubular fluid in PCT and LH
• Prevent passive water reabsorption- lead to increased urine volume/output and may lead to hypernatremia
  Ex. Mannitol, (used in cerebral oedema and used to reduce intraocular pressure before eye surgery)

Side effects: Hyperkalaemia, Dehydration and hypernatremia
Extracellular volume expansion can complicate heart failure & produce pulmonary oedema

Question 5

What are Loop Diuretics?
Example?
What are they used to treat? (3)

Answer 5

• “High-ceiling” diuretics due to very powerful diuretic effect
• Cause 15-25% of filtered Na+ to be excreted
• Block Na+/K+/2Cl- symporter @ thick ascending limb of the LH
  Ex. Furosemide (frusemide), bumetanide

USE:
* Chronic heart failure: reduce pulmonary and peripheral oedema
* Venodilators: a rapid effect in acute left ventricular failure
* Acute renal failure to improve diuresis

Question 6

What are the SE of loop diuretics?

Answer 6

• Hypokalaemia (Increases Na+ delivery to DCT and promotes K+ loss)
• Disturb the hyperosmotic interitem in the medulla
• Decrease reabsorption of calcium and magnesium (due to the loss of transepithelial potential)
• Decrease NaCl entry into macula densa tubular cells
  -promotes renin release and increased AngII activity

After some hours of LD use, the kidney becomes refractory

Question 7

What are Thiazide & Thiazide-Like Diuretics?

Answer 7

• Moderately powerful diuretics
  (~5% of filtered Na+ to be excreted)
• Block Na+ / Cl- symporter of early DCT
• Inhibit active Na+ reabsorption and accompanying Cl- transport (promote natriuresis and diuresis)

‘ide’ & ‘one’ drugs
* Bendroflumethiazide
* Thiazide-related:
-chlortalidone, indapamide

Question 8

Side effects of Thiazide & Thiazide-Like Diuretics?

Answer 8

*Hypokalaemia (Potassium loss due to increased sodium delivery to distal tubule)
*metabolic alkalosis (increased hydrogen ion loss in the urine)
*dehydration (hypovolemia),
*leading to hypotension
* hyponatremia

• Major clinical problem:
• more negative membrane potential
  → cardiac arrhythmias
  → reduce the activity of Na+/K+ ATPase pump

Clinical considerations
o Potassium supplements
o Potassium-sparing diuretics
o ACEi’s (as they cause hyperkalaemia)

Question 9

What are Potassium-Sparing Diuretics?

Answer 9

• Aldosterone receptor antagonists (spironolactone, eplerenone)
  – Antagonize aldosterone (mineralocorticoid) receptors
  – Prevent insertion of pumps (Na+/K+ ATPase) and channels (ENaC) in late DCT and CD.
  – Used in primary and secondary hyperaldosteronism.
  – Also, oedema and ascites associated with liver failure
• Na+ channel blockers (Amiloride and triamterene)
• Block apical ENaC in late DCT and CD
• Na+ no longer retained at expense of K+