Diuretics Flashcards
Recap renal physiolpogy
Recap - see slides
How do diuretics work?
Inhibit the reabsorption of Na+and Cl- –> increase excretion therefore more water will follow.
Increase the osmolarity of tubular fluids. i.e decrease the osmotic gradient acrross the epithelia
What are the five main classes of diuretics?
- Osmotic diuretics - mannitol
- Carbonic anhydrase inhibitors - acetazolamide
Going to look at the bottom 3.
- Loop diuretics - frusemide (furosemide)
- Thiazides - bendrofluazide (bendroflumethiazide)
- Potassium sparing diuretics - amiloride, spironolactone.
Where do all 5 classes of diuretics act?
See diagram
Where is the action of loop diuretics?
Frusemide - act on the ascending limb blocking the Na+/2Cl-/K+ reuptake protein.
It reduces the counter current effect - most powerful diuretics we have. Can promote a 15-30% water excretion
Increase in tubular fluid osmolarity/decrease in osmolarity of medullary interstitium = decreased water reabsorption in the CD.
Side effects:
More potassium loss - the kidney will increase potassium loss to try to absorb more sodium in exchange. Decreased blood potassium
Slow leak of K+ creates a positive lumen potential. This positive change forces other positive ions to pass out of the lumen (Ca2+ and Mg2+) via the paracellular route. Because loop diuretics cause a big reduction in K+ reabsorption as well there is loss of these ions as well. Loss of positive lumen potential. Loss of K+ recycling.
Where do thiazide diuretics target?
DCT - block the Na+/Cl- cotrasnporter. Retain sodium in the tubule = increased water loss 10% water loss
Bendroflumethiazaide
What are the other effect of thiazide diuretics?
increase delivery of Na+ to distal tubule increase K+ loss (increase Na+/K+ exchange) – is common with thiazides
Increase Mg2+ loss and Increase Ca2+ reabsorption (unknown)
What is the problem with thiazide and loop diuretics?
Chronic use - fall in blood sodium. This means that over time that means the sodium filtered through the kidney will also be lower.
This will stimulate renin secretion, sensed by the macula densa.
Added problem with loop diuretics is than they directly inhibit the protein that brings Na+ into the cell.
You get a competition between the angiotensin and loop diuretics.
What are the classes of K+ sparing diuretics?
Aldosterone receptor antagonists - spirnolactone
Inhibitors of aldosterone-sensitive Na+ channels - amiloride
40% Na+ - PCT
35% Na+ - Ascending limb
10% Na+ - DCT
Target the DCT only 5% of absorption is inhibited
Other effects:
Decrease reabsorption of Na+ to distal tubule increase H+ retention (decrease Na+/H+ exchange)
Common side effects of loop diuretics and thiazides?
Hypokalemia Hyponatremia Hypovolemia Metabolic alkalosis Hyperuricemia - too much uric acid in the blood due to the organic anion transporter which is used to transport diuretics and uric acid to the lumen. When you use diuretics there is a competition.
What are the common side effects of potassium sparing diuretics?
Less Na/K+ exchange - hyperkalemia
What are diuretics used for?
Hypertension - thiazide type diuretic. Reserved for salt sensitive hypetension - better treated with thiazide diuretics.
Why use thiazides versus other diuretics?
Initial response (4-6weeks) - due to reduction plasma volume
After 4-6 weeks plasma volume restored - due to the renin angiotensin system
Chronic thiazides: very good vasodilators decreasing TPR. They activate eNOS (endothelium), Ca2+ channel antagonism, opening Kca channels (smooth muscle hyperpolarisation)
How are diuretics used in the treatment of heart failure?
See slide 59
Reduced CO
Increased SNS –> increased RAS.
Angiotensin II –> vasocontriction, cardiac remodelling
Loop diuretics are mainly used for heart failure - reduce pressure in the system so reduce pressure in the failing heart. Induce rapid fluid loss.
Chronically loop diuretics leads to RAS activation.
