Week 7 Diuretics Flashcards
What is the clinical use of diuretics?
Useful in conditions where Na and water retention causes expansion of ECF volume- heart failure
How does the normal tubular reabsorption of Na occur- what Na transporters are located on each tubule segment?
Na pumped across basolateral membrane by Na-K ATPase
Na across apical membrane down conc grad- water follows
PCT- Na-H anti porter , symporters- Na-glucose, Na-AA
Loop of Henle- Na-K-2Cl symporter
Early DT- Na-Cl symporter
Late DT and CD- ENaC in principle cells
How does ENaC in the Late DCT and CD affect K secretion?
Principle cells- Na reabsorbed by ENaC favours K secretion through K channels by creating a lumen negative potential
- diuretics block ENaC also reducing K secretion - K sparing
What are the 4 ways in which diuretics work?
- direct action on cells blocking Na transporters in luminal membrane
- antagonising aldosterone
- modification of filtrate- osmotic diuresis- small molecules freely filtered are not reabsorbed- increase osmolarity of filtrate-
What is a diuretic?
Diuresis- increased formation of urine by kidneys
Diuretics- substance/drug that promotes a diuresis
- they increase the renal excretion of water and Na= reduction in ECF volume
- fraction excretion (FE) increased
in what clinical situations are loop diuretics used?
- heart failure- diuretic effect- vaso and venodilaton (
in what clinical situations are early DCT diuretics used?
less potent- only 5% of Na reabsorption inhibited
inafective in renal failure
widely used in hypertension- vasodilation BUT higher incidence of hypokalaemia
what clinical situations are aldosterone antagonists affecting the late DCT and CD useful?
best drugs for treatment of hypertension due to primary hyperaldosteronism (conns syndrome) - due to adrenal hyperplasia or adrenal tumour= increased secretion of aldosterone= hypertension
- preferred drug for ascites and oedema in cirrhosis
- used in addition to loop diuretics in heart failure
what clinical situations are ENaC blockers affecting the late DCT and CD useful?
mild diuretics with K sparing effect- used in combination with K loosing diuretics such as loop or thiazide to minimise K loss
What diuretics work on the loop of henle and by what mechanism?
loop diuretics- Block Na-K-2Cl cotransporter in ascending limb
Eg furosemide, bumetanide
as 25% of filtered Na is reabsorbed in loop- blocking this leaves little chance for Na to be reabsorbed later on
how does aldosterone affect Na reabsorption and how do/ which diuretics affect this?
acts on principle cells of late DCT and CD - >Na reabsorption via ENaC
diuretics- aldosterone antagonists eg spironolactone- competitive inhibition of aldosterone receptor-
What diuretics work on the early DCT and by what mechanism?
thiazide diuretics- Block Na-Cl cotransporter- results in increased Ca reabsorption so less lost in urine
Eg bendroflimethiazide, metolazone
how does carbonic anhydrase affect Na reabsorption and what affect do diuretics have on this, give example?
enzyme affects Na and HCO3 reabsorption in PCT- diuretics inhibit this
eg acetazolamide
how do loop diuretics get to their site of action?
secreted into the lumen in PCT via anion pathway and then travel downstream to act on certain site
What diuretics work on the late DCT and the collecting duct and by what mechanism?
K sparing diuretics
- block ENac - amiloride, triamterene
- aldosterone antagonists
- both reduce loss of K and reduce Na channel activity- mild- only affect 2% of Na reabsorption
- both can produce life threatening hyperkaleamia- especially if used with ACE inhibitors, K supplements or in pts with renal impairment
