Urinary: Diuretics Flashcards
What is a diuretic?
A drug that promotes a diuresis by increasing renal excretion of water and sodium which causes a reduction in ECF volume.
What are some clinical conditions where diuretics should be considered?
Conditions where sodium and water retention cause expansion of ECF volume.
- heart failure
- cirrhosis
- nephrotic syndrome
What are the different classes of diuretics?
and give an example for each
- Loop diuretics eg furosemide
- Thiazide diuretics eg bendroflumethiazide
- Potassium sparing diretics
- Inhibitors of renal Na channels eg amiloride
- Aldosterone antagonists eg spironolactone
- Carbonic anhydrase inhibitors eg acetazalamide
- Osmotic diuretics eg mannitol
How do loop diuretics work?
Act on the loop of henle and block Na-K-2Cl cotransporter.
Usually in the LoH 25% of Na+ is reabsorbed, and then the K+ drifts back into lumen via K channels. This creates a lumen positive potential which helps to drive absorption of positive ions such as Ca2+ and Mg2+.
Therefore can be used in hypercalcaemia to increase calcium excretion.
They are very potent diuretics (25% of Na)
How do thiazide diuretics work?
When are they used?
Act on the early distal tubule and block the Na-Cl symporter.
Blocking Na absorption in the PCT increases calcium absorption so they are good for use in the elderly and people with osteporosis.
Not very potent (only 5% Na) and widely used in hypertension.
How do K+ sparing diretics work?
When should they NOT be used and why?
Act on late DCT and CD and block ENaC
Mild diuretic - only affects 2% of Na+ reab, and reduce the loss of K+
Therefore should not be used with ACE inhibitors, K+ supplements or renal impairment
How do aldosterone antagonists work?
When should they NOT be used and why?
Aldosterone usually acts on principle cells of late DT and CD to increase Na+ reabsorption via ENaC.
Aldosterone antagonists competitively bind to the aldosterone receptor to reduce the effect of aldosterone and decrease Na+ reabsorption.
Mild diuretic - only affects 2% of Na+ reab, and reduce the loss of K+
Therefore should not be used with ACE inhibitors, K+ supplements or renal impairment
How do osmotic diuretics work?
(note these are not usually used but useful for cerebral oedema)
They modify the filtrate content:
They are small molecules that are freely filtered by the glomerulus but not absorbed, therefore increase osmolarity of the filtrate which reduces Na+ and water reab throughout the tubule.
How do carbonic anhydrase inhibitors work?
(note these are not usually used however useful in the treatment of glaucoma as they reduce formation of aqueous humour by ~50%)
They inhibit carbonic anhydrase in the PCT which interferes with Na+ and HCO3- reab in PCT.
When are loop diuretics used?
Used in heart failure for diuretic effect and they also reduce after and preload due to vaso and venodilation.
Furosemide is given IV in acute pulmonary oedema for rapid action - takes around 30 mins to work.
Can be used in hypercalcaemia but given with IV fluids to prevent dehydration and hypokalaemia.
Used in nephrotic syndrome, renal failure and cirrhosis
Explain why there is an increase in ECF volume in renal failure
There is reduced renal perfusion which activates the RAAS system
This causes Na and water retention leading to an increase in ECF volume and oedema
Explain why there is an increase in ECF volume in congestive heart failure
There is an increase in systemic venous pressure leading to peripheral oedema. There is a drop in cardiac output.
Both lead to reduced renal perfusion which activates the RAAS system
This causes Na and water retention leading to an increase in ECF volume
