Diuretics Flashcards
What are diuretics?
Diuretics are a common medication that work to diminish sodium reabsorption at different sites of the nephron in order to increase urinary sodium and water loss.
What is acetazolamide?
A carbonic anhydrase inhibitor (form of diuretic)
What is the main use of carbonic anhydrase inhibitors such as acetazolamide?
The main use of these drugs is not as a diuretic, but is used in the treatment of glaucoma, epilepsy and mountain sickness (as it can induce a metabolic acidosis to compensate for the respiratory alkalosis that occurs with hyperventilation at altitude)
Explain how carbonic anhydrase inhibitors (such as acetazolamide) act as diuretics
You stop reabsorbing sodium, and you stop excreting hydrogen ions which means that more water leaves the blood due to the increased levels of sodium in the renal tubule
What are the side-effects of carbonic anhydrase inhibitors such as acetazolamide?
Metabolic acidosis can occur (contra-indicated in significant chronic kidney disease), sedation and can lead to bone marrow suppression (due to action as a sulphonamide antibiotic)
What is the most potent type of diuretic?
Loop diuretic
What are frusemide and bumetanide?
Loop diuretics
What are loop diuretics used to treat?
This is the most potent diuretic and it is used in the treatment of hypertension, heart failure and volume overload fom chronic renal failure
Explain the mechanism of action of loop diuretics
Blockage of the Na+/K+/Cl- transporter leads to the dysfunction of the entire loop mechanism as these aren’t pumped out of the tubule into the interstitium in the thick ascending limb, and therefore water and electrolytes won’t diffuse down the concentration gradient at the thin descending limb, and therefore the urine will remain dilute a nd there will be loss of sodium, magnesium, sodium and calcium
Name two loop diuretics
Frusemide and bumetanide
What are the side-effects of loop diuretics?
hypokalaemia, dehydration (which can lead to acute renal failure), kidney stones and deafness
What are Bendroflumethiazide and Hydrochlorothiazide?
Thiazide diuretics
Name some thiazide diuretics
Bendroflumethiazide, Hydrochlorothiazide and Thiazide-like drugs such as Chlorthalidone, Indapamide and Metolazone
Why may an individual be prescribed thiazide diuretics?
Primarily used as an anti-hypertensive but can also work to reduce plasma volume and peripheral resistance
What is the mechanism of action of thiazide diuretics?
Inhibits the Na+/Cl- symporter in the distal convoluted tubule, therefore these molecules remain in the tubular fluid and cause the formation of more dilute urine
What are the side-effects of thiazide diuretics?
Hypokalaemia, hypercalcaemia, hyponatraemia, hyperglycaemia and hypercholesterolaemia
Which kinds of diuretics are ‘potassium-sparing’?
Epithelial sodium channel antagonists (amiloride and triamterene) and aldosterone antagonists (spironolactone and epleronone)
What are amiloride and triamterene?
These are epithelial sodium channel antagonists, and are therefore potassium-sparing diuretics
What are spironolactone and eplerenone?
Aldosterone antagonists which are a form of potassium-sparing diuretic
Why may an individual be prescribed amiloride (an epithelial sodium channel antagonist)?
Amiloride this is used in the treatment of heart failure, hypokalamia (produced by other diuretics) and liver cirrhosis
Explain the mechanism of action of amiloride (epithelial sodium channel antagonist)
It blocks the sodium channel on the principal cells of the collecting tubule and therefore prevents the diffusion of sodium into the cells and into the blood where there would be an osmotic gradient for water reabsorption.
What side-effects may occur as a result of taking amiloride or triamterene (epithelial sodium channel antagonists)?
Hyperkalaemia (it’s a potassium-sparing diuretic) and hyponatraemia
Why may an individual be prescribed spironolactone or eplerenone (aldosterone antagonist)?
Used in hyperaldosteronism, heart failure, hypokalaemia (from other diuretics) and cirrhosis
Explain the mechanism of action of spironolactone or eplerenone (aldosterone antagonist)
Antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site; this causes increased potassium uptake but increased sodium and water excretion –> increased water loss.
What side effects may occur as a result of taking spironolactone or eplernone (aldosterone antagonist)?
HYPERKALAEMIA! Gynaecomastia (not with epleronone) and hyponatraemia
Name two types of osmotic diuretic?
Mannitol and glucose
Why may an individual be prescribed an osmotic diuretic?
If they have cerebral oedema and oliguric (reduced urinary output) acute renal failure
How do osmotic diuretics work?
These are osmotically active molecules that are freely filtered in the glomerulus and not reabsorbed by the tubules water follows this osmotic gradient into the tubule fluid and also decreased the reabsorption of all solutes in general such as sodium, potassium, urea and ‘drags’ sodium from the interstitial space
What are the potential consequences of using osmotic diuretics?
Can cause transient fluid overload which can lead to pulmonary oedema
When shouldn’t you use diuretics?
If an individual is hypotensive, dehydrated, hypokalaemia (no thiazide or loop diuretics) or hyperkalaemic (no spironolactone or amlidoride), or post-surgery if there’s a low urinary output.
On which cells do thiazide diuretics act?
Distal convoluted tubule
On which cells do loop diuretics act?
Thick ascending limb of Loop of Henle
On which cells do carbonic anhydrase inhibitors act?
Proximal convoluted tubule
Where do potassium sparing diuretics act?
Collecting tubule
