Diuretics Flashcards
what is the basic mechanisms of diruetics
- they reduce the sodium reabsorption at different sites of the nephron
- therefore they cause an increase in urinary sodium and water loss
What are the three ways in which the kidney handles sodium
Filtration
Reabsorption
Excretion
describe how the loop of Henle works
You take filtrates and the fluid comes down the loop of Henle and the descending walls are permeable to sodium and chloride, diffuse down there concentration gradient into the medulla and water follows down the concentration gradient
Makes the solute more concentrated therefore at the tip of the loop of henle it is most concentration
Then at the ascending limb the walls are water tight so water cant leave
Activate transport of sodium chloride and this dilutes the filtrate again and you end up with more dilute urine then what you started with
Name the 5 Different classes of diuretics
Carbonic anhydrase inhibitors Loop Thiazide Potassium sparing diuretics Osmotic diuretics
what is an example of carbonic anhydrase inhibitor
Acetazolamide
How does a carbonic anhydrase inhibitor work as a loop diuretic
Normally
- In the proximal convoluted tubule have salt and water in the tubular lumen,
- normally bicarbonate joins with the hydrogen ions and forms H2CO3 this then dissociates into water and CO2 which diffuse into PCT cells,
- CA controls this,
in the cell this same reaction happens but in reverse - CA also controls this
- the hydrogen ions via a sodium hydrogen antiporter diffuse back into the lumen urine therefore for every hydrogen entering the lumen uirne sodium diffuses back into the proximal convulted tubule
- the bicarbonate diffuses back into the blood and is reabsorbed down the concentration gradient
Therefore a carbon anhydrase inhibitor blocks this action by preventing H2CO3 being converted inot H20 and CO2 and preventing CO2 and H20 converting back to H2CO3
- therefore either are no hydrogen ions for the sodium hydrogen antiporter therefore sodium does not diffuse into the proximal convoluted tubule and is excreted this causes water to be excreted
what is the main use of acetazolamide (carbonic anhydrase)
- main use is not as a diuretic
- glaucoma
- epilepsy
- mountain sickness - causes a metabolic acidosis to counteract respiratory alkalosis
what are the side effects of acetazolamide (carbonic anhydrase)
metabolic acidosis - contraindicated in significant CKD
- sedation
- sulphonamide antibiotics which can lead to bone marrow suppression
Name two types of loop diuretics
Frusemide
Bumetanide
How do loop diuretics work
= works in the thick ascending limb
- Blocks the Na/K/2Cl
- this means sodium remains in the urine therefore water reabsorption is inhibited
- can also loose calcium and magnesium due to the need to maintain electroneutrality of the cell
what does loop direutics cause in terms of calcium and magensium
Hypocalemia
hypomagensium
- increase in these in the urine and decrease in the blood
what is the most potent direutic
loop diuretic
what does loop diuretics excrete
Excretion of potassium, sodium and water, calcium magnesium
when would you use a loop diuretic
Hypertension
Heart failure
Volume overload from CKD
What are the side effects of loop diuretics
Hypokalaemia
Dehydration…Acute renal failure
Kidney stones - high amount of calcium in the urine
Deafness- only in high doses
what are the examples of thiazides
Bendroflumethiazide
Hydrochlorothiazide
Thiazide like drugs: - do the same job of thiazide
- Chlorthalidone
- Indapamide
- Metolazone
Name some thiazide like diruetics
Thiazide like drugs: - do the same job of thiazide
- Chlorthalidone
- Indapamide
- Metolazone
How do a thiazide diuretic work
= works in the distal convoluted tubule
- blocks sodium and chloride symporter
- this prevents sodium entering the distal convulted tubule therefore prevents water reabsorption
what is the effect of thiazide diuretics on calcium
- cause hypercalemia as they cause calcium to enter the distal convulted tubule to maintian electroneutralisity thereofre they increase the amoutn of calcium being reasborbed in the blood
what are thiazide used for
- Primarily an antihypertensive
Effect beyond diuretic effects…
- Reduction in plasma volume
- Reduction in peripheral resistance
what are the side effects of thiazide diuretics
Electrolyte effects:
- Hypokalaemia
- Hypercalcaemia
- Hyponatraemia (particularly in old people)
Hyperglycaemia
Hypercholesterolaemia
what are the two different types of potassium sparing direutics
- epithelial sodium channel antagonists
- aldosterone antagonists
name some examples of potassium sparing diuretics
Epithelial Na Channel antagonists
- Amiloride
- Triamterene
Aldosterone antagonists:
- Spironolactone
- Eplerenone
How does epithelial sodium channel antagonists work (amiloride and triamterene)
= collecting tubule
- it blocks the EnAC sodium reabsorption
- this prevents sodium reasborption
- this means that potassium isnt excreted in order to maintain electroneturality
why do some diuretics end up with hypokalemia
In the collecting tubule there is a sodium channel and a potassium channel
- the more sodium ions that are reabsorbed the more potassium ions that are excreted out of the collecting tubule in order to maintain the electroneutrlaitiy of the collecting tubule
- therefore more potassium is excreted
- thiazides cause more sodium lumen urine thereofre when you get to the collecting tubule more sodium is reabsorebd by the sodium channel thereofr ethis casues more potassium ions to be excreted
what are the clinical uses of epithelial sodium channel antagonists work (amiloride and triamterene)
Heart failure
Hypokalaemia (from other diuretics)
- Co-amilofruse (amiloride and fruesmodie)
- Co-amilozide ( amiloride and thiazide)
Cirrhosis
what are the side effects of epithelial sodium channel antagonists (amiloride and triamterene)
Hyperkalaemia
Hyponatraemia
How do aldosterone antagonists work (spironolactone)
- they prevent aldosterone from acting -
take a bit of time to work - this prevents the insertion of sodium EnAC channels
- therefore prevents sodium reabsorption and excrete less potassium
what are the uses of aldosterone antagonists work (spironolactone)
Hyperaldosteronism (Conns)
Heart failure
Hypokalaemia (from other diuretics)
Cirrhosis
What are the side effects of aldosterone antagonists work (spironolactone)
Hyperkalaemia
Gynecomastia (not eplerenone)
Hyponatraemia (Cirrhosis)
How do osmotic direusis work
- any osmotically active molecule that is freely filtered in the glomerulus and is not reabsorbed by the tubules e.g. not clincially (glucose)
- this works by water reasborption
- it also reasborbs sodium potassium and urea
what is the most clinical osmotic diuresis
Mannitol
when can osmotic diuretics be used
Cerebral oedema - causes fluid to go out of the interstitial tissues and into the blood leading to excretion of fluid and stopping brain swelling
Oliguric acute renal failure
What are the side effects of osmotic diuresis
Transient fluid overload
- Pulmonary odema
Other non pharmacological osmotic diuretics
- Glucose- DKA/HHS
- Urea - Disequilibrium syndrome
When do you not use diuretics
When hypotensive – make blood pressure worst
When dehydrated – don’t want to loose more fluid
When hypokalaemic (Loop/Thiazide) – loop potassium should stop loop and thiazide
When hyperkalaemic (Amiloride, aldosterone antagonists) – stop potassium sparing direutics
Post surgery, with a poor urine output – need to give fluids and not diuretics – people who have had surgery and pass less urine don’t make it artificial with diuretics
