Diuretics

Question 1

what is the basic mechanisms of diruetics

Answer 1

• they reduce the sodium reabsorption at different sites of the nephron
• therefore they cause an increase in urinary sodium and water loss

Question 2

What are the three ways in which the kidney handles sodium

Answer 2

Filtration
Reabsorption
Excretion

Question 3

describe how the loop of Henle works

Answer 3

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

Question 4

Name the 5 Different classes of diuretics

Answer 4

Carbonic anhydrase inhibitors
Loop
Thiazide
Potassium sparing diuretics
Osmotic diuretics

Question 5

what is an example of carbonic anhydrase inhibitor

Answer 5

Acetazolamide

Question 6

How does a carbonic anhydrase inhibitor work as a loop diuretic

Answer 6

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

Question 7

what is the main use of acetazolamide (carbonic anhydrase)

Answer 7

• main use is not as a diuretic
• glaucoma
• epilepsy
• mountain sickness - causes a metabolic acidosis to counteract respiratory alkalosis

Question 8

what are the side effects of acetazolamide (carbonic anhydrase)

Answer 8

metabolic acidosis - contraindicated in significant CKD

• sedation
• sulphonamide antibiotics which can lead to bone marrow suppression

Question 9

Name two types of loop diuretics

Answer 9

Frusemide

Bumetanide

Question 10

How do loop diuretics work

Answer 10

= 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

Question 11

what does loop direutics cause in terms of calcium and magensium

Answer 11

Hypocalemia
hypomagensium
- increase in these in the urine and decrease in the blood

Question 12

what is the most potent direutic

Answer 12

loop diuretic

Question 13

what does loop diuretics excrete

Answer 13

Excretion of potassium, sodium and water, calcium magnesium

Question 14

when would you use a loop diuretic

Answer 14

Hypertension
Heart failure
Volume overload from CKD

Question 15

What are the side effects of loop diuretics

Answer 15

Hypokalaemia

Dehydration…Acute renal failure

Kidney stones - high amount of calcium in the urine

Deafness- only in high doses

Question 16

what are the examples of thiazides

Answer 16

Bendroflumethiazide
Hydrochlorothiazide

Thiazide like drugs: - do the same job of thiazide

• Chlorthalidone
• Indapamide
• Metolazone

Question 17

Name some thiazide like diruetics

Answer 17

Thiazide like drugs: - do the same job of thiazide

• Chlorthalidone
• Indapamide
• Metolazone

Question 18

How do a thiazide diuretic work

Answer 18

= works in the distal convoluted tubule

• blocks sodium and chloride symporter
• this prevents sodium entering the distal convulted tubule therefore prevents water reabsorption

Question 19

what is the effect of thiazide diuretics on calcium

Answer 19

• 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

Question 20

what are thiazide used for

Answer 20

• Primarily an antihypertensive

Effect beyond diuretic effects…

• Reduction in plasma volume
• Reduction in peripheral resistance

Question 21

what are the side effects of thiazide diuretics

Answer 21

Electrolyte effects:

• Hypokalaemia
• Hypercalcaemia
• Hyponatraemia (particularly in old people)

Hyperglycaemia

Hypercholesterolaemia

Question 22

what are the two different types of potassium sparing direutics

Answer 22

• epithelial sodium channel antagonists

- aldosterone antagonists

Question 23

name some examples of potassium sparing diuretics

Answer 23

Epithelial Na Channel antagonists

• Amiloride
• Triamterene

Aldosterone antagonists:

• Spironolactone
• Eplerenone

Question 24

How does epithelial sodium channel antagonists work (amiloride and triamterene)

Answer 24

= collecting tubule

• it blocks the EnAC sodium reabsorption
• this prevents sodium reasborption
• this means that potassium isnt excreted in order to maintain electroneturality

Question 25

why do some diuretics end up with hypokalemia

Answer 25

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

Question 26

what are the clinical uses of epithelial sodium channel antagonists work (amiloride and triamterene)

Answer 26

Heart failure Hypokalaemia (from other diuretics) - Co-amilofruse (amiloride and fruesmodie) - Co-amilozide ( amiloride and thiazide) Cirrhosis

Question 27

what are the side effects of epithelial sodium channel antagonists (amiloride and triamterene)

Answer 27

Hyperkalaemia Hyponatraemia

Question 28

How do aldosterone antagonists work (spironolactone)

Answer 28

- 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

Question 29

what are the uses of aldosterone antagonists work (spironolactone)

Answer 29

Hyperaldosteronism (Conns) Heart failure Hypokalaemia (from other diuretics) Cirrhosis

Question 30

What are the side effects of aldosterone antagonists work (spironolactone)

Answer 30

Hyperkalaemia Gynecomastia (not eplerenone) Hyponatraemia (Cirrhosis)

Question 31

How do osmotic direusis work

Answer 31

- 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

Question 32

what is the most clinical osmotic diuresis

Answer 32

Mannitol

Question 33

when can osmotic diuretics be used

Answer 33

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

Question 34

What are the side effects of osmotic diuresis

Answer 34

Transient fluid overload - Pulmonary odema Other non pharmacological osmotic diuretics - Glucose- DKA/HHS - Urea - Disequilibrium syndrome

Question 35

When do you not use diuretics

Answer 35

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