Diuretics

Question 1

What are diuretics?

Answer 1

Increase water loss from kidneys by decreasing sodium reabsorption at different sites

Question 2

What are the 5 classes of diuretics?

Answer 2

Carbonic anhydrase inhibitors
Thiazide diuretics
Loop diuretics
Potassium sparing diuretic
Osmotic diuretics

Question 3

What is the mechanism of carbonic anhydrase inhibitors?

Answer 3

• work on the PCT
• carbonic anhydrase converts H2CO3 into H2O and CO2 which is absorbed by the PCT
• acts within PCT to transform H2CO3 to H+ and HCO3- and HCO3- is absorbed into blood whilst H+ excreted to restarts process
• therefore CA inhibitors stop reabsorption of bicarbonate

Question 4

When are CA inhibitors used clinically?

Answer 4

Lead to metabolic acidosis
Counteract AMS, HACE, PACE - counter-acts respiratory alkalosis due to hyperventilation
ACETAZOLAMIDE

Question 5

Side effects of CA inhibitors?

Answer 5

• metabolic acidosis
• sedation
• bone marrow suppression

Question 6

What is the mechanism of thiazide like diuretics?

Answer 6

Work on the DCT

• Na/K+ ATPase pump out Na+ and pump in K+
• Na+ and Cl- are reabsorbed from DCT lumen due to conc gradient created
• diuretics BLOCK Na+/Cl- symport transporter decreasing sodium reabsorption as no conc. gradient = diuresis as water will follow sodium into lumen

Question 7

What are the clinical effects of thiazide like diuretics?

Answer 7

Hypertension

Blood volume reduction

Question 8

Side effects of thiazide diuretics

Answer 8

Hypokalemia
Hyponatremia
Hypercalcaemia
Hyperglycaemia

Question 9

Examples of thiazide like diuretics

Answer 9

Bendroflumethiazide

Hydrochlorothiazide

Question 10

What is the mechanism of loop diuretics?

Answer 10

• work on ascending limb of LOH
• inhibits Na/K/2CL co-transporter
• decreases absorption of magnesium and calcium (through inhibiting potassium reabsorption into the cell as co-transporter inhibition prevents conc. gradient forming to allow Na+/K+ ATPase to function for K+ to re-enter the cells)

Question 11

Side effects of loop diuretics?

Answer 11

Hypokalemia as potassium excreted not absorbed
Dehydration
Kidney stones
Deafness
Hypotension

Question 12

Examples of loop diuretics?

Answer 12

Furosemide

Bumetanide

Question 13

What is the mechanism of potassium sparing diuretics?

Answer 13

• act on collecting tubules
• epithelial sodium channel antagonists:
  block channels, do not affect potassium channels, increased sodium loss = diuresis

Question 14

What is the clinical use of potassium sparing diuretics?

Answer 14

Heart failure
Hypokalaemia
Cirrhosis

Question 15

Side effects of potassium sparing diuretics

Answer 15

Hyperkalaemia

Hyponatremia

Question 16

What are spironolactone and eplerenone examples of?

Answer 16

Aldosterone antagonists

• upregulate epithelial sodium channels (ENACs)
• decrease sodium reabsorption = diuresis
• K+ not affected

Question 17

What is the clinical use of spironolactone/eplerenone?

Answer 17

Heart failure
Hyperaldosteronism
Hypokalaemia
Cirrhosis

Question 18

What are the side effects of spironolactone/eplerenone?

Answer 18

Hyperkalaemia
Hyponatraemia
Gynecomastia

Question 19

Examples of osmotic diuretics?

Answer 19

Mannitol

Question 20

Mechanism of osmotic diuretics

Answer 20

Any osmotically active molecule is free filtered from glom and not reabsorbed in tubules so sodium/potassium/water all dragged out from interstitial space

Question 21

What is the clinical use of osmotic diuretics?

Answer 21

Cerebral oedema/raised intracranial pressure

Question 22

Side effects of osmotic diuretics

Answer 22

Pulmonary oedema