Cardiovascular diuretics

Question 1

What is the main role of diuretics?

Answer 1

Used to reduce sodium and water retention (oedema)

Question 2

Briefly describe how diuretics work

Answer 2

• Increase the excretion of sodium, and thus water
• Act directly by acting on the cells of the nephron
• Act indirectly by modifying filtrate content

Question 3

Diuretic working on which part of the nephron have the greatest effect and why?

Answer 3

The PCT/early in the nephron as they are able to block more sodium and chloride reabsorption

Question 4

In order to increase the volume of urine, give the order diuretics act on the nephron

Answer 4

• Osmotic diuretics
• Carbonic anhydrase inhibitors
• Loop diuretics – most important in vet practice
• Thiazides
• Potassium sparing diuretics

Question 5

Describe the mechanism of action of mannitol (an osmotic diuretic)

Answer 5

• Filtered but not reabsorbed so excreted unchanged so it maintains osmotic pressure within the filtrate
• main effects on parts of the nephron that are freely permeable to water
• Increases filtrate in PCT and decreases Na absorption

Question 6

When would an osmotic diuretic be used?

Answer 6

• Forced diuresis – e.g. poisoning
• Oliguric renal failure to stimulate urine output
• Cerebral oedema & glaucoma

Question 7

What is the main adverse effect of osmotic diuretics?

Answer 7

Cause an initial increase in ECF so may worsen pulmonary oedema or CHF

Question 8

What is the main drug used to treat glaucoma?

Answer 8

Carbonic anhydrase inhibitors

Question 9

Describe the mechanism of action of carbonic anhydrase inhibitors

Answer 9

• Distributed to tissues with high carbonic anhydrase activity (eye, kidney & RBCs)
• Reversibly inhibit CA enzyme predominantly in PCT leading to decreased H+ production and reduced Na+ H+ exchange.
• Bicarbonate reabsorption from the PCT is reduced and excretion of bicarbonate increases
• This results in diuresis and alkaline urine

Question 10

Why can carbonic anhydrase inhibitors not be used in liver disease?

Answer 10

Alkaline urine means that ammonium produced in the kidney is not lost in urine but is put into systemic circulation

Question 11

What is the most powerful diuretic?

Answer 11

Loop diuretics

Question 12

Name an example loop diuretic

Answer 12

Furosemide

Question 13

Loop diuretics inhibit what in the Loop of Henle? What are the effects of this?

Answer 13

The NaKCl2 cotransporter

- Increased delivery of sodium ions to the DCT, causing increased excretion

Question 14

What are the 2 main uses of loop diuretics?

Answer 14

• Treatment of oedema

- Essential management of CHF

Question 15

What are the adverse effects of loop diuretics?

Answer 15

• Excessive sodium and water loss leading to dehydration and hypovolaemia
• Hypokalaemia

Question 16

Name an example of a thiazide?

Answer 16

Hydrochlorothiazide

Question 17

Where do thiazides act?

Answer 17

DCT

Question 18

What makes thiazides less powerful diuretics than loop diuretics?

Answer 18

A high majority of sodium has already been reabsorbed

Question 19

Thiazides decrease excretion of…?

Answer 19

Calcium

Question 20

When are potassium sparing diuretics use?

Answer 20

Used with thiazides and loop diuretics to help prevent hypokalaemia

Question 21

Describe the MOA of potassium sparing diuretics

Answer 21

• Act on the principle cells of the DCT and CD
• Competitive inhibitors of aldosterone
• cause inhibition of sodium reabsorption and thus Na+ K+ ATPase activity

Question 22

Why do diuretics often cause hypokalaemia?

Answer 22

They also increase K ion loss in the urine