Diuretics

Question 1

Recall the transporters present on the apical and basal membranes of the proximal convoluted tubule

Answer 1

Apical: Na+ channels, Na+/H+ countertransporter
Basal: Na+/K+ ATPase, Na+/HCO3- cotransporter
Water enters apical membrane via osmosis
Water, glucose and amino acids follow Na+ movement

Question 2

In which part of the nephron is carbonic anhydrase active?

Answer 2

PCT

Question 3

Which class of diuretic acts specifically on the PCT? Give an example

Answer 3

Carbonic anhydrase inhibitors eg acetazolamide

Question 4

Recall the MOA of carbonic anhydrase inhibitors

Answer 4

Inhibits CA, therefore Na+ cannot be transported in with H+, so less Na+ is reabsorbed

Question 5

Recall the transport that takes place in the DL of the LOH

Answer 5

Only water movement

Question 6

Recall the transporters present in the apical and basal membranes of the AL of the LOH

Answer 6

Apical: triple transporter than cotransports Na+, K+ and 2Cl- into cell
Basal: Na+/K+ ATPase, K+/Cl- cotransporter

Question 7

Which class of diuretic acts on the AL of the LOH specifically?

Answer 7

Loop diuretics

Question 8

Give an example of a loop diuretic

Answer 8

Frusemide

Question 9

Recall the MOA of frusemide

Answer 9

1. Inhibits triple transporter so less Na+ reabsorbed

2. Inhibits K+ cycling, which reduces electrochemical gradient, so less Mg++ and Ca++ is lost too

Question 10

Recall the indications for loop diuretics

Answer 10

Oedema

Question 11

Recall the side effects of loop diuretics

Answer 11

Hypokalaemia, hypovolaemia, metabolic alkalosis, Mg++, Ca++ and K+ loss

Question 12

Recall the transporters present in the apical and basal membranes of the early DCT

Answer 12

Apical: Na+/Cl- cotransporter
Basal: Na+/k+ ATPase, K+/Cl- cotransporter

Question 13

Recall which class of diuretics act on the early DCT specifically and give an example

Answer 13

Thiazides - bendoflumethiazide

Question 14

Recall the MOA of thiazide diuretics

Answer 14

Inhibit the Na+/Cl- cotransporter on the apical membrane so less Na+ can be reabsorbed

Question 15

Recall the side effects of thiazide diuretics

Answer 15

Metabolic alkalosis due to hypokalaemia, decreased insulin production

Question 16

Recall the indications for thiazide diuretics

Answer 16

Hypertension, cardiac failure, idiopathic hypercalciuria, nephrogenic DI

Question 17

What is the main drawback of thiazide diuretics? Describe how this is managed

Answer 17

As Na+ resorption is reduced, blood [Na+] also decreases and so amount of Na+ delivered to the macula densa area of the DCT is decreased. This stimulates renin secretion, which has a vasoconstricting and aldosterone-promoting effect, increasing Na+ resorption. Thiazides therefore have to be coadministered with ACE inhibitors so that they do not lose thier efficacy

Question 18

Recall the transporters present in the apical and basal membranes of the distal DCT and collecting duct and the control mechanisms they are under

Answer 18

Apical: Na+ channels (inserted by aldosterone when bound to MR), AQP2 (triggered by ADH binding V2)
Basal: Na+/K+ ATPase (aldosterone) and AQPs3+4 (ADH)

Question 19

Recall what class of diuretic acts on the distal DCT and collecting tubule specifically and give examples

Answer 19

K+ sparing: Spironolactone and amiloride

Question 20

Recall the MOA of spironolactone and its indications

Answer 20

Inhibits MR receptor to reduce effect of aldosterone

Indications: heart failure, hypertension, hyperaldosteronism

Question 21

Recall the MOA of amiloride and its indications

Answer 21

Inhibits Na+ channels on apical membrane

Use in conjunction with K+-wasting diuretics

Question 22

Recall the 5 classes of diuretic

Answer 22

1. Osmotic
2. Carbonic anhydrase inhibitors
3. Loop diuretics
4. Thiazides
5. K+ sparing

Question 23

Recall the MOA of osmotic diuretics and an example of one of these

Answer 23

Eg = mannitol

MOA: pharmacalogically inert: increases osmotic pressure of lumen to draw Na+ out of cells, acts all along renal tubule

Question 24

Which class of diuretic is the most potent, and what % of fluid loss do they cause?

Answer 24

Loop diuretics

15-20%

Question 25

Recall the side effects of K+-sparing diuretics

Answer 25

HYPERkalaemia
Spironolactone specifically: gynaecomastia, testicular atrophy, menstrual disturbance (due to low specificity for MR receptors)

Question 26

Which classes of diuretic have an associated rebound problem with renin release?

Answer 26

Thiazides and osmotic diuretics