Diuretics

Question 1

Name and describe the actions of osmotic diuretics, including clinical use.

Answer 1

Mannitol
Increases the conc. of the tubular fluid so there is less water reabsorption.
Acts in the PCT, descending limb and collecting duct.
Results in more water excretion and small increase in Na and Cl excretion.
Clinical use; oedema, acute renal failure

Question 2

Name and describe the actions of carbonic anhydrase inhibitors, including clinical use.

Answer 2

Acetozolamide
Inhibits both carbonic anhydrase on the apical surface and inside the tubule cell.
Prevents reabsorption of HCO3 and Na+ -> less water reabsorption.
Therefore, increased tubular osmolarity.
Clinical use: renal stones, metabolic alkalosis, glaucoma

Question 3

What are the side effects of carbonic anhydrase inhibitors?

Answer 3

They are weak diuretics and so Na+ and H20 reabsorption will still occur downstream.
Na+ reabsorption downstream will cause K+ loss in DCT -> HYPOKALAEMIA
Metabolic acidosis

Question 4

Name and describe the actions of loop diuretics, including clinical use.

Answer 4

Frusemide
Acts in the ascending limb, promotes 15-20% fluid loss.
Inhibits the Na/2Cl/K transporter so there is increased tubular osmolarity.
Due to increased Na+, K+ excretion increases.
Clinical use: oedema, heart failure, hypertension

Question 5

What is the positive lumen potential and what drives it?

Answer 5

K+ recycling

It drives the reabsorption of positive ions (Mg2+, Na+, Ca2+) via the transcellular route.

Question 6

What are some side effects of loop diuretics?

Answer 6

Hypovolaemia
Hypotension
Metabolic alkalosis
K+, Mg2+, Ca2+ loss

Question 7

Name and describe the actions of thiazides, including clinical use.

Answer 7

Bendroflumethiazide
Inhibits the Na/Cl cotransporter in the DCT (therefore weaker diuretic as most Na has already been reabsorbed).
Increased Na reabsorption in tubular fluid promotes K+ loss.
Increased Mg loss.
Increased Ca reabsorption.
Clinical use: heart failure, idiopathic hypercalciuria, hypertension and diabetic nephropathy.

Question 8

What is the problem with thiazides and how do you resolve this?

Answer 8

They activate the Renin-angiotensin system.
As diuretics promote Na+ loss, the macula densa cells sense this and will stimulate renin release.
This will cause aldosterone to be secreted which is a powerful vasoconstrictor.
You often give ACEi along with the thiazide to combat this. (Also, potassium sparing diuretics)

Question 9

What are the two classes and therefore examples of potassium sparing diuretics?

Answer 9

Aldosterone receptor antagonists: Spirinolactone

Inhibitors of aldosterone-sensitive Na+ channels: Amiloride

Question 10

How do potassium sparing diuretics work and their clinical uses?

Answer 10

Inhibits Na+ reabsorption in early distal tubule
Inhibits K+ secretion
Increased H+ retention (Na+/H+ exchange)
Increased tubular fluid osmolarity
Clinical use:
Amiloride with K+ losing diuretics
Spirinolactone in hypertension and hyperaldosteronism

Question 11

What are some adverse effects of potassium sparing diuretics?

Answer 11

Hyperkalaemia
Metabolic acidosis
Spirinolactone: gynaecomastia, menstrual disorders, testicular atrophy

Question 12

What is the effect on uric acid in using diuretics?

Answer 12

Hyperuricaemia
Diuretics act on the same organic anion transporter so there is reduced excretion of uric acid.
More urate in the body can cause gout.

Question 13

Which diuretics cause metabolic alkalosis and how does this occur?

Answer 13

Loop diuretics
Thiazides
Cl- loss

Question 14

Which diuretics cause metabolic acidosis and how does this occur?

Answer 14

Carbonic anhydrase inhibitors

HCO3- loss

Question 15

How do chronic thiazides decrease TPR indefinitely?

Answer 15

eNOS activation, Ca channel antagonism, Opening of K channel (smooth muscle)