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What are diuretics?

A compound that causes the excretion of an increased volume of urine of the body (more water and solutes excreted)


What is natriuresis?

The increased excretion of Na+


What is kaliuresis?

The increased excretion of K+


How do diuretics increase water and Na+ excretion?

- They reduce reabsorption of Na+ from the filtrate
- This leads to more water being lost also


What is an aquaretic diuretic?

A diuretic that increases urine excretion without increasing Na+ excretion


What are the main uses of diuretics?

- To reduce circulating fluid volume
- To remove excess body fluid (oedema)


What are the classes of diuretic agents?

- Carbonic anhydrase inhibitors
- Osmotic diuretics
- Loop diuretics
- Thiazides and Thiazide-likes
- Potassium-sparing diuretics


How do loop diuretics work?

- Inhibits NKCC2 transporters in the thick ascending limb of the loop of Henle
- This leads to a reduced intake of Na+, K+ and Cl-
- Therefore, more water gets exerted (increased urine volume)


Methods of loop diuretic administration

- Oral absorption which leads to diuresis in 1 hour and lasts for 4-6 hours
- IV administration which leas to diuresis in 5 minutes and lasts for 2 hours
- Intramuscular (IM) administration (injection into the muscle) which starts diuresis in 30 minutes


Unwanted effects of loop Diuretics

- Dehydration
- Hypokalaemia
- Metabolic alkalosis (due to loss of H+ to urine
- Deafness


What can loop diuretics be used for?

- Acute pulmonary oedema
- Chronic heart failure
- Liver cirrhosis
- Resistant hypertension


How do loop diuretics cause hypokalaemia?

- Because loop diuretics inhibit the NKCC2 inhibitors in the thick ascending limb of he loop of Henle, more Na+ recaches the DT
- This leads to an increased Na+ intake via Na+/K+ATPase which gets exchanged for K+
- Therefore there is an increased K+ loss


How do thiazides work?

Act on the DT and inhibit the apical Na+/Cl- co-transporter, leading to Na+ excretion and therefore increased water excretion. They are not as powerful as loop diuretics.


Examples of thiazides

- Bendrofluazide (treats mild heart failure)
- Inadapamide (can treat hypertension)


What can thiazides be used to treat?

- Hypertension
- Oedema
- Mild heart failure


Unwanted effects of thiazides

- Hypokalaemia
- Metabolic alkalosis (due to H+ loss to urine)
- Increased uric acid in plasma
- Hyperglycaemia
- Increased plasma cholesterol
- Male impotence


Why is Indapamide preferred over Bendrofluazide?

Because it has fewer unwanted effects


What can mild hypokalaemia lead to?

- Fatigue
- Drowsiness
- Dizziness
- Muscle weakness


What can sever hypokalaemia lead to?

- Abnormal heart rhythm
- Muscle paralysis
- Death


What are potassium-sparing diuretics?

- Diuretics that do not lead to hypokalaemia
- They do so by acting on the DT to inhibit Na + reabsorption and K+ doesn't get secreted into the DT
- They are less effective than thiazides and loop diuretics


What are the two types of potassium-sparing diuretics?

- Aldosterone antagonists (e.g. eplerenone and spironolactone)
- Non-aldosterone antagonists (e.g. amiloride and triamterene)


How does Spironolactone work?

- Spironolactone get metabolised to canrenone, a competitive antagonist of aldosterone
- This reduces Na+ reabsorption from the DT because less Na+ channels will be expressed
- It is less effective than eplerenone


Unwanted effects of Spironolactone

- Hyperkalaemia
- Metabolic acidosis
- GI upsets


What can Spironolactone treat?

- Heart failure
- Oedema


How do non-aldosterone antagonists work?

- Act on DT by inhibiting Na+ reabsorption and decreasing K+ excretion
- It does this by blocking luminal Na+ channels, where aldosterone has its main effects produced


What can potassium-depleting diuretics (e.g. thiazides and loop diuretics) be given with to limit hypokalaemia?

Potassium-sparing diuretics


Why are some diuretic drugs given in combination with other diuretic drugs?

- To increase diuretic effect because some patients may not respond well to a certain type of diuretic
- To prevent hypokalaemia


Describe carbonic anhydrase inhibitors

- Block the reabsorption of NaHCO3 in the PT
- Not used as a diuretic because it only causes weak diuresis
- One of the earliest diuretics produced


What can carbonic anhydrase inhibitors treat?

- Glaucoma
- Epilepsy


Why is water a diuretic agent?

- High volumes of water intake leads to less ADH being secreted
- Therefore, less AQP2 channels are expressed in the late DT and early collecting duct
- So more water gets excreted