Flashcards in Drugs Affecting the Kidneys (L6) Deck (30):
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
- Metabolic alkalosis (due to loss of H+ to urine
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?
- Mild heart failure
Unwanted effects of thiazides
- Metabolic alkalosis (due to H+ loss to urine)
- Increased uric acid in plasma
- Increased plasma cholesterol
- Male impotence
Why is Indapamide preferred over Bendrofluazide?
Because it has fewer unwanted effects
What can mild hypokalaemia lead to?
- Muscle weakness
What can sever hypokalaemia lead to?
- Abnormal heart rhythm
- Muscle paralysis
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
- Metabolic acidosis
- GI upsets
What can Spironolactone treat?
- Heart failure
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?
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?