Diuretics

Question 1

What is the action of carbonic anhydrase inhibitors?

Answer 1

• Acts on the PCT and decreases Na+ and HCO3- reabsorption.

- This will result in metabolic acidosis.

Question 2

What does the blocking of carbonic anhydrase do to the kidney tubule further down?

Answer 2

• High Na+ results in upregulation of the ENAC in distal DCT and collecting duct. So, increased sodium reabsorption and more potassium is secreted.
• Results in hypokalaemia.

Question 3

What are carbonic anhydrase inhibitors used in?

Answer 3

• Glaucoma

- Altitude sickness

Question 4

What is the mechanism of action of SGLT-2 inhibitors?

Answer 4

• Decreases sodium and glucose reabsorption at the PCT.
• Results in glucosuria and natriuresis.
• Loss of gradient for reabsorption results in increased uric acid secretion.

Question 5

Why are SGLT-2 inhibitors beneficial for those with Type II diabetes?

Answer 5

• They decrease renin release by the MD cells so decreases hyperfiltration in diabetes so less glucose is reabsorbed.

Question 6

What is the mechanism of furosemide (loop diuretics)?

Answer 6

• Acts on the Loop of Henle and blocks the NKCCT channels on the thick ascending limb.

Question 7

What is the consequence of the action of furosemide?

Answer 7

• Results in the loss of the medullary gradient and therefore, lack of paracellular uptake of Ca2+ and Mg2+. Hypocalcaemia
• Loss of H+ as less is reabsorbed = metabolic alkalosis risk.
• ENAC unregulated at distal DCT and collecting duct = increased K+ excretion = hypokalaemia.

Question 8

Dangerous side effect of furosemide?

Answer 8

• Ototoxicity (hearing loss)

Question 9

Contraindication of loop diuretics

Answer 9

• Aminoglycoside because it interact with cell membranes in inner ear so increased risk of hearing loss - ototoxicity.

Question 10

What is the mechanism of action of spironolactone?

Answer 10

• Blocks ROMK in the thick ascending limb of the Loop of Henle
• Also a mineralcorticoid receptor antagonists so blocks the effects of aldosterone on the CD.

Question 11

Consequences of spironolactone use

Answer 11

• Hyperkalaemia as it inhibits K+ secretion via aldosterone

Question 12

Contraindication of spironolactone

Answer 12

• ACEi because it also causes hyperkalaemia. Enhanced hyperkalaemia can lead to bradycardia and therefore, asystole.

Question 13

In what patients should you avoid the use of spironolactone in?

Answer 13

• Addison’s disease as they have decreased cortisol so already there is less response at the aldosterone receptors and therefore, hyperkalaemia is existent. Can exacerbate this with the use of spironolactone.

Question 14

What is the action of thiazide diuretics?

Answer 14

• Acts on the DCT and blocks NCCT (sodium chloride channel co transporter).

Question 15

What are the consequences of the action of thiazide at the DCT?

Answer 15

• Low [Na] intracellularly, unregulated the Na+/Ca2+ pump on the basolateral membrane and therefore,increased calcium reabsorption occurs = hypercalcaemia
• Increased uric acid reabsorption = Gout.
• Greater electrolyte disturbance
• Loss of H+ = metabolic alkalosis
• ENaC is unregulated at the distal DCT and collecting duct = hypokalaemia = VF

Question 16

Contraindications of thiazide diuretics

Answer 16

• Beta blockers = increases the antihypertensive effect as thiazide causes diuresis = hypotension.
• Carbamazepine = exacerbation of hyponatraemia

Question 17

What is the mechanism of action of ADH antagonists/ aqauretics?

Answer 17

• Acts on the collecting duct and reduces the concentration ability of urine in the CD as less water is reabsorbed.

Question 18

Mechanism of action of tolvaptan?

Answer 18

• Blocks the V2 receptor (located on the basolateral membrane of the CD tubule in kidneys). NB: V1 receptor is found on the blood vessels.

Question 19

What is tolvaptan used to treat?

Answer 19

• Hyponatraemia due to a decreased diluting effect.

- Cyst enlargement = APCKD

Question 20

Mechanism of action of lithium at the CD as an ADH antagonist?

Answer 20

• Inhibits action of ADH

- Acts as a diuretic but not natriuretic.

Question 21

Contraindications of Loop and DCT diuretics (furosemide and thiazide)

Answer 21

• Digoxin and steroids (both cause hypokalaemia)
• Lithium (the ionic gradient created by the furosemide and thiazide may promote the excretion of water along with lithium as an ion)

Question 22

Where do osmotic diuretics act?

Answer 22

• All throughout the kidneys but mainly at the PCT

Question 23

What is the main osmotic diuretic and it’s mechanism of action?

Answer 23

• Mannitol

- It is osmotically active so draws water from the cell into the lumen.

Question 24

Consequences of osmotic diuretics?

Answer 24

• Since they draw fluid into the lumen, this decreases plasma volume and therefore, hypernatraemia occurs.
• Reduces high intracerebral pressure

Question 25

What is the effect of alcohol on the kidney tubules?

Answer 25

• Inhibits ADH release so less water reabsorption at the CD and increased urination.

Question 26

What is the action of caffeine on the kidney tubules?

Answer 26

• Increases the GFR and decreases tubular sodium reabsorption.
• Natriuresis

Question 27

What diuretics are used to treat hypertension?

Answer 27

• Thiazide = causes vasodilation as well as diuresis
• Spironolactone
• Problem with using loop diuretics is that body reaccomodates as ENAC is unregulated further down.

Question 28

What diuretics are used to treat HF?

Answer 28

• Loop diuretics for symptom relief. Has less electrolyte disturbance compared to thiazides.
• Spironolactone - used for its non-diuretic benefit. It decreases risk of hypokalaemia especially if heart is not in good condition and hypokalaemia caused by the loop diuretic can cause VF.

Question 29

What diuretics are used to treat liver disease?

Answer 29

• Spironolactone (1st line)

- Loop diuretic

Question 30

What diuretics are used to treat nephrotic/ CKD?

Answer 30

• Loop diuretics

- Can give thiazide or spironolactone for nephrotic syndrome.