Diuretics

Question 1

What is the most commonly used loop diuretic?

Answer 1

Furosemide

Question 2

Loop diuretics half life and potency?

Answer 2

Short and very potent

Question 3

Mechanism of action of loop diuretics, and effect

Answer 3

Inhibit Na/K/2Cl channel in TALH where 25% of Na is reabsorbed

Filtrate entering DT more concentrated so less water reabsorbed in collecting duct

Medullary interstitium surrounding collecting duct has lower osmolarity so less water reabsorption

Question 4

2 main side effects of loop diuretics (just simple answers)?

Answer 4

Hypokalaemia

Hypotension

Question 5

What is the mechanism of hypokalaemia caused by diuretics?

Answer 5

1 - increased [Na] due to inhibition of NKCC leads to more Na uptake by DCT and collecting duct
- in the process of reabsorbing sodium, potassium and protons are lost in the urine, causing hypokalaemia and mild alkalaemia

2 - RAAS activated due to high NaCl in urine detected by macula densa cells

• granular cells produce renin —> aldosterone eventually released
• aldosterone increases Na/K activity and also increases transcription of Na transporters to increase Na uptake
• large increase in Na reabsorption alters charge gradient such that potassium and H+ ions are excreted into urine, causing hypokalaemia and mild alkalaemia

Question 6

Give an example of a thiazide diuretic

Answer 6

Bendroflumethiazide

Question 7

What is the half life and potency of thiazide diuretics?

Answer 7

Long and mild potency

Question 8

Mechanism of action of thiazide diuretics.

Answer 8

Inhibit the apical Na/2Cl symporter in the DCT

Question 9

Side effects and comparison with loop diuretics

Answer 9

Hypotension and hypokalaemia

Hypokalaemia more mild and drugs is less potent

Question 10

Which diuretic causes calcium loss in urine?

Furosemide vs bendroflumethiazide

Answer 10

Furosemide

Question 11

Basic mechanistic principle behind potassium-sparing diuretics?
Give two examples

Answer 11

Amiloride = ‘functional aldosterone antagonist’ that blocks apical eNaC in collecting duct, reducing basolateral Na/K activity and therefore apical K+ excretion through K+ channels

Spironolactone = Antagonist of mineralocorticoid receptors (on which aldosterone mediates its effects)

Aldosterone cause hypokalaemia through up regulating transcription of Na reabsorption proteins that cause the excretion of K+ and H+ into the urine

Question 12

Side effects of potassium-sparing diuretics?

Answer 12

Very few as very specific

If dose too high, hyperkalaemia can occur but can easily be fixed by reducing dosage

Question 13

Example of osmotic diuretic

Answer 13

mannitol

Question 14

Administration and mechanism of action of osmotic diuretics?

Answer 14

IV

Increase osmotic pressure of plasma
Oedemous fluid moves into blood
Osmotic diuretic freely filtered in glomerulus, taking water with it
Water not reabsorbed because osmolarity of filtrate increased significantly

Question 15

What type of drug is acetazolamide?

Answer 15

Carbonic anhydrase inhibitor

Question 16

Actions of acetazolamide?

Side effects?

Answer 16

Sodium bicarbonate (and sodium chloride) are excreted into urine - water follows

Acidaemia due to excretion of bicarbonate which usually acts to buffer protons in the blood (pH of urine consequently goes up)

Question 17

How does NH4Cl administered intragastrically cause acidification of urine?

Answer 17

Liver deals with Ammonia and generates urea
Urea cycle releases protons
Protons combine with Cl- to make non-volatile HCl
HCl causes a significant decrease in plasma pH, and is filtered into the urine to correct for the acidaemia

Question 18

What is isotonic saline?

Answer 18

0.9g% per 100ml of solution

Question 19

How does administering hypotonic fluid affect blood cells?

Answer 19

Causes RBC lysis

Question 20

What cardiovascular effects do general anaesthetics have?

Answer 20

Reduced cardiac output —> hypotension

Question 21

Why is acetazolamide not good for treating chronic long term conditions that require increased diuresis?

Answer 21

It is self limiting
The more sodium bicarbonate that is excreted, the lower the plasma pH goes, the less free bicarbonate there is to excrete as it begins buffering H+ ions

Question 22

Why would furosemide cause a drop in urinary pH?

Answer 22

Inhibits sodium reabsorption in LoH, so more sodium reabsorption in DCT
This makes urine more negative, inducing charge gradient across apical surface
DCT has potassium and H+ ion efflux channels so urinary pH drops

Question 23

Which drug inhibits ENaC?

Answer 23

Amiloride