Diuretics

Question 1

What is the glomerular filtration barrier?

Answer 1

• Capillaries in Bowman’s capsule
• Endothelial cells - holes
• Basement membrane
• GFB has selective permeability
• GFB damage starts to lose proteins into urine
• Ascending LOH impermeable to water

Question 2

Can water pass through the ascending LOH?

Answer 2

No

Question 3

Function of diuretics

Answer 3

• Inhibit reabsorption of sodium at different levels

- More sodium excreted = more water excreted

Question 4

Osmotic diuretics

Answer 4

• Glomerular capillaries highly permeable to water and electrolytes
• Mannitol
• Increases plasma osmolarity
• Filtered at glomerulus and poorly reabsorbed
• Increases osmotic pressure in glomerular filtrate
• Decreases water reabsorption from nephron
• Doesn’t enter brain or eye
• Uses: forces diuretics (poison), glaucoma, cerebral oedema
• Slow IV infusion of 5-20% solution

Question 5

Carbohydrase inhibitors

Answer 5

Increase excretion of HCO3-

• PCT: reabsorption of sodium, water and bicarbonate
• Carbonic anhydrase: between water and CO2 to form carbonic acid which releases ions
• Sodium hydrogen transports sodium inside cells and hydrogen outside
• Sodium enters blood
• Water follows sodium
• Sodium remains inside tubule
• Water remains inside lumen instead of going to blood
• E.g. acetazolamide - suppresses H+ production and reduces Na+/H+ exchange but effect is self limiting - hydrogen ion re-formed
• Increase excretion of HCO3-
• Uses: glaucoma - inhibits CA in eyes to reduce formation of humour, adjunct therapy in metabolic alkalosis, prophylaxis of altitude sickness
• Adverse effects: dizziness light headache, blurred vision, GI symptoms
• Mannitol worsens pulmonary oedema

Question 6

What is reabsorbed in the PCT?

Answer 6

Sodium, water and bicarbonate

Question 7

What does carbonic anhydrase do?

Answer 7

Between water and CO2 to form carbonic acid - releases H+

Question 8

Sodium hydrogen transporter function

Answer 8

Sodium hydrogen transports sodium inside cells and hydrogen outside

Question 9

Which ion does water follow?

Answer 9

Sodium

Question 10

Example of carbonic anhydrase diuretics

Answer 10

E.g. acetazolamide - suppresses H+ production and reduces Na+/H+ exchange but effect is self limiting - hydrogen ion re-formed

Question 11

Function of thiazides

Answer 11

Act on DCT which normally absorbs sodium with chloride

Stops sodium-chloride co-transporter

Question 12

Thiazides

Answer 12

• Act on DCT which normally reabsorbs sodium with Cl-
• Thiazides stop sodium - transporter
• E.g. hydrochlorothiazide
• Blocks sodium-chloride co-transporter = higher osmolarity of urine and decreased water reabsorption
• Effect is self limiting: hypovolaemia → renin secretion → angiotensin formation → aldosterone secretion → limitation of thiazide effect
• Uses: long term management, congestive HF, hypertension
• Side effects: hypokalaemia, hypocalcaemia, hyponatraemia, hyperuricaemia, hyperglycaemia, high cholesterol

Question 13

ACEi function

Answer 13

Inhibit production of angiotensin ii

Question 14

How is glucose reabsorbed from tubule?

Answer 14

Reabsorbed with sodium - co-transporter

Enters blood by diffusion

Question 15

Function of SGLT2

Answer 15

Treat diabetes by preventing glucose re-uptake

Question 16

ACEi characteristics

Answer 16

• Enalapril
• Inhibits production of angiotensin ii
• Use: hypertension, reduce oedema from HF, renal failure - antiproteinuric and protective effect
• Side effects: headache, cough, dizziness, hyperkalaemia

Question 17

Function of K+ sparing diuretics

Answer 17

• Act in collecting duct
• Normally in CD sodium reabsorbed, exchanged with potassium and hydrogen
• Activity is dependent on tubular sodium conc
• Activity regulated by aldosterone
• ADH acts to increase AQPs normally
• Aldosterone increases number of sodium-potassium ATPases
  Anti-aldosteronics
  Inhibit sodium channels - potassium not eliminated but kept in blood
  Action: block epithelial sodium channel in DCT, CT and CD, in conjunction with loop and thiazide diuretics to maintain K+

Question 18

Side effects of K+ sparing diuretics

Answer 18

hyperkalaemia, GI disturbances, rashes

Question 19

K+ sparing diuretics examples

Answer 19

Triamterene and amiloride

Question 20

Aldosterone antagonist example

Answer 20

Spironolactone

Question 21

Side effects of aldosterone antagonists

Answer 21

hyperkalaemia (fatal with ACEi or angiotensin receptor antagonist), GI disturbance, menstrual disorders

Question 22

Aldosterone antagonist function

Answer 22

• E.g. spironolactone
• Early phase increases opening of ENaC
• Late phase promotes DNA transcription - increases synthesis of ENaC, Na+, K+, ATPase
• Used in conjunction with loop and thiazide diuretics, hyperaldosteronism, primary failure and secondary failure
• Side effects: hyperkalaemia (fatal with ACEi or angiotensin receptor antagonist), GI disturbance, menstrual disorders

Question 23

What do renin-angiotensin-aldosterone blockers do

Answer 23

Decrease renal perfusion - release of renin from kidneys

• Renin converts in angiotensin 1
• ACE converts into angiotensin 2
• Angiotensin 2 big effector - increases sympathetic activity, water retention, release of aldosterone, vasoconstriction, release of ADH