Diuretics Flashcards
What is the glomerular filtration barrier?
- 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
Can water pass through the ascending LOH?
No
Function of diuretics
- Inhibit reabsorption of sodium at different levels
- More sodium excreted = more water excreted
Osmotic diuretics
- 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
Carbohydrase inhibitors
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
What is reabsorbed in the PCT?
Sodium, water and bicarbonate
What does carbonic anhydrase do?
Between water and CO2 to form carbonic acid - releases H+
Sodium hydrogen transporter function
Sodium hydrogen transports sodium inside cells and hydrogen outside
Which ion does water follow?
Sodium
Example of carbonic anhydrase diuretics
E.g. acetazolamide - suppresses H+ production and reduces Na+/H+ exchange but effect is self limiting - hydrogen ion re-formed
Function of thiazides
Act on DCT which normally absorbs sodium with chloride
Stops sodium-chloride co-transporter
Thiazides
- 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
ACEi function
Inhibit production of angiotensin ii
How is glucose reabsorbed from tubule?
Reabsorbed with sodium - co-transporter
Enters blood by diffusion
Function of SGLT2
Treat diabetes by preventing glucose re-uptake
ACEi characteristics
- Enalapril
- Inhibits production of angiotensin ii
- Use: hypertension, reduce oedema from HF, renal failure - antiproteinuric and protective effect
- Side effects: headache, cough, dizziness, hyperkalaemia
Function of K+ sparing diuretics
- 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+
Side effects of K+ sparing diuretics
hyperkalaemia, GI disturbances, rashes
K+ sparing diuretics examples
Triamterene and amiloride
Aldosterone antagonist example
Spironolactone
Side effects of aldosterone antagonists
hyperkalaemia (fatal with ACEi or angiotensin receptor antagonist), GI disturbance, menstrual disorders
Aldosterone antagonist function
- 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
What do renin-angiotensin-aldosterone blockers do
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
