Diuretics Flashcards
What is the most commonly used loop diuretic?
Furosemide
Loop diuretics half life and potency?
Short and very potent
Mechanism of action of loop diuretics, and effect
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
2 main side effects of loop diuretics (just simple answers)?
Hypokalaemia
Hypotension
What is the mechanism of hypokalaemia caused by diuretics?
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
Give an example of a thiazide diuretic
Bendroflumethiazide
What is the half life and potency of thiazide diuretics?
Long and mild potency
Mechanism of action of thiazide diuretics.
Inhibit the apical Na/2Cl symporter in the DCT
Side effects and comparison with loop diuretics
Hypotension and hypokalaemia
Hypokalaemia more mild and drugs is less potent
Which diuretic causes calcium loss in urine?
Furosemide vs bendroflumethiazide
Furosemide
Basic mechanistic principle behind potassium-sparing diuretics?
Give two examples
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
Side effects of potassium-sparing diuretics?
Very few as very specific
If dose too high, hyperkalaemia can occur but can easily be fixed by reducing dosage
Example of osmotic diuretic
mannitol
Administration and mechanism of action of osmotic diuretics?
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
What type of drug is acetazolamide?
Carbonic anhydrase inhibitor
Actions of acetazolamide?
Side effects?
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)
How does NH4Cl administered intragastrically cause acidification of urine?
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
What is isotonic saline?
0.9g% per 100ml of solution
How does administering hypotonic fluid affect blood cells?
Causes RBC lysis
What cardiovascular effects do general anaesthetics have?
Reduced cardiac output —> hypotension
Why is acetazolamide not good for treating chronic long term conditions that require increased diuresis?
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
Why would furosemide cause a drop in urinary pH?
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
Which drug inhibits ENaC?
Amiloride