Diuretics Flashcards
Recall the transporters present on the apical and basal membranes of the proximal convoluted tubule
Apical: Na+ channels, Na+/H+ countertransporter
Basal: Na+/K+ ATPase, Na+/HCO3- cotransporter
Water enters apical membrane via osmosis
Water, glucose and amino acids follow Na+ movement
In which part of the nephron is carbonic anhydrase active?
PCT
Which class of diuretic acts specifically on the PCT? Give an example
Carbonic anhydrase inhibitors eg acetazolamide
Recall the MOA of carbonic anhydrase inhibitors
Inhibits CA, therefore Na+ cannot be transported in with H+, so less Na+ is reabsorbed
Recall the transport that takes place in the DL of the LOH
Only water movement
Recall the transporters present in the apical and basal membranes of the AL of the LOH
Apical: triple transporter than cotransports Na+, K+ and 2Cl- into cell
Basal: Na+/K+ ATPase, K+/Cl- cotransporter
Which class of diuretic acts on the AL of the LOH specifically?
Loop diuretics
Give an example of a loop diuretic
Frusemide
Recall the MOA of frusemide
- Inhibits triple transporter so less Na+ reabsorbed
2. Inhibits K+ cycling, which reduces electrochemical gradient, so less Mg++ and Ca++ is lost too
Recall the indications for loop diuretics
Oedema
Recall the side effects of loop diuretics
Hypokalaemia, hypovolaemia, metabolic alkalosis, Mg++, Ca++ and K+ loss
Recall the transporters present in the apical and basal membranes of the early DCT
Apical: Na+/Cl- cotransporter
Basal: Na+/k+ ATPase, K+/Cl- cotransporter
Recall which class of diuretics act on the early DCT specifically and give an example
Thiazides - bendoflumethiazide
Recall the MOA of thiazide diuretics
Inhibit the Na+/Cl- cotransporter on the apical membrane so less Na+ can be reabsorbed
Recall the side effects of thiazide diuretics
Metabolic alkalosis due to hypokalaemia, decreased insulin production
Recall the indications for thiazide diuretics
Hypertension, cardiac failure, idiopathic hypercalciuria, nephrogenic DI
What is the main drawback of thiazide diuretics? Describe how this is managed
As Na+ resorption is reduced, blood [Na+] also decreases and so amount of Na+ delivered to the macula densa area of the DCT is decreased. This stimulates renin secretion, which has a vasoconstricting and aldosterone-promoting effect, increasing Na+ resorption. Thiazides therefore have to be coadministered with ACE inhibitors so that they do not lose thier efficacy
Recall the transporters present in the apical and basal membranes of the distal DCT and collecting duct and the control mechanisms they are under
Apical: Na+ channels (inserted by aldosterone when bound to MR), AQP2 (triggered by ADH binding V2)
Basal: Na+/K+ ATPase (aldosterone) and AQPs3+4 (ADH)
Recall what class of diuretic acts on the distal DCT and collecting tubule specifically and give examples
K+ sparing: Spironolactone and amiloride
Recall the MOA of spironolactone and its indications
Inhibits MR receptor to reduce effect of aldosterone
Indications: heart failure, hypertension, hyperaldosteronism
Recall the MOA of amiloride and its indications
Inhibits Na+ channels on apical membrane
Use in conjunction with K+-wasting diuretics
Recall the 5 classes of diuretic
- Osmotic
- Carbonic anhydrase inhibitors
- Loop diuretics
- Thiazides
- K+ sparing
Recall the MOA of osmotic diuretics and an example of one of these
Eg = mannitol
MOA: pharmacalogically inert: increases osmotic pressure of lumen to draw Na+ out of cells, acts all along renal tubule
Which class of diuretic is the most potent, and what % of fluid loss do they cause?
Loop diuretics
15-20%
Recall the side effects of K+-sparing diuretics
HYPERkalaemia
Spironolactone specifically: gynaecomastia, testicular atrophy, menstrual disturbance (due to low specificity for MR receptors)
Which classes of diuretic have an associated rebound problem with renin release?
Thiazides and osmotic diuretics
