Session 3 Diuretics Flashcards
What does a diuretic do?
increases production of urine
What does a natriuretic do?
increases the loss of sodium in urine
What does an aquaretic do?
increases the loss of water without electrolytes
What part of the tubule do carbonic anhydrase inhibitors work on?
main usage?
PCT
main usage = glaucoma, altitude sickness
MoA of Carbonic Anhydrase Inhibitors
drug name?
- effect is due to its action in the kidney on the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid
= loss of bicarbonate which carries out sodium, water and potassium with it
drug name = acetazolamide
disadvantages of carbonic anhydrase inhibitors?
hypokalemic metabolic acidosis
renal stones
tolerance develops after 2-3 days
Where do osmotic agents act?
give an example of drug name
main usage?
PCT and descending loop of Henle
- mannitol
- main usage = reduce high intracerebral pressure
MoA of osmotic agents (mannitol)
promote loss of water so reduce intracellular volume
disadvantages of osmotic agents?
risk of hyPERnatremia
also associated with allergic reactions
Where do SGLT2 inhibitors act?
PCT
MoA of SGLT2 inhibitors?
reduce glucose by stimulating urinary glucose excretion
while simultaneously improving other risk factors in a glucose-independent manner
* decrease:
plasma glucose
body weight
BP
plasma uric acid (increase uric acid secretion)
glomerular hyperfiltration
where do loop diuretics act?
main usage?
thick ascending limb
main usage = oedema (+/- hypertension in advanced CKD)
MoA of loop diuretics
promote loss of Na and water by inhibiting NaK2Cl
* enhanced Na delivery results in loss in K+ in collecting duct
other things you may get with loop diuretics / side effects
hypokalemic metabolic alkalosis
increased Ca2+ loss
increase urate and lipids
where do thiazide diuretics act?
drug name?
main usage?
DCT
thiazide = bendroflumethiazide
thiazide-like = indapamide
main usage = hypertension
MoA of thiazide diuretics?
loss of Na and water
inhibit the Na/Cl cotransporter
* enhanced Na+ delivery results in K+ loss in the collecting duct
* lower Na in interstitium facilitates Ca reabsorption by Na/Ca exchange
other things associated with thiazide diuretics
hypokalemic metabolic alkalosis
increased Ca2+ reabsorption
metabolic effects = increased urate, glucose, lipids, impotence
what does aldosterone do?
increases the expression of ENaC and Na/K/ATPase in principal cells of the collecting duct
What is the drug Tolvaptan classed as?
ADH antagonist (aquaretics) - blocks V2 receptors
so is a diuretic but not natriuretic
NB: lithium also does this but has unwanted side effects
what is tolvaptan used to treat?
hyponatraemia (and prevent cyst enlargement in APCKD)
diuretic action of alcohol?
inhibits ADH release
diuretic action of caffeine?
increases GFR and decreases tubular Na reabsorption
what are the generic adverse drug reactions of diuretics?
hypovolaemia and hypotension * activates RAAS but can lead to AKI electrolyte disturbances metabolic abnormalities anaphylaxis / photosensitivity rash (rare)
ADR of thiazides
gout hyperglycaemia erectile dysfunction increased LDL and increased TG hypercalcaemia
ADR of spironolactone
hyperkalaemia
impotence
painful gynaecomastia
ADR of frusemide
ototoxicity
alkalosis
increased LDL and increased TG
gout
ADR of bumetanide
myalgia
DDI:
ACEi with K+ sparing drugs
increased hyperkalaemia can lead to cardiac problems
DDI:
aminoglycosides with loop diuretics
ototoxicity and nephrotoxicity
DDI:
digoxin with thiazide and loop
hypokalaemia can lead to increased digoxin binding and toxicity
DDI:
beta blockers with thiazide
hyperglycemia, hyperlipidemia, hyperuricaemia
DDI:
steroids with thiazide and loop
increased risk of hypokalaemia
DDI:
lithium with thiazide and loop
lithium toxicity (thiazides) reduced lithium levels (loop)
DDI:
carbamazepine with thiazide
increased risk of hyponatraemia
What would you use to treat hypertension?
thiazide (cause vasodilation as well as diuresis)
spironolactone
(loop diuretics)
plus non-diuretics:
- ACEi / ARB
- beta blockers
What are the traditional methods and novel methods of treating HF?
Traditional
- loop diuretics
- spironolactone (had non-diuretic benefits)
- ACEi / ARB / beta-blockers
novel
- SGLT2 inhibitors
- tolvaptan
what are the traditional and novel methods of treating decompensated liver diseases?
traditional
- spironolactone
- loop diuretics
novel
* tolvaptan
treatment of nephrotic syndrome?
loop diuretics (big doses needed)
+/- thiazides
+/- potassium sparing diuretic / potassium supplements
what should you generally avoid prescribing with CKD?
K+ sparing diuretics
steps in managing refractory oedema?
- check salt intake
- give furosemide IV if gut oedema is likely
- find minimum effective dose
- give repeated bolus or infusion as shot half life
potassium sparing diuretics
name?
usage?
side effects?
name = amiloride
usage = HF, ascites, hypertension and hyperadrenalism
side effects = hyperkalaemia, hynaecomastia (spironolactone)
ADH antagonist
usage?
side effects?
usage = hyponatraemia
side effects = hypernatraemia, deranged liver function
