Session 3: Diuretics & Drugs in Kidney Failure Flashcards
Renal functions
Regulatory
Excretory
Endocrine
Metabolism
Regulatory functions.
Fluid balance
Acid-base balance
Electrolyte balance
Excretory functions
Waste products
Drug elimination
Endocrine functions
Renin
EPO
Prostaglandins
1-alpha calcidol
Metabolism functions
Vit D
Polypeptides (insulin)
Drugs (Morphine, paracetamol)
Give examples of drugs acting on renal tubules.
Carbonic anhydrase inhibitors (acetazolamide)
Osmotic diuretics
SGLT2 inhibitors
Loop diuretics
Thiazides
K+ sparing
Aldosterone antagonists
ADH antagonists
Definition of diuretic
Increased production of urine
Definition of natriuretic
Loss of sodium in urine
Definition of aquaretic.
Loss of water without electrolytes
Give an example of an aquaretic.
ADH antagonists
Give an example of an ADH antagonist.
Tolvaptan
Explain the action of tolvaptan.
Inhibits the V2 receptor which is suppose to cause transport of aquaporin to the apical membrane.
It is used to treat hyponatraemia and prevent cyst enlargement in APCKD.
Explain the action of lithium in the collecting duct.
Act on prinical cells as well but on the Gs causing the same outcome as Tolvaptan
Explain alcohol as an diuretic.
Inhibits ADH release
Explain caffeine as a diuretic.
Increased GFR and reduced tubular Na+ reabsorption
Generic adverse drug reactions of diuretics.
Hypovolaemia and hypotension
This activates RAAS and can lead to AKI.
Electrolyte imbalance
Metabolic abnormalities
Anaphylaxis/photosensitivity rash
Adverse drug effects of thiazides.
Gout
Hyperglycaemia
ED
LDL and TG increase
Hypercalcaemia
Adverse drug effects of Spironolactone
Hyperkalaemia
Impotence
Painful gynaecomastia
Adverse drug effects of furosemide
Ototoxicity
Alkalosis
LDL and TG increase
Gout
Adverse drug effects of Bumetanide
Myalgia
Examples of uses of diuretics.
Hypertension
Heart failure
Decompensated liver disease
Nephrotic syndrome
CKD
Oedema
Examples of drugs used in hypertension.
Thiazide diuretics
Spironolactone
Loop diuretics
ARBs
ACEi
CCBs
Beta-blockers
Traditional treatment of HF
Loop diuretics
Spironolactone
ACEi/ARBs
Betablockers
Novel treatment of HF
SGLT2-inhibitors
Tolvaptan
Traditional treatment of decompensated liver disease
Spironolactone
Loop diuretics
Novel treatment of decompensated liver disease
Tolvaptan
Treatment of nephrotic syndrome
Loop diuretics
+/- thiazides
+/- K+ sparing/K+ supplements
Lithium is used to treat bipolar disorder.
What is an unwanted side effect of lithium?
Inhibits action of ADH and causes dilute urine, increased free water clearance an raising serum sodium
Treatment of CKD
The reduced GFR leads to salt and water retention
Therefore Loop diuretics are very good.
The alkalosis and potassium effects are also potentially beneficial.
Should avoid K+ sparing
Why might furosemide not work in gut oedema?
The furosemide is not absorbed adequately orally in the gut.
Why might furosemide not work in hypoalbuminaemia?
Because albumin is needed to carry the furosemide.
If there is no albumin to carry it is rendered more or less useless.
Why is salt management important with diuretics?
Because diuretics will not work properly if there is a large intake of salt constantly.
Management of refractory oedema
Check salt intake to see if sodium excretion is necessary
Give IV furosemide if gut oedema is likely.
Find the minimum effective dose and give repeated bolus or infusion
Briefly explain Bartter’s and Gitelman syndrome.
Bartter cause NKCC2 to not work properly and patients will exhibit the same signs and symptoms as being on loop diuretics.
Gitelman cause NaCl to not work properly and patients will exhibit the same signs and symptoms as being on thiazide diuretics.
Briefly explain Liddle’s syndrome
Increased function of ENaC leading to similar sympoms and signs as being on amiloride.
Explain action of a carbonic anhydrase inhibitor such as acetazolamide.
Inhibits H2O and CO2 to be converted into H+ and HCO3-.
The H+ is then supposed to be transported out into the lumen in exchange for Na+ via the Na+/H+ antiporter.
Side effects of carbonic anhydrase inhibitors.
Loss of NaHCO3
Hypokalaemic metabolic acidosis (Due to loss of HCO3- as well as reabsorption of Na+ in CD in exchange for K+ being excreted)
Renal stones
Why is acetazolamide not commonly used as a diuretic?
When is it used instead?
Because the patient will quickly build tolerance to the drug and it will not have any effect.
It’s used instead in glaucoma, altitude sickness and rare cases of epilepsy
Explain action of mannitol.
Works like an osmotic agents and pulls H2O into the lumen.
Side effects of mannitol
Loss of water
Reduced intracellular volume
Hypernatraemia
Allergic reactions
When is mannitol used?
To reduce high intracerebral pressure
Explain the action of SGLT2 inhibitors.
Causes inhibition of SGLT2 leading to Na+ and glucose not to be absorbed.
This leads to the macula densa to absorb Na+ and Cl- and via tubuloglomerular feedback it causes vasoconstriction of the afferent arteriole. This is preferential in cases of glomerular hyperfiltration.
Effects of SGLT2 inhibitors.
Lowered plasma glucose
Loss of weight
Lowered BP
Lowered plasma uric acid
Lowered glomerular hyperfiltration
Explain the action of loop diuretics.
Blocks the NKCC2 cotransporter.
This leads to Na+ not being reabsorbed in the same amounts.
Side effects of loop diuretics.
Loss of Na+ and water
Hypokalaemic metabolic alkalosis
Increased Ca2+ loss
Explain why you might get hypocalcaemia in loop diuretics.
Because since K+ is no longer be reabsorbed ROMK will stop working which is supposed to create a positive luminal membrane that is the driving force for reabsorption of Ca2+ and Mg2+
Explain the action of thiazide diuretics.
Block the NCCT (Na+/Cl- cotransporter)
Side effects of thiazide diuretics.
Loss of Na+ and water
Hypokalaemic metabolic alkalosis
Increased Ca2+ reabsorption
Explain why hypercalcaemia might occur in thiazide diuretics.
Less Na+ reabsorbed. This leads to more Na+ secreted from interstitium to tubule cell in order to compensate for the loss of Na+. A transporter exchanging Ca2+ for Na+ on the basolateral membrane is responsible for this. This leads to more Ca2+ going into interstitium.
Usage of loop diuretics.
Oedema and hypertension in advanced CKD
Usage of Thiazides and thiazide-like diuretics.
Hypertension
Use of amiloride.
Low potassium where diuretic required.
Side effects of amiloride
Hyperkalaemia
Usage of spironlactone
HF
Ascites
Hypertension
Hyperadrenalism
Side effects of spironolactone
Hyperkalaemia
Gynaecomastia
Usage of ADH antagonist such as tolvaptan.
Hyponatraemia
Side effects of tolvaptan
Hypernatraemia
Deranged liver function
