Diuretics Flashcards
What do each other following types of drugs cause: diuretic, natriuretic, aquaretic?
Diuretic - increased production of urine
Natriuretic - loss of sodium in urine
Aquaretic - loss of water without electrolytes
Where do the following drugs work on the nephron: Thiazides K+ sparing diuretics Carbonic Anhydrase inhibitors Osmotic diuretics ADH blockers Loop diuretics SGLT2 inhibitors ?
DCT
Collecting duct
PCT
Everywhere but mostly PCT
Collecting duct
AL LOH
PCT
How do carbonic anydrase inhibitors work?
85% of H2CO3 is reabsorbed in the PCT
Normal mechanism:
NA/ H exchanger -> H+ moved into lumen from cell + HCO3- -> H2CO3 (carbonic anhydrase) -> H2P + CO2 -> diffuses back into cell (carbonic anhydrase) -> H2CO3 -> transported into blood (H+ + HCO3-) through channel
CAI inhibit carbonic anhydrase so this can’t occur -> loss of NaHCO3 in urine
What are carbonic anhydrase inhibitors used to treat? What are the side effects and why?
✅glaucoma
✅mountain sickness
❌ bc there is more NaHCO3 reaching the collecting ducts - increased ENAC channels to help reabsorb Na but this drives Na/ K exchanger so can -> hypokalaemia metabolic acidosis (feel sick)
Tolerance develops after 2-3days
How do osmotic agents work? Give an example. Side effects? What’s it used to treat?
They act as a solute in the lumen to increase water lost in the urine
E.g. Mannitol
❌loss of water - reduced intracellular volume - hypernatremia risk
✅ raised ICP
Mostly PCT
How do SGLT2 inhibitors work? Why is this also beneficial to people with metabolic syndrome and hypertension?
Pct
They block the SGLT2 Na/ glucose cotransporter (from lumen to cell) increasing excretion glucose + Na
✅diabetes
-> increased Uric acid secretion (✅metabolic syndrome = hyperuraemia)
✅hypertension - acts as diuretic + increased detection Na macula densa DCT stops hyperfiltration/ RAAS
How do loop diuretics work? Give an example. Why can this be used to treat hypercalcaemia? Side effect
AL LOH
Block the Na/K/ 2cl channel (from lumen to cell)
E.g. furosemide
K in cell diffuses back into lumen via ROMK this (back-diffusion creates positive luminal membrane Vm this drives cation reabsorption) increases reabsorption Ca2+ + Mg
❌hypokalaemia metabolic alkalosis (increased excretion CL compared bicarbonate) - increased ENAC (which drives Nakatpase -> K excretion ) collecting duct
How do thiazide diuretics work? How does this effect calcium? Side effects?
DCT
Block Na/ CL cotransporter (from lumen to cell)
Less Na in cell upregulates Ca/ Na exchanger (Na in, Ca into blood) and the TRPV5 Ca channel (lumen to cell) to increase Ca reabsorption
❌more Na-> CD ENAC increases -> more K lost in urine -> hypokalaemic metabolic alkalosis (increased excretion CL compared to bicarbonate)
❌hyperuricaemia -> gout
How do K+ sparing diuretics work and why are they K+ sparing?
Collecting duct
Normally:
Aldosterone binds to mineralocorticoid receptor -> increased ENAC expression
But: spironolactone stops aldosterone binding. Amiloride/ triamterene block ENAC channels
ENAC causes Na reabsorption and K+ excretion through Na/K ATPase so when blocked the body keeps more K
How do aquarectics work? Give two examples and what they’re typically used to treat
On principle cells
ADH antagonists
Tolvaptan - blocks V2 receptors to stop ADH binding and preventing insertion of aquaporins-2
✅hyponatraemia
✅adult polycystic kidney disease - prevents cyst enlargement
Lithium -
✅bipolar but unwanted side effect is inhibits ADH (Through G protein inhibition)
❌ polyuric -> dehydration
What are two non-pharmacological substances which act as diuretics and how do they work?
Alcohol - inhibits ADH release
Caffeine - increases GFR and decreases tubular Na reabsorption
Generic adverse drug reactions to diuretics
Fluid loss -> hypovolaemia + hypotension -> activates RAAS -> acute kidney injury
Electrolyte disturbance - Na, k, mg, Ca
Metabolic abnormalities - acid/ base balance
Anaphylaxis/ photosensitive rash etc
Adverse thiazide reactions and drug drug interactions
Gout Hyperglycaemia Erectile dysfunction Increased LDL, TG Hypercalcaemia
hypokalaemia -> increased digoxin binding and toxicity
+ beta-blockers -> hyperglycaemia, hyperlipidemia, hyperuricaemia
+ steroids -> increased risk hypokalaemia
+ lithium -> lithium toxicity
+ carbamazepine -> increased risk of hyponatraemia
Adverse affects of frusemide
Ototoxicity
Alkalosis
Increased LDL, TG
Gout
Adverse affects of spironolactone
Hyperkalaemia
Impotence
Painful gynaecomastia (enlargement man’s breast)
