DIuretics Flashcards
What is the target organ organ for diuretics? describe physiology
KIDNEYS
Describe the physiology of proximal tubule
remember: proximal tubule -tubule cell w/ microvilli around lumen+capillary on other side
Proxmial tubule-permeable to water and Na-drawn by oncotic pressure-but need channels -Na/K Atpase exchange other side
Paracellular- Na, H2O, Cl, HCO3- also pass due to oncotic pressure
Also glucose and AA reabsorb for Na
and HCO3+-carbonic anhydrase transforn to CO2+H2O-both taken in-and then made back to HCO3-
and H+ release vs NA
Describe physiology of descending loop of henle? and ascending? rememeber countercurrent effect
Permeable to water-and hypertonic interstitium/blood-
Ascending limb-not permeable to water but triple transporter for Na, Cl and K+
As Na can only leave in ascending and water stays-concentrate through Na increase
Descending limb can only let water through-goes to where Na is
Even more important for collecting duct-aquaporin-has strong concentration ready to absorb water
Physiology of distal tubule
early-Na and Cl co transporter.
Late-become aldosterone sensitive, Na/CL transpoter
Aquaporin also there (with ADH effect)-and no gap so water has to pass by Aqpr
Physiology of collecting duct
very aldosterone sensititive-Na intake (provide osmotic force + countercurrent)
Large Aqpr for H2O intake
What are the 2 categories of diuretics mechanism of action?
MOST-inhbit reabsorption of Na and Cl-
few increase osmolarity of tubular fluid-lower gradient
What are the 5 classes of diuretics and where do they act?
osmotic-mannital-increase tubular osmolarity-
Carbonic anhydrase inhbitors-proximal tubule
Loop diruretics-furosemide-ascending limn
Thiazides-bendrofluazide-dsital tubule
Potassium sparing-spirolactone-collecting duct
use mostly last 3-focus on them
How do Loop diuretics work?
Furosemide-strong diuretics
block triple transporter in ascending limb-Na, Cl, K
Impair ability to concentrate collecting duct-no countercurrent-cant reabsorb water later
can lose 30% fluid
issue: as decrease positive lumen potential that pushies Ca and Mg in-less reabsorbed
Also other part of kidney will try and reabsorb that sodium-at the price of Potassium-lose K+
How do thiazides work?
Like bendroflumethazide
Block Na/Cl co transporter-reduce the reuptake
no impacting countercurrent-not as powerful
Fluid osmolarity in collecting duct up-less water reabsorbed
issues: also causes low Mg. Ca and K
What effects do thiazides and loop diuretics have on renin?
Stimuli for renin is low tubular sodium-
initially as more Na to macula densa-inhbit renin
But as Na goes down chronically-Na conc down-stimulate renin
also macula densa samples blood using the triple transporter-think v low sodium
so chornically-activate renin and goes against diuretics
Why need ACE inhbitors at the same time
How do potassium sparing diuretics?
Spirolactine, amiloride-at collecting tube
Eithe aldosterone receptor antagonist-spirolactone
Or inhbitors of aldosterone Na channels amiloride
sodium just isnt taken in-so dont lose K+ either
can cause H+ retention
What are the common side effects of Loop diuretics and thiazide?
Share side effect-but loop much stronger
Hyponatremia, Hypovolemia, Hypokalemia
Metabolic alkalosis-via Cl ion loss
Hyperuricemia (uric acid)
side effects of potassium sparing?
Hyperkalemia
Explain why loop diuretics and thiazide cause hyperuriciema?
Drugs are taken orally but act in lumen-needs to transport to lumen-excreted naturally by kidney as drugs
Believes Hyperuricemia is cause diuretics using same transporter that uric acid would be using
What are the clinical use for thiazide?
Thiazide-in older people-1st line for Hypotensive-lot of evidence that are the best (from Ca channel blocker and ACE inhbitor)
issue: pee all the time
BUT tolerance happen fasts-4-6weeks
But unsure why after that-acts as a vasodilator-
-still works well
