Diuretics Flashcards
What is the basic urine forming unit of the kidney? AKA the workforce of the kidney
The nephron
How much CO goes to the kidney?
25%
How much overall oxygen consumption occurs from the kidney?
7%
Where does most of the filtered sodium get reabsorbed in the kidney?
Proximal tubule, 65% approximately
How much filtered sodium is reabsorbed in the loop of henle?
25%
Whats the amount of carbon dioxide in the atmosphere?
0.0414%
What is the one carbonic anhydrase inhibitor mentioned?
Acetazolamide
What is the MOA of CAI?
Inhibits sodium bicarb reabsorption, producing metabolic acidosis eventually
Increases bicarb in the lumen, increasing urinary pH, increases NA concentration in the urine, causing increased diuresis
What is the driving force for Na reabsorption throughout the entire GI/GU system?
Na/K ATPase
What are the ADEs with CIA?
Acetazolamide is a sulfa derivative, so it can lead to bone marrow suppression
Skin rashes
Hypersensitivity- Allergic reactions
Kidney- Precipitation of calcium phosphate creating crytalluria
What are the uses of CAI?
Open angle glaucoma
Epilepsy
Mountain sickness prophylaxis
Diuretic
What is the MOA of Osmotic diuretics?
They are fully filtered at the glomerulus, enter the lumen of the nephron (undergo very little reabsorption), thereby increasing the osmolality of the fluid.
Water follows solutes, so less water in reabsorbed
What is the effects of urine osmolality on renal blood flow? Why?
Increased renal blood flow because there is more water because fluid is pulled from extracellular spaces, increasing blood volume
Can you give mannitol to a patient with heart failure?
Bad idea
Where are some other places mannitol will specifically have reabsorption?
Brain and eye
What are some ADE’s to mannitol?
Hyponatremia- Initially
Hypernatremia- After extensive diuresis
What are the uses of mannitol?
Acute renal failure technically
Dialysis disequilibrium syndrome
Closed head injury
What are the specific osmotic dieuretics we discussed?
Mannitol, glycerin, glucose
What is the electrochemical driving force for BOTH Na sodium absorption and glucose reabsorption?
Na/K ATPase
What is the MOA of sodium glucose cotransporter 2 inhibitor?
Blocks SGLT2 in the proximal tubule, causing osmotic effect and increasing glucose in the urine, leading to increased dieuresis
Are SGLT2 inhibitors super strong?
No, fairly weak
What are some other important uses/effects of SGL2 inhibitors?
Helps treat DM be increasing glucose secretion, lowering HGA1C by 0.5-1%
CHF- Reduces systolic bp, reduces risk of CKD
What are the specific SGL2 inhibitors?
Daoagliflozin, canagliflozin, empagliflozin, ertugliflozin
What are the ADEs for SGL2 inhibitors?
Hypoglycemic- not super common ironically
Fluid/electrolyte imbalance- Not common either, but all diuretics’ theoretically have this ADE
AKI- Initial diuresis can cause reduction in bp that some patients don’t initially tolerate
Skeletal system- Increased risk of fractures
What is the MOA for adenosine A1 receptor antagonists?
Inhibits Na reabsorption by blocking A1 receptor in the proximal tubule (A1 receptors cause Na reabsorption)
What are the different A1 receptor antagonists?
Methylxanthines: Caffeine, theophylline, theobromine
What is the MOA of loop dieuretics?
Inhibit the Na/K/2Cl symporter in the thick ascending limb of the loop of henle
What electrolytes do loop diuretics specifically reduce reabsorption of?
Na, K, Cl, Ca and Mg
What are all loop dieuretics derivatives of? With one exception
Sulfonamides
What do sulfonamides do to carbonic anhydrase?
Inhibit it
How do loop dieuretics affect renal blood flow?
Increases it because they block Na uptake in the macula densam thereby interfering with its ability to sense sodium
How does loop diuretics affect Mg and Ca?
Decreases it by reducing electrochemical gradient when the Na/Cl/K is inhibited, causing Mg and Ca to just be excreted instead of being reabsorbed
What are the other loop diuretics effects?
Reduced LV filling pressure
Inhibits inner ear electrolyte transport, altering ability to send APs
Are loop diuretics highly protein bound?
Yes, so they do not get filtered in the glomerulus, but instead secreted by the renal proximal tubular cells
What is the one loop dieurtic thats not mainly secreted in the urine?
Torosemide
What are the ADEs of loop diuretics?
Fluid/electrolyte imbalance
Ototoxicity
Sulfonamide like reactions
Hyperlipidemia-Increased LDL, decreased HDL
What is the heavily mentioned DDI with loop diuretics?
Aminoglycosides- The “Mycins”, leading to synergistic ototoxicity
What is the drug mentioned that inhibits tubular secretion of many drugs, including loop diuretics?
Probenicid
What are the loop diuretics to know?
Furosemide, bumetanide, torsemide, ethacryanic acid
What is the MOA of thiazide and thiazide like diuretics?
Inhibit the Na/Cl symporter in the distal tubule
Are thiazides highly protein bound?
Yep
What are the ADEs for thiazide and thiazide like diuretics?
Electrolyte imbalances CNS-Vertigo, HA, parathesias GI- N/V, anorexia, diarrhea, constipation Sulfa like reaction Sexual dysfunction Hyperglycemia-Reduced insulin secretion
What are thiazides used for aside from diuretics?
Htn-reduced morbidity and mortality
Edema
What is the preferred thiazide and thiazide like diuretic?
Chlorothiazide, longer half life
How do K sparring diuretics work?
Na channel inhibitors in the late distal tubule and collecting duct
What are the provided K sparring diuretics?
Amiloride and Triamterene
What are the DDI to be aware of with K sparring diuretics?
NSAIDS, ACE inhibitors, K Supplements
What is the MOA of mineralocorticoid receptor antagonists?
Blocks MR??
What are the ADEs for spironolactone?
Hyperkalemia
Endocrine effects- Ability to interact with androgen related receptors
GI- Gastric bleeding
CNS- Drowsiness, lethargy, ataxia,
