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USMLE - Pharm

Kaplan Section 3 Chapter 6 Diuretics

What do in addition to diuresis, what do diuretics do? Loop and thiazide diuretics cause significant vasodilation --> that's why they are so clinically effective against HTN and heart failure
What is the % of Na reabsorption that happens in each of these segments of the renal tubule? Proximal convoluted tubule (PCT), Thich ascending limb (TAL), Distal convoluted tubule (DCT), and Collecting tubules/ducts (CT) PCT - 60%, TAL - 25%, DCT - 10%, CT - 4%
What is the consequence ofblockNa reabsorption above the collecting ducts? more Na traveling along the tubule --> increased Na load to the CT downstream --> inc LOSS of K+ (hypoK+) as well as LOSS of H+ (alkalosis) for loop and thiazide diuretics
Where do carbonic anhydrase inhibitors work? i.e. acetazolamide; in the proximal tubule; H+ + HCO3- ---> H2CO3 ---(carbonic anhydrase)---> H2O + CO2
Where do osmotic diuretics work? i.e. mannitol; throughout the renal tubule (but mainly in PCT)
Where do loop diuretics work? i.e. lasix, furosamide; in the thick ascending limb
Where do thiazide diuretics work? i.e. hydrochlorothiazide; in the early distal convoluted tubule
Where do K+ sparing diuretics work? i.e. amiloride and triamterene (Na channel blockers), spironolactone; early collecting duct
Where do aldosterone antagonist diuretics work? i.e. spironolactone; early collecting duct
What do osmotic diurectics do? inhibits H2O reabsorption --> inc urine volume
What would you use osmotic diuretics for specifically? 1. prevent anuria in hemolysis and rhabdomyolysis; 2. facilitates elimination of toxic drugs like cisplatin; 3. can also be used to decrease intraocular and intracerebral pressure because has osmotic actions in ECF of other tissues
Adverse effects of osmotic diuretics NV, chills, electrolyte imbalance, hypovolemia, chest pain
What are acetazolamide and dorzolamide? What is the mechanism? CA inhibs-->inhib of CO2 formation in the lumen-->less CO2 available in cells-->dec intracellular HCO3- -->H+ not regenerated-->not enough H+ for the Na/H antiporter on luminal membrane-->dec Na reabsorp-->more Na & HCO3- to travel downstream in the urine
What do you use CA inhibitors for? 1. glaucoma (dec formation of aqueous humor --> dec IOP); 2. acute mntn sickness (dec edema in lungs and brain); 3. thiazide-induced metabolic alkalosis (gets rid of HCO3's); 4. elimination of acidic drugs (like ASA, uric acid)
Adverse effects of CA inhibitors Acidosis (you're losing lots of HCO3-), bicarbonaturia (pee lots of HCO3- out), hypoK+ (huge Na load to CT's downstream --> lose K+), hyperCl- (lose lots of K+ so don't get rid of Cl-); paresthesias, renal stone (hyperCa and phosphaturia)
What is ethacrynic acid? Loop diuretic
What is furosemide Loop diuretic
Why do loop diuretics achieve high levels in the tubular lumen? they are weak acids so they are filtered and secreted --> high levels in lumen
What do loop diuretics do? inhibit Na/K/Cl (all transported from lumen into the cell) cotransporter in the TAL
What is the mechanism of loop diuretics? block Na/K/2Cl cotransporter --> dec K inside cell --> dec K back diffusion out to the lumen --> don't create a + electrical potential --> no driving force to reabsorb Mg and Ca --> loss of Mg, Ca, Na, K, Cl in the urine
How do loop diuretics affect what is happening in the CT's? Na load from loops (TAL) hits downstream at CT's --> enhances loss of K and K
What do you use loop diurectics for? 1. acute pulm edema, 2. acute renal failure, 3. anion OD, 4. CHF, 5. hyperCa states, 6. HTN, 7. refractory edemas
What are the adverse effects of loop diuretics? 1. allergies, 2. alkalosis (losing H+ in the CT's), 3. hypoK (lose K from CT's), 4. hypoMg, 5. hypoCa, 6. hyperUricemia (too many ions in urine drives urea to be reabsorbed?), 8. hypovolemia, 9. ototoxicity enhanced by aminoglycosides.
What are the drug interactions of loop diuretics? decreases Lithium clearance
Created by: christinapham