| Flap 1 | Flap 2 |
| 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 |
