renal drugs

Question 1

mannitol: MOA, use, toxicity

Answer 1

mannitol is an osmotic diuretic: incr. tubular fluid osmolality, incr. urine flow, decr. intracranial/intraocular pressure.
use: drug overdose, high intracranial or intraocular pressure.
toxicity: pulmonary edema, dehydration. contraindicated in anuria, CHF.
works on PCT

Question 2

acetazolamide: MOA, use, toxicity

Answer 2

carbonic anhydrase inhibitor that can cause a metabolic acidosis. causes self-limited NaHCO3 diuresis and decreased total body HCO3 stores. works on the PCT

use: glaucoma, to make urine more alkaline, to treat a metabolic alkalosis, altitude sickness, pseudotumor cerebri (idiopathic cerebral edema without a tumor).
toxicity: hyperchloremic metabolic acidosis, paresthesias, NH3 toxicity, sulfa allergy

Question 3

ethacrynic acid MOA, use, toxicity

Answer 3

loop diuretic.
phenoxyacetic acid derivative (NOT a sulfonamide). acts like furosemide (inhibits Na/K/2Cl).
used as a diuretic in pts allergic to sulfa.
toxicity: similar to furosemide (ototoxicity, hypokalemia, dehydration, interstitial nephritis, gout).

Question 4

furosemide MOA, use, toxicity

Answer 4

mechanism: sulfonamide loop diuretic. inhibits Na/K/2Cl of thick ascending loop of Henle. abolishes the hypertonicity of the medulla, preventing concentration of the urine. stimuates PGE release (vasodilatory effect on afferent aretriole), inhibited by NSAIDs. increase Ca excretion (loops loose calcium)
use: CHF, cirrhosis, nephrotic syndrome, pulm edema, HTN, hypercalcemia
toxicity: OH DANG: ototoxicity, hypokalemia, dehydration, allergy (sulfa), interstitial nephritis, gout

Question 5

hydrochlorothiazide MOA, use, toxicity

Answer 5

mechanism: inhibits NaCl reapsorption in DCT. decreases the diluting capacity of the nephron. decreases Ca excretion (I think this is because HCT inhibits Na/Cl cotransporter, but Na/K ATPase is still working. Na will want to come in to replace the Na being pumped out by the ATPase. It can no longer come in from the luminal side, but will instead increase the activity of the Na/Ca exchanger on the blood/interstium side. more calcium in the blood is less calcium excretion).
use: HTN, CHF, idiopathic hypercalciuria, nephrogenic diabetes insipidis, osteoporosis. (diabetes insipidus: can’t concentrate the urine, so you excrete more water than salt. makes the blood too concentrated, so patient drinks more water, which doesn’t solve the problem. this diuretic allows for more salt excretion along with the urine).
toxicity: hypokalemic metabolic alkalosis, hyponatremia, hyperGlycemia, hyperLipidemia, hyperUricemia, hyperCalcemia. slufa allergy. (hyperGLUC)

Question 6

K-sparing diuretics: MOA, use, toxicity, names

Answer 6

spironolactone and eplerenone are competitive aldo receptor antagonists in cortical collecting tubule. triamterene and amiloride act by blocking the Na channels in the CCT.
used for hyperaldosteronism, K depletion, CHF.
toxicity: hyperkalemia (can cause arrhythmias), endocrine effects of spironolactone.

Question 7

diuretic electrolyte changes. how will urine NaCl change?

Answer 7

increase in all diuretics except acetazolamide. serum NaCl may decrease as a result

Question 8

blood pH and diuretics: which ones can cause acidemia?

Answer 8

acidemia: may be seen with carbonic anhydrase inhibitors (acetazolamide) because of reduced bicarb reabsorption. may also bee seen with K sparing diuretics (spironolactone, eplerenone, triamterene, amiloride) because aldo blockade prevents K secretion and H secretion). additionally, hyperkalemia leads to K entering all cells via a H/K exchanger, so there will be more protons in blood

Question 9

blood pH and diuretics: which ones cause alkalemia?

Answer 9

loop diuretics and thiazides.
many mechanisms: volume contraction –> ATII –> incr Na/H exchanger in the PCT –> incr. HCO3- resorption
K loss leads to K exiting all cells (via H/K exchanger)- less H in blood
in low K state, H rather than K is exchanged for Na in the CCT. this causes alkalosis and a paradoxical aciduria.

Question 10

urine calcium and diurectis: when is it high? when is it low?

Answer 10

high with loop diuretics.

low with thiazide diuretics

Question 11

ACE inhibitors: side effects

Answer 11

cough, angioedema (contraindicated in C1 esterase inhibitor deficiency), teratogen (fetal renal malformations), incr. creatinine (d/t decr. GFR), hyperkalemia, hypotension. avoid in bilateral renal artery stenosis because ACE inhibitors will further decr. GFR and cause renal failure.