Renal Pharm Flashcards
Mannitol is an osmotic diuretic that increases tubular osmolarity which will bring water into the lumen increasing urine flow. What are the clinical uses of mannitol? What about side effects?
Clinical uses: drug overdose, elevated intracranial/intraocular pressure b/c mannitol can decrease intracranial/intraocular pressure.
Toxicity: Pulmonary edema, dehydration (preferential water diuresis can –> hypernatremia (mild-lethargy, weakness, edema; severe-seizures, coma)
Contraindicated in anuria, and heart failure (b/c initial retention of mannitol can exacerbate volume expansion)
Acetazolamide is a carbonic anhydrase inhibitor that works at the PCT that causes self-limited NaHCO3 diuresis and decrease total bicarb body stores. What is acetazolamide used for? Toxcity?
Clinical uses: glaucoma, urinary alkalinization, metabolic alkalosis, altitude sickness, pseudotumor cerebri
Toxicity: hyperchloremic metabolic acidosis (b/c removing bicarb stores), parethesias, NH3 toxicity, sulfa allergy
How do the loop diuretics work? What are they used in? Toxicity?
Loop diuretics (furosemide, bumetanide, torsemide) inhibit Na/K/2Cl transporter in the thick ascending limb of loop of henle that will abolish hypertonicity of medulla, preventing concentration of urine. They also stimulate PGE release (vasodilatory effects on afferent arteriole –> increase GFR); Increase Ca2+ and Mg2+ excretion
Used in: edematous states (HF, cirrhosis, nephrotic syndrome, pulmonary edema, hypertension, hypercalcemia (parathyroidism)
Toxicity: ototoxicity, hypokalemia, dehydration, sulfa allergy, nephritis, gout
Which diuretic works similarly to loops and is a good option if pt has sulfa allergy?
Ethacrynic acid is a phenoxyacetic acid derivative that is not a sulfonamide with essentially the same action as furosemide (inhibit na/k/2cl transporter at taL). Side effect are also similar to loops.
Thiazide diuretics (hydrochlorothiazide, chlorthalidone) work by inhibiting NaCl reabsorption in early DCT –> decrease diluting capacity of nephron; also decrease Ca2+ excretion. What are they used in? List side effects?
Clinical uses: HTN, HF, idiopathic hypercalciuria, nephrogenic diabetes insipidus, osteoporosis
toxicity: hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia (contraindicated in diabetics), hyperlipidemia, hyperuricemia, hypercalcemia, sulfa allergy.
Of the diuretics, which has been shown to improve mortality in treatment of CHF?
only spironolactone
list the 4 K+ sparring diuretics and separate them in terms of their MOA. Uses? Side effects?
1) competitive aldosterone receptor antagonists in cortical collecting tubule: spironolactone, eplerenone
2) block epithelial Na+ channels in cortical collecting tubule: triamterene and amiloride
uses: hyperaldosteronism (aldosterone will cause increase Na+ reabsorption + K+ secretion or H+ secretion in the late distal collecting tubule), K+ depletion/hypokalemia, heart failure
toxicity: hyperkalemia –> arryhthmias, endocrine effects with spironlactone (gynecomastia, anti-androgen effects)
Effects of diuretics (mannitol, acetazolamide, loops, thiazides, K+ sparing) on urine NaCl (make sure to list exceptions)
Increase NaCl in urine EXCEPT acetalozamide. Serum NaCl may increase as a result.
Effects of diuretics (mannitol, acetazolamide, loops, thiazides, K+ sparing) on urine K+ (make sure to list exceptions)
Urine K+ increases with loop diuretics and thiazides
Effects of diuretics (mannitol, acetazolamide, loops, thiazides, K+ sparing) on decreasing blood pH (make sure to list exceptions)
blood pH decreases (acidemia) -retaining more H+ or losing HCO3-
- carbonic anhydrase inhibitors like acetazolamide that causes self-limited NaHCO3 diuresis
- K+ sparring diuretics (triamterene, amiloride, spironolactone, eplenerone): hyperkalemia, will stimulate H+/K+ exchangers = K+ in cells, H+ into blood
Effects of diuretics (mannitol, acetazolamide, loops, thiazides, K+ sparing) on increasing blood pH (make sure to list exceptions)
blood pH increases (alkalemia): loops and thiazides
- volume contraction –> increase renin –> increase AII –> increase Na/H exchanger in PCT –> increase HCO3- reabsorption (“contraction alkalosis”)
- K+ loss leads to K+ exiting all cells (via H+/K+ exchanger) in exchange for H+ entering cells
- In low K+ state, H+ (rather K+) is exchanged for Na+ in cortical collecting tubule –> alkalosis and paradoxical aciduria
Effects of diuretics (mannitol, acetazolamide, loops, thiazides, K+ sparing) on urine Ca2+ (make sure to list exceptions)
- urine Ca2+ will increase with loop diuretics due to decrease paracellular Ca2+ reabsorption –> hypocalcemia
- urine Ca2+ will decrease with thiazides due to enhanced Ca2+ reabsorption in DCT.
ACE Inhibitors (-pril) inhibit ACE (impt in making angiotensin I –> angiotensin II). No angiotensin II = no vasoconstriction of efferent arterioles –> decrease GFR. Decrease GFR will activate RAS –> increased renin.
Inhibition of ACE also prevents breakdown of bradykinin, a potent vasodilator (increased bradykinin is the main cause of cough). What are the clinical uses of ACEI?
Clinical uses:
- HTN
- heart failure
- proteinuria
- diabetic nephropathy (decrease intraglomerular pressure, slowing GBM thickening)
- prevent unfavorable heart remodeling as a result of chronic HTN.
ACE Inhibitors (captopril, enalapril, lisinopril, ramipril) inhibit ACE (impt in making angiotensin I –> angiotensin II). No angiotensin II = no vasoconstriction of efferent arterioles –> decrease GFR. Decrease GFR will activate RAS –> increased renin.
Inhibition of ACE also prevents breakdown of bradykinin, a potent vasodilator (increased bradykinin is the main cause of cough). What are the side effects of ACEI?
“CATCHH”
- cough
- angioedema therefore ACEI contraindicated in hereditary angioedema -def in C1 esterase inhibitor
- teratogen (fetal RENAL malformations)
- creatinine (increase cre due to decrease GFR)
- hyperkalemia (b/c decrease AII –> decrease aldosterone –> decrease Na2+ reabsorption and decrease K+ excretion)
- hypotension
In which pt population should you avoid using ACEI?
- hereditory angioedema b/c ACEI can cause angioedema
- pregnancy b/c it’s teratogenic
- bilateral renal artery stenosis b/c ACE inhibitors will further decrease GFR –> renal failure
