Renal Flashcards
Mannitol
(Acts at PCT)
MECHANISM: Osmotic diuretic, increases tubular fluid osmolarity, producing increased urine flow, decreased intracrainial/intraocular pressure
CLINICAL USE: drug overdose, elevated intracranial/intraocular pressure; rapidly decreases blood volume.
TOXICITY: Dehydration, Pulmonary edema (mannitol brings fluid out of cells and into blood/interstitium, especially if pt is already congested - contraindicated in CHF). Chronic use may lead to hypernatremia. Contraindicated in anuria.
Acetazolamide
MECHANISM: Carbonic anhydrase inhibitor. Causes limited NaHCO3 diuresis (prevents reabsorption of filtered HCO3-), causes a reduction in total-body HCO3- stores.
CLINICAL USE: Glaucoma, urinary alkalinization, metabolic alkalosis, altitude sickness (decreased PaO2, hyperventilate to compensate --\> decreased PaCO2 --\> Respiratory alkalosis). Pseudotumor cerebri (increased intracranial pressure - idiopathic)
TOXICITY: Hyperchloremic metabolic acidosis (nl anion gap; H+ and Cl- reabsorbed together from lumen), paresthesias, NH3 toxicity, sulfa allergy.
Loop Diuretics
Bumetanide, Torsemide, Furosemide, Ethacrynic Acid
Furosemide
Furosemide: Loop Diuretic
MECHANISM: Sulfonamide loop diuretic. Inhibits cotransport system (Na+/K+/2Cl-) of thick ascending limb of loop of Henle. Abolishes hypertonicity of medulla (lose corticopapillary gradient necessary to concentrate urine in CCT), preventing concentration of urine.
Stimulates PGE release (vasodilatory effect on afferent arteriole); inhibited by NSAIDS.
Inc Ca2+ excretion (Wasting due to lack of K+ backleak to set up (+) lumen potential).
“Loops Lose calcium”
CLINICAL USE: Edematous states (CHF, cirrhosis, nephrotic syndrome, pulmonary edema), HTN, hypercalcemia
TOXICITY: Ototoxicity (esp when used w Aminoglycosides), Hypokalemia (K+ wasting), Dehydration, Allergy (sulfa), Nephritis (interstitial), Gout (hyperuricemia), hypo Mg+
“Oh Dang!”
Ethacrynic Acid
Ethacrynic Acid - Loop Diuretic, same mechanism as Furosemide:
MECHANISM: Sulfonamide loop diuretic. Inhibits cotransport system (Na+/K+/2Cl-) of thick ascending limb of loop of Henle. Abolishes hypertonicity of medulla (lose corticopapillary gradient necessary to concentrate urine in CCT), preventing concentration of urine.
Stimulates PGE release (vasodilatory effect on afferent arteriole); inhibited by NSAIDS.
Inc Ca2+ excretion (Wasting due to lack of K+ backleak to set up (+) lumen potential).
“Loops Lose calcium”
CLINICAL USE: Diuresis in pts allergic to sulfa drugs. Edematous states (CHF, cirrhosis, nephrotic syndrome, pulmonary edema), HTN, hypercalcemia
TOXICITY: Similar to Furosemide… Can Cause Gout (hyperuricemia)
Hydrochlorothiazide
Hydrochlorothiazide, Indapamide, metolazone, Chlorthalidone (similar to HCTZ)
MECHANISM: Thiazide diuretic. Inhibits NaCl reabsorption in early distal tubule, reducing diluting of the nephron. (Also increases intraluminal Na+, activate voltage-gated Ca2+ channel, Ca2+ influx into tubule cell –> Increases basolateral Na+/Ca2+exchange –> Inc Ca2+ diffusion into tubule epithelial cell/into interstitium: Decreases Ca2+ excretion, “Ca2+ sparing”)
CLINICAL USE: HTN (first line for essential HTN), CHF, idiopathic hypercalcuria (i.e. Ca2+ kidney stone prevention), nephrogenic diabetes insipidus
TOXICITY: Hypokalemic metabolic alkalosis (K+ wasting), hyponatremia, hyperGlycemia, hyperLipidemia, hyperUricemia (hypovolemia inc uric acid reabsorption in PCT), and hyerCalcemia. Sulfa Allergy.
“HyperGLUC”
K+-sparing diuretics
K+-sparing diuretics
Spironolactone, epleronone, Triamterine (leg cramps), Amiloride (The K+ STAys)
MECHANISM:
Spironolactone and epleronone are competitive aldosterone receptor antagonists in the cortical collecting tubule.
Triamterene and amiloride act at the same part of the tubule by blocking Na+ channels in the CCT (–>ENaC inhibitors)
CLINICAL USE: Hyperaldosteronism, K+ depletion, CHF
TOXICITY: Hyperkalemia (can lead to arrhythmias), endocrine effects with spironolactone (e.g. gynecomastia (weak progesterone agonist), antiandrogen effects (androgen receptor antagonist, 17-alpha-OHase inhibitor (dec androgen synthesis), and 5alpha-reductase inhibitor (dec DHT)
Diuretics: electrolyte changes
Urine NaCl
Urine NaCl
Increased with all diuretics. Serum NaCl may decrease as a result
Diuretics: electrolyte changes
Urine K+
Urine K+
Increased in all except K+-sparing diuretics. Serum K+ may decrease as a result
Diuretics: electrolyte changes
Blood pH
Blood pH with diuretics:
pH Decreased (acidemia):
carbonic anhydrase inhibitors: decreases HCO3- reabsorption.
K+ sparing: aldosterone blockade prevents K+ secretion and H+ secretion.
pH Increased (alkalemia):
Loop diuretics and thiazides cause alkalemia through several mechanisms.
a) Volume contraction –> contraction alkalosis
- loss of volume and osmolytes –> increased ATII –> Inc Na+in/H+out exchanger in proximal tubule –> increases HCO3- reabsorption via H+out/HCO3-in exchanger
- K+ loss–> K+ restored by K+ exiting cells/H+ entering cells (via H+K+ exchanger)
- in low K+ states: H+ instead of K+ is exchanged for Na+ in cortical collecting tubule–> alkalosis and “paradoxical aciduria”
- –> vomiting
- –> lose K+/H+ –> huge decrease in K+ forces Na+ K+ exchanger
Paradoxical aciduria: acidic urine in setting of metabolic alkalosis (with decreased underlying K+)
Diuretics: electrolyte changes
Urine Ca2+
Urine Ca2+ with diuretics
Ca Increases with loop diuretics: decreased paracellular Ca2+ reabsorption –> hypocalcemia.
- Ca2+ Decreases with thiazides (volume depletion, inc Na+ reabsorption in loop –> increased K+ backleak –> increased (+) lumen potential –> Increased Ca2+ reabsorption (paracellular)
Thiaxides … enhanced paracellular Ca2+ in proximal tubule in proximal tubule (Ca2+ follows Na+ reabsorption) and loop of henle
ACE inhibitors
ACE Inhibitors - Captopril, enalapril, lisinopril
MECHANISM: Inhibit ACE –> dec angiotensin II __> Dec GFR by preventing constriction of efferent arterioles. LEvels of renin increase as a result of loss of feedback inhibition. INhibition of ACE also prevents inactivation of bradykinin, a potent vasodilator. (–> inc bradykinin)
Angiotensin II receptor blockers (-sartans) have effects similar to ACE inhibitors but do not increase bradykinin –> no cough or angioedema (dermis swelling)
CLINICAL USE: HTN, CHF, proteinuria, diabetic renal disease. Prevent unfavorable heart remodeling as a result of chronic HTN
TOXICITY: Cough, angioedema (via increased bradykinin), teratogen (fetal renal malformations), creatinine increase (dec GFR due to dec afferent arteriole vasoconstriction secondary to dec AII), hyperkalemia, and hypotension.
Avoid in bilateral renal artery stenosis because ACE inhibitors will furter decrease GFR –> renal failure.
