Renal pharmacology Flashcards
Mannitol
MECHANISM Osmotic diuretic. increased tubular fluid osmolarity –> increase urine flow, decreased intracranial/intraocular pressure.
CLINICAL USE Drug overdose, elevated intracranial/intraocular pressure.
ADVERSE EFFECTS Pulmonary edema, dehydration, hypo- or hypernatremia. Contraindicated in anuria, HF.
Acetazolamide
MECHANISM Carbonic anhydrase inhibitor. Causes self-limited NaHCO3 diuresis and decreased total body HCO3 − stores.
CLINICAL USE Glaucoma, metabolic alkalosis, altitude sickness, pseudotumor cerebri. Alkalinizes urine.
ADVERSE EFFECTS Proximal renal tubular acidosis, paresthesias, NH3 toxicity, sulfa allergy, hypokalemia. Promotes calcium phosphate stone formation (insoluble at high pH).
Loop diuretics: Furosemide, bumetanide, torsemide
MECHANISM Sulfonamide loop diuretics. Inhibit cotransport system (Na+/K+/2Cl−) of thick ascending limb of loop of Henle. Abolish hypertonicity of medulla, preventing concentration of urine. Stimulate PGE release (vasodilatory effect on afferent arteriole); inhibited by NSAIDs. increased Ca2+ excretion.
CLINICAL USE Edematous states (HF, cirrhosis, nephrotic syndrome, pulmonary edema), hypertension, hypercalcemia
ADVERSE EFFECTS Ototoxicity, Hypokalemia, Hypomagnesemia, Dehydration, Allergy (sulfa), metabolic Alkalosis, Nephritis (interstitial), Gout.
Ethacrynic acid
MECHANISM Nonsulfonamide inhibitor of cotransport system (Na+/K+/2Cl−) of thick ascending limb of loop of Henle.
CLINICAL USE Diuresis in patients allergic to sulfa drugs
ADVERSE EFFECTS Similar to furosemide, but more ototoxic
Loop earrings hurt your ears
Thiazide diuretics: Hydrochlorothiazide, chlorthalidone, metolazone.
MECHANISM Inhibit NaCl reabsorption in early DCT –> decreased diluting capacity of nephron. decreased Ca2+ excretion
CLINICAL USE Hypertension, HF, idiopathic hypercalciuria, nephrogenic diabetes insipidus, osteoporosis.
ADVERSE EFFECTS Hypokalemic metabolic alkalosis, hyponatremia, hyperGlycemia, hyperLipidemia, hyperUricemia, hyperCalcemia. Sulfa allergy.
Potassium-sparing diuretics: Spironolactone, Eplerenone, Amiloride, Triamterene
MECHANISM Spironolactone and eplerenone are competitive aldosterone receptor antagonists in cortical collecting tubule. Triamterene and amiloride act at the same part of the tubule by blocking Na+ channels in the cortical collecting tubule.
CLINICAL USE Hyperaldosteronism, K+ depletion, HF, hepatic ascites (spironolactone), nephrogenic DI (amiloride), antiandrogen.
ADVERSE EFFECTS Hyperkalemia (can lead to arrhythmias), endocrine effects with spironolactone
Diuretics: electrolyte changes
Urine NaCl: increased with all diuretics (strength varies based on potency of diuretic effect). Serum NaCl may decrease as a result
Urine K+: increased especially with loop and thiazide diuretics. Serum K+ may decrease as a result
urine Ca:
- increased with loop diuretics: decreased paracellular Ca2+ reabsorption –> hypocalcemia.
-decreased with thiazides: enhanced Ca2+ reabsorption
Blood pH: decreased (acidemia): carbonic anhydrase inhibitors: decreased HCO3 − reabsorption. K+ sparing: aldosterone blockade prevents K+ secretion and H+ secretion. Additionally, hyperkalemia leads to K+ entering all cells (via H+/K+ exchanger) in exchange for H+ exiting cells.
increased (alkalemia): loop diuretics and thiazides cause alkalemia through several mechanisms:
Volume contraction –> increased AT II –> increased Na+/H+ exchange in PCT –> increased 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 than K+) is exchanged for Na+ in cortical collecting tubule –> alkalosis and “paradoxical aciduria”
Angiotensinconverting enzyme inhibitors: Captopril, enalapril, lisinopril, ramipril.
MECHANISM: Inhibit ACE –> decreased AT II –> decreased GFR by preventing constriction of efferent arterioles. increased renin due to loss of negative feedback. Inhibition of ACE also prevents inactivation of bradykinin, a potent vasodilator.
clinical use: Hypertension, HF (decreased mortality), proteinuria, diabetic nephropathy. Prevent unfavorable heart remodeling as a result of chronic hypertension.
In chronic kidney disease (eg, diabetic nephropathy), decreased intraglomerular pressure, slowing GBM thickening.
ADVERSE EFFECTS Cough, Angioedema (both due to increased bradykinin; contraindicated in C1 esterase inhibitor deficiency), Teratogen (fetal renal malformations), increased Createinine (decreased GFR), Hyperkalemia, and Hypotension.
Used with caution in bilateral renal artery stenosis because ACE inhibitors will further decreased GFR –> renal failure.
Angiotensin II receptor blockers: Losartan, candesartan, valsartan.
MECHANISM Selectively block binding of angiotensin II to AT1 receptor. Effects similar to ACE inhibitors, but ARBs do not increase bradykinin.
CLINICAL USE: Hypertension, HF, proteinuria, or chronic kidney disease (eg, diabetic nephropathy) with intolerance to ACE inhibitors (eg, cough, angioedema).
ADVERSE EFFECTS Hyperkalemia, decreased GFR, hypotension; teratogen.
Aliskiren
MECHANISM Direct renin inhibitor, blocks conversion of angiotensinogen to angiotensin I
CLINICAL USE Hypertension.
ADVERSE EFFECTS Hyperkalemia, decreased GFR, hypotension, angioedema. Relatively contraindicated in patients already taking ACE inhibitors or ARBs and contraindicated in pregnancy.
