Flashcards in Renal Deck (47)
What drugs act on the proximal tubule?
Mannitol and Acetazolamide. Mannitol also works on the descending loop of Henle and the collecting duct.
What drugs act on the thick ascending limb of the loop of Henle?
Loop diuretics (Furosemide and Ethacrynic acid)
What drugs act on the distal convoluted tubule?
What drugs act on the cortical collecting duct?
K+ sparing diuretics
What drugs act on the collecting tubule?
What is the mechanism of Mannitol?
Osmotic diuretic, ↑ tubular fluid osmolarity, producing ↑ urine flow, ↓ intracranial/intraocular pressure.
What is the clinical use of Mannitol?
Drug overdose, ↑ intracranial/intraocular pressure.
What is the toxicity of Mannitol?
Pulmonary edema, dehydration. Contraindicated in anuria, CHF.
What is the mechanism of Acetazolamide?
Carbonic anhydrase inhibitor. Causes self-limited NaHCO3 diuresis and ↓ total-body HCO3− stores.
What is the clinical use of Acetazolamide?
Glaucoma, urinary alkalinization, metabolic alkalosis, altitude sickness, pseudotumor cerebri.
What is the toxicity of Acetazolamide?
Hyperchloremic metabolic acidosis, paresthesias, NH3 toxicity, sulfa allergy.
Loop diuretics - What is the mechanism of Furosemide?
Sulfonamide loop diuretic. Inhibits cotransport system (Na+/K+/2 Cl−) of thick ascending limb of loop of Henle. Abolishes hypertonicity of medulla, preventing concentration of urine.
Stimulates PGE release (vasodilatory effect
on afferent arteriole); inhibited by NSAIDs.
↑ Ca2+ excretion. Loops Lose calcium.
Loop diuretics - What is the clinical use ofFurosemide?
Edematous states (CHF, cirrhosis, nephrotic syndrome, pulmonary edema), hypertension, hypercalcemia.
Loop diuretics - What is the toxicity of Furosemide?
OH DANG! - Ototoxicity, Hypokalemia, Dehydration, Allergy (sulfa), Nephritis (interstitial), Gout.
Loop diuretics - What is the mechanism of Ethacrynic acid?
Phenoxyacetic acid derivative (not a sulfonamide). Essentially same action as furosemide.
Loop diuretics - What is the clinical use of Ethacrynic acid?
Diuresis in patients allergic to sulfa drugs.
Loop diuretics - What is the toxicity of Ethacrynic acid?
Similar to furosemide; can cause hyperuricemia; never use to treat gout.
What is the mechanism of Hydrochlorothiazide?
Thiazide diuretic. Inhibits NaCl reabsorption in early distal tubule, ↓ diluting capacity of the nephron. ↓ Ca2+ excretion.
What is the clinical use of Hydrochlorothiazide?
Hypertension, CHF, idiopathic hypercalciuria, nephrogenic diabetes insipidus, osteoporosis.
What is the toxicity of Hydrochlorothiazide?
Hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia, hyperlipidemia, hyperuricemia, and hypercalcemia. Sulfa allergy.
What are the K+ sparing diuretics?
Spironolactone and eplerenone; Triamterene, and Amiloride.
What is the mechanism of K+ sparing diuretics?
Spironolactone and eplerenone 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.
What is the clinical use of K+ sparing diuretics?
Hyperaldosteronism, K+ depletion, CHF
What is the toxicity of K+ sparing diuretics?
Hyperkalemia (can lead to arrhythmias), endocrine effects with spironolactone (e.g., gynecomastia, antiandrogen effects).
What effect do diuretics have on Urine NaCl?
↑ (all diuretics except acetazolamide). Serum NaCl may ↓ as a result.
What effect do diuretics have on Urine K+?
↑ with loop and thiazide diuretics. Serum K+ may ↓ as a result.
Describe how diuretics can cause acidemia.
↓ (acidemia): carbonic anhydrase inhibitors— ↓ 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.
Describe how diuretics can cause alkalemia.
↑ (alkalemia): loop diuretics and thiazides cause alkalemia through several mechanisms:
▪ Volume contraction → ↑ AT II → ↑ Na+/H+ exchange in proximal tubule → ↑ 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”
What effect do diuretics have on Urine Ca2+?
↑ with loop diuretics: ↓ paracellular Ca2+ reabsorption → hypocalcemia
↓ with thiazides: Enhanced paracellular Ca2+ reabsorption in distal tubule
What are the ACE inhibitors?
Captopril, enalapril, lisinopril
What is the mechanism of ACE inhibitors?
Inhibit ACE → ↓ angiotensin II → ↓ GFR by preventing constriction of efferent arterioles. Levels of renin ↑ as a result of loss of feedback inhibition. Inhibition of ACE also prevents inactivation of bradykinin, a potent vasodilator.
Angiotensin II receptor blockers (-sartans) have effects similar to ACE inhibitors but do not ↑ bradykinin → ↓ risk of cough or angioedema.
What is the clinical use of ACE inhibitors?
Hypertension, CHF, proteinuria, diabetic nephropathy. Prevent unfavorable heart remodeling as a result of chronic hypertension
What are the toxicities of ACE inhibitors?
Cough, Angioedema (contraindicated in C1 esterase inhibitor deficiency), Teratogen (fetal renal malformations), ↑ Creatinine (↓ GFR), Hyperkalemia, and Hypotension. Avoid in bilateral renal artery stenosis, because ACE inhibitors will further ↓ GFR → renal failure.
Prostaglandins dilate the afferent arteriole (↑ RPF, ↑ GFR, so FF remains constant). What drug inhibits this?
NSAIDs; use may result in acute renal failure
Angiotensin II preferentially constricts efferent arteriole (↓ RPF, ↑ GFR, so FF increases). What drug inhibits this?
What is Hartnup disease treated with?
High-protein diet and nicotinic acid
What is Liddle syndrome treated with?
What drugs shift K+ out of cell (causing hyperkalemia)
Digitalis and β-adrenergic antagonist
What drugs shift K+ into cell (causing hypokalemia)?
β-adrenergic agonist (↑ Na+/K+ ATPase)
What drugs cause Type 1 Renal tubular acidosis (distal, pH >5.5)?
Amphotericin B toxicity. Analgesic nephropathy is also a cause.
What drugs cause Type 2 Renal tubular acidosis (proximal, pH <5.5)?
Carbonic anydrase inhibitors
What drugs cause Type 3 Renal tubular acidosis (hyperkalemic, pH <5.5)?
K+ sparing diuretics
What drugs cause Membranous nephropathy?
What drug is used to treat Minimal change disease (lipoid nephrosis)?
Excellent response to corticosteroids
What drugs are treatments for recurrent kidney stones (Calcium)?
Thiazides and citrate
What drugs cause Drug-induced interstitial nephritis (tubulointerstitial nephritis)?
Certain drugs (e.g., diuretics, penicillin derivatives, sulfonamides, rifampin)