Acetazolamide
Carbonic anhydrase inhibitor. Causes self-limited NaHCO3 diuresis and ↓ total body HCO3- stores. 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 (precipitate at high pH)
Furosemide, bumetanide, torsemide
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.↑ Ca2+ excretion. Use:- Edematous states (HF, cirrhosis, nephrotic syndrome, pulmonary edema)- Hypertension- Hypercalcemia Adverse effects:- Ototoxicity- Hypokalemia- Hypomagnesemia- Dehydration- Sulfa allergy- Metabolic alkalosis- Interstitial nephritis- Gout
Ethacrynic acid
Nonsulfonamide inhibitor of cotransport system (Na+/K+/2Cl-) of thick ascending limp of loop of Henle. Use: Diuresis in patients allergic to sulfa drugs. Adverse effects: Similar to furosemide, but more ototoxic.
Spironolactone, Eplerenone
Competitive aldosterone receptor antagonists in cortical collecting tubule Clinical use:- Hyperaldosteronism- K+ depletion- HF- Hepatic ascites (spironolactone)- Antiandrogen Adverse effects:- Hyperkalemia (can lead to arrhythmias)- Endocrine effects with spironolactone (eg, gynecomastia, antiandrogen effects)
Amiloride, Triamterene
Act at the cortical collecting tubule by blocking Na+ channels in the cortical collecting tubule. Use:- Hyperaldosteronism- K+ depletion- HF- Nephrogenic DI (amiloride)- Antiandrogen Adverse effects:- Hyperkalemia (can lead to arrhythmias)
Diuretics: electrolyte changes
Urine NaCl: ↑ with all diuretics. Serum NaCl may decrease as a result. Urine K+: ↑ especially with loop and thiazide diuretics. Serum K+ may decrease as a result. Blood pH: ↓ (acidemia): carbonic anhydrase inhibitors: ↓ HCO3- reabsorption. K+ sparing: aldosterone blockade prevents K+ secretion and H+ secretion. Additionally, hyperkalemia leads to K+ entering all cells in exchange for H+ exiting cells.↑ (alkalemia): loop diuretics and thiazides cause alkalemia through several mechanisms:- Volume contraction → ↑ AT II → ↑ Na+/H+ exchange in PCT → ↑ HCO3- reabsorption- 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" Urine Ca2+:↑ with loop diuretics: ↓ paracellular Ca2+ reabsorption → hypocalcemia↓ with thiazides: enhanced Ca2+ reabsorption
Captopril, enalapril, lisinopril, ramipril
Inhibit ACE → ↓ AT II → ↓ GFR by preventing constriction of efferent arterioles. ↑ renin due to loss of negative feedback. Inhibition of ACE also prevents inactivation of bradykinin, a potent vasodilator. Use:- Hypertension- HF (↓ mortality)- Proteinuria- Diabetic nephropathy- Prevent unfavorable heart remodeling as a result of chronic hypertension.- In chronic kidney disease (eg, diabetic nephropathy), ↓ intraglomerular pressure, slowing GBM thickening. Adverse effects:- Cough and angioedema (both due to ↑ bradykinin; contraindicated in C1 esterase inhibitor deficiency)- Teratogen (fatal renal malformations)- ↑ creatinine (↓ GFR)- Hyperkalemia- Hypotension- Used with caution in bilateral renal artery stenosis because ACE inhibitors will further ↓ GFR → renal failure.
Losartan, candesartan, valsartan
Selectively block binding of angiotensin II to AT1 receptor. Effects similar to ACE inhibitors, but ARBs do not increase bradykinin. Use:- Hypertension- HF- Proteinuria- Chronic kidney disease (eg, diabetic nephropathy) with intolerance to ACE inhibitors (eg, cough, angioedema) Adverse effects:- Hyperkalemia- ↓ GFR- Hypotension- Teratogen
Aliskiren
Direct renin inhibitor, blocks conversion of angiotensinogen to angiotensin I. Use: Hypertension Adverse effects:- Hyperkalemia- ↓ GFR- Hypotension- Angioedema- Relatively contraindicated in patients already taking ACE inhibitors or ARBs- Contraindicated in pregnancy
