Renal Drugs


Mannitol

MECHANISM
  • Osmotic diuretic
  • tubular fluid osmolarity
  • Producing urine flow
  • intracranial/intraocular pressure.
CLINICAL USE
  • Drug overdose
  •  intracranial/intraocular pressure.
TOXICITY
  • Pulmonary edema, dehydration.
  • Contraindicated in anuria, CHF.
 

Acetazolamide

MECHANISM
  • Carbonic anhydrase inhibitor.
  • Causes self-limited NaHCO3 diuresis and total-body HCO3- stores.
CLINICAL USE
  • Glaucoma
  • Urinary alkalinization
  • Metabolic alkalosis
  • Altitude sickness
  • Pseudotumor cerebri.
TOXICITY
  • Hyperchloremic metabolic acidosis
  • Paresthesias,
  • NH3 toxicity
  • Sulfa allergy.
"ACID”azolamide causes ACIDosis.
 

Loop Diuretics

Furosemide, Torsemide, Bumetanide

Lasix (Furosemide), Demadex (Torsemide), Bumex (Bumetanide)
MECHANISM
  • 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)
CLINICAL USE
  • Edematous states (CHF, cirrhosis, nephrotic syndrome, pulmonary edema)
  • Hypertension
  • Hypercalcemia.
TOXICITY
  • Ototoxicity
  • Hypokalemia
  • Dehydration
  • Allergy (sulfa)
  • Nephritis (interstitial)
  • Gout.
OH DANG!
 

Ethacrynic acid

Ethacrynic acid
MECHANISM
  • Phenoxyacetic acid derivative (not a sulfonamide).
  • Essentially same action as furosemide.
CLINICAL USE
  • Diuresis in patients allergic to sulfa drugs.
TOXICITY
  • Similar to furosemide; can cause hyperuricemia; never use to treat gout.
  • More Ototoxic, Rarely used
 

Equivalents
PO equivalents:
  • Furosemide 40mg = Torsemide 20mg = Bumetanide 1mg
IV/PO conversion
  • Torsemide and bumetanide 1:1
  • Furosemide is 1:2

Hydrochlorothiazide

MECHANISM
  • Thiazide diuretic.
  • Inhibits NaCl reabsorption in early distal tubule,  diluting capacity of the nephron. 
  • Ca2+ excretion.
CLINICAL USE
  • Hypertension,
  • CHF,
  • Idiopathic hypercalciuria,
  • Nephrogenic diabetes insipidus,
  • Osteoporosis.
TOXICITY
  • Hypokalemic metabolic alkalosis
  • Hyponatremia,
  • HyperGlycemia
  • HyperLipidemia,
  • HyperUricemia
  • HyperCalcemia.
  • Sulfa allergy.
HyperGLUC.

K+Sparing diuretics

Spironolactone and eplerenone; Triamterene, and Amiloride.
MECHANISM
  • Spironolactone and eplerenone:
    • 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.
CLINICAL USE
  • Hyperaldosteronism
  • K+ depletion
  • CHF
TOXICITY
  • Hyperkalemia (can lead to arrhythmias)
  • Endocrine effects with spironolactone (e.g., gynecomastia, antiandrogen effects).

Diuretics: electrolyte changes

Urine NaCl   ↑ ↓ (all diuretics except acetazolamide).
Serum NaCl may  as a result
Urine K+  with loop and thiazide diuretics.
Serum K+ may  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 (via H+/K+ exchanger) in exchange for H+ exiting cells.
 (alkalemia): loop diuretics and thiazides cause alkalemia through several mechanisms:
  • ƒƒVolume contraction ŽŽAT II Na+/H+ exchange in proximal tubule Ž HCO3- reabsorption (“contraction alkalosis”)
  • ƒK+ 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, Ž Ž alkalosis and “paradoxical aciduria”
Urine Ca2+  with loop diuretics:  paracellular Ca2+ reabsorption Ž hypocalcemia.
with thiazides: Enhanced paracellular Ca2+ reabsorption in distal tubule.

ACE inhibitors

Captopril, enalapril, lisinopril.
MECHANISM
  • Inhibit ACE Ž  angiotensin II ŽŽ   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.
(ARBS) Angiotensin II receptor blockers (-sartans) have effects similar to ACE inhibitors but do not   bradykinin Ž  risk of cough or angioedema
CLINICAL USE
  • Hypertension
  • CHF
  • Proteinuria
  • Diabetic nephropathy.
  • Prevent unfavorable heart remodeling as a result of chronic hypertension.
NOTE:
ACE inhibitors such as lisinopril do not need to be discontinued unless baseline creatinine increases by >30%.
Small increases in creatinine have been associated with long-term preservation of renal function, and may be a marker of changes in intraglomerular pressure.

Ref:
 AAFP ITE 2014, Q# 27
TOXICITY
  • Cough
  • Angioedema (contraindicated in C1 esterase inhibitor deficiency)
  • Teratogen (fetal renal malformations)
  • Creatinine ( GFR)
    • ACE inhibitors such as lisinopril do not need to be discontinued unless baseline creatinine increases by >30%
  • Hyperkalemia
  • Hypotension.
  • Avoid in bilateral renal artery stenosis, because ACE inhibitors will further  GFR Ž renal failure

Captopril’s CATCHH

 

 

Ref: FA Step 1, 2014