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Medications> Hypertension>
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Diuretics

Lipika Samal M.D. and Paul A. Pham, Pharm.D.
02-02-2011

INDICATIONS

FDA

  • Hypertension
  • Congestive Heart Failure
  • See table for diuretic specific FDA indications

MECHANISM

  • Diuretics are classified according to their mechanism: thiazide diuretics, loop diuretics, distal tubule or potassium-sparing diuretics, osmotic diuretics, and carbonic anhydrase inhibitors.
  • Thiazide diuretics increase the excretion of sodium, chloride, and water by inhibiting both sodium ion transport across the renal tubular epithelium and active chloride reabsorption.
  • Loop diuretics inhibit the reabsorption of sodium and chloride by interfering with the chloride-binding of the Na+/K+/2Cl- cotransport system.
  • Potassium-sparing diuretics either inhibit the sodium-potassium ion exchange mechanism in the distal renal tubule independently of aldosterone (amiloride and triamterene) or only in the presence of aldosterone (spironolactone).
  • Osmotic diuretics increase the osmotic pressure of the glomerular filtrate and inhibit reabsorption of water and solutes.--- Carbonic anhydrase inhibitors decrease hydrogen ion concentrations in the renal tubule lumen and increase excretion of bicarbonate, sodium, potassium, and water.
.

USUAL ADULT DOSING

  • Hydrochlorothiazide: 12.5-50 mg/day
  • Chlorothiazide: 125-250 mg daily initially. Can titrate up to 500 mg daily.
  • Metolazone: 2.5-10 mg once daily (max 20 mg once daily for edema). For HTN: 2.5-5 mg/dose once daily.
  • Spironolactone: 25-200 mg/day in 1-2 divided doses (edema); HTN: 25-50 mg/day in 1-2 divided doses. Heart failure (NYHA Class III, IV): 12.5-25 mg/day (max 50 mg)
  • Triamterene: 50-100 mg/day (max 300 mg/day)
  • Furosemide: for edema/heart failure, initially 20-80 mg/dose (edema/heart failure); if response not adequate, may increase dose by 20-40 mg/dose q 6-8 hours (max 600 mg/day)
  • Bumetanide: for edema/heart failure, initially 0.5-2 mg/dose (max dose 10mg/day ) 1-2 times/day

ADVERSE DRUG REACTIONS

OCCASIONAL

  • Hypokalemia, hyponatremia, and hypochloremic alkalosis (thiazide and loop diuretics)
  • Hyperkalemia (potassium-sparing diuretics)
  • Photosensitivity
  • Profound diuresis resulting in dehydration and pre-renal acute tubular necrosis (more common with loop diuretics)
  • Gynecomastia (spirinolactone)
  • Loss of blood sugar control (thiazides)
RARE

  • Sulfa cross-allergy
  • Ototoxicity (loop diuretics, especially with aminoglycoside co-administration)
  • Hyperuricemia (loop diuretics)

DRUG INTERACTIONS

  • All diuretics may increase lithium serum concentration. Co-administer with close monitoring for lithium toxicity and serum concentrations.
  • Thiazide and loop diuretics-amiodarone: hypokalemia may reduce the effect of amiodarone, or cause it to become arrhythmogenic.
  • Thiazide and loop diuretics-dofetilide: electrolyte imbalance can cause pro-arrhythmic events. Dofetilide clearance reduced by 16%.
  • Potassium-sparring diuretics (e.g. spironolactone, triamterene) co-administration with eplerenone, angiotensin II receptor antagonists, ACE inhibitors, tacrolimus, trimethoprim, and cyclosporine can cause hyperkalemia. Use with close monitoring for hyperkalemia. Lithium clearance may be decreased with potassium-sparring diuretics.
  • Colestipol and cholestyramine decreases furosemide bioavailability by 80% and 95%, respectively. Avoid co-administration. Similarly, sucralfate may significantly decrease furosemide serum concentrations.
  • Furosemide-risperidone: several trials involving elderly pts with dementia-related psychosis observed an increased mortality with furosemide and risperidone co-administration.
  • Agents that result in electrolyte wasting (e.g. amphotericin, foscarnet) may worsen hypokalemia with diuretics co-administration.

PHARMACOKINETIC

COMMENTS

  • Tight blood pressure control is advantageous regardless of agent used, with target generally considered to be 130/80.
  • Thiazide diuretics, particularly in the setting of hypokalemia, increase insulin resistance such that treatment of blood glucose may have to be intensified.
  • Diuretics modestly decrease HDL.
  • A number of studies show that conventional dose thiazide diuretics decrease insulin sensitivity (Pollare).
  • However, studies comparing low dose bendrofluazide to conventional dose show that low dose is as effective with less adverse metabolic effects (Harper).

REFERENCES

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