Medical Pharmacology Chapter 26:  Renal Pharmacology

Clinical uses of diuretics

• Carbonic Anhydrase Inhibitors

  • Acetazolamide (Diamox)

    • Glaucoma:

      • Decreases rate of aqueous humor production which leads to a declining in intraocular pressure

      • Most common indication for use of carbonic anhydrase inhibitors

      • Dorzolamide (Trusopf): topical carbonic anhydrase inhibitor.

        • No diuretic or systemic metabolic effects

        • Reduction in intraocular pressure comparable to oral agents

    • Urinary Alkalinization:

      • Increased uric acid and cystine solubility by alkalinizing the urine (by increasing bicarbonate excretion)

      • For prophylaxis of uric acid renal stones, bicarbonate administration (baking soda) may be required

    • Metabolic Alkalosis:

      • Results from:

        • Decreased total potassium with reduced vascular volume

        • High mineralocorticoid levels

        • These conditions are usually managed by treating the underlying causes; however, in certain clinical settings acetazolamide may assist in correcting alkalosis {e.g. alkalosis due to excessive diuresis in CHF patients}

    • Acute Mountain Sickness:

      • Symptoms: weakness, insomnia, headache, nausea, dizziness (rapid ascension of all of 3000 meters); symptoms -- usually mild

      • In serious cases: life-threatening cerebral or pulmonary edema

      • Acetazolamide (Diamox) reduces the rate of CSF formation and decreases cerebral spinal fluid pH.

      • Prophylaxis against acute mountain sickness may be appropriate

    • Other Uses:

      • Some role in management of epilepsy

      • Hypokalemia periodic paralysis

      • Increase urinary phosphate excretion during severe hyperphosphatemia.

• Loop Diuretics

  • Furosemide (Lasix), bumetanide (Bumex), torsemide (Demadex), ethacrynic acid (Edecrin)

    • Major Clinical uses:

      • Acute pulmonary edema

      • Acute hypercalcemia

      • Management of edema

    • Other uses:

      •   Hyperkalemia:

        • Loop diuretics increase potassium excretion

        • Effect increased by concurrent administration of NaCl and water.

      •  Acute renal failure:

        •  May increase rate of urine flow and increase potassium excretion.

        •  May convert oligouric to non-oligouric failure {easier clinical management}

        •  Renal failure duration -- not affected

      •  Anion overload:

        •  Bromide, chloride, iodide: all reabsorbed by the thick ascending loop:

        •  Systemic toxicity may be reduced by decreasing reabsorption

          • Concurrent administration of sodium chloride and fluid is required to prevent volume depletion.

• Thiazides

  • Major Clinical Uses:

    • Hypertension

    • Congestive heart failure

    • Nephrolithiasis (due to idiopathic hypercalciuria)

    • Nephrogenic diabetes insipidus

  • Thiazides

    • Bendroflumethazide	Benzthiazide	Chlorothiazide (Diuril)	Chlorthalidone (Hygroton)
      Hydrochlorothiazide (HCTZ, Esidrix, HydroDIURIL)	Hydroflumethiazide	Indapamide (Lozol)	Methyclothiazide
      Metolazone (Zaroxolyn, Mykrox)	Polythiazide	Quinethazone	Trichlomethiazide

       

       

• Osmotic Diuretics

  • Mannitol (Osmitrol)

    • To increase urine volume:

      •  May be used to prevent anuria if the kidney due to hemolysis or rhabdomyolysis is presented with a large pigmented load.

      •  When renal hemodynamics are compromised

    • To decrease intracranial or intraocular pressure:

      • Mannitol extract water from intracellular compartments, reducing total body water

      • Following IV administration, intracranial pressure falls within 60-90 minutes.

       

• Potassium Sparing Agents

  • Amiloride (Midamor), triamterene (Dyrenium), spironolactone (Aldactone)

    • Reduction of potassium loss associated with thiazide or loop diuretic administration

    • Mineralocorticoid excess:

      • Conn's syndrome (primary hypersecretion)

      • Ectopic ACTH production (primary hypersecretion)

      • Secondary aldosteronism caused by:

        •  Congestive heart failure

        •  Hepatic cirrhosis

        •  Nephrotic syndrome

        •  Conditions that cause renal salt retention with reduced intravascular volume

          • Other diuretics may further reduce intravascular volume thus worsening secondary aldosteronism

           

• Diuretic-Other Drug Interactions

  Cardiac glycosides	Oral hypoglycemics	Aminoglycoside antibiotics
  Oral anticoagulants	Uricosuric drugs	Non-steroidal anti-inflammatory drugs