Nursing Pharmacology Chapter 26:  Renal Pharmacology

Adverse Diuretic effects and contraindications

Adverse Effects:  Carbonic Anhydrase Inhibitors (Acetazolamide)

• Toxicity

  • Hyperchloremic metabolic acidosis

    • Due to reduction in body bicarbonate stores

  • Renal stones

    • Bicarbonate loss is associated with:

      •  Phosphaturia

      •  Hypercalciuria (calcium salts, relatively insoluble at alkaline pH)

  • Renal potassium loss

    • Increased sodium bicarbonate in the collecting tubule increases the lumen-negative and in inelectrical potential -- enhances potassium excretion

      • Counteracted by potassium chloride administration

  • Others

    • Drowsiness, parathesias

    • Accumulation in renal failure (CNS toxicity)

    • Hypersensitivity reactions

  •   Contraindications

    • Hepatic cirrhosis

      • Urinary alkalinization will decrease ammonium ion trapping, increasing the likelihood of hepatic encephalopathy.

Adverse Effects:  Loop Diuretics

•  Toxicity

  •  Hypokalemia metabolic alkalosis

    • Increased delivery of NaCl and water to the collecting duct increases potassium and proton secretion-- causing a hypokalemic metabolic alkalosis

    • In managed by potassium replacement and by ensuring adequate fluid intake

  •  Ototoxicity

    • Dose-related hearing loss (in usually reversible)

    • More common:

      • With decreased renal function

      • With concurrent administration of other ototoxic drugs such as aminoglycosides

  •  Hyperuricemia

    • May cause gout

    • Loop diuretics cause increased uric acid reabsorption in the proximal tubule, secondary to hypovolemic states.

  •  Hypomagnesemia

    1. Reduction in sodium chloride reabsorption

    2. Decreases normal lumen-positive potential (secondary to potassium recycling)

    3. Positive lumen potential: drives divalent cationic reabsorption (calcium magnesium)

    4. Therefore, loop diuretics increase magnesium and calcium excretion.

       • Hypomagnesemia may occur in some patients.

       • Reversed by oral magnesium administration

  • Allergic reactions

    • Furosemide: skin rash, eosinophilia, interstitial nephritis(less often)

  • Other toxicities

    • Dehydration (may be severe)

    • Hyponatremia (less common than with thiazides thought may occur in patients who increased water intake in response to a hypovolemic thirst)

    • Hypercalcemia may occur in severe dehydration and if a hypercalcemia condition {e.g. oat cell long carcinoma} is also present.

Adverse Effects:  Thiazides

• Toxicity

  • Hypokalemic metabolic alkalosis and hyperuricemia

  • Impaired carbohydrate tolerance

    • May induce hyperglycemia

      • Impaired pancreatic insulin release

      • Decreased tissue glucose utilization

      • Hyperglycemia may be partially reversed by correcting a hypokalemic state

  • Hyperlipidemia

    • 5% to 15% increase in serum cholesterol and an increase in low-density lipoproteins.

  • Hyponatremia

    • Significant adverse effect, occasionally life-threatening

    • Mechanism:

      •   Hypovolemia-induced increase in ADH

      •   Reduced renal diluting capacity

      •   Increased thirst

      •   Prevention: decreasing the drug dose or limiting fluid intake

  • Allergic reactions

    • Thiazides are sulfonamides: cross-reactivity within the group

    • Photosensitivity {rare}

    • Dermatitis {rare}

    • Extremely rare reactions:

      • Hemolytic anemia

      • Thrombocytopenia

      • Acute necrotizing pancreatitis

  • Other reactions

    • Weakness

    • Fatigue

    • Paresthesias

Adverse Effects:  Osmotic Diuretics

•   Toxicity

  • Volume expansion effects are associated with increased extra cellular fluid volume and hyponatremia may result in pulmonary edema which complicates management of congestive heart failure.

  • Headache, nausea, vomiting are commonly observed

  • Dehydration and hypernatremia:

    • Leads to significant dehydration and in the absence of adequate fluid replacement leads to hypernatremia.

Adverse Effects:  Potassium-Sparing Diuretics

•   Toxicity:

  • Hyperkalemia:

    • Potassium-sparing diuretics can cause significant hyperkalemia

    • Factors that increase the likelihood of hyperkalemia:

      • Renal disease

      • Presence of agents that reduce renin:

        •   β-blockers

        •   Nonsteroidal anti-inflammatory drugs (NSAIDs)

        •   ACE inhibitors

        •   Angiotensin receptor blockers

    • Hyperkalemia more likely when potassium-sparing diuretics are used as the only diuretic drug or in the presence of renal insufficiency.

      •  Given in combination with thiazides, hypokalemia and metabolic alkalosis associated with thiazide use may be balanced by aldosterone antagonists

      •  Since thiazide adverse effects may predominate {hyponatremia, metabolic alkalosis}, due to variations in bioavailability, individual dose adjustment of the two drugs may be better.

  • Hyperchloremic Metabolic Acidosis

    • Acidosis cause by inhibition of proton secretion along with potassium secretion {similar to type IV renal tubular acidosis

  • Gynecomastia

    •   Endocrine abnormalities associated with synthetic steroids --spironolactone:

      •    Gynecomastia (breast enlargement)

      •    Impotence

      •    Benign prostatic hyperplasia

  • Acute Renal Failure

    •   Triamterene (Dyrenium) plus indomethacin

  • Kidney Stones

    •  Triamterene (Dyrenium) (poorly soluble) may precipitate in urine, causing renal stones:

•   Contraindications

  • May cause severe (potentially fatal) hyperkalemia

  • Potassium supplements should be discontinued prior to administration of aldosterone antagonists

  • Patients with chronic renal insufficiency are at particular risk

  • Hyperkalemia is also more likely to occur or it if beta-blockers or ACE inhibitors are concurrently administered

  • Impairment of hepatic metabolism of triamterene spironolactone may require dose adjustment

Jackson, E.K. Diuretics In, Goodman and Gillman's The Pharmacological Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp. 685- 713

Jackson, E.K. Vasopressin and Other Agents Affecting the Renal Conservation of Water In, Goodman and Gillman's The Pharmacological Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp.715-732