Nursing Pharmacology Chapter 26:  Renal Pharmacology

Thiazides

• Introduction:

  • Thiazides inhibit NaCl transport at the distal convoluted tubule

  • Prototypical thiazide:  hydrochlorothiazide

   

• Properties

  • Oral administration

  • Secreted by the organic acid secretory system

    • Competes with uric acid for secretion, uric acid secretory rates may decline.

  • Differences between thiazides:

    • Chlorothiazide (Diuril): less lipid soluble (requires relatively large doses)

    • Chlorthalidone (Hygroton): slowly absorbed -- longer duration of action

    • Indapamide (Lozol): mainly biliary secretion

• Mechanism of action

  • Diuretic action: Inhibition of NaCl reabsorption from the distal convoluted tubule (luminal side).

  • Enhanced calcium reabsorption in the distal convoluted tubule (unknown mechanism).

    • Thiazides infrequently cause hypercalcemia but can unmask hypercalcemia due to other causes such as carcinoma, sarcoidosis, or hyperparathyroidism.

• Clinical Uses

  • Hypertension

  • Congestive heart failure

  • Nephrolithiasis (due to idiopathic hypercalciuria

  • Nephrogenic diabetes insipidus

•  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

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) TheMcGraw-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