Nursing Pharmacology Chapter 26:  Renal Pharmacology

Potassium-Sparing Diuretic Agents

• Introduction

  • These diuretics inhibit the effects of aldosterone at the cortical collecting tubule and late distal tubule.

• Mechanisms of action

  • In the collecting tubule and duct, sodium reabsorption and potassium excretion is regulated by aldosterone.

    • Aldosterone increases potassium secretion by increasing Na/K ATPase activity and sodium and potassium channel activity.

    • Normally, sodium absorption in the collecting tubule results in a lumen-negative electrical force that drives potassium excretion.

    • Aldosterone antagonists interfere with this effect

    • Aldosterone antagonists act similarly with respect to proton movement, accounting for metabolic acidosis associated with aldosterone antagonists.

  • Pharmacologic antagonism at mineralocorticoid receptors occurs withspironolactone (Aldactone) administration.

  • Inhibition of sodium transport through the luminal membrane is associated with triamterene (Dyrenium) and amiloride (Midamor) administration.

    • Some Potassium-Sparing effects occur with nonsteroidal anti-inflammatory drugs, beta-blockers, converting enzyme-inhibitors, and angiotensin receptor blockers.

• Spironolactone (Aldactone)

  • Synthetic steroid: competitive aldosterone antagonist

    • Binds to cytoplasmic mineralocorticoid receptors, preventing receptor complex translocation to the nucleus.

    • Spirolactone, by inhibiting the enzyme 5-alpha reductase, decreases formation of active metabolites of aldosterone.

  • Hepatic inactivation

  • Slow onset of action

• Triamterene (Dyrenium)

  • Renal excretion; extensive hepatic metabolism results in a short half-life.

    • Directly blocks Na entry through sodium-specific channels (apical collecting tubule membrane)

    • Since potassium secretion is coupled to sodium entry, potassium secretion is reduced due to potassium-sparing activity.

• Amiloride (Midamor)

  • Excreted unchanged (urine)

  • Directly blocks Na⁺ entry through sodium-specific channels at the apical collecting tubule membrane.

    • Since potassium secretion is coupled to sodium entry, potassium secretion is reduced.

•  Clinical Uses

  • 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.

•  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 due to variations in bioavailability, individual dose adjustment of the two drugs may be better.

  • Hyperchloremic Metabolic Acidosis

    • Acidosis caused by inhibition of proton secretion along with potassium secretion may occur.

  • Gynecomastia

    •  Endocrine abnormalities associated with synthetic steroids such as spironolactone (Aldactone).

      • 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