POTASSIUM-SPARING DIURETICS

   Mechanisms   Potassium is normally secreted in the collecting ducts of the
      kidney, under the control of aldosterone and in proportion to the
      amount of sodium appearing in the lumen at this level. The aldosterone
      level is increased when there is a net sodium loss or a decrease in the
      "effective circulating blood volume." Most diuretics increase the
      amount of potassium excreted because they present more sodium to the
      collecting ducts and increase the circulating aldosterone level. The
      potassium-sparing agents effectively reduce sodium reabsorption in this
      part of the tubule and thereby reduce potassium excretion.
   * Aldosterone inhibition: Spironolactone is a direct aldosterone receptor
      antagonist in the cells of the collecting duct of the nephron and
      modifies protein synthesis as a result. Spironolactone also has other
      endocrine effects, including an antiandrogenic action.
   * Sodium transport inhibitors: Amiloride and triamterene block a channel
      necessary for sodium reabsorption in the collecting duct. Amiloride may
      also have an inhibitory effect on Na,K-ATPase in this part of the
      tubule.



                                                     (PgDn key for more text)

   Major indications
   * Congestive heart failure, especially in patients with severe potassium
      wasting: amiloride, spironolactone, triamterene may all be used.   
   * Primary aldosteronism and hyperaldosteronism secondary to cirrhosis or
      nephrotic syndrome: spironolactone is labeled for this use.
   * Hirsuitism (unlabeled): spironolactone (antiandrogenic action).
   * Lithium-induced diabetes insipidus: amiloride can block lithium absorp-
      tion in the collecting tubule and may correct lithium-induced diabetes
      insipidus.

   Pharmacokinetics 
   * Spironolactone is over 90% absorbed after oral administration, is
      strongly protein-bound, and is excreted after extensive metabolism. It
      has a very slow onset of action, partially due to the lag inherent in
      the action of drugs that modify gene expression. It has an active me-
      tabolite, canrenone.
   * Amiloride has a low but predictable bioavailability and a much faster
      onset of action than spironolactone.
   * Triamterene has an intermediate degree of bioavailability and the
      shortest duration of action of the potassium-sparing diuretics. It has
      an active metabolite and is extensively metabolized before excretion.

                                                     (PgDn key for more text)

   Contraindications and Warnings

   * All 3 drugs: hypersensitivity, hyperkalemia (above 5.5 mEq), anuria. Do
      not give concurrently with dietary potassium supplementation.
   * Warnings: do not use more than one potassium-sparing diuretic at a time.
      Use caution in administering amiloride to patients in metabolic or
      respiratory acidosis, or with renal insufficiency.
   * Warning: Because it is an aldosterone antagonist, spironolactone has low
      efficacy in patients whose aldosterone is low or normal. Patients not
      responding to normal dosages of the drug should not have the dose in-
      creased without monitoring urinary potassium excretion. Patients with
      low K excretion levels (less than 30 mEq/d) will usually respond to in-
      creased dosing.

   Adverse Reactions
   * Amiloride:
      - Electrolytes: hyperkalemia, acidosis.
      - CNS: headache, paresthesia, insomnia, depression, loss of libido.
      - GI: nausea, anorexia, diarrhea, vomiting.
      - Musculoskeletal: weakness, fatigue, muscle cramps.
      - Skin: rash.

                                                     (PgDn key for more text)

   * Spironolactone:
      - Electrolytes: hyperkalemia, acidosis.
      - GI: cramping, diarrhea.
      - CNS: drowsiness, lethargy, ataxia.
      - Endocrine: gynecomastia, impotence in men; irregular menses or
      amenorrhea in women.
   * Triamterene:
      - Electrolytes: hyperkalemia, acidosis.
      - GI: diarrhea, nausea, vomiting.
      - Rare: interstitial nephritis; blood dyscrasias, nephrolithiasis.

   Toxicity and Overdosage
   * Electrolyte disorders (hyperkalemia): Monitor serum potassium carefully;
      if over 6.5 mEq/L, consider treatment with IV glucose and insulin or     
      dialysis to reduce serum K.  Dialysis is ineffective in removing
      spironolactone  but may be of some benefit in triamterene intoxication.






                                                     (PgDn key for more text)


   Interactions
   * Combination with other potassium-sparing diuretics, dietary potassium
      supplements, beta-blockers, or captopril lead to a  high incidence of
      hyperkalemia. Do not combine these therapies, especially in patients
      with renal insufficiency.
   * All 3 K-sparing agents may reduce lithium clearance.
   * Amiloride and spironolactone may increase digoxin clearance; triamterene
      may increase digitalis serum levels.
   * Triamterene in combination with nonsteroidal anti-inflammatory drugs may
      result in acute renal failure.
   * Spironolactone may interfere with laboratory tests for digoxin levels;
      triamterene may interfere with the test for quinidine.








                                          (Home key to return to top of file)