IV. ANGIOTENSIN CONVERTING ENZYME INHIBITORS

       The angiotensin converting enzyme (ACE) inhibitors are effective
   antihypertensive agents and have other indications as well. The 2 avail-
   able drugs in this group are very similar in their effects and may be
   discussed together. The major difference between them is that captopril
   is an active drug with a shorter duration of action 8-12 hours) while
   enalapril is a prodrug that must be metabolized to the active form,
   enalaprilat, which has a longer duration of action (12-24 hours).
   Mechanisms:
   * Inhibition of angiotensin converting enzyme results in decreased cir-
   culating levels of angiotensin II as well as increased levels of
   bradykinin, a vasodilator polypeptide.   
   Indications:
   * Chronic hypertension.
   * Captopril is also labeled for the treatment of congestive heart fail-
   ure that is unresponsive to digitalis and diuretics (see Chapter 4).




                                           
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   Contraindications and Warnings:
   * Hypersensitivity
   * Blood dyscrasias (Warning) have resulted from the use of ACE in-
   hibitors, see adverse reactions.
   * Renal impairment (Warning): These drugs interfere with the action of
   the renin-angiotensin-aldosterone system and may contribute to a hyper-
   kalemic state. These drugs should not be given to patients taking potas-
   sium supplements or potassium-sparing diuretics.
   Adverse Reactions:
   * Hematologic: Reversible neutropenia or thrombocytopenia. The effect is
   more common in patients with elevated BUN or other evidence of impaired
   renal function (for captopril, 1 case in 500 patients with creatinine
   above 1.6 mg/dL versus 1 in 8600 patients with normal serum creatinine).
   * Renal: increased levels of serum creatinine and BUN and, rarely, acute
   renal failure may occur, especially in patients with bilateral renal
   artery stenosis.
   * Electrolyte: elevated serum potassium occurs in about 1% of patients,
   probably as a result of reduced aldosterone levels.
   * Dysgeusia, an aberration of taste, has been reported in about 2-4% of
   patients, a higher rate than for most drugs.
   * Rash, with or without pruritis, has been reported in 4-7% of patients
   taking captopril and somewhat less commonly in patients on enalapril.
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   * Nonspecific neurologic and gastrointestinal symptoms occur in 1-3% of
   patients on either drug.
   Overdose Toxicity: 
   Hypotension is the major manifestation of serious
   overdosage. Symptomatic management is usually sufficient (see Chapter
   24) but both captopril and enalapril may be removed by hemodialysis if
   necessary.
   Interactions:
   * Other hypotensive agents: predictable additive hypotensive interac-
   tions, especially in diuretic-induced hypovolemia.
   * Potassium-sparing diuretics: predictable hyperkalemia occurs.
   * Aspirin and NSAIDs may interfere with the hypotensive action of these
   agents









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