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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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