Anatomical Therapeutic Chemical Classification System
Benazepril is a prodrug which, after hydrolysis to the active substance benazeprilat, inhibits the angiotensin-converting enzyme (ACE) and so blocks the conversion of angiotensin I to angiotensin II. This reduces all the effects mediated by angiotensin II – i.e. vasoconstriction and production of aldosterone, which promotes the reabsorption of sodium and water in the renal tubules – and elevates cardiac output.
Captopril is a highly specific, competitive inhibitor of angiotensin-I converting enzyme (ACE inhibitors). Inhibition of ACE results in decreased plasma angiotensin-II, which leads to decreased vasopressor activity and to reduced aldosterone secretion. In patients with hypertension, captopril causes a reduction in supine and erect blood pressure, without inducing any compensatory increase in heart rate, nor water and sodium retention.
Cilazapril is a specific, long-acting angiotensin-converting enzyme (ACE) inhibitor which suppresses the renin-angiotensin-aldosterone system and thereby the conversion of the inactive angiotensin I to angiotensin II, which is a potent vasoconstrictor.
Enalapril is a derivative of two amino-acids, L-alanine and L-proline. After absorption, enalapril is hydrolysed to enalaprilat, which inhibits ACE. Inhibition of ACE results in decreased plasma angiotensin II, which leads to increased plasma renin activity (due to removal of negative feedback of renin release), and decreased aldosterone secretion.
Fosinopril is the pro-drug (ester) of the long acting active ACE inhibitor fosinoprilat. After oral administration fosinopril is quickly and fully metabolised to the active fosinoprilat. Fosinopril contains a phosphinic group capable of a specific binding to the active site of the angiotensin converting enzyme, preventing the conversion of angiotensin I in angiotensin II.
Lisinopril is a peptidyl dipeptidase inhibitor. It inhibits the angiotensin-converting enzyme (ACE) that catalyses the conversion of angiotensin I to the vasoconstrictor peptide, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Inhibition of ACE results in decreased concentrations of angiotensin II which results in decreased vasopressor activity and reduced aldosterone secretion.
Perindopril is an inhibitor of the enzyme that converts angiotensin I into angiotensin II (Angiotensin Converting Enzyme ACE). The converting enzyme, or kinase, is an exopeptidase that allows conversion of angiotensin I into the vasoconstrictor angiotensin II as well as causing the degradation of the vasodilator bradykinin into an inactive heptapeptide. Inhibition of ACE results in a reduction of angiotensin II in the plasma, which leads to increased plasma renin activity (by inhibition of the negative feedback of renin release) and reduced secretion of aldosterone. Since ACE inactivates bradykinin, inhibition of ACE also results in an increased activity of circulating and local kallikrein-kinin systems (and thus also activation of the prostaglandin system).
Quinapril is a potent angiotensin-converting enzyme (ACE) inhibitor. The mode of action of quinapril in humans and animals is to inhibit circulating and tissue ACE activity, thereby decreasing vasopressor activity and aldosterone secretion.
Ramiprilat, the active metabolite of the prodrug ramipril, inhibits the enzyme dipeptidylcarboxypeptidase I (synonyms: angiotensin-converting enzyme; kininase II). In plasma and tissue this enzyme catalyses the conversion of angiotensin I to the active vasoconstrictor substance angiotensin II, as well as the breakdown of the active vasodilator bradykinin. Reduced angiotensin II formation and inhibition of bradykinin breakdown lead to vasodilatation.
Trandolapril is a prodrug, which is rapidly, non-specifically hydrolysed to its potent, long-acting active metabolite, trandolaprilat (other metabolites are inactive) and acts as an orally-active angiotensin converting enzyme inhibitor (ACE inhibitor) without a sulphydryl group. In addition to inhibition of plasma ACE, trandolapril has been experimentally shown to inhibit tissue ACE (particularly vascular, cardial and adrenal). The clinical relevance of tissue ACE inhibition has not been established in humans.
The beneficial effects of zofenopril in hypertension and acute myocardial infarction appear to result primarily from the suppression of the plasma renin-angiotensin aldosterone system. Inhibition of ACE (Ki 0.4nM in rabbit lung for arginine salt of zofenoprilat) results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to reduced aldosterone secretion.