ACE inhibitors or angiotensin-converting enzyme inhibitors, are a
group of pharmaceuticals that are used primarily in treatment of
hypertension and congestive heart failure though they are also
sometimes used in patients with cardiac failure, renal disease or
systemic sclerosis.
The first step in the development of (ACE) inhibitors was the
discovery of angiotensin converting enzyme (ACE) in plasma by Leonard
T. Skeggs and his colleagues in 1956. Brazilian scientist Sergio
Ferreira reported in 1965 of a 'bradykinin potentiating factor (BPFs)
present in the venom of bothrops jararaca, a South American pit viper.
Dr SH Ferreira then proceeded to John Vanes laboratory as a Post-Doc
with his already isolated BPFs. The conversion of the inactive
angiotensin I to the potent angiotensin II was thought to take place in
the plasma. However, in 1967, Kevin K. F. Ng and John R. Vane showed
that the plasma (ACE) was too slow to account for the conversion of
angiotensin I to angiotensin II ''in vivo''. Subsequent investigation
showed that rapid conversion occurs during its passage through the
pulmonary circulation.
Bradykinin is rapidly inactivated in the circulating blood and it
disappears completely in a single passage through the pulmonary
circulation. Angiotensin I also disappears in the pulmonary circulation
due to its conversion to angiotensin II. Furthermore, angiotensin II
passes through the lungs without any loss. The inactivation of
bradykinin and the conversion of angiotensin I to angiotensin II in the
lungs was thought to be caused by the same enzyme. In 1970, Ng and Vane
using bradykinin potentiating factor (BPF) provided by Sérgio Henrique
Ferreira showed that the conversion of angiotensin I to angiotensin II
was inhibited during its passage through the pulmonary circulation.
Bradykinin potentiating factor (BPF) is derived from the venom of
the pit viper (''Bothrops jararaca''). It is a family of
peptides and its potentiating action is linked to inhibition of
bradykinin by ACE. Molecular analysis of BPF yielded a nonapeptide BPF
teprotide (SQ 20,881) which showed the greatest (ACE) inhibition
potency and hypotensive effect ''in vivo''. Teprotide had limited
clinical value, due to its peptide nature and lack of activity when
given orally. In the early 1970s, knowledge of the structure-activity
relationship required for inhibition of ACE was growing. David Cushman,
Miguel Ondetti and colleagues used peptide analogues to study the
structure of ACE, using carboxypeptidase A as a model. Their
discoveries led to the development of captopril, the first
orally-active ACE inhibitor in 1975.
Captopril was approved by the United States Food and Drug
Administration in 1981. The first non-sulfhydryl-containing (ACE)
inhibitor enalapril was marketed two years later. Since then, at least
twelve other ACE inhibitors have been marketed.
In 1991, Japanese scientists created the first ever milk-based ACE
inhibitor in the form of a fermented milk drink, using specific
cultures to liberate the IPP from the dairy protein. Interestingly,
Val-Pro-Pro is also liberated in this process—another milk tripeptide
with a very similar chemical structure to IPP. Together, these peptides
are now often referred to as lactotripeptides. Shortly after this, in
1996, the first human study confirmed the blood pressure lowering
effect of IPP in fermented milk. Although twice the amount of VPP is
needed to achieve the same ACE inhibiting activity as the originally
discovered IPP, it is assumed that VPP also adds to the total blood
pressure lowering effect.
ACE inhibitors can be divided into three groups based on their
molecular structure:
Sulfhydryl-containing agents
- Captopril (trade name Capoten), the first ACE inhibitor
- Zofenopril
Dicarboxylate-containing agents
This is the largest group, including:
Phosphonate-containing agents
- Fosinopril (Monopril) is the only member of this group
Naturally occurring
- Casokinins and lactokinins are breakdown products of casein and
whey that occur naturally after ingestion of milk products, especially
cultured milk. Their role in blood pressure control is uncertain.
- The Lactotripeptides Val-Pro-Pro and Ile-Pro-Pro produced by the
probiotic ''Lactobacillus helveticus''
or derived from casein have been shown to have ACE-inhibiting and
antihypertensive functions.
| ACE inhibitors
dosages for hypertension |
| |
|
Dosage |
Note: bid = 2 times a day, tid = 3 times a day, d
= daily
Drug dosages from Drug Lookup, Epocrates Online. |
| Name |
Equivalent daily dose |
|
Start |
Usual |
Maximum |
| Benazepril |
10 mg |
|
10 mg |
20–40 mg |
80 mg |
| Captopril |
50 mg (25 mg bid) |
|
12.5–25 mg bid-tid |
25–50 mg bid-tid |
450 mg/d |
| Enalapril |
5 mg |
|
5 mg |
10–40 mg |
40 mg |
| Fosinopril |
10 mg |
|
10 mg |
20–40 mg |
80 mg |
| Lisinopril |
10 mg |
|
10 mg |
10–40 mg |
80 mg |
| Moexipril |
7.5 mg |
|
7.5 mg |
7.5–30 mg |
30 mg |
| Perindopril |
4 mg |
|
4 mg |
4–8 mg |
16 mg |
| Quinapril |
10 mg |
|
10 mg |
20–80 mg |
80 mg |
| Ramipril |
2.5 mg |
|
2.5 mg |
2.5–20 mg |
20 mg |
| Trandolapril |
2 mg |
|
1 mg |
2–4 mg |
8 mg |
| Name |
Equivalent daily dose |
|
Start |
Usual |
Maximum |
Note: bid = 2 times a day, tid = 3 times a day, d
= daily
Drug dosages from Drug Lookup, Epocrates Online. |
| ACE inhibitors dosages for hypertension |
Further Reading
This article is licensed under the Creative Commons Attribution-ShareAlike License.
It uses material from the Wikipedia article on
"ACE inhibitor"
All material adapted used from Wikipedia is available under the terms of the
Creative Commons Attribution-ShareAlike License.
Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.