Category:Angiotensin converter enzyme inhibitor
These block the formation of Angiotensin II from Angiotensin I. Please see Renin-Angiotensin-Aldosterone.
Drs Haralambos Gavras and Erivine Erdos first characterised the role of angiotensin-converting enzyme (ACE) and its potential role in human disease. John Laragh and Hans Brunner independently confirmed this work. Sergio Ferreira discovered in the 1960's that bradykinin potentiating factor (BPF), an extract of the venom of the Brazilian viper Bothrops jararaca, potentiated bradykinin. He joined John R. Vane's research group and at Vane’s request, BPF was tested on angiotensin converting enzyme (ACE) which it inhibited. Dr Erdös had actually first demonstrated that the enzyme kininase II, which degrades bradykinin, and ACE, which forms angiotensin II, was identical. At this time ACE was only thought important in maligant hypertension, not a financially viable market. Vane’s analysis of the probable role of the ACE system in so-called "essential hypertension" was brought by him to the attention of E. R. Squibb and Sons to whom he was a consultant. Charles G. Smith who was in charge and David Cushman and Miguel Ondetti did some pure and very expensive R&D for Squibb, isolating a puified injectable protein (teprotide). A mentor to both Smith and Vane was Prof. Arnold Welch. The initial experiments in man to demonstrate inhibition of ACE had to be done in the U.K. as the F.D.A. refused to authorise them. Once done however the F.D.A. allowed further human research in the U.S.A.. Dr John Laragh, who had previously demonstated the actions on the renin-angiotensin-aldosterone axis of beta blockers (1972–1973) and the octapeptide angiotensin II receptor blocker saralasin (1973–1974) then proceeded to reduce the blood pressure of 14 out of 17 patients with essential hypertension with teprotide. About a decade later Squibb got its blockbuster captopril (Capoten®) to the market. As is usual with such a development much of the pure science was initially funded by public research, but the research to get a product usable in man needed other sources of funding.
Unlike the angiotension-II inhibitors as a group there is strong evidence in those with coronary artery disease and atherosclerosis that ACE inhibitors:
- beneficial by reducing mortality
- beneficial by reducing cardiovascular events
In a relatively low risk population with stable vascular disease and no heart failure or left ventricular dysfunction you prevent 21 serious adverse events for every 1000 patients treated for 4.5 years (18% odds reduction) and in a more typical elderly population with left ventricular dysfunction you would protect 50 out of 1000 treated for 3 years (21% odds reduction)
Group Side effects
- Cough (interestingly ACE inhibitor use is associated with reduced risk of pneumonia)
- All can be regarded as having teratogenic potential at any stage of human pregnancy now (interestingly not case in animals). Ace inhibitor fetopathy has now been shown to have potential long term implications such as renal dysfunction and polycythaemia.
- Angioedema is well-known with them. It may occur after a long period on the drug. It may be lethal (but usually is not). There is no reason to think that this carries an increased risk of angioedema from angiotensin 2 antagonist drugs and thus changing without delay to one of these is the obvious response.
- Hyperkalaemia especially in renal artery stenosis and when combined with potassium-sparing diuretics and/or NSAIDs.
- Hyponatraemia - can be by inappropriate secretion of antidiuretic hormone
- ↑ Smith CG, Vane JR. The discovery of captopril. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2003;17:788-9.
- ↑ Gavras H. The discovery of captopril: reply. FASEB J. 2004;18:225
- ↑ Smith CG, Vane JR. The discovery of captopril: a reply. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2004;18:935.
- ↑ Danchin N, Cucherat M, Thuillez C, Durand E, Kadri Z, Steg PG. Angiotensin-converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction: an overview of long-term randomized controlled trials. Archives of internal medicine. 2006;166:787-96. (Direct link – subscription may be required.)
- ↑ Dagenais GR, Pogue J, Fox K, Simoons ML, Yusuf S. Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials. Lancet. 2006;368:581-8. (Direct link – subscription may be required.)
- ↑ Caldeira D, Alarcão J, Vaz-Carneiro A, Costa J. Risk of pneumonia associated with use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers: systematic review and meta-analysis BMJ 2012;345:e4260
- ↑ Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer S, Gideon PS, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. The New England journal of medicine. 2006;354:2443-51.
- ↑ Laube GF, Kemper MJ, Schubiger G, Neuhaus TJ. Angiotensin-converting enzyme inhibitor fetopathy: long-term outcome. Archives of disease in childhood. Fetal and neonatal edition. 2007 Sep; 92(5):F402-3.(Link to article – subscription may be required.)
- ↑ Izzedine H, Fardet L, Launay-Vacher V, Dorent R, Petitclerc T, Deray G. Angiotensin-converting enzyme inhibitor-induced syndrome of inappropriate secretion of antidiuretic hormone: case report and review of the literature. Clinical pharmacology and therapeutics. 2002 Jun; 71(6):503-7.(Link to article – subscription may be required.)