Category:Angiotensin converter enzyme inhibitor

From Ganfyd

Introduction

These block the formation of Angiotensin II from Angiotensin I. Please see Renin-Angiotensin-Aldosterone.

History

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.^[1][2][3]

Indications

• Hypertension
• After myocardial infarction
• Left ventricular failure

Unlike the angiotension-II inhibitors as a group there is strong evidence in those with coronary artery disease and atherosclerosis that ACE inhibitors:^[4]

• 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)^[5]

Group Side effects

• Cough (interestingly ACE inhibitor use is associated with reduced risk of pneumonia^[6])
• All can be regarded as having teratogenic potential at any stage of human pregnancy now^[7] (interestingly not case in animals). Ace inhibitor fetopathy has now been shown to have potential long term implications such as renal dysfunction and polycythaemia^[8].
• 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^[9]

Group Interactions

Special advice

External links

Drug Update ACE Inhibitors

References