ACE Inhibitor Clinical Use Mechanism Of Action Effects Of ACE

In several of these indications, ACE inhibitors are used first-line as several agents in the class have been clinically shown to be superior to other classes of drugs in the reduction of morbidity and mortality.

ACE inhibitors are often combined with diuretics in the control of hypertension (usually a thiazide), when an ACE inhibitor alone proves insufficient; and in chronic heart failure (usually furosemide) for improved symptomatic control. Thus there exists, on the market, combination products combining an ACE inhibitor with a thiazide (usually hydrochlorothiazide) in a single tablet to allow easy administration by patients.

2 Mechanism of action

They work by modulating the renin-angiotensin-aldosterone (RAS or RAAS) system. By inhibiting angiotensin converting enzyme, ACE inhibitors significantly (but not completely) block the conversion of angiotensin IAngiotensinogen angiotensin I and angiotensin II are peptides involved in maintenance of blood volume and pressure. They play an important role in the renin-angiotensin system. Angiotensinogen Angiotensinogen is the precursor molecule, and it is produced to angiotensin IIAngiotensinogen angiotensin I and angiotensin II are peptides involved in maintenance of blood volume and pressure. They play an important role in the renin-angiotensin system. Angiotensinogen Angiotensinogen is the precursor molecule, and it is produced. As a complementary action, ACE inhibitors also reduce the degradation of bradykininBradykinin is a peptide of the kinin group of proteins and consists of 9 amino acids. The kininogenase kallikrein makes bradykinin by proteolytic cleavage of its kininogen precursor, high-molecular weight kininogen (HMWK). It is a potent vasodilator, caus. Thus ACE inhibitors work to lower blood pressure by decreasing the formation of a potent vasoconstrictor (angiotensin II) and decreasing the degradation of a potent vasodilator (bradykinin).

3 Effects of ACE inhibitors

ACE inhibitors lower arteriolarAn arteriole is a blood vessel that extends and branchs out from an artery and leads to capillaries. Arterioles have thick muscularized walls and are the primary site of vascular resistance''. The mean blood pressure in the arteries supplying the body is resistance and increase venous capacitance; increase cardiac outputCardiac output is the volume of blood being pumped by the heart in a minute. It is equal to the heart rate multiplied by the stroke volume. So if there are 70 beats per minute, and 70 ml blood is ejected with each beat of the heart, the cardiac output is and cardiac index , stroke work and volumeStroke volume is the amount of blood ejected with each beat of the heart. Men, on average, have higher stroke volumes than women due to the larger size of their hearts. Stroke volume can also be increased by long term ( aerobic) exercise, which frequently, lower renovascular resistance, and lead to increased natriuresis (excretion of sodiumSodium is the chemical element in the periodic table that has the symbol Na Natrium in Latin) and atom number 11. Sodium is a soft, waxy, silvery reactive metal belonging to the alkali metals that is abundant in natural compounds (especially halite). in the urine).

ACE inhibitors have been shown to be effective for indications other than hypertension even in patients with normal blood pressure. The use of a maximum dose of ACE inhibitors in such patients; including for prevention of diabetic nephropathy, congestive heart failure, prophylaxis of cardiovascular events; is justified because it improves clinical outcomes, independent of the blood pressure lowering effect of ACE inhibitors. Such therapy, of course, requires careful and gradual titration of the dose to prevent the patient suffering from the effects of rapidly decreasing their blood pressure (dizziness, fainting, etc).

4 Adverse effects

Common adverse drug reactions include: hypotension, cough, hyperkalaemia, headache, dizziness, fatigue, nausea, renal impairment (Rossi, 2004).

A persistent dry cough is a relatively common adverse effect believed to be associated with the increases in bradykinin levels produced by ACE inhibitors. Patients who experience this cough are often switched to angiotensin II receptor antagonists.

Rash and taste disturbances, infrequent with most ACE inhibitors, are more prevalent in captopril and is attributed to its sulfhydryl moiety. This has led to decreased use of captopril in clinical setting, although it is still used in scintigraphy of the kidney.

Renal impairment is a significant adverse effect of all ACE inhibitors, and is associated with their effect on angiotensin II-mediated homeostatic functions such as renal bloodflow. ACE inhibitors can induce or exacerbate renal impairment in susceptible patients. This is especially a problem if the patient is also concomitantly taking an NSAID and a diuretic - the so-called "triple whammy" effect - such patients are at very high risk of developing renal failure (Thomas, 2000).

Some patients develop angioedema due to increased bradykinin levels. There appears to be a genetic predisposition towards this side-effect in patients who degrade bradykinin slower than average (Molinaro 2002).

5 Examples of ACE inhibitors

ACE inhibitors can be divided into three groups based on their molecular structure:

5.1 Sulfhydryl-containing ACE inhibitors

captopril (Capoten®), the first ACE inhibitor

5.2 Dicarboxylate-containing ACE inhibitors

This is the largest group, including:

enalapril (Vasotec®/Renitec®)
ramipril (Altace®/Tritace®)
quinapril (Accupril®)
perindopril (Coversyl®)
lisinopril (Lisodur®)

5.3 Phosphonate-containing ACE inhibitors

fosinopril (Monopril®), the only member

6 Comparative information

Comparatively, all ACE inhibitors have similar antihypertensive efficacy when equivalent doses are administered. The main point-of-difference lies with captopril, the first ACE inhibitor, which has a shorter duration of action and increased incidence of certain adverse effects (see the captopril article for more detail).

Certain agents in the ACE inhibitor class have been proven, in large clinical studies, to reduce mortality post- myocardial infarct, prevent development of heart failure, etc. While these effects are likely to be class-effects, good evidence-based medicine practice would direct the use of those agents with established clinical efficacy (see AMH 2004, or other sources for more details on specific agents).

7 Contraindications

The ACE inhibitors are contraindicated in:

angioedema
aortic valve stenosis or cardiac outflow obstruction
renal artery stenosis (bilateral, or unilateral with a solitary functioning kidney)

8 Angiotensin II receptor antagonists

ACE inhibitors many common characteristics with another class of cardiovascular drugs called angiotensin II receptor antagonists, which are often used when patients are intolerant of the adverse effects produced by ACE inhibitors. ACE inhibitors do no completely prevent the formation of angiotensin II, as there are other conversion pathways, and so angiotensin II receptor antagonists act to prevent the action of angiotensin II at the AT₁ receptor.

9 References

Molinaro G, Cugno M, Perez M, Lepage Y, Gervais N, Agostoni A, Adam A. Angiotensin-converting enzyme inhibitor-associated angioedema is characterized by a slower degradation of des-arginine(9)-bradykinin. J Pharmacol Exp Ther 2002;303:232-7. PMID 12235256.
Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. BooksEnthsiast.com.
Thomas, M.C. (2000). Diuretics, ACE inhibitors and NSAIDs - the triple whammy. Med J Aust 172, 184–185.

ACE inhibitors Pharmacologic agents Cardiology

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Home > ACE inhibitor

1 Clinical use

2 Mechanism of action

3 Effects of ACE inhibitors

4 Adverse effects

5 Examples of ACE inhibitors

5.1 Sulfhydryl-containing ACE inhibitors

5.2 Dicarboxylate-containing ACE inhibitors

5.3 Phosphonate-containing ACE inhibitors

6 Comparative information

7 Contraindications

8 Angiotensin II receptor antagonists

9 References

Topics: ACE Inhibitor, Clinical Use, Mechanism Of Action, Effects Of...