Short Notes on ACE Inhibitors

[SudaMediCa]

ACE Inhibitors (ACEIs), or inhibitors of Angiotensin-Converting Enzyme, are a group of pharmaceuticals that are used primarily in treatment of hypertension and congestive heart failure, in most cases as the drugs of first choice.
Use

Indications for ACE inhibitors include:

* Prevention of cardiovascular disorders
* Congestive heart failure
* Hypertension
* Left ventricular dysfunction
* Prevention of nephropathy in diabetes mellitus

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.
Side effects

Common adverse drug reactions (=1% of patients) include: hypotension, cough, hyperkalemia, headache, dizziness, fatigue, nausea, renal impairment

A persistent dry cough is a relatively common adverse effect believed to be associated with the increases in bradykinin levels produced by ACE inhibitors, although the role of bradykinin in producing these symptoms remains disputed by some authors. 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. The reason for this is still unknown. Some suggest that it is associated with their effect on angiotensin II-mediated homeostatic functions such as renal blood flow. Renal blood flow may be affected by angiotensin II because it vasoconstricts the efferent arterioles of the glomeruli of the kidney, thereby increasing glomerular filtration rate (GFR). Hence, by reducing angiotensin II levels, ACE inhibitors may reduce GFR, a marker of renal function. Specifically, ACE inhibitors can induce or exacerbate renal impairment in patients with renal artery stenosis. This is especially a problem if the patient is also concomitantly taking an NSAID and a diuretic. When the three drugs are taken together, there is a very high risk of developing renal failure

Some patients develop angioedema due to increased bradykinin levels. There appears to be a genetic predisposition towards this adverse effect in patients who degrade bradykinin slower than average.
Groups

Sulfhydryl-containing ACE inhibitors

* Captopril (Capoten ®), the first ACE inhibitor

Dicarboxylate-containing ACE inhibitors

This is the largest group, including:

* Enalapril (Vasotec®/Renitec®)
* Ramipril (Altace®/Tritace®/Ramace®/Ramiwin®)
* Quinapril (Accupril®)
* Perindopril (Coversyl®)
* Lisinopril (Lisodur®/Lopril®/Prinivil®/Zestril®)
* Benazepril (Lotensin®)

Phosphonate-containing ACE inhibitors

* Fosinopril (Monopril®)

Contraindications

The ACE inhibitors are contraindicated in patients with:

* Previous angioedema associated with ACE inhibitor therapy
* Renal artery stenosis (bilateral, or unilateral with a solitary functioning kidney)

ACE inhibitors should be used with caution in patients with:

* Impaired renal function
* Aortic valve stenosis or cardiac outflow obstruction
* Hypovolaemia or dehydration
* Haemodialysis with high flux polyacrylonitrile membranes

ACE inhibitors are ADEC Pregnancy category D, and should be avoided in women who are likely to become pregnant. In the U.S., ACE inhibitors are required to be labelled with a "black box" warning concerning the risk of birth defects when taking during the second and third trimester. It has also been found that use of ACE inhibitors in the first trimester is also associated with a risk of major congenital malformations, particularly affecting the cardiovascular and central nervous systems.

Potassium supplementation should be used with caution and under medical supervision owing to the hyperkalaemic effect of ACE inhibitors.


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