The ability to reduce levels of angiotensin II (AnglI) with orally effective inhibitors of angiotensin-converting enzyme (ACE) represents an important advance in the treatment of hypertension. Captopril (Capoten), enalapril (Vasotec), lisinopril (prinivil), quinapril (accupril), ramipril (altace), benazepril (Lotensin), moexipril (univasc), fosinopril (monopril), trandolapril (mavik), and perindopril (aceon) have proven to be very useful for the treatment of hypertension because of their efficacy and their very favorable profile of adverse effects, which enhances patient adherence. Chapter 30 presents the pharmacology of ACE inhibitors in detail.
The ACE inhibitors appear to confer a special advantage in the treatment of patients with diabetes mellitus, slowing the development and progression of diabetic glomerulopathy. They also are effective in slowing the progression of other forms of chronic renal disease, such as glomeru-losclerosis, and many of these patients also have hypertension. An ACE inhibitor is the preferred initial agent in these patients. Patients with hypertension and ischemic heart disease are candidates for treatment with ACE inhibitors because administration of ACE inhibitors in the immediate post-myocardial infarction period has been shown to improve ventricular function and reduce morbidity and mortality (see Chapter 33).
The decreased biosynthesis of AnglI impacts a number of facets of hypertension treatment. Because ACE inhibitors blunt the rise in aldosterone concentrations in response to Na+ loss, the normal role of aldosterone to oppose diuretic-induced natriuresis is diminished. Consequently, ACE inhibitors tend to enhance the efficacy of diuretics. Thus, even very small doses of diuretics may substantially improve the antihypertensive efficacy of ACE inhibitors, while the use of high doses of diuretics together with ACE inhibitors may lead to excessive blood pressure reduction and volume depletion.
The attenuation of aldosterone production by ACE inhibitors also influences K+ homeostasis. There is only a very small and clinically unimportant rise in serum K+ when these agents are used alone in patients with normal renal function. However, substantial K+ retention can occur in patients with renal insufficiency. Furthermore, the potential for developing hyperkalemia must be considered when ACE inhibitors are used with other drugs that can cause K+ retention, including K+-sparing diuretics (amiloride, triamterene, and spironolactone), NSAIDs, K+ supplements, and p receptor antagonists. Some patients with diabetic nephropathy may be at greater risk of hyperkalemia.
There are several cautions in the use of ACE inhibitors. Angioedema is a rare but potentially fatal adverse effect of the ACE inhibitors. Patients starting treatment with these drugs should be explicitly warned to discontinue their use with the advent of any signs of angioedema. Due to the risk of severe fetal adverse effects, ACE inhibitors are contraindicated during pregnancy, a fact that must be communicated to women of childbearing age.
In most patients there is no appreciable change in glomerular filtration rate following the administration of ACE inhibitors. In renovascular hypertension, however, the glomerular filtration rate generally is maintained by AngII-driven increased resistance in the postglomerular arteriole. Accordingly, in patients with bilateral renal artery stenosis or stenosis in a sole kidney, the administration of an ACE inhibitor will substantially reduce glomerular filtration rate. Similar effects are seen in some patients with preexisting renal disease.
ACE inhibitors decrease blood pressure to some extent in most patients with hypertension. Following the initial dose of an ACE inhibitor, some patients exhibit a considerable fall in blood pressure that is a function of plasma renin activity prior to treatment. Because of this, therapy is initiated with low doses, especially in patients who may have a very active renin-angiotensin system supporting blood pressure (e.g., diuretic-induced volume contraction or congestive heart failure). With continuing treatment, there usually is a progressive fall in blood pressure that often takes several weeks and is not strongly correlated with the pretreatment plasma renin activity. Younger Caucasian patients are more likely to respond to ACE inhibitors, while elderly African American patients generally are more resistant to the hypotensive effect of these drugs. While most ACE inhibitors are approved for once-daily dosing for hypertension, a significant fraction of patients have a response that lasts for less than 24 hours and require twice-daily dosing for optimal blood pressure control.
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Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...