An Introduction to ACE Inhibitors

• Due to the antihypertensive properties of snake venom, the first ACE inhibitor, captopril was developed in 1977, followed by enalapril in 1980. 
• ACE inhibitors stand for angiotensin-converting enzyme inhibitors. 
• Due to the variety of issues ACE inhibitors can be used for, it is important for nurses to remember dosing information, contraindications, and side effects to better help patients. 

ACE Inhibtors

ACE inhibitors stand for angiotensin-converting enzyme inhibitors.  

They were first derived from the venom of a Brazilian snake, Bothrops jararaca in the mid 1950’s. It was found that it has a substance that can inhibit kininase II. Later it was discovered that kininase II are angiotensin-converting enzymes.  

Due to the antihypertensive properties of snake venom, the first ACE inhibitor, captopril was developed in 1977, followed by enalapril in 1980. There are many other ACE inhibitors commonly used nowadays. 

ACE inhibitors have a suffix -ril. 

Examples of angiotensin-converting enzyme inhibitors include: 

• Benazepril  
• Captopril  
• Enalapril  
• Fosinopril  
• Lisinopril  
• Moexipril  
• Quinapril  
• Ramipril  

Indications

ACE inhibitors are indicated in the following conditions: 

• Hypertension  
• Congestive heart failure 
• Myocardial infarction 
• Diabetic nephropathy and pheochromocytoma  
• Aortic and mitral valve regurgitation
  

In hypertension, angiotensin-converting enzyme inhibitors are considered first-line therapy, alone or in combination with a diuretic. They are useful in decreasing elevated blood pressure by lowering the total peripheral resistance or afterload. They dilate the veins and arteries due to the reduced formation of angiotensin II. Due to this, these drugs can cause natriuresis and diuresis, hence decreasing blood volume and cardiac output. These drugs also help in lowering arterial pressure. 

They are also essential in treating hypertension due to renal artery stenosis, in which renin-dependent hypertension occurs due to increased renin release from the kidney. 

In heart failure, ACE inhibitors reduce afterload and slightly increase the stroke volume and cardiac output. They also cause a decrease in left ventricular filling pressures, mean arterial pressure, and pulmonary and systemic vascular resistance without an increase in heart rate.  

They can also decrease the high levels of catecholamines indirectly. They reduce plasma vasopressin and endothelial levels that are elevated in congestive heart failure and cause an increase in vascular resistance.  

Moreover, they can slow down the progress of congestive heart failure by limiting left ventricular hypertrophy. 

ACE inhibitors are used as monotherapy if a patient is asymptomatic. But if the patient is symptomatic, ACE inhibitors should be combined with a diuretic. ACE inhibitors, combined with diuretics, prevent diuretic-induced activation of the renin-angiotensin system and do not cause hyperkalemia. 

In myocardial infarction, ACE inhibitors have shown improvement in survival and morbidity. In the acute phase, they reduce the incidence of ventricular arrhythmias and reduce catecholamine levels. In the chronic phase, ACE inhibitors reduce the incidence of congestive heart failure. Also, they prevent ventricular remodeling. They should be started within 24 hours of myocardial infarction and can be used as a long-term therapy. 

These drugs help in the management of diabetic nephropathy due to type I insulin-dependent diabetes mellitus. They reduce the progress of renal insufficiency and stop the worsening of renal function. ACE inhibitors can also be used in pheochromocytoma because they can decrease elevated blood pressure due to increased plasma renin. 

ACE inhibitors are indicated in aortic valve regurgitation because they increase left ventricular ejection fraction (LEVF) while keeping the forward fraction of systolic volume (SV) unchanged. In mitral valve regurgitation, they keep the left-ventricular ejection fraction unchanged while increasing the systolic volume. 

ACE Inhibitors’ Mechanism of Actions

ACE inhibitors exert effect by inhibition of “renin-angiotensin system” or RAS. They stop the conversion of angiotensin I to angiotensin II which is responsible for causing an increase in blood pressure, increase salt and water content in the body, and breakdown of bradykinin (a vasodilator). Angiotensin II also causes vasoconstriction of blood vessels. Therefore, its inhibition produces vasodilation of blood vessels and increases the bradykinin level.

They also cause a decrease in sodium and water retention due to a decrease in aldosterone secretion. All these effects help lower blood pressure by increasing cardiac output and decreasing venous tone and vascular resistance. 

Side Effects of ACE Inhibitors

The common side effects of angiotensin-converting enzyme inhibitors are:

• Maculopapular rash 
• Fever  
• Initial dose hypotension 
• Angioneurotic edema 
• Dysgeusia-by captopril and fosinopril due to the presence of sulphydryl moiety. 
• Hyperkalemia- due to decreased aldosterone secretion, it triggers a rise in potassium levels. 
• Persistent dry cough- due to increased levels of bradykinin in the pulmonary tree. 

Clinical Considerations

• ACE inhibitors are contraindicated with potassium-sparing diuretics or potassium supplements because they can result in hyperkalemia- which can cause fatal arrhythmias. Serum potassium levels should be monitored with ACE inhibitors therapy. 
• ACE inhibitors are contraindicated in patients with bilateral renal artery disease or unilateral renal artery stenosis and one kidney. It may result in renal failure or paradoxical malignant hypertension in these conditions. 
• Food reduces their bioavailability. Therefore they should be taken one hour before the meal. 
• Antacids may decrease the bioavailability of ACE inhibitors, while NSAIDs may decrease the effectiveness of ACE inhibitors. 
• They can cause an increase in serum lithium levels, causing toxicity. 
• ACE inhibitors should be administered cautiously to patients with renal impairment or systemic lupus erythematosus or scleroderma. It is because they may cause bone marrow suppression in these patients. Also, it should be administered with caution to patients with blood dyscrasias or other complications that can cause bone marrow suppression. 
• Avoid having a potassium-rich diet with these medications, as it can cause hyperkalemia, leading to fatal adverse effects. 
• It has been reported that ACE inhibitors can cause anaphylaxis reactions in patients having hemodialysis with high flux polyacrylonitrile membranes. Therefore caution should be exercised with their concomitant use. 

That completes the pharmacological review of angiotensin-converting enzyme inhibitors. 

Read More