Continuing Education Activity
Benazepril is a drug used in the management of hypertension. It is in the ACE inhibitor class of medications. This activity outlines the indications, action, and contraindications for benazepril as a valuable agent in the management of hypertension (and other disorders when applicable). This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for members of the healthcare team in the management of patients with hypertension and related conditions.
- Outline the indications for initiating therapy with benazepril.
- Describe the mechanism of action of benazepril.
- Identify the potential side effects of benazepril therapy.
- Summarize interprofessional team strategies for improving care coordination and communication to improve patient-centered outcomes in patients receiving treatment with benazepril.
Benazepril is FDA approved for the treatment of hypertension, either alone or in combination with other antihypertensive agents. Benazepril can be combined with thiazide diuretics.
Mechanism of Action
Reduction of Blood Pressure
Angiotensin-converting enzyme (ACE) plays a critical role in the renin-angiotensin-aldosterone system. This pathway is a process that eventually results in vasoconstriction, increased sympathetic activity, and Na+ retention, which in turn increased water retention and blood pressure. One step in this pathway is the cleavage of angiotensin I to angiotensin II, performed by the ACE enzyme. ACE inhibitors, therefore, block the renin-angiotensin pathway by halting this step, and thus leading to decreased systemic arterial blood pressure and increased Na+ excretion in the urine.
ACE inhibitors also play a role in bradykinin metabolism. Bradykinin, a natural vasodilator, is degraded by ACE enzymes into inactive metabolites. However, with the ACE enzyme inhibited, this vasodilator’s effect is preserved and also contributes to the effect of ACE inhibitors reducing blood pressure via vasodilation.
Reduction of Adverse Heart Remodeling in HF
In patients in heart failure, the renin-angiotensin-aldosterone system (RAAS) becomes active due to the low cardiac output leading to reduced renal artery perfusion, which activates the RAAS pathway to increase intravascular volume in to augment blood pressure, which would increase the cardiac output via the Frank-Starling mechanism (which states that the greater amount of stretch force put upon the heart walls results in a stronger contraction). However, this attempt at maintaining homeostasis only results in increased preload into the heart. It, therefore, encourages excessive heart remodeling (in response to the larger preload stretching the ventricular walls further). This heart remodeling process can quickly become detrimental and result in conditions such as eccentric hypertrophy.
Because ACE inhibitors inhibit the RAAS system, which eventually leads to increased strain on a failing heart, these ACE inhibitors also have the result of reducing adverse heart remodeling in patients in heart failure.
Patients who adhere to a low-potassium diet, monitor blood pressure and renal function regularly, and adhere to a strict regimen of consistent dosage times with benazepril should expect a lower blood pressure and reduced adverse heart remodeling.
Benazepril should be taken once or twice a day at consistent times, and administration can be without regard to food. There are differences in efficacy in the morning versus afternoon dosages, with morning administration resulting in a more sustained effect (effectiveness lasting approximately 19 hours).
In adults, the starting recommended dosage is 10 mg once a day, with a maintenance dosage range of 20 to 40 mg/day, in either one full dose or two equal doses. Benazepril should be taken once or twice a day at consistent times, and patients can take it with or without food.
In children, the recommended starting dosage is 0.2 mg/kg once daily, and the maintenance dosage is 0.1 to 0.6 mg/kg daily, taken in one dosage.
In patients managing hypertension and renal impairment, the starting dose is 5 mg/day in one dosage. The dosage can increase in a stepwise fashion up to a maximum daily dose of 40 mg or until achieving the desired blood pressure.
Head and Neck Angioedema
In the United States clinical trials, benazepril was shown to cause angioedema in approximately 0.5% of patients (compared to a placebo group rate of 0%). If the angioedema present involves the tongue, glottis, or larynx, then usage should be stopped, as these side effects can progress to airway obstruction.
Patients presenting with abdominal pain require monitoring for intestinal angioedema. In some cases, the abdominal pain also presented with nausea and vomiting. CT or ultrasound is necessary to diagnose rule out or confirm intestinal angioedema.
ACE inhibitors have shown to cause hepatic failure. This process begins with cholestatic jaundice and progresses to fulminant hepatic necrosis with possible death. This complication is quite rare; however, patients on ACE inhibitors who develop jaundice and/or hepatic enzyme elevation should stop taking the ACE inhibitor and be monitored closely for signs of progressing hepatic failure.
In patients who have renal impairment, as well as systemic lupus erythematosus (SLE), captopril (an ACE inhibitor) has induced agranulocytosis and bone marrow depression. If a patient is known to have a collagen-vascular disease that is associated with reduced renal function, then white blood cell counts should be closely monitored.
Other Adverse Effects
The mechanism of action that causes a dry cough in patients taking ACE inhibitors is thought to be related to the reduced bradykinin metabolism as a result of these inhibitors. Bradykinin (BK) is a known pertussive mediator and appears to accumulate in the upper respiratory tract. The incidence of ACE inhibitor-related cough is reportedly present in 5 to 35% of patients on this medication.
Rarely, benazepril can cause hypotension in volume or salt-depleted patients (seen primarily in patients on a diuretic, low-sodium diet, dialysis, or subject to diarrhea or vomiting).
In patients with congestive heart failure, if a patient presents with oliguria azotemia, then the patient is at risk or acute renal failure and subsequent death. Therefore, if a patient is known to have CHF, monitor the dosage and its effects carefully.
In patients with volume depletion, hypotension leading to decreased renal perfusion can occur. To avoid or reduce permanent damage due to this, the clinician should take action to restore normal fluid volume in the patient and reduce the dosage of the ACE inhibitor. Furthermore, if a patient has bilateral renal artery stenosis, then initiation of an ACE inhibitor therapy can precipitate renal failure due to the reduction of glomerular hydrostatic pressure.
Because ACE inhibitors reduce the serum aldosterone concentration, it can increase serum K+ concentration. If a patient has renal insufficiency, diabetes, is taking potassium-sparing diuretics, or has any other condition that can increase the serum K+ concentration, then hyperkalemia can result.
Benazepril is contraindicated in pregnancy, and usage should be stopped immediately upon confirmation of pregnancy. Failure to cease an ACE inhibitor can result in fetal morbidity and death.
Contraindications include if a patient is hypersensitive to benazepril or any other ACE inhibitor.
The drug is also contraindicated if a patient has a history of angioedema or a history of angioedema caused by ACE inhibitors.
Do not take benazepril if the patient has taken valsartan or sacubitril within the last 36 hours. Contraindications to benazepril also include diabetic patients taking aliskiren.
Consider reducing doses of other prescriptions of diuretics, lithium, and potassium or carefully monitor for side effects.
When determining proper maintenance dosages, the patient’s blood pressure requires daily monitoring to establish the resultant range of blood pressures. Benazepril efficacy diminishes after 12 to 19 hours, so blood pressure monitoring should be planned accordingly.
The renal function of patients requires evaluation via serum creatinine, potassium, and BUN monitoring. In patients with renal dysfunction, evaluation of baseline kidney function should take place before treatment, and afterward at two-week intervals for three months after initiation of treatment.
There are no reports of renal failure in patients taking benazepril, and the frequency of neutropenia and proteinuria was insignificant (benazepril correlated with those side effects to the same degree as a placebo group). When compared to other ACE inhibitors, benazepril demonstrated a relatively reduced rate of inducing systematic hypotension, and a relatively same rate of inducing side effects such as coughing, hyperkalemia, and serum creatinine elevation.
Enhancing Healthcare Team Outcomes
Clinicians starting patients on benazepril for any of its indicated uses should coordinate their efforts with other members of the healthcare team, including any specialists that the patient may be seeing, a pharmacist, and nursing staff. Pharmacists can check for any potential drug interactions and contraindications, as well as verify dosing. Nurses should counsel the patient on administration and monitor for adverse effects, and success or lack of same with the regimen. An interprofessional team approach is always necessary when administering any medication, and benazepril is no exception; this will increase the chances of therapeutic success and minimize adverse reactions. [Level 5]