Background
Benazepril is an angiotensin converting enzyme inhibitor, also called an
ACE inhibitor or simply an ACEI. In order to understand what this means, it
helps to have some understanding of the body’s renin-angiotensin system, an
important hormonal mechanism used in times of low blood pressure.
The kidney is a uniquely well-perfused organ, directly receiving approximately
25% of the blood pumped by the heart. Given this fact, it is not surprising
that the kidney would possess special areas for sensing blood pressure changes.
In the event of a drop in blood pressure, as might occur with a significant
bleed or in heart failure, the kidney’s sensors perceive this drop and release
a special hormone called renin.
The healthy liver normally produces a substance called angiotensinogen that
innocuously floats around in the blood in case of a blood pressure emergency.
Should Angiotensinogen meet up with Renin, an activation reaction occurs,
leading to the conversion of angiotensinogen to angiotensin I. Angiotensin
I circulates in the blood, eventually reaching the lungs where an enzyme called
angiotensin converting enzyme converts angiotensin I into angiotensin II.
Angiotensin II acts as the superhero in this time of need. It is probably
the most powerful constrictor of blood vessels known. Angiotensin II constricts
outer blood vessels (those in the periphery - the limbs, skin etc.), closing
them off to circulation and thus centralizing the blood flow. This essentially
creates a smaller, less elaborate course for the circulation of blood so that
normal blood pressure can be maintained with a smaller than normal blood volume.
This re-routing of the circulation functions to preserve blood flow to the
most important organs: the brain, heart and kidney.
As you might guess, an angiotensin converting enzyme inhibitor curtails
the conversion of angiotensin I to angiotensin II. If angiotensin II is such
a good thing, why might we want to stop making it? It turns out the renin-angiotensin
system evolved to maintain blood pressure in the event of blood loss, such
as might occur in an attack from an enemy or predator. The system turns out
not to be such a good thing when blood pressure drops more chronically as
in heart disease.
When blood pressure drops from heart failure, there is no blood loss; the
amount of blood is the same as always. The problem in heart failure is that
the heart is not pumping enough blood forward. When the renin-angiotensin
system activates, it ends up confining the same amount of blood to a smaller
circulatory route, essentially forcing the already diseased heart to pump
blood faster to keep up. This obviously weakens the heart further and exacerbates
heart failure.
Benazepril effectively acts as a dilator of blood vessels. This effect opens
up circulation peripherally. (If you think of the circulation as a roadway
system, this is analogous to achieving less highway congestion by opening
more side streets). Blood pressure drops to normal and the heart has less
work.
How this Medication is Used Benazepril is used in the treatment of high blood pressure, in the treatment
of congestive heart failure, and in the treatment of renal (kidney) protein
loss. In cats, amlodipine is felt to have more reliable effect in treating
high blood pressure but if the cat also has renal protein loss, then benazepril
is generally preferred. In dogs, enalapril and lisinopril tend to be the preferred
ACE inhibitors.
The effect of benazepril in the kidney bears a special discussion. The kidney
consists of millions of tiny filtration units called glomeruli, which are
part of larger excretory units called nephrons.
This depiction of a nephron shows a glomerulus
and blood vessels.
A tiny blood vessel enters each glomerulus, carrying blood to be filtered,
and another tiny blood vessel carries blood out after it has been filtered.
ACE inhibitors dilate the exiting vessel without dilating the entering vessel.
(Think of a sink full of water with the faucet on and the drain open. As long
as water coming in matches water draining, the sink stays full. The ACE inhibitor
opens the drain further. The sink doesn't empty all the way but there is
less water maintained in the sink then there was before.)
This effect amounts to less blood pressure inside the glomerulus (the sink)
which means less filtration. When the glomerulus is leaking protein, less
filtration means less urinary protein loss, which is good. If the kidney is
failing or if the patient is very dehydrated, less filtration means less kidney
function, which is bad. This makes ACE inhibitor use a bit tricky in heart
failure patients where we do not want to treat the heart disease at the expense
of the kidneys. For patients without heart failure, where one is treating
high blood pressure or renal protein loss, the drop in kidney function that
comes with ACE inhibitor use is not significant.
In heart failure patients, when benazepril is commonly given in conjunction
with a diuretic (like furosemide), kidney parameters (BUN and creatinine)
should be measured prior to benazepril use, again 3 to 7 days after benazepril
therapy has started, and periodically thereafter.
Kidney function should also be rechecked after any dose change in the heart
failure patient.
Kidney function should also be rechecked after any dose change in the heart
failure patient.
Benazepril may be given with or without food and is usually given once a
day.
Side Effects
Nausea, appetite loss, and/or diarrhea are sometimes observed with this
medication. In some patients, these effects are severe enough to preclude
the use of benazepril.
In some patients, blood pressure can drop too low as the peripheral blood
vessels are dilated. This manifests as listlessness and lethargy. Often the
dose of benazepril can be modified should this side effect occur.
Benazepril may lead to elevations in potassium blood levels.
Interactions with Other Drugs
Benazepril is commonly used in combination with diuretics, especially furosemide.
In this situation, monitoring kidney parameters is especially important as
both these medications serve to decrease blood supply to the kidney as they
support the heart. Should a heart failure crisis occur while a patient is
on these two medications, it will become necessary to rely on the diuretic
to resolve the crisis. High doses of diuretic are typically needed. This can
easily lead to kidney failure although there is no alternative when the heart
is failing.
Blood potassium levels can become dangerously high when benazepril is used
with other medications that elevate blood potassium level. Such drugs might
include: potassium supplements (Polycitra, or Urocit-K) or spironolactone
(a potassium-sparing diuretic.)
Benazepril is less effective when used with aspirin or other NSAIDs.
Concerns and Cautions
Benazepril is inactive when it is consumed and must be activated into “benazeprilat”
(its active form) by the liver. If the patient’s liver is in failure and cannot
reliably perform this conversion, an ACE inhibitor that does not require conversion
can be used.
Benazepril probably should not be used in patients with impaired kidney
function.
This medication should not be used in pregnancy or lactation.
Date Published: 11/5/2007 12:11:00 PM
This work was originally published by Veterinary Information Network,
Inc. (VIN) and is republished with VIN's permission.
Copyright 2007 - 2008 by the Veterinary Information Network, Inc.
All rights reserved.
