By Wendy C. Brooks, DVM, DipABVP
Educational Director, VeterinaryPartner.com
Brand Name: Vasotec
Available in 2.5 mg, 5 mg, 10 mg and 20 mg tablets; oral solution
Enalapril is an angiotensin converting enzyme inhibitor, also called an ACE inhibitor or simply an ACEI. In order to understand what this means, it is important to have some understanding of the body’s renin-angiotensin system, an important hormonal mechanism used in times of low blood pressure. Enalapril is generally used in three situations: to dilate peripheral blood vessels in time of heart failure (a story that will make much more sense shortly), to treat high blood pressure, and to reduce excessive urinary protein loss.
The renin-angiotensin system maintains normal blood pressure in time of need.
The kidney is a uniquely well perfused organ, receiving approximately 25 percent of the blood pumped by the heart directly. Given this fact, it is not surprising that the kidney would possess specific 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 hormone called renin.
The healthy liver normally produces a substance called angiotensinogen, which 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 in the blood circulates, eventually reaching the lungs where an enzyme called angiotensin converting enzyme converts angiotensin I into angiotensin II.
Angiotensin II acts as the super-hero 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 rerouting of the circulation functions to preserve blood flow to the most important organs: the brain, heart, and kidney.
Why Should we Ever Want to Block the Renin-Angiotensin System?
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 centralizes the blood, it effectively confines the same amount of blood to a smaller circulatory route, essentially forcing the already diseased heart to pump blood faster to keep up. This amounts to more work for the already overworked heart.
Enalapril 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 like to achieving less highway congestion by opening more side streets.) Blood pressure drops to normal and the heart has less work. This makes enalapril a good choice in heart failure as well as a good medication to treat high blood pressure.
Enalapril for Urinary Protein Loss
The effect of enalapril 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.
Graphic by MarVistaVet.
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 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 you are treating high blood pressure or renal protein loss, the drop in kidney function that comes with ACE inhibitor use is not significant.
How this Medication is Used
Enalapril is used to treat congestive heart failure; and kidney protein-loss (such as glomerulonephritis). It has not been found to be effective for treating high blood pressure.
In heart failure patients, when enalapril is commonly given in conjunction with a diuretic (like furosemide), kidney parameters (BUN and creatinine) should be measured prior to enalapril use, again 3-7 days after enalapril therapy has started, and periodically thereafter. Kidney function should also be rechecked after any dose change in the heart failure patient.
Enalapril may be given with or without food.
Enalapril is given once or twice daily and the dose is commonly altered depending on response.
If you miss a dose, do not double up on the next dose. Simply give the medication when it is remembered and schedule the next dose accordingly.
Nausea, appetite loss, or diarrhea are sometimes seen with this medication. In some patients, these effects are severe enough that enalapril cannot be used.
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 enalapril can be modified should this side effect occur.
Enalapril may lead to elevations in potassium blood levels.
Interactions with other Drugs
Enalapril 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 potentially lead to kidney failure although there is no alternative when the heart is failing.
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 potentially lead to kidney failure though there is no alternative when the heart is failing.
Blood potassium levels can become dangerously high when enalapril is used with other medications that elevate it. Such drugs might include: potassium supplements (Polycitra, or Urocit-K) or spironolactone (a potassium-sparing diuretic).
Enalapril is less effective when used with aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs).
Enalapril may increase the risk of hypoglycemia (low blood sugar) when used concurrently with insulin.
The risk of creating an accidental low blood pressure situation is increased when enalapril is used with diphenhydramine (more commonly know as Benadril®), buspirone, or sildenafil.
Concerns and Cautions
Enalapril is inactive when it is consumed and must be activated into enalaprilat (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.
Enalapril probably should not be used in patients with impaired kidney function.
This medication should not be used in pregnancy or lactation.
Store enalapril at room temperature and away from light.
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