ACE INHIBITORS

By Dr. Kinza Munir (Pharm-D)

ACE inhibitors, or angiotensin converting enzyme inhibitors, is a class of drugs that interact with blood enzymes to help relax your veins and arteries to lower your blood pressure. ACE inhibitors prevent an enzyme in your body from producing angiotensin II, a substance that narrows your blood vessels. This narrowing can cause high blood pressure and force your heart to work harder.

Examples of ACE inhibitors include:

• Benazepril (Lotensin)
• Captopril (Capoten, Capril)
• Enalapril (Vasotec, Cardiotec, Renitec)
• Fosinopril (Monopril)
• Lisinopril (Corace, Zestril, Prinvil)
• Moexipril (Univasc)
• Perindopril (Aceon, Coversyl, Coversam)
• Quinapril (Accupril)
• Ramipril (Ramipace, Altace, Tritace)
• Trandolapril (Mavlk)

Clinical Application

Of course, they’ll help manage high blood pressure (Hypertension). But your doctor may prescribe an ACE inhibitor for these other heart conditions:

Heart failure: They can prevent further weakening of your heart and prolong your life.

Heart attack: When given after one, some ACE inhibitors may lessen the impact on your heart strength and help you live longer.

Diabetes: Some can slow the process that leads to kidney damage in many people with type 2 diabetes.

Heart disease prevention: If you’re at high risk, they’ve been shown to lessen your chance of having a heart attack or stroke.

How ACE inhibitors work (Mechanism of Action)

ACE inhibitors inhibit the converting enzyme peptidyl dipeptidase that hydrolyzes angiotensin I to angiotensin II and inactivates bradykinin, a potent vasodilator. Their site activity results both from an inhibitory action on renin-angiotensin system and a stimulating action on the kallikrein-kinin system.

Angiotensin II is a very potent chemical produced by the body that primarily circulates in the blood. It causes the muscles surrounding blood vessels to contract, thereby narrowing the vessels. The narrowing of the vessels increases the pressure within the vessels causing increases in blood pressure (hypertension). Angiotensin II is formed from angiotensin I in the blood by the enzyme angiotensin converting enzyme (ACE). (Angiotensin I in the blood is itself formed from angiotensinogen, a protein produced by the liver and released into the blood.) Angiotensin converting enzyme inhibitors slow (inhibit) the activity of the enzyme ACE, which decreases the production of angiotensin II. As a result, blood vessels enlarge or dilate, and blood pressure is reduced. This lower blood pressure makes it easier for the heart to pump blood and can improve the function of a failing heart. In addition, the progression of kidney disease due to high blood pressure or diabetes is slowed.

Benefits of ACE Inhibitors

In addition to high blood pressure, ACE inhibitors prevent, treat or improve symptoms in conditions such as:

• Coronary artery disease
• Heart failure
• Diabetes
• Certain chronic kidney diseases
• Heart attacks
• Scleroderma — a disease that involves hardening of the skin and connective tissues
• Migraines

Side Effects

The most common side effects are;

• Dry cough
• Increased potassium levels in the blood (hyperkalemia)
• Fatigue
• Low blood pressure
• Headaches
• Altered sense of taste
• Allergic skin rash

The most serious, but rare side effects of ACE inhibitors are:

• Kidney failure
• Pancreatitis
• Liver dysfunction
• A decrease in white blood cells
• Swelling of tissues (angioedema)

Contraindications

ACE inhibitors are contraindicated during the second and third trimesters of pregnancy because of the risk of fetal hypotension, anuria and renal failure, sometimes associated with fetal malformations or deaths.

Also contraindicated in previous angioedema associated with ACE inhibitor therapy.

Interactions

Concomitant use with potassium supplements or potassium sparing diuretics results in hyperkalemia.

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve), impair the hypotensive effects of of ACE inhibitors by blocking bradykinin mediated vasodilation.

How should I take them?

Usually on an empty stomach, an hour before meals. Follow the directions on the label about how often to take it. The number of doses you take each day, the time between them, and how long you’ll need to take it will depend on the type of ACE inhibitor you’re prescribed, and your condition.s

While taking them, have your doctor check your blood pressure and kidney strength regularly.

References

Basic & Clinical Pharmacology

(12th edition, by Bertram G. Katzung, Susan B. Masters, and Anthony J. Trevor)