How does metoprolol work?

Metoprolol is used to treat high blood pressure as well as a variety of cardiovascular conditions.  How does metoprolol work, what is it used for, and what are the common side effects?

Metoprolol is a part of the group of prescription medications commonly referred to as beta blockers.  It is available in a variety of different forms, such as metoprolol tartrate, also known as Lopressor, and metoprolol succinate, also known as Toprol XL.^1,2  The primary difference between these two different metoprolol salts is that Toprol XL is an extended-release form of metoprolol, which may be convenient for patients as it generally only needs to be taken once daily.³

Metoprolol is approved by the FDA to treat many different conditions, including chest pain (angina), heart failure, heart attacks, and high blood pressure (hypertension).  It is also FDA-approved to treat a form of irregular heartbeat called atrial fibrillation, which results in an accelerated heart rate and a lack of collaboration between the upper chambers (atria) and lower chambers (ventricles).^1,4

Metoprolol is also prescribed off-label to treat thyroid storms, which essentially describes a severe and potentially dangerous increase in thyroid activity, as well as certain types of abnormally high heart rate (tachycardia). ^1,5  These drugs are also sometimes prescribed off-label for treating the physical symptoms of anxiety-related conditions, as they inhibit the effects of the sympathetic nervous system which, in turn, inhibits the “fight or flight” response associated with fear and anxiety. ⁸

How was metoprolol discovered?

Beta-blockers were discovered by Sir James Black in the late 1950s, and the first major beta blocker that was synthesized was propranolol. ⁶  Some other examples of beta-blockers include bisoprolol, atenolol, acebutolol, and timolol.  The original purpose of beta-blockers was to treat irregular heartbeat and angina; however, they have been shown to be effective in treating hypertension, heart failure, and even other conditions such as glaucoma, migraines, and anxiety.⁷

How does metoprolol work?

Metoprolol, as a beta blocker, works by blocking the beta-1 adrenergic receptors, also known as the B1 receptors, which are a part of the sympathetic nervous system.  Binding of the B1 receptors by catecholamines such as epinephrine and norepinephrine induces the rate of production and transmission speed of action potentials.⁸  An action potential is essentially an electrical charge that drives directed messages (impulses) across nerve cells (neurons), in order to allow communication throughout the nervous system. 

Binding of the B1 receptor may also facilitate the release of an enzyme called renin from the kidneys, which in turn may increase blood pressure.⁹  By inhibiting the activity of the B1 receptors, metoprolol helps reduce the activation of the sympathetic nervous system and the resulting effects, which for some, can be beneficial.

Metoprolol is a relatively cardioselective beta-blocker, which means it binds the B1 receptors significantly more so than other beta receptors, such as B2 or B3 receptors.¹⁰  Many previous beta-blockers are not as selective for the B1 receptor.  For example, metoprolol’s inhibitory effect on the B2 receptor is only one to two percent of that of propranolol, despite having the same magnitude of inhibitory effects on the B1 receptor.¹⁰  B2 receptors have different effects on the body, and some patients may not want inhibition of these effects, so some doctors may choose to prescribe one or the other depending on the individual patient’s needs.

Side effects of metoprolol

Metoprolol, like many other medications, may be associated with adverse effects for some people.  Some reported adverse effects may include fatigue, depression, glucose intolerance, decreased libido, diarrhea, and ringing inside the ears (tinnitus).¹  It is important to tell your doctor or pharmacist about any adverse side effects that you may be experiencing while taking metoprolol, as they may be able to adjust your dose or try a different treatment.

Some patients who suddenly stop metoprolol without the guidance of health professionals may experience withdrawal symptoms; for example, some patients with ischemic heart disease may experience angina and an increased risk of adverse cardiovascular events after suddenly stopping treatment.¹¹  To avoid withdrawal symptoms and their potential consequences, many doctors recommend slowly decreasing the dose over a period of several days.

There are a few reasons why someone may not be an ideal candidate for metoprolol.  Firstly, metoprolol should not be taken by someone with an allergy to metoprolol, as they may have an allergic reaction, which can be dangerous.  Additionally, patients taking other medications, such as metformin, that lower blood sugar should take caution when taking metoprolol, as metoprolol may increase the risk of low blood sugar (hypoglycemia).¹¹ 

This article is not medical advice, and it is not intended to prescribe, diagnose, or promote specific treatments for any condition.

References

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2. RxList Professional (2020, October 22). Toprol XL. RxList. Accessed 2021, March 30, from https://www.rxlist.com/toprol-xl-drug.htm#description
3. Morris, J., Dunham, A. (2021, February 21). Metoprolol. StatPearls [Internet].  Accessed 2021, March 30, from https://www.ncbi.nlm.nih.gov/books/NBK532923/
4. National Heart, Lung, and Blood Institute (n.d.). Atrial Fibrillation. National Institutes of Health. Accessed 2021, March 30, from https://www.nhlbi.nih.gov/health-topics/atrial-fibrillation
5. Carroll, R., Matfin, G. (2010, June). Endocrine and metabolic emergencies: thyroid storm. Ther Adv Endocrinol Metab 1(3): 139-145. Doi: 10.1177/2042018810382481.
6. Oliver, E., Mayor, F., D’Ocon, P. (2019). Beta-blockers: Historical Perspective and Mechanisms of Action. Revista Espanola de Cardiologia (English Edition) 72(10): 853-862. Doi: 10.1016/j.rec.2019.04.006
7. Baker, J.G., Hill, S.J., Summers, R.J. (2011, April). Evolution of B-blockers: from anti-anginal drugs to ligand-directed signalling. Trends Pharmacol Sci 32(4-2): 227-234. Doi: 10.1016/j.tips.2011.02.010
8. Farzam, K., Jan, A. (2021, March 12). Beta Blockers. StatPearls [Internet]. Accessed 2021, March 31, from https://www.ncbi.nlm.nih.gov/books/NBK532906/
9. Persson, P.B. (2003, November 1). Renin: origin, secretion, and synthesis. J Physiol 552(Pt 3): 667-671. Doi: 10.1113/jphysiol.2003.049890
10.  Nguyen, L.P., Gerstein, N.S. (2019). Chapter 11 – Cardiovascular Pharmacology in Noncardiac Surgery. Essentials of Cardiac Anesthesia for Noncardiac Surgery: A Companion to Kaplan’s Cardiac Anesthesia. P247-288. Doi: 10.1016/B978-0-323-56716-0.00011-4.
11. MedicineWise (2020, June 1). Consumer medicine information; Metoprolol Sandoz: Metoprolol tartrate. NPS. Accessed 2021, March 31, from https://www.nps.org.au/medicine-finder/metoprolol-sandoz-tablets#full-pi
12. Image by Arek Socha from Pixabay