Beta-blockers such as metoprolol are used to treat hypertension, among other conditions. These drugs form the first line of treatment for hypertension (Dézsi & Szentes, 2017). Normally, epinephrine, norepinephrine, and catecholamine bind to beta-1 receptors leading to increased cardiac activity but, metoprolol, a cardio-selective inhibitor of beta-1 adrenergic receptors, alienate their activity (Morris & Dunham, 2018). It only binds to beta-1 receptors and not beta-2 or beta-3 receptors (Farzam & Jan, 2020). Moreover, it competitively antagonizes catecholamine effects at the peripheral neuronal sites, causing a decrease in cardiac output. Additionally, it inhibits the release of renin, which plays a role in increasing blood pressure.
The use of metoprolol may result in several adverse effects. In the cardiovascular system, the drug may cause hypotension, exacerbation of heart failure, and cold extremities. This is because of an excessive decrease in cardiac excitability. Bradycardia may also occur in due interaction of the drug with cytochrome P450 enzymes (Berger et al., 2018). The effects on the gastrointestinal system include glucose intolerance, diarrhea, and mask hypoglycemia (Uddin et al., 2020). Moreover, a sudden stop in using the drug will cause withdrawal syndrome, leading to myocardial infarction and angina (Morris & Dunham). The syndrome is accompanied by signs such as tachycardia and hypertension. Other adverse effects include depression, bronchospasm, and reduced exercise tolerance.
A negative chronotrope refers to drugs that decrease the heart rate. Normally, alpha-1 receptors initiate a rise in cardiac chronotrope and vasoconstriction. Therefore, agonism of the receptors results in increased heart rate and blood pressure, respectively. However, though a beta-1 blocker, metoprolol has antagonistic effects on alpha-1 receptors and causes negative chronotrope and vasodilation, which causes decreased heart rate and blood pressure (Farzam & Jan, 2020). The negative chronotrope effect of metoprolol is essential as it augments its clinical effect in managing hypertension.
Calcium channel blockers, also known as calcium channel antagonists, are used in the management of hypertension. They bind to the L-type voltage-gated calcium channels in the pancreas, vascular smooth muscles, and the heart (Bakris & Sorrentino, 2017). This inhibits the movement of extracellular calcium ions into the cells (Lin & Ma, 2018). There are two groups of calcium channel blockers based on their physiologic effects. The dihydropyridines have less effect on the myocardium, but they act on the peripheral vasodilators (McKeever & Hamilton, 2020). The non-dihydropyridines affect the atrioventricular and sinoatrial nodes, leading to slowed contractility and conduction of the heart (Overbeek & Shaffer, 2020). These drugs lead to vasodilation and decrease heart rate; hence they are used to manage hypertension.
Monotherapy in the management of hypertension yields lower results since the condition is associated with other concomitant issues such as old age, smoking, diabetes, or obesity. It becomes difficult to achieve blood pressure control, and so the European Society of Hypertension recommends a combination of drugs to manage hypertension (Mancia & Tsioufis, 2019). This results in a greater blood pressure reduction, better response, and decreased heterogeneity of the blood pressure response.
However, in such therapy, some drug-drug interactions can lead to severe effects. Calcium channel blockers such as verapamil interfere with the CYP3A4 and P-glycoprotein-mediated drug transport mechanism (Fravel & Ernst, 2021). This alters the absorption of other drugs such as metoprolol from the intestines and their distribution among peripheral tissues (Saedder et al., 2019). The use of combined therapy may increase plasma concentrations of metoprolol leading to drug toxicity, and consequently, hypotension and sinus bradycardia. The heart becomes insufficient, and blood pressure is remarkably reduced, and the patient can collapse or die in severe cases.
References
Bakris, G. L., & Sorrentino, M. (2017). Hypertension: A companion to Braunwald’s heart disease. Elsevier Health Sciences.
Berger, B., Bachmann, F., Duthaler, U., Krähenbühl, S., & Haschke, M. (2018). Cytochrome P450 enzymes involved in metoprolol metabolism and use of metoprolol as a CYP2D6 phenotyping probe drug. Frontiers in Pharmacology, 9, (774), 1-11. Web.
Dézsi, C. A., & Szentes, V. (2017). The real role of β-blockers in daily cardiovascular therapy. American Journal of Cardiovascular Drugs, 17(5), 361-373. Web.
Farzam, K., & Jan, A. (2020). Beta blockers. StatPearls. Web.
Fravel, M. A., & Ernst, M. (2021). Drug interactions with antihypertensives. Current Hypertension Reports, 23(3), 1-8. Web.
Lin, Y., & Ma, L. (2018). Blood pressure lowering effect of calcium channel blockers on perioperative hypertension: A systematic review and meta-analysis. Medicine, 97(48), e13152. Web.
Mancia, G., & Tsioufis, K. (2019). Current perspective on the use of calcium channel blockers to treat hypertensive patients: The role of lercanidipine. Future Cardiology, 15(04), 259-266. Web.
McKeever, R. G., & Hamilton, R. J. (2020). Calcium channel blockers. StatPearls. Web.
Morris, J., & Dunham, A. (2018). Metoprolol. StatPearls. Web.
Overbeek, D., & Shaffer, R. W. (2020). Management of beta blocker and calcium channel blocker toxicity. In R. C. Hyzy & J. McSparron (Eds.), Evidence-based critical care (pp. 57-62). Springer.
Saedder, E. A., Thomsen, A. H., Hasselstrøm, J. B., & Jornil, J. R. (2019). Heart insufficiency after combination of verapamil and metoprolol: A fatal case report and literature review. Clinical Case Reports, 7(11), 2042-2048. Web.
Uddin, M. B., Ali, M. S., & Faizan, M. A. (2020). A case report on metoprolol overdose. IP International Journal of Forensic Medicine and Toxicological Sciences, 5(2), 74-76. Web.