Monographs of Topical Drugs that Have Caused Contact Allergy/Allergic Contact Dermatitis
Anton C. de Groot in Monographs in Contact Allergy, 2021
Metoprolol is a cardioselective competitive β1-adrenergic receptor antagonist with antihypertensive properties. This agent antagonizes β1-adrenergic receptors in the myocardium, thereby reducing the rate and force of myocardial contraction, leading to a reduction in cardiac output. Metoprolol is indicated for the treatment of angina, heart failure, myocardial infarction, atrial fibrillation, atrial flutter and hypertension. Off-label uses of metoprolol include supraventricular tachycardia and thyroid storm. In pharmaceutical products, metoprolol is most often employed as metoprolol succinate (CAS number 98418-47-4, EC number not available, molecular formula C34H56N2O10) or as metoprolol tartrate (CAS number 56392-17-7, EC number 260-148-9, molecular formula C34H56N2O12) (1).
Substrates of Human CYP2D6
Shufeng Zhou in Cytochrome P450 2D6, 2018
Metoprolol is a cardioselective β1-blocker, clinically used in the treatment of hypertension, angina pectoris, and arrhythmia. The drug is marketed as a racemic mixture, but its pharmacological effect resides in the S-enantiomer. The S-metoprolol enantiomer has approximately 500-fold more affinity for the β1-adrenergic receptor than its R-antipode (Dayer et al. 1985). Metoprolol is metabolized through a-hydroxylation (~10% of dose), O-demethylation (65% of dose), and N-dealkylation by oxidative deamination (<10% of dose) (Borg et al. 1975). a-Hydroxylation of metoprolol is catalyzed almost entirely by CYP2D6 and O-demethylation via CYP2D6 and 3A4 (Figure 3.67) (Hoffmann et al. 1980; Johnson and Burlew 1996; Otton et al. 1988). Hydroxylation of the aliphatic chain of metoprolol adds a new chiral center to the corresponding a-hydroxymetoprolol, generating four optical isomers. The pharmacokinetics of metoprolol is stereoselective.
Genetically Determined Ventricular Arrhythmias
Andrea Natale, Oussama M. Wazni, Kalyanam Shivkumar, Francis E. Marchlinski in Handbook of Cardiac Electrophysiology, 2020
Among symptomatic patients, nadolol and propranolol performed better than metoprolol. The risk of cardiac events was 3.9-fold greater when patients were treated with metoprolol.29 However, in another recent large retrospective study assessing the efficacy of the 4 most commonly prescribed β-blockers (atenolol, metoprolol, nadolol, and propranolol) in 1530 patients, all β-blockers were equally effective in reducing the risk of a first cardiac event. In the subcohort of patients with LQT1 (n = 379), no β-blocker was superior, whereas in LQT2 (n = 406), nadolol was slightly more effective than other β-blockers. In patients with at least one cardiac event while taking β-blockers, propranolol appeared to be the least effective drug.30 The data from the retrospective studies clearly underline the beneficial effect of β-blocker therapy in LQTS but caution should be exercised before drawing conclusions about their relative efficacy. There is agreement that nadolol is probably one of the more effective drugs for this condition.31 Abrupt discontinuation of beta-blockers should be avoided.
Development of metoprolol tartrate-loaded sustained-release pellets: effect of talc on the mechanism of drug release
Published in Pharmaceutical Development and Technology, 2018
Yuli Wang, Meiyan Yang, Ruifang Shen, Shuai Shao, Lu Chen, Wei Gong, Li Shan, Chunsheng Gao
Metoprolol tartrate (MT), a highly water-soluble drug (above 70% w/v), has been widely used in the treatment of hypertension, angina pectoris and arrhythmias. Because of its good absorption in the entire gastrointestinal tract5, rapid elimination (the half-life of 3–4 h)6 and a well-defined relationship between the beta-blocking effect and plasma drug concentration7, MT is a suitable candidate for oral SR administrations. There have been several approaches to the design of SR delivery systems for MT. For example, the slow release encapsulated tablet8, the extended-release matrix tablet9, the extended release hydrophilic gel-based swellable polyethylene oxide tablet1, the three-layer guar gum matrix tablet10, the bilayer floating tablet11, the prolonged release mini tablets coated with Eudragit NE 40 D12 and the reservoir pellets with plasticized isolated ethylcellulose/hydroxypropyl methylcellulose films13. Among these SR strategies, a pellet-based formulation can minimize the risk of dose dumping and because of its multiple-particulate nature, has the potential to improve the safety and efficacy of the active ingredient and thus has potential for use in the controlled release of the highly water-soluble MT in oral delivery14. When compared to matrix pellets, polymer-coated pellets are the most commonly applied formulation used to achieve a required and reproducible drug release rate over an extended period of time15.
Effects of garden cress, fenugreek and black seed on the pharmacodynamics of metoprolol: an herb-drug interaction study in rats with hypertension
Published in Pharmaceutical Biology, 2021
Yousef A. Bin Jardan, Abdul Ahad, Mohammad Raish, Mohd Aftab Alam, Abdullah M. Al-Mohizea, Fahad I. Al-Jenoobi
In this study, we used L-NAME-induced hypertension models to investigate the antihypertensive effects of three commonly used herbs, namely, garden cress (GC), fenugreek (FG), and black seed (BS); for this purpose, L-NAME was orally administered in rats, which induced a substantial increase in blood pressure. The outcomes of this study showed that metoprolol tartrate (MT) alone, herbs alone, and their combination showed a decrease in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) in hypertensive rats. Heart rate (HR), which was depleted following treatment with L-NAME alone, improved following treatment with MT alone, herbs alone, and herbs + MT. A more potent blood pressure-lowering effect of MT was observed when administered in combination with herbs. Furthermore, the concurrent administration of drugs, particularly those predominantly cleared through CYP2D-catalyzed metabolism, with the three herbs under study should be considered with caution.
Metoprolol in the treatment of cardiovascular disease: a critical reappraisal
Published in Current Medical Research and Opinion, 2018
The use of metoprolol in the treatment of arterial hypertension is supported by the bulk of evidence and clinical experience, starting from the mid-1970s. The research was initially focused on the characterization of the hemodynamic effects of metoprolol on 24-h ambulatory pressure, organ damage, and metabolic profile. Simultaneously, in-depth assessments of the efficacy and tolerability of the drug vs other commonly used anti-hypertensive drugs have been published. Metoprolol was compared with alpha methyldopa and thiazide diuretics, ACE inhibitors, and calcium channel blockers. Overall, the results of these studies have highlighted the efficacy of metoprolol against the reference drugs under investigation37. Over the last decade, the comparative evaluation of metoprolol in the therapy of essential hypertension was performed against the new β-blockers endowed with vasodilatatory properties mediated by nitric oxide, such as nebivolol38. In Europe, the use of the newer β-blockers for the treatment of hypertension is limited, and probably inferior to the rate of use of the old-generation β-blockers in the same scenario.
Related Knowledge Centers
- Angina
- Beta Blocker
- Cyp2D6
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- Myocardial Infarction
- Syncope
- Tachycardia
- Hypertension
- Migraine
- Oral Administration