This preferential effect is not absolute, however, and at higher plasma concentrations, Lopressor also inhibits beta2- adrenoreceptors, chiefly located in the bronchial and vascular musculature. In a 2-year study in rats at three oral dosage levels of up to 800 mg/kg per day, there was no increase in the development of spontaneously occurring benign or malignant neoplasms of any type. Oral maintenance therapy with Metoprolol or placebo was then continued for 3 months. Vomiting was a common occurrence.
Animal and human experiments indicate that Metoprolol slows the sinus rate and decreases AV nodal conduction.Significant beta-blocking effect (as measured by reduction of exercise heart rate) occurs within one hour after oral administration, and its duration is dose related. Patients should be warned against interruption or discontinuation of therapy without the physician’s advice. The mean elimination half-life of Metoprolol is 3 to 4 hours; in poor CYP2D6 metabolizers the half-life may be 7 to 9 hours. Vertigo, sleep disturbances, hallucinations, headache, dizziness, visual disturbances, confusion, and reduced libido have also been reported, but a drug relationship is not clear.In the randomized comparison of Metoprolol and placebo described in the Dyspnea of pulmonary origin has been reported in fewer than 1 of 100 patients.Nausea and abdominal pain have been reported in fewer than 1 of 100 patients.Rash and worsened psoriasis have been reported, but a drug relationship is not clear.Unstable diabetes and claudication have been reported, but a drug relationship is not clear.A variety of adverse reactions not listed above have been reported with other beta-adrenergic blocking agents and should be considered potential adverse reactions to Metoprolol.Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics.Agranulocytosis, nonthrombocytopenic purpura and thrombocytopenic purpura.Fever combined with aching and sore throat, laryngospasm and respiratory distress.The following adverse reactions have been reported during post-approval use of Metoprolol: confusional state, an increase in blood triglycerides and a decrease in High Density Lipoprotein (HDL). The only histologic changes that appeared to be drug-related were an increased incidence of generally mild focal accumulation of foamy macrophages in pulmonary alveoli and a slight increase in biliary hyperplasia. Severe exacerbation of angina, myocardial infarction and ventricular arrhythmias have been reported in patients with coronary artery disease following the abrupt discontinuation of therapy with beta-blockers. In other words, those muscles get tired and fail to work properly. Because of variable plasma levels attained with a given dose and lack of a consistent relationship of antihypertensive activity to dose, selection of In several studies of patients with acute myocardial infarction, intravenous followed by oral administration of Metoprolol caused a reduction in heart rate, systolic blood pressure and cardiac output. Embryotoxicity and/or fetotoxicity in rats and rabbits were noted starting at doses of 50 mg/kg in rats and 25 mg/kg in rabbits, as demonstrated by increases in preimplantation loss, decreases in the number of viable fetuses per dose, and/or decreases in neonatal survival. However, antihypertensive activity does not appear to be related to plasma levels. Metoprolol is not a significant P-glycoprotein substrate.Metoprolol is primarily metabolized by CYP2D6. Metoprolol tartrate tablets should be taken with or immediately following meals.The usual initial dosage of Metoprolol tartrate tablets is 100 mg daily in single or divided doses, whether used alone or added to a diuretic.
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