|Composition||Metoprolol Succinate 25/50 mg ER Tablets|
|Indication||To treat high blood pressure, chest pain due to poor blood flow to the heart, and a number of conditions involving an abnormally fast heart rate.|
|Mechanism of Action||
Metoprolol blocks ß1 adrenergic receptors of cardiomyocytes, thus it decreases the slope of phase 4 in the nodal action potential (reduces Na+ uptake) and prolongs repolarization of phase 3 (slows down K+ release). It also suppresses the norepinephrine-induced increase in the sarcoplasmic reticulum (SR) Ca2+ leak and the spontaneous SR Ca2+ release, which are the major triggers for atrial fibrillation.
Metoprolol has a short half-life of 3 to 7 hours, so is taken at least twice daily or as a slow-release preparation.
It undergoes α-hydroxylation and O-demethylation as a substrate of the cytochrome liver enzymes CYP2D6 and a small percentage by CYP3A4, resulting in inactive metabolites.
Side effects, especially with higher doses, include dizziness, drowsiness, fatigue, diarrhea, unusual dreams, ataxia, trouble sleeping, depression, and vision problems. It may also reduce blood flow to the hands and feet, causing them to feel numb and cold; smoking may worsen this effect. Due to the high penetration across the blood-brain barrier, lipophilic beta blockers such as propranolol and metoprolol are more likely than other less lipophilic beta blockers to cause sleep disturbances such as insomnia and vivid dreams and nightmares.
Serious side effects that are advised to be reported immediately include symptoms of bradycardia (resting heart rate slower than 60 beats per minute), persistent symptoms of dizziness, fainting and unusual fatigue, bluish discoloration of the fingers and toes, numbness/tingling/swelling of the hands or feet, sexual dysfunction, erectile dysfunction (impotence), hair loss, mental/mood changes, depression, trouble breathing, cough, dyslipidemia, and increased thirst. Taking it with alcohol might cause mild body rashes, so is not recommended.
Ischemic Heart Disease
Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, myocardial infarction have occurred. When discontinuing chronically administered METOZOX, particularly in patients with ischemic heart disease, gradually reduce the dosage over a period of 1 - 2 weeks and monitor the patient. If angina markedly worsens or acute coronary ischemia develops, promptly reinstate METOZOX, and take measures appropriate for the management of unstable angina. Warn patients not to interrupt therapy without physician’s advice. Because coronary artery disease is common and may be unrecognized, avoid abruptly discontinuing METOZOX in patients treated only for hypertension.
Worsening cardiac failure may occur during up-titration of METOZOX. If such symptoms occur, increase diuretics and restore clinical stability before advancing the dose of METOZOX [see DOSAGE]. It may be necessary to lower the dose of METOZOX or temporarily discontinue it. Such episodes do not preclude subsequent successful titration of METOZOX.
PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD, IN GENERAL, NOT RECEIVE BETA-BLOCKERS. Because of its relative beta1 cardio-selectivity, however, METOZOX may be used in patients with bronchospastic disease who do not respond to, or cannot tolerate, other antihypertensive treatment. Because beta1 -selectivity is not absolute, use the lowest possible dose of METOZOX. Bronchodilators, including beta2 -agonists, should be readily available or administered concomitantly [see DOSAGE].
If METOZOX is used in the setting of pheochromocytoma, it should be given in combination with an alpha blocker, and only after the alpha blocker has been initiated. Administration of beta-blockers alone in the setting of pheochromocytoma has been associated with a paradoxical increase in blood pressure due to the attenuation of beta-mediated vasodilatation in skeletal muscle.
Avoid initiation of a high-dose regimen of extended-release metoprolol in patients undergoing noncardiac surgery, since such use in patients with cardiovascular risk factors has been associated with bradycardia, hypotension, stroke and death.
Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery, however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.
Diabetes And Hypoglycemia
Beta-blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected.
Consider initiating METOZOX therapy at doses lower than those recommended for a given indication; gradually increase dosage to optimize therapy, while monitoring closely for adverse events.
Beta-adrenergic blockade may mask certain clinical signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal of beta-blockade may precipitate a thyroid storm.
While taking beta-blockers, patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated challenge and may be unresponsive to the usual doses of epinephrine used to treat an allergic reaction.
Peripheral Vascular Disease
Beta-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease.
Calcium Channel Blockers
Because of significant inotropic and chronotropic effects in patients treated with beta-blockers and calcium channel blockers of the verapamil and diltiazem type, caution should be exercised in patients treated with these agents concomitantly.
The usual initial dosage is 25 to 100 mg daily in a single dose. The dosage may be increased at weekly (or longer) intervals until optimum blood pressure reduction is achieved. In general, the maximum effect of any given dosage level will be apparent after 1 week of therapy.