indication

For the management of acute myocardial infarction, angina pectoris, heart failure and mild to moderate hypertension. May be used to treat supraventricular and tachyarrhythmias and as prophylaxis for migraine headaches.

pharmacology

Metoprolol, a competitive, beta1-selective (cardioselective) adrenergic antagonist, is similar to atenolol in its moderate lipid solubility, lack of intrinsic sympathomimetic activity (ISA), and weak membrane stabilizing activity (MSA).

mechanism of action

Metoprolol competes with adrenergic neurotransmitters such as catecholamines for binding at beta(1)-adrenergic receptors in the heart. Beta(1)-receptor blockade results in a decrease in heart rate, cardiac output, and blood pressure.

toxicity

LD₅₀=5500 mg/kg (orally in rats), toxic effects include bradycardia, hypotension, bronchospasm, and cardiac failure. LD₅₀=2090 mg/kg (orally in mice)

biotransformation

Primarily hepatic

absorption

Rapid and complete, 50%

half life

3-7 hours

route of elimination

Less than 5% of an oral dose of metoprolol is recovered unchanged in the urine; the rest is excreted by the kidneys as metabolites that appear to have no beta-blocking activity.

drug interactions

Acetohexamide: The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.

Chlorpropamide: The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.

Cimetidine: Cimetidine may increase the serum concentration of metoprolol by decreasing its metabolism.

Citalopram: The SSRI, citalopram, may increase the bradycardic effect of the beta-blocker, metoprolol.

Clonidine: Increased hypertension when clonidine stopped

Dihydroergotamine: Ischemia with risk of gangrene

Dihydroergotoxine: Ischemia with risk of gangrene

Diltiazem: Increased risk of bradycardia

Disopyramide: The beta-blocker, metoprolol, may increase adverse effects of disopyramide.

Epinephrine: Hypertension, then bradycardia

Ergonovine: Ischemia with risk of gangrene

Ergotamine: Ischemia with risk of gangrene

Escitalopram: The SSRI, escitalopram, may increase the bradycardic effect of the beta-blocker, metoprolol.

Fenoterol: Antagonism

Fluoxetine: The SSRI, fluoxetine, may increase the bradycardic effect of the beta-blocker, metoprolol.

Formoterol: Antagonism

Gliclazide: The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.

Glipizide: The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.

Glisoxepide: The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.

Glyburide: The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.

Glycodiazine: The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.

Hydralazine: Increased effect of both drugs

Ibuprofen: Risk of inhibition of renal prostaglandins

Indomethacin: Risk of inhibition of renal prostaglandins

Insulin Glargine: The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.

Isoproterenol: Antagonism

Lidocaine: The beta-blocker, metoprolol, may increase the effect and toxicity of lidocaine

Methysergide: Ischemia with risk of gangrene

Orciprenaline: Antagonism

Paroxetine: The SSRI increases the effect of the beta-blocker

Phenobarbital: The barbiturate decreases the effect of the metabolized beta-blocker

Pipobroman: Antagonism

Pirbuterol: Antagonism

Piroxicam: Risk of inhibition of renal prostaglandins

Prazosin: Risk of hypotension at the beginning of therapy

Primidone: The barbiturate decreases the effect of metabolized beta-blocker

Procaterol: Antagonism

Propafenone: Propafenone may increase the effect of beta-blocker, metoprolol.

Repaglinide: The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.

Rifampin: Rifampin may decrease the serum concentration of metoprolol by increasing its metabolism.

Salbutamol: Antagonism

Salmeterol: Antagonism

Sertraline: The SSRI increases the effect of the beta-blocker

Telithromycin: Telithromycin may possibly increase metoprolol effect

Terazosin: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Terbinafine: Terbinafine may reduce the metabolism and clearance of Metoprolol. Consider alternate therapy or monitor for therapeutic/adverse effects of Metoprolol if Terbinafine is initiated, discontinued or dose changed.

Terbutaline: Antagonism

Tolazamide: The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.

Tolbutamide: The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.

Verapamil: Increased effect of both drugs