Metoprolol is a selective beta-1 blocker that reduces heart rate, myocardial contractility, and blood pressure. Available in immediate-release and extended-release formulations.
Also known as: Lopressor, Toprol-XL
Metoprolol masks the adrenergic symptoms of overnight/between-meal hypoglycaemia induced by NPH insulin (4–12 h peak).
The NPH peak often occurs overnight; beta-blockade suppresses the tachycardia warning and reduces hepatic β2 glycogenolysis (Prontuário 8.4.1).
Overnight glucose, sweating, morning neurological status (headache).
Nightmares, morning headache, sweat-soaked clothing (nocturnal hypoglycaemia).
Regular overnight glucose monitoring; educate on "silent" hypoglycaemia; adjust basal insulin and bedtime snack.
INFARMED Prontuário Terapêutico (11th ed., 2012), 8.4.1 Insulins; DailyMed — Humulin N (NPH) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6edd793-440b-40c2-96b5-c16133b7a921
Beta-blocker + SSRI: CYP2D6 inhibition increases metoprolol levels.
Fluoxetine potently inhibits CYP2D6, increasing metoprolol plasma levels 2-5 fold. Risk of bradycardia and hypotension.
DailyMed/FDA (NIH/NLM) — approved Metoprolol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5466243e-1e3d-175e-e063-6394a90a5dee
Beta-blocker + antiarrhythmic: risk of severe bradycardia and AV block.
Both reduce AV conduction and heart rate. The combination can cause severe bradycardia, AV block, and cardiac arrest.
DailyMed/FDA (NIH/NLM) — approved Metoprolol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5466243e-1e3d-175e-e063-6394a90a5dee
Beta-blocker + non-dihydropyridine CCB: risk of AV block and heart failure.
Both reduce AV conduction and contractility. The combination can cause severe AV block, bradycardia, and heart failure.
DailyMed/FDA (NIH/NLM) — approved Metoprolol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5466243e-1e3d-175e-e063-6394a90a5dee
Methyldopa plus metoprolol adds hypotensive and bradycardic effects; abrupt beta-blocker withdrawal can cause rebound hypertension.
Both reduce cardiac output and peripheral resistance; rebound results from abrupt beta-blocker withdrawal with increased sympathetic activity.
Orthostatic blood pressure, bradycardia, rebound signs after withdrawal.
Dizziness on standing, pulse < 50 bpm, hypertensive headache.
Never stop the beta-blocker abruptly; monitor blood pressure and pulse in combination.
DailyMed — Methyldopa and Metoprolol Tartrate labels, beta-blocker interactions: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=485f1fdb-6543-4f47-e063-6394a90a2459
Hydralazine causes reflex tachycardia, usually controlled by metoprolol; stopping the beta-blocker exposes the tachycardia and ischemia risk.
Direct arterial vasodilator plus beta-blocker: classic combinations (e.g., for pregnancy hypertension) but dependent on the beta-blocker.
Heart rate, angina, blood pressure.
Palpitations, angina after stopping the beta-blocker.
The combination is intentional in several protocols; never stop the beta-blocker without replacement; monitor pulse.
DailyMed — Hydralazine Hydrochloride (reflex tachycardia; use with beta-blocker) and Metoprolol labels: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=47ad263b-ad3d-4f98-b0aa-d9e82ab6cb67
Metoprolol may block the beta-2 vasodilating component of ephedrine, favouring excessive hypertensive response and reflex bradycardia.
Ephedrine is a mixed (α and β) sympathomimetic; β1-selective blockade leaves α vasoconstriction unbalanced by β2 (ephedrine labels: hypertension with beta-blockers).
Frequent invasive/non-invasive blood pressure, heart rate.
Sudden hypertension, headache, bradycardia, angina.
For anaesthetic hypotension in beta-blocked patients, use ephedrine in smaller doses with continuous monitoring; consider phenylephrine as an alternative with caution.
DailyMed — Ephedrine Sulfate Tablet label [CVS Pharmacy], Warnings (hypertension, adrenergic interactions): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e338deef-efad-1d82-e053-2995a90a1bf9
Metoprolol masks the adrenergic symptoms of hypoglycaemia (tachycardia, tremor) and may prolong insulin-induced hypoglycaemia.
Beta-blockade blunts the compensatory adrenergic response (tachycardia, tremor) and blocks hepatic β2 (glycogenolysis); Prontuário 8.4.1: "special concern with insulin administration in patients ... on beta-adrenergic blockers".
Capillary glucose, atypical heart rate, neurological status.
Sudden sweating without tachycardia, confusion, loss of consciousness (unrecognised hypoglycaemia).
Reinforce education on "neuroglycopenic" hypoglycaemia (persistent sweating, confusion); more frequent capillary glucose; consider cardioselective beta-blocker at minimum dose.
INFARMED Prontuário Terapêutico (11th ed., 2012), 8.4.1 Insulins (p. 358) — beta-adrenergic blockers; DailyMed — Humulin R (human regular insulin) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6edd793-440b-40c2-96b5-c16133b7a921
β1 blockade directly antagonises the inotropic effect of dobutamine, with a risk of haemodynamic deterioration in patients dependent on the inotrope.
The inotropic effect of dobutamine derives from cardiac β1 receptor stimulation and is reversed by concomitant beta-blocker administration; with β1 blocked, alpha-agonist effects become dominant and may cause peripheral vasoconstriction and a rise in blood pressure.
Invasive blood pressure, cardiac index, continuous ECG, lactate, urine output and peripheral perfusion.
Refractory hypotension, arrhythmias, oliguria, lactic acidosis, cold extremities.
Titrate the dose under haemodynamic monitoring; in patients on chronic beta-blockade expect a reduced inotropic response and consider non-adrenergic alternatives (phosphodiesterase III inhibitors or calcium sensitisers) or, in beta-blocker poisoning, treat the antagonism first.
Dobutamine label (Pfizer labeling) — "The inotropic effect of dobutamine stems from stimulation of cardiac beta1 receptors, this effect is reversed by concomitant administration of beta-blockers": https://labeling.pfizer.com/ShowLabeling.aspx?id=16395; EMC-UK — Dobutamine 5 mg/ml solution for infusion, SmPC 4.5 (unopposed alpha effects with vasoconstriction and hypertension): https://www.medicines.org.uk/emc/product/6462/smpc
Metoprolol blunts the reflex tachycardia that compensates nitroprusside-induced vasodilation, potentially worsening hypotension and bradycardia.
Additive hypotensive effect: nitroprusside dilates arterioles and veins while the beta-blocker prevents the compensatory chronotropic response; the Prontuário (Annex 7) lists beta-adrenergic blockers among drugs that increase the hypotensive effect.
Continuous blood pressure, heart rate, ECG, urine output, lactate; during prolonged infusion, cyanide/thiocyanate toxicity.
Hypotension, bradycardia, syncope, oliguria, confusion.
Reduce the initial infusion rate and titrate slowly by invasive blood pressure; if symptomatic bradycardia occurs, reduce or stop the beta-blocker and consider an alternative vasodilator.
INFARMED Prontuário Terapêutico (11th ed., 2012), Annex 7 — ARA II table: "Beta-adrenergic blockers ... Sodium nitroprusside" among drugs that increase the hypotensive effect.
Food slightly reduces metoprolol bioavailability without clinically relevant consequence on usual schedules.
Take with or without food, at the same time.
EMC-UK — Metoprolol SmPC 4.2 (with or without food).
May cause bronchospasm in asthmatic patients. Prefer cardioselective beta-blocker.
Avoid in severe asthma. Use minimum dose if necessary.
DailyMed/FDA (NIH/NLM) — approved Metoprolol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5466243e-1e3d-175e-e063-6394a90a5dee
Use only if benefit justifies risk. May cause neonatal bradycardia and hypoglycaemia.
Avoid in 3rd trimester if possible.
Excreted in breast milk. Generally compatible with breastfeeding.
Monitor neonate for bradycardia and hypoglycaemia at delivery.
DailyMed/FDA (NIH/NLM) — approved Metoprolol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5466243e-1e3d-175e-e063-6394a90a5dee
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Selective beta-1 blocker that reduces heart rate, contractility, and AV conduction. Minimal effect on pulmonary beta-2 receptors.
Selectively blocks cardiac beta-1 receptors, reducing heart rate, myocardial contractility, and AV conduction. Dose-dependent effect.
Oral bioavailability: ~50% (extensive first-pass hepatic metabolism). Food increases absorption. Tmax: 1-2 hours.
Extensively metabolised by CYP2D6. Inhibited by fluoxetine, paroxetine, quinidine. Induced by rifampicin. CYP2D6 genetic polymorphism.
3-7 hours. Elimination: ~95% urine (metabolites), <5% unchanged. Adjust in hepatic impairment.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
