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metoprolol (Lopressor Toprol XL, Kapspargo)

Tradename: Lopressor, Toprol XL. A selective beta-1 antagonist. Indications: - hypertension - chronic stable angina - unstable angina [8] - secondary prevention in patients with cardiovascular disease - reduces risk of cardiovascular mortality in hemodynamically stable patients with acute myocardial infarction - supraventricular tachycardia - paroxysmal supraventricular tachycardia - paroxysmal atrial tachycardia - multifocal atrial tachycardia - control of ventricular rate in atrial fibrillation or atrial flutter - long QT syndrome [8] - mitral valve prolapse [8] - pheochromocytoma [8] - thyrotoxicosis - reduces mortality in high-risk patients indgoing non-cardiac surgery - heart failure (Toprol XL is FDA approved) - migraine prophylaxis [8] Contraindications: 1) asthma 2) overt heart failure 3) cardiogenic shock 4) bradycardia Dosage: 1) acute MI: 5 mg increments IV every 2 hours up to 15 mg 2) hypertension: start 50 mg PO BID, max 450 mg/day Injection: 1 mg/mL (5 mL). Tabs: 50 100 mg. metoprolol succinate, Toprol XL*, Kapspargo (extended release): 1) start 50-100 mg PO QD, max 400 mg/day 2) heart failure: [5] a) start 12.5 mg QD (class III), 25 mg QD (class II) b) increase dose slowly, up to 200 mg QD Tabs: 25 mg (scored), 50, 100, 200 mg. * ok to crush, except XL. * generic extended-release metoprolol succinate may have different pharmacokinetics than Toprol-XL [9] * Kapspargo available in sprinkle Pharmacokinetics: 1) 1st pass hepatic metabolism with oral administration - metabolized by cyt P450 2D6 2) 11% of the drug is bound to plasma proteins 3) 78% crosses blood-brain barrier 4) excreted in the urine 5) elimination 1/2life is 3-4 hours 6) dialyzable [12] 7) no good correlation between serum levels & therapeutic effect Adverse effects: 1) common (> 10%) - depression, fatigue, weakness, dizziness 2) less common (1-10%) - bradycardia, wheezing, irregular heartbeat, diminished peripheral circulation, heartburn 3) uncommon (< 1%) - rash, chest pain, constipation, sexual dysfunction, itching, nausea/vomiting, dyspepsia, insomnia, heart failure, Raynaud's phenomena, nightmares, confusion, headache, cold extremities 4) other - orthostatic hypotension - elevated liver function tests (LFTs) - mucocutaneous vesiculobullous dermatitis - lichenoid dermatitis (lichen planus) [10,11] - xerostomia (dry mouth) [10,11] Drug interactions: 1) blocks bronchodilator effects of beta adrenergic agonists 2) barbiturates may enhance metoprolol metabolism 3) phenothiazines & cimetidine may increase plasma concentrations 4) any pharmaceutical agent that inhibits cyt P450 2D6 may increase levels of metoprolol Laboratory: 1) specimen: a) serum, plasma (EDTA, heparin) b) urine c) stable for 4 months at -20 degrees C 2) methods: a) serum/plasma: GLC, GC-MS b) urine: HPLC Mechanism of action: 1) selective beta-1 adrenergic receptor antagonist 2) at higher doses, beta-2 adenergic receptor antagonism occurs

Interactions

drug interactions drug adverse effects (more general classes)

Related

African American Study of Kidney Disease & Hypertension (AASK) cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)

General

antiarrhythmic agent, Group II beta-1 adrenergic receptor antagonist (beta-1 blocker) propanolamine

Properties

MISC-INFO: elimination route LIVER 1/2life 3.0-3.4 HOURS therapeutic-range 75-200 NG/ML protein-binding 13% elimination by hemodialysis + pregnancy-category C safety in lactation +

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
  5. Prescriber's Letter 8(4):20 2001
  6. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  7. Alessi C In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
  8. Deprecated Reference
  9. Orciari Herman A FDA Planning Study of Generic Metoprolol Over Safety, Efficacy Concerns. NEJM Journal Watch. May 9, 2014 Massachusetts Medical Society (subscription needed) http://www.jwatch.org
  10. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
  11. Habbab KM, Moles DR, Porter SR. Potential oral manifestations of cardiovascular drugs. Oral Dis. 2010 Nov;16(8):769-73. PMID: 20604876
  12. Zhou H et al beta-blocker use and risk of mortality in heart failure patients initiating maintenance dialysis. Am J Kidney Dis 2021 May; 77:704 PMID: 33010357 https://www.ajkd.org/article/S0272-6386(20)31001-5/fulltext

Component-of

atenolol/metoprolol hydrochlorothiazide/metoprolol/succinate hydrochlorothiazide/metoprolol; HCTZ/metoprolol (Lopressor HCTZ, Dutoprol)