Metoprolol
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| Clinical data |
| Pronunciation |
, |
| Trade names |
Lopressor, Metolar XR |
| AHFS/Drugs.com |
Monograph |
| MedlinePlus |
a682864 |
| License data |
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Pregnancy
category |
- AU: C
- US: C (Risk not ruled out)
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Routes of
administration |
By mouth, IV |
| Drug class |
Beta blocker |
| ATC code |
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| Legal status |
| Legal status |
- In general: ℞ (Prescription only)
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| Pharmacokinetic data |
| Bioavailability |
50% (single dose)[1]
70% (repeated administration)[2] |
| Protein binding |
12% |
| Metabolism |
Liver via CYP2D6, CYP3A4 |
| Biological half-life |
3–7 hours |
| Excretion |
Kidney |
| Identifiers |
IUPAC name
- 1-[4-(2-Methoxyethyl)phenoxy]-3-[(propan-2-yl)amino]propan-2-ol
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| CAS Number |
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| PubChem CID |
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| IUPHAR/BPS |
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| DrugBank |
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| ChemSpider |
|
| UNII |
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| KEGG |
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| ChEBI |
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| ChEMBL |
|
| ECHA InfoCard |
100.048.603 |
| Chemical and physical data |
| Formula |
C15H25NO3 |
| Molar mass |
267.364 g/mol |
| 3D model (JSmol) |
|
| Chirality |
Racemic mixture |
| Melting point |
120 °C (248 °F) |
SMILES
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O(c1ccc(cc1)CCOC)CC(O)CNC(C)C
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InChI
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InChI=1S/C15H25NO3/c1-12(2)16-10-14(17)11-19-15-6-4-13(5-7-15)8-9-18-3/h4-7,12,14,16-17H,8-11H2,1-3H3 Y
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Key:IUBSYMUCCVWXPE-UHFFFAOYSA-N Y
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| (verify) |
Metoprolol, marketed under the tradename Lopressor among others, is a medication of the selective β1 receptor blocker type.[3] It is used 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.[3] It is also used to prevent further heart problems after myocardial infarction and to prevent headaches in those with migraines.[3]
It is sold in formulations that can be taken by mouth or given intravenously.[3] The medication is often taken twice a day.[3] The extended-release formulation is taken once per day.[3] Metoprolol may be combined with hydrochlorothiazide (a diuretic) in a single tablet.[3]
Common side effects include trouble sleeping, feeling tired, feeling faint, and abdominal discomfort.[3] Large doses may cause serious toxicity.[4][5] Risk in pregnancy has not been ruled out.[3][6] It appears to be safe in breastfeeding.[7] Greater care is required with use in those with liver problems or asthma.[3] Stopping this drug should be done slowly to decrease the risk of further health problems.[3]
Metoprolol was first made in 1969.[8] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[9] It is available as a generic drug.[3] In 2013, metoprolol was the 19th-most prescribed medication in the United States.[10]
Contents
- 1 Medical uses
- 2 Adverse effects
- 2.1 Precautions
- 2.2 Pregnancy and lactation
- 3 Overdose
- 4 Pharmacology
- 5 Chemistry
- 6 Mechanism of action
- 7 References
- 8 External links
Medical uses
Metoprolol is used for a number of conditions, including hypertension, angina, acute myocardial infarction, supraventricular tachycardia, ventricular tachycardia, congestive heart failure, and prevention of migraine headaches.[11]
- Treatment of heart failure[12]
- Vasovagal syncope[13][14]
- Adjunct in treatment of hyperthyroidism[15]
- Long QT syndrome, especially for patients with asthma, as metoprolol's β1 selectivity tends to interfere less with asthma drugs, which are often β2-adrenergic receptor-agonist drugs[citation needed]
- Prevention of relapse into atrial fibrillation (controlled-release/extended-release form)[16]
Due to its selectivity in blocking the beta1 receptors in the heart, metoprolol is also prescribed for off-label use in performance anxiety, social anxiety disorder, and other anxiety disorders.
Adverse effects
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.[17] 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.[18]
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.[17]
Precautions
Metoprolol may worsen the symptoms of heart failure in some patients, who may experience chest pain or discomfort, dilated neck veins, extreme fatigue, irregular breathing, an irregular heartbeat, shortness of breath, swelling of the face, fingers, feet, or lower legs, weight gain, or wheezing.[19]
This medicine may cause changes in blood sugar levels or cover up signs of low blood sugar, such as a rapid pulse rate.[19] It also may cause some people to become less alert than they are normally, making it dangerous for them to drive or use machines.[19]
Pregnancy and lactation
It is pregnancy category C in the United States, meaning that a risk for the fetus cannot be ruled out,[3] and category C in Australia, meaning that it may be suspected of causing harmful effects on the human fetus (but no malformations).[6]
Overdose
Excessive doses of metoprolol can cause severe hypotension, bradycardia, metabolic acidosis, seizures, and cardiorespiratory arrest. Blood or plasma concentrations may be measured to confirm a diagnosis of overdose or poisoning in hospitalized patients or to assist in a medicolegal death investigation. Plasma levels are usually less than 200 μg/l during therapeutic administration, but can range from 1–20 mg/l in overdose victims.[20][21][22]
Pharmacology
- beta-1 selective
- moderately lipophilic
- without intrinsic sympathomimetic activity
- with weak membrane stabilizing activity
- decreases heart rate, contractility, and cardiac output, therefore decreasing blood pressure
Pharmacokinetics
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[23][24] and a small percentage by CYP3A4, resulting in inactive metabolites.
Chemistry
Metoprolol has a very low melting point; around 120 °C (248 °F) for the tartrate, and around 136 °C (277 °F) for the succinate. Because of this, metoprolol is always manufactured in a salt-based solution, as drugs with low melting points are difficult to work with in a manufacturing environment. The free base exists as a waxy white solid, and the tartrate salt is finer crystalline material.[citation needed]
The active substance metoprolol is employed either as metoprolol succinate or as metoprolol tartrate (where 100 mg metoprolol tartrate corresponds to 95 mg metoprolol succinate). The tartrate is an immediate-release formulation and the succinate is an extended-release formulation.[25]
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).[26] 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.[26]
References
- ^ "Metolar 25/50 (metoprolol tartrate) tablet" (PDF). FDA. Archived (PDF) from the original on 3 March 2016. Retrieved 5 May 2015.
- ^ Jasek, W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. pp. 916–919. ISBN 978-3-85200-181-4.
- ^ a b c d e f g h i j k l m "Metoprolol". The American Society of Health-System Pharmacists. Archived from the original on 2014-03-12. Retrieved Apr 21, 2014.
- ^ Pillay (2012). Modern Medical Toxicology. Jaypee Brothers Publishers. p. 303. ISBN 9789350259658. Archived from the original on 2017-07-07.
- ^ Marx, John A. Marx (2014). "Cardiovascular Drugs". Rosen's emergency medicine : concepts and clinical practice (8th ed.). Philadelphia, PA: Elsevier/Saunders. pp. Chapter 152. ISBN 1455706051.
- ^ a b "Prescribing medicines in pregnancy database". Australian Government. 3 March 2014. Archived from the original on 8 April 2014. Retrieved 22 April 2014.
- ^ Medical Toxicology. Lippincott Williams & Wilkins. 2004. p. 684. ISBN 9780781728454. Archived from the original on 2017-07-07.
- ^ Carlsson, edited by Bo (1997). Technological systems and industrial dynamics. Dordrecht: Kluwer Academic. p. 106. ISBN 9780792399728. Archived from the original on 2017-03-03.
- ^ "WHO Model List of Essential Medicines" (PDF). World Health Organization. October 2013. Archived (PDF) from the original on 23 April 2014. Retrieved 22 April 2014.
- ^ "Top 100 Drugs for 2013 by Units Sold". Drugs.com. February 2014. Archived from the original on 22 March 2015. Retrieved 22 March 2015.
- ^ "Metoprolol". The American Society of Health-System Pharmacists. Archived from the original on 25 April 2011. Retrieved 3 April 2011.
- ^ MERIT-HF Study Group (1999). "Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)". Lancet. 353 (9169): 2001–2007. PMID 10376614. doi:10.1016/S0140-6736(99)04440-2.
- ^ Biffi, M.; Boriani, G.; Sabbatani, P.; Bronzetti, G.; Frabetti, L.; Zannoli, R.; Branzi, A.; Magnani, B. (Mar 1997). "Malignant vasovagal syncope: a randomised trial of metoprolol and clonidine.". Heart. 77 (3): 268–72. PMC 484696 . PMID 9093048. doi:10.1136/hrt.77.3.268.
- ^ Zhang Q, Jin H, Wang L, Chen J, Tang C, Du J (2008). "Randomized comparison of metoprolol versus conventional treatment in preventing recurrence of vasovagal syncope in children and adolescents". Medical Science Monitor. 14 (4): CR199–CR203. PMID 18376348. Archived from the original on 2012-05-17.
- ^ Geffner DL, Hershman JM (July 1992). "β-Adrenergic blockade for the treatment of hyperthyroidism". The American Journal of Medicine. 93 (1): 61–8. PMID 1352658. doi:10.1016/0002-9343(92)90681-Z.
- ^ Kühlkamp, V; Schirdewan, A; Stangl, K; Homberg, M; Ploch, M; Beck, OA (2000). "Use of metoprolol CR/XL to maintain sinus rhythm after conversion from persistent atrial fibrillation". J Am Coll Cardiol. 36 (1): 139–146. doi:10.1016/S0735-1097(00)00693-8. Archived from the original on 2014-02-25.
- ^ a b "Metoprolol". Drugs.com. Archived from the original on 2010-01-21.
- ^ Cruickshank JM (2010). "Beta-blockers and heart failure". Indian Heart Journal. 62 (2): 101–110. PMID 21180298.
- ^ a b c "Metoprolol (Oral Route) Precautions". Drug Information. Mayo Clinic. Archived from the original on 2009-04-16.
- ^ Page C, Hacket LP, Isbister GK (2009). "The use of high-dose insulin-glucose euglycemia in beta-blocker overdose: a case report". Journal of Medical Toxicology. 5 (3): 139–143. PMID 19655287. doi:10.1007/bf03161225.
- ^ Albers S, Elshoff JP, Völker C, Richter A, Läer S (2005). "HPLC quantification of metoprolol with solid-phase extraction for the drug monitoring of pediatric patients". Biomedical Chromatography. 19 (3): 202–207. PMID 15484221. doi:10.1002/bmc.436.
- ^ Baselt R (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 1023–1025.
- ^ Swaisland HC, Ranson M, Smith RP, Leadbetter J, Laight A, McKillop D, Wild MJ (2005). "Pharmacokinetic drug interactions of gefitinib with rifampicin, itraconazole and metoprolol". Clinical Pharmacokinetics. 44 (10): 1067–1081. PMID 16176119. doi:10.2165/00003088-200544100-00005.
- ^ Blake, CM.; Kharasch, ED.; Schwab, M.; Nagele, P. (Sep 2013). "A meta-analysis of CYP2D6 metabolizer phenotype and metoprolol pharmacokinetics.". Clin Pharmacol Ther. 94 (3): 394–9. PMC 3818912 . PMID 23665868. doi:10.1038/clpt.2013.96.
- ^ Cupp M (2009). "Alternatives for Metoprolol Succinate" (pdf). Pharmacist's Letter / Prescriber's Letter. 25 (250302). Retrieved 2012-07-06.
- ^ a b Suita, Kenji; Fujita, Takayuki; Hasegawa, Nozomi; Cai, Wenqian; Jin, Huiling; Hidaka, Yuko; Prajapati, Rajesh; Umemura, Masanari; Yokoyama, Utako (2015-07-23). "Norepinephrine-Induced Adrenergic Activation Strikingly Increased the Atrial Fibrillation Duration through β1- and α1-Adrenergic Receptor-Mediated Signaling in Mice". PLOS ONE. 10 (7): 1–13. ISSN 1932-6203. PMC 4512675 . PMID 26203906. doi:10.1371/journal.pone.0133664. Archived from the original on 2017-03-28.
External links
- U.S. National Library of Medicine: Drug Information Portal - Metoprolol
|
Beta blockers (C07)
|
| β, non-selective |
- Alprenolol
- Bopindolol
- Bupranolol
- Carteolol
- Cloranolol
- Mepindolol
- Nadolol
- Oxprenolol
- Penbutolol
- Pindolol/Iodopindolol
- Propranolol
- Sotalol
- Tertatolol
- Timolol
|
| β1-selective |
- Acebutolol
- Atenolol
- Betaxolol
- Bevantolol
- Bisoprolol
- Celiprolol
- Epanolol
- Esmolol
- Landiolol
- Metoprolol
- Nebivolol
- Practolol
- S-Atenolol
- Talinolol
|
| β2-selective |
|
| α1- + β-selective |
- Arotinolol
- Carvedilol
- Labetalol
|
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
|
