Metoprolol
|
| Systematic (IUPAC) name |
|
(RS)-1-(Isopropylamino)-3-[4-(2-methoxyethyl)phenoxy]propan-2-ol
|
| Clinical data |
| Pronunciation |
, |
| Trade names |
Lopressor, Metolar XR |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a682864 |
| Licence data |
US FDA:link |
Pregnancy
category |
- AU: C
- US: C (Risk not ruled out)
|
| Legal status |
|
Routes of
administration |
Oral, IV |
| Pharmacokinetic data |
| Bioavailability |
50%[1] |
| Protein binding |
12% |
| Metabolism |
Liver via CYP2D6, CYP3A4 |
| Biological half-life |
3-7 hours |
| Excretion |
Kidney |
| Identifiers |
| CAS Registry Number |
51384-51-1 Y |
| ATC code |
C07AB02 |
| PubChem |
CID: 4171 |
| IUPHAR/BPS |
553 |
| DrugBank |
DB00264 Y |
| ChemSpider |
4027 Y |
| UNII |
GEB06NHM23 Y |
| KEGG |
D02358 Y |
| ChEBI |
CHEBI:6904 Y |
| ChEMBL |
CHEMBL13 Y |
| Chemical data |
| Formula |
C15H25NO3 |
| Molecular mass |
267.364 g/mol |
SMILES
-
O(c1ccc(cc1)CCOC)CC(O)CNC(C)C
|
InChI
-
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
-
Key:IUBSYMUCCVWXPE-UHFFFAOYSA-N Y
|
| Physical data |
| Melting point |
120 °C (248 °F) |
| Y (what is this?) (verify) |
Metoprolol, marketed under the tradename Lopressor among others, is a selective β1 receptor blocker medication.[2] 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. It is also used to prevent further heart problems after myocardial infarction and to prevent headaches in those with migraines.[2]
It comes in formulations that can be taken by mouth or given intravenously. The medication is often taken twice a day. There is an extended release formulation that is once per day. Metoprolol may be combined with hydrochlorothiazide in a single tablet.[2]
Common side effects include trouble sleeping, feeling tired, feeling faint, and abdominal discomfort.[2] Large doses may cause serious toxicity.[3][4] Risk in pregnancy has not been ruled out.[2][5] It appears to be safe in breastfeeding.[6] Greater care is required with use in those with liver problems or asthma.[2] If stopped this should be done slowly to decrease the risk of further health problems.[2]
Metoprolol was first made in 1969.[7] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[8] It is available as a generic drug.[2] In 2013, metoprolol was the 19th most prescribed medication in the United States.[9]
Contents
- 1 Medical uses
- 2 Adverse effects
- 2.1 Precautions
- 2.2 Overdosage
- 3 Pregnancy and lactation
- 4 Physical properties
- 5 Metabolism
- 6 Pharmacology
- 7 Brand names
- 8 References
- 9 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.[10]
- Treatment of heart failure[11]
- Vasovagal syncope[12][13]
- Adjunct in treatment of hyperthyroidism[14]
- 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)[15]
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.[16] 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.[17]
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.[16]
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.[18]
This medicine may cause changes in blood sugar levels or cover up signs of low blood sugar, such as a rapid pulse rate.[18] It also may cause some people to become less alert than they are normally, making it dangerous for them to drive or use machines.[18]
Overdosage
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.[19][20][21]
Pregnancy and lactation
It is pregnancy category C in the United States and category C in Australia, meaning evidence of harm is possible.[2][5]
Physical properties
Metoprolol has a very low melting point, the tartrate's is around 120 °C (248 °F), and the succinate's around 136 °C (277 °F). 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.[22]
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 and the succinate is an extended-release formulation.[23]
Metabolism
Metoprolol undergoes a-hydroxylation and O-demethylation as a substrate of the cytochrome liver enzymes CYP2D6[24][25] and a small percentage by CYP3A4.
Pharmacology
- Selective
- Moderately lipophilic
- Without intrinsic sympathomimetic activity
- With weak membrane stabilizing activity
- Short half-life, therefore must be taken at least twice daily or as a slow-release preparation
- Decreases heart rate, contractility, and cardiac output, therefore decreasing blood pressure
- Metabolized in the liver to inactive metabolite
Brand names
It is marketed under the brand name Lopressor by Novartis, and Toprol-XL (in the USA); Selokeen (in the Netherlands); as Minax by Alphapharm and Metrol by Arrow Pharmaceuticals (in Australia), as Betaloc by AstraZeneca, as Bloxan by Krka (company) (in Slovenia), as Neobloc by Unipharm (in Israel), Presolol by Hemofarm (in Serbia), and Corvitol by Berlin-Chemie AG (in Germany). In India, this drug is available under the brand names Met-XL, Metolar, Starpress, and Restopress. A number of generic products are available, as well.
References
- ^ "Metolar 25/50 (metoprolol tartrate) tablet" (PDF). FDA. Retrieved 5 May 2015.
- ^ a b c d e f g h i "Metoprolol". The American Society of Health-System Pharmacists. Retrieved Apr 21, 2014.
- ^ Pillay (2012). Modern Medical Toxicology. Jaypee Brothers Publishers. p. 303. ISBN 9789350259658.
- ^ 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. Retrieved 22 April 2014.
- ^ Medical Toxicology. Lippincott Williams & Wilkins. 2004. p. 684. ISBN 9780781728454.
- ^ Carlsson, edited by Bo (1997). Technological systems and industrial dynamics. Dordrecht: Kluwer Academic. p. 106. ISBN 9780792399728.
- ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- ^ "Top 100 Drugs for 2013 by Units Sold". http://www.drugs.com/. 2014-02. Retrieved 22 March 2015.
- ^ "Metoprolol". The American Society of Health-System Pharmacists. 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. doi:10.1016/S0140-6736(99)04440-2. PMID 10376614.
- ^ 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. doi:10.1136/hrt.77.3.268. PMC 484696. PMID 9093048.
- ^ 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.
- ^ Geffner DL, Hershman JM (July 1992). "β-Adrenergic blockade for the treatment of hyperthyroidism". The American Journal of Medicine 93 (1): 61–8. doi:10.1016/0002-9343(92)90681-Z. PMID 1352658.
- ^ 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.
- ^ a b "Metoprolol". Drugs.com.
- ^ 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.
- ^ 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. doi:10.1007/bf03161225. PMID 19655287.
- ^ 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. doi:10.1002/bmc.436. PMID 15484221.
- ^ Baselt R (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 1023–1025.
- ^ .(Metox-Wockhardt)
- ^ Cupp M (2009). "Alternatives for Metoprolol Succinate" (pdf). Pharmacist's Letter / Prescriber's Letter 25 (250302). Retrieved 2012-07-06.
- ^ 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. doi:10.2165/00003088-200544100-00005. PMID 16176119.
- ^ 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. doi:10.1038/clpt.2013.96. PMC 3818912. PMID 23665868.
External links
- AstraZeneca's page for Toprol-XL
- Novartis's page for Lopressor (PDF)
- 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
- Propranolol
- Sotalol
- Tertatolol
- Timolol
|
|
| β1-selective |
- Acebutolol
- Atenolol
- Betaxolol
- Bevantolol
- Bisoprolol
- Celiprolol
- Epanolol
- Esmolol
- Metoprolol
- Nebivolol
- Practolol
- S-Atenolol
- Talinolol
|
|
| β2-selective |
|
|
| α1- + β-selective |
|
|
-
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
|
|
|
Index of the circulatory system
|
|
| Description |
- Anatomy
- Arteries
- head and neck
- arms
- chest
- abdomen
- legs
- Veins
- head and neck
- arms
- chest
- abdomen and pelvis
- legs
- Development
- Cells
- Physiology
|
|
| Disease |
- Congenital
- Neoplasms and cancer
- Lymphatic vessels
- Injury
- Vasculitis
- Other
- Symptoms and signs
|
|
| Treatment |
- Procedures
- Drugs
- beta blockers
- channel blockers
- diuretics
- nonsympatholytic vasodilatory antihypertensives
- peripheral vasodilators
- renin–angiotensin system
- sympatholytic antihypertensives
- vasoprotectives
|
|
|
