Metoprolol

From Wikipedia, the free encyclopedia
  (Redirected from Toprol)
Jump to: navigation, search
Metoprolol
Metoprolol structure.svg
Systematic (IUPAC) name
(RS)-1-(Isopropylamino)-3-[4-(2-methoxyethyl)phenoxy]propan-2-ol
Clinical data
Trade names Lopressor, Toprol-xl
AHFS/Drugs.com monograph
MedlinePlus a682864
Licence data US FDA:link
Pregnancy cat. C (AU) C (US)
Legal status Prescription only
Routes Oral, IV
Pharmacokinetic data
Bioavailability 12%
Metabolism Hepatic via CYP2D6, CYP3A4
Half-life 3-7 hours
Excretion Renal
Identifiers
CAS number 51384-51-1 YesY
ATC code C07AB02
PubChem CID 4171
IUPHAR ligand 553
DrugBank DB00264
ChemSpider 4027 YesY
UNII GEB06NHM23 YesY
KEGG D02358 YesY
ChEBI CHEBI:6904 YesY
ChEMBL CHEMBL13 YesY
Chemical data
Formula C15H25NO3 
Mol. mass 267.364 g/mol
Physical data
Melt. point 120 °C (248 °F)
 YesY (what is this?)  (verify)

Metoprolol (/mɛˈtprlɑːl/, /mɛtˈprlɑːl/) is a selective β1 receptor blocker used in treatment of several diseases of the cardiovascular system, especially hypertension. 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.[1]

Medical uses[edit]

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.[2]

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[edit]

Side-effects, especially with higher dosages, include the following: 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.[7] 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.[8]

Serious side-effects that are advised to be reported immediately include, but are not limited to, 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. Other highly unlikely symptoms include easy bruising or bleeding, persistent sore throat or fever, yellowing skin or eyes, stomach pain, dark urine, and persistent nausea. Symptoms of an allergic reaction include: rash, itching, swelling, and severe dizziness. Taking it with alcohol might cause mild body rashes and therefore is not recommended.[7]

Precautions[edit]

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.[9]

This medicine may cause changes in blood sugar levels or cover up signs of low blood sugar, such as a rapid pulse rate.[9]

This medicine may cause some people to become less alert than they are normally, making it dangerous for them to drive, use machines, or do other things.[9]

Overdosage[edit]

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 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.[10][11][12]


Physical properties[edit]

Metoprolol has a very low melting point, tartrate around 120°C, succinate around 136°C. 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.(Metox-Wockhardt)

Metabolism[edit]

Metoprolol undergoes a-hydroxylation and O-demethylation as a substrate of the cytochrome liver enzymes CYP2D6 [13][14] and a small percentage by CYP3A4.

Pharmacology[edit]

  • Selective
  • Moderately lipophilic
  • Without intrinsic sympathomimetic activity (ISA)
  • 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

Chemistry[edit]

Metoprolol, 1-(iso-propylamino)-3-[4′(2-methoxyethyl)phenoxy]-2-propanol, is synthesized by reacting 4-(2-methoxyethyl)phenol with epichlorohydrin in the presence of a base, isolating 1,2-epoxy-3-[4′(2-methoxyethyl)phenoxy]propane, the subsequent reaction with isopropylamine, gives an opening of the epoxide ring and leads to the formation of metoprolol.

Metoprolol synthesis.png
  • P. A. E. Carlsson, S. A. I. Carlsson, H. R. Corrodi, L. Ek, B. A. H. Ablad, A. E. Brandstrom, U.S. Patent 3,873,600 (1975).
  • A. E. Brandstrom, P. A. E. Carlsson, S. A. I. Carlsson, H. R. Corrodi, L. Ek, DE 2106209  (1971).

Brand names[edit]

Cortel M combination of Amlodipine and Metoprolol with 25 and 50 mg claim for Metoproplol(Corona - India)

Toprol XL 50 mg

It is marketed under the brand name Lopressor by Novartis, and Toprol-XL (in the USA); Selokeen (in the Netherlands); as Minax by Alphapharm (in Australia), 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 as Corvitol by Berlin-Chemie AG (in Germany). In India, this drug is available under the brand names of Met-XL, Metolar and Starpress,Restopress. A number of generic products are available as well.

References[edit]

  1. ^ Cupp M (2009). "Alternatives for Metoprolol Succinate" (pdf). Pharmacist's Letter / Prescriber's Letter 25 (250302). Retrieved 2012-07-06. 
  2. ^ "Metoprolol". The American Society of Health-System Pharmacists. Retrieved 3 April 2011. 
  3. ^ 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. 
  4. ^ 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. PMID 9093048. 
  5. ^ 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. 
  6. ^ 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
  7. ^ a b "Metoprolol". Drugs.com. 
  8. ^ Cruickshank JM (2010). "Beta-blockers and heart failure". Indian Heart Journal 62 (2): 101–110. PMID 21180298. 
  9. ^ a b c "Metoprolol (Oral Route) Precautions". Drug Information. Mayo Clinic. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ Baselt R (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 1023–1025. 
  13. ^ 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. 
  14. ^ 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. PMID 23665868. 

External links[edit]