Metoprolol

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Metoprolol
Metoprolol structure.svg
Systematic (IUPAC) name
(RS)-1-(Isopropylamino)-3-[4-(2-methoxyethyl)phenoxy]propan-2-ol
Clinical data
Pronunciation /mɛˈtoʊproʊlɑːl/, /mɛtoʊˈproʊlɑːl/
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
  • ℞ (Prescription only)
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 Number 51384-51-1 YesY
ATC code C07AB02 (WHO)
PubChem CID: 4171
IUPHAR/BPS 553
DrugBank DB00264 YesY
ChemSpider 4027 YesY
UNII GEB06NHM23 YesY
KEGG D02358 YesY
ChEBI CHEBI:6904 YesY
ChEMBL CHEMBL13 YesY
Chemical data
Formula C15H25NO3
Molecular mass 267.364 g/mol
  • O(c1ccc(cc1)CCOC)CC(O)CNC(C)C
  • 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 YesY
  • Key:IUBSYMUCCVWXPE-UHFFFAOYSA-N YesY
Physical data
Melting point 120 °C (248 °F)
  (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]

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]

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

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 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

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  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ 5.0 5.1 Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ 16.0 16.1 Lua error in package.lua at line 80: module 'strict' not found.
  17. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  18. ↑ 18.0 18.1 18.2 Lua error in package.lua at line 80: module 'strict' not found.
  19. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  20. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  21. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  22. ↑ .(Metox-Wockhardt)
  23. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  24. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  25. ↑ Lua error in package.lua at line 80: module 'strict' not found.

External links

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