What Is Metoprolol?

Metoprolol is used to treat various types of hypertension (can be combined with diuretics and vasodilators) and angina pectoris. Intravenous injection is also effective for arrhythmias, especially supraventricular arrhythmias.

Drug type: Essential medicines
Drug name: Metoprolol

English name: Metoprolol
Chinese alias: Metoprolol; metoprolol; metoprolol
English alias: Lopresor; Betaloc; Seloken

Metoprolol Compounds

Metoprolol Basic Information

Chinese name

Chinese alias: (R)-(+)-Metoprolol; (±) -1-isopropylamino-3- [p- (2-methoxyethyl) phenoxy] -2-propanol; Doxanol; Medolol; Betaxol; Methoxyzol; Suclide; Metoprolol tartrate; Metaxol

English name: (2R) -1- [4- (2-methoxyethyl) phenoxy] -3- (propan-2-ylamino) propan-2-ol

English alias: (2R) -metoprolol; d-Metoprolol; (R) -metoprolol; (R) -1-isopropylamino-3- [4- (2-metoxyethyl) phenoxy] propan-2-ol; (+)-Metoprolol ; Metoprolol; MET; Lopreser; Seloken; Betaloc; Lopresor; Betaloc; Seloken

CAS number: 81024-43-3

Molecular formula: C ₁₅ H ₂₅ NO ₃

Structural formula:

Molecular weight: 267.36400

Exact mass: 267.18300

PSA: 50.72000

LogP: 2.00410

Metoprolol physical and chemical properties

Density: 1.033g / cm ³

Melting point: 39-42ºC

Boiling point: 398.6ºC at 760 mmHg

Flash point: 194.9ºC

Refractive index: 1.507

Storage conditions: -20ºC refrigerator in inert gas ^[1]

Its tartrate is commonly used as a white or off-white crystalline powder; it is odorless and bitter. The melting point is 120-124 ° C. Very soluble in water, soluble in ethanol or chloroform, slightly soluble in anhydrous ethanol, slightly soluble in acetone, almost insoluble in ether or benzene; soluble in glacial acetic acid.

Metoprolol Pharmacopoeia Standard

[Identification] (1) Take about 0.3g of this product, put it in a clean test tube, add 10ml of water to dissolve it, and add silver nitrate test solution in excess to form a white precipitate. Add ammonia test solution dropwise to dissolve the precipitate, and place the test tube in a water bath. When heated, the silver is free and attached to the inner wall of the tube to form a silver mirror. (2) Take this product and add ethanol to make a solution containing about 20 g per ml. According to ultraviolet-visible spectrophotometry (Appendix IV A), it has a maximum absorption at a wavelength of 224 nm. (3) Take an appropriate amount of this product, dissolve it with water, and then alkalize with ammonia test solution, extract with dichloromethane, and let it stand. Take an appropriate amount of dichloromethane solution, evaporate to dryness in a water bath, and place in a phosphorus pentoxide dryer. Let stand overnight and measure according to law. The infrared absorption spectrum of this product should be consistent with the control spectrum (spectrum set 685).

[Check] Take 1.0g of this product, add 10ml of water to dissolve it, and then measure it according to law (Appendix VI H). The pH value should be 6.0 7.0. Related substances (1) Take this product, add methanol to dissolve and quantitatively dilute to make a solution containing about 50mg per lml, as a test solution; take an appropriate amount of precise amount, and quantitatively dilute with methanol to make 0 per lml. .1 mg and 0.25 mg solutions were used as control solutions (1) and (2). According to the thin-layer chromatography (Appendix VB) test, measure 5 l of each of the above three solutions, point them on the same silica gel G thin-layer plate, and use methanol-ethyl acetate (10:90) as the developing agent (bottom of the chromatography tank). Place 2 small beakers containing a concentrated ammonia solution of 30% by volume of the developing agent and equilibrate for more than 1 hour in advance. After deployment, dry in air for 3 hours, then place in an iodine vapor cylinder for 15 hours, remove, and inspect immediately Except for the main spot and the origin, the color of the test solution, such as a significant impurity spot, must not be deeper than the main spot of the control solution (2), and the impurity spots deeper than the main spot of the control solution (1) should not be more than 1 Each. (2) Take an appropriate amount of this product, accurately weigh, dissolve and quantitatively dilute with mobile phase to make a solution containing 2mg per lml as the test solution; take an appropriate amount of precise amount, and make quantitative dilution with mobile phase to make each lml. A 10 g solution was used as a control solution. Test according to high performance liquid chromatography (Appendix VD). Use octadecylsilane-bonded tannin gum as filler; use acetate buffer solution (take 3.9 g of ammonium acetate and dissolve in 810 ml of water, add 2.0 ml of triethylamine, 10.0 ml of glacial acetic acid, 3.0 ml of phosphoric acid, and shake well ) -Acetonitrile (824: 146) is the mobile phase; the flow rate is 2 ml per minute; the column temperature is 30 ° C; the detection wavelength is 280 nm. In addition, take the metoprolol sparnate reference substance, add the mobile phase to dissolve and dilute it to make a solution containing 2mg per 1ml, place it in a quartz cup, and place it for 5 hours at a distance of 5cm from the UV lamp (254nm). System suitability test solution. Take 20l of the system suitability test solution and inject it into the liquid chromatograph. The retention time of metoprolol tartrate is about 7 minutes, and the relative retention time is about 0.3 at 4-[(2RS) -2-hydroxy-3-[( 1-isopropyl) amino] propoxy] benzaldehyde (impurity I) peak, the resolution of metoprolol tartrate and impurity I peak should be greater than 10.0. Take 20l of the control solution and inject it into the liquid chromatograph. Adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 10% of the full scale. The theoretical plate number is calculated to be not less than 3000 based on metoprolol tartrate. Then accurately measure 20 l each of the test solution and the control solution, and respectively inject them into the liquid chromatograph, and record the chromatogram to three times the peak retention time of the main component. If the chromatogram of the test solution has chromatographic peaks consistent with the retention time of impurity I, the peak area multiplied by the correction factor of 0.1 shall not be greater than 0.6 times (0.3%) the main peak area of the control solution; the peak area of other single impurities shall not be greater than The area of the main peak of the control solution is 0.6 times (0.3%); the sum of the areas of the impurity peaks (the area of the peak of the impurity multiplied by the correction factor of 0.1) must not be greater than the area of the main peak of the control solution (0.5%). Any chromatographic peak in the chromatogram of the test solution that is less than 0.1 times the main peak area of the control solution is ignored. Take this product after losing weight and dry it under reduced pressure at 60 to constant weight. The weight loss should not exceed 0.5% (Appendix L). Take 2.0g of this product and check it according to law (Appendix N). The remaining residue should not exceed 0.1%. The heavy metal shall be taken as the residue left under the burning residue, and shall be inspected in accordance with the law (Appendix H second method). The content of heavy metal shall not exceed 10 parts per million.

[Content determination] Take about 0.3g of this product, accurately weigh, add 20ml of glacial acetic acid, dissolve at a slight temperature, add 1 drop of crystal violet indicator solution, and titrate with perchloric acid titration solution (0.1mol / L) until the solution becomes pure Blue, and the results of the titration are corrected with a blank test. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 34.24mg of (C15H25 N03) 2 · C4H606.

[Category] Beta adrenergic blockers.

[Storage] shading and sealed.

Metoprolol Drug Description

Metoprolol dosage form

1. Tablets: 50mg, 100mg each;

2. Capsule: 50mg;

3. Sustained-release tablets: 100mg, 200mg;

4. Injection: 5mg.

Metoprolol pharmacological action

The effect of metoprolol is similar to that of atenolol, with selective blocking of 1 receptors and very weak blocking of 2 receptors. There is no intrinsic sympathomimetic activity and membrane stabilization. Elimination is mainly in the liver, little excretion of the original drug in urine, effective blood concentration of 252ng / ml. The absorption rate is 95%, the first-pass effect is high, reaching 50% to 60%, the plasma protein binding rate is 13%, the bioavailability is about 38%, and the half-life is 3.2 ± 0.2h.

Metoprolol pharmacokinetics

Oral absorption is rapid and complete, the absorption rate is> 90%, the blood concentration reaches 1.5 to 2 hours after oral administration, and the bioavailability is about 50%, the effective blood concentration is 0.05-0.1 g / ml, and the drug-plasma protein binding rate is about 12% It has a half-life of 3 to 4 hours, is lipophilic, and is mainly metabolized by the liver. Metoprolol is mainly excreted from the kidneys as a metabolite.

Metoprolol indication

It is mainly used for mild to moderate essential hypertension; it is also used for labor angina pectoris, class II prevention after myocardial infarction, and arrhythmia.

Metoprolol contraindications

Heart rate is lower than 45 beats per minute, to degree atrioventricular block, PR interval is greater than or equal to 0.24 seconds, systolic blood pressure is lower than 13.33kPa, and moderate to severe heart failure.

Metoprolol precautions

1. (1) history of allergies; (2) congestive heart failure; (3) first degree atrioventricular block; (4) diabetes; (5) emphysema or non-allergic bronchitis; (6) liver function Incompleteness; (7) Hypothyroidism; (8) Raynaud's syndrome or other peripheral vascular disease; (9) Renal dysfunction; (10) Pregnant and lactating women; (11) Patients under anesthesia or surgery.

2. Blood tests, blood pressure, heart function, liver function, kidney function should be checked or monitored before, after and during medication. Diabetics should check blood glucose regularly.

3. Individual differences are large, the dosage should be individualized.

4. At high doses, the beta 1 receptor of metoprolol gradually disappears. Patients with bronchospasm need to be used with caution, generally only a small amount, and timely addition of 2 receptor agonists.

5. Patients with no previous history of heart failure may show signs of heart failure during long-term use of metoprolol, and should be added with heart-strengthening drugs and / or diuretics, such as heart failure symptoms should be discontinued.

6. Intravenous administration can quickly control heart rate and myocardial contractility. Studies have shown that intravenous administration is better than oral administration within a few hours of the onset of myocardial infarction symptoms. After myocardial infarction, intravenous administration and then oral maintenance treatment are better than one method alone.

7. Opinions on whether to stop the drug before surgery are still inconsistent. After beta blockade, the heart's response to reflexive sympathetic stimulation is reduced, which increases the risk of general anesthesia and surgery. However, dobutamine or isoprenaline can be used. Adrenaline is reversed. Withdrawal can cause angina pectoris and / or high blood pressure rebound, which may be more dangerous than the cardiac depression caused by the surgery itself.

8. When applied to hyperthyroidism, some symptoms such as tachycardia can be masked. Sudden stoppage should be avoided when suspected of hyperthyroidism to avoid thyroid crisis.

9. Avoid sudden withdrawal. When metoprolol is withdrawn, the dose should be gradually reduced to avoid serious cardiovascular events, such as myocardial infarction, arrhythmia, and sudden death. Physical activity is an important cause of angina pectoris, so the amount of activity should be limited as much as possible during the period of discontinuation and 2 to 3 weeks after discontinuation.

10. Treatment of overdose: (1) give atropine or isoproterenol when bradycardia, install artificial pacemaker if necessary; (2) give lidocaine or phenytoin during ventricular premature beats; 3) Give oxygen during heart failure. Digitalis or diuretics; (4) infusion and booster drugs when hypotension; (5) diazepam or phenytoin sodium during convulsions; (6) isoproterenol adrenaline during bronchospasm.

Metoprolol adverse reactions

The heart is the same as atenolol, because the drug can pass the blood-cerebrospinal fluid barrier, and the concentration in the cerebrospinal fluid is about 70% of the blood concentration, which causes dizziness, headache, fatigue, insomnia, and dreams, and has little effect on blood sugar and blood lipids.

Metoprolol dosage

6.25 to 50 mg each time, 2 to 3 times a day, the dose can be started from a small dose according to the condition and needs, and then gradually increased.

Metoprolol interaction with other drugs

1. In combination with monoamine oxidase inhibitors, it can cause extreme hypotension and should be disabled.

2. Quinidine can reduce the clearance of metoprolol, resulting in bradycardia, fatigue, shortness of breath, etc. If it must be combined, the heart function should be closely monitored, and the dosage of the two drugs should be adjusted if necessary.

3. Propafenone can increase the concentration of metoprolol and cause a significant reduction in supine blood pressure. If it must be combined, carefully monitor heart function, especially blood pressure, and adjust metoprolol dosage if necessary.

4. Combined with amiodarone, obvious bradycardia and sinus arrest can occur.

5. Combination with dihydropyridine calcium channel blockers is effective in treating angina pectoris or hypertension, but it can also cause severe hypotension or decreased heart reserve. Cardiac function should be carefully monitored during combination, especially in patients with impaired left ventricular function, arrhythmia, or aortic stenosis.

6. Diltiazem can enhance the pharmacological effects of -blockers and is beneficial to patients with normal cardiac function. However, there have been reports of hypotension, left ventricular failure, and atrioventricular block after combined use. If combined, the patient's cardiac function should be closely monitored, especially in the elderly, left ventricular failure, aortic valve stenosis, and the use of both drugs.

7. Verapamil and metoprolol have direct negative muscle strength and negative conduction, which may cause hypotension, bradycardia, congestive heart failure, and conduction disorders. The risk increases with left ventricular dysfunction, aortic stenosis, or both doses. Cardiac function should be closely monitored when the two drugs are combined.

8. Combined with mibediril can cause hypotension, bradycardia, or decreased heart reserve. Mbetidil should be discontinued for 7 to 14 days before starting beta blocker therapy. If combined, cardiac function should be monitored, especially in elderly patients with decreased left ventricular function, decreased cardiac conduction, or aortic stenosis.

9. Hydrazine can increase the bioavailability of metoprolol, which is prone to occur when fasting. Hydrazine has no effect on metoprolol sustained-release preparations. If combined, they should be taken with meals or switched to a slow-release formulation.

10. Combined with phenylethylhydrazine, it can cause a decrease in heart rate. If combined use should be carefully monitored.

11. Combined with lisepine, the effects of the two are added together, -blocking effect is enhanced, bradycardia and hypotension may occur.

12. Combined with propoxyphenol, it can increase the risk of hypotension and bradycardia. Pay attention to monitoring when combined.

13. Combined with oloflex, it can cause hypotension or hypertension with bradycardia. Patients' blood pressure and heart rate should be closely monitored when combined.

14. Metoprolol can cause severe hypotension during fentanyl anesthesia.

15. Cimetidine may increase the plasma concentration of metoprolol. Heart function should be closely monitored when combined. If necessary, the dose should be adjusted.

16. Ciprofloxacin can increase the concentration of metoprolol, leading to hypotension and bradycardia. Combined use should monitor blood pressure and cardiac function.

17. Diphenhydramine, paroxetine, hydroxychloroquine, etc. can change the pharmacokinetics of metoprolol, enhance drug efficacy, and increase the risk of adverse reactions. If combined, metoprolol should be reduced and monitored for signs of metoprolol toxicity such as bradycardia and selective loss of heart.

18. Fluoxetine can cause increased metoprolol plasma concentration and increased toxicity, so you should pay attention to monitoring and reduce the dosage of metoprolol if necessary.

19. Ritonavir can increase blood concentration and toxicity of metoprolol. If combined, the amount of metoprolol should be reduced.

20. Fluvoxamine can inhibit the metabolism of metoprolol, resulting in bradycardia and / or hypotension. If combined, it is recommended that the starting dose of metoprolol should be small, carefully adjust the dose, and monitor heart rate and blood pressure.

21. Amfepramone can increase the blood concentration of metoprolol. The combination of the two should be cautious, and the starting dose should be small.

22. Angelica sinensis extract can inhibit the metabolism of metoprolol by liver cytochrome P450 enzymes. If used in combination, attention should be paid to monitoring blood pressure.

23. Hydroxychloroquine can inhibit the metabolism of metoprolol by the liver cytochrome P450 2D6 enzyme. If used in combination, attention should be paid to monitoring blood pressure.

24. Although there is no report on the interaction between benzprodil, flunarizine, lidofloxazine, golopamide, perhexiline, and metoprolol, all of these drugs can reduce myocardial contraction and reduce Slow atrioventricular node conduction leads to decreased blood pressure, bradycardia, or decreased heart reserve. Therefore, if it must be combined, cardiac function should be monitored, especially in patients with decreased left ventricular function, decreased cardiac conduction function, or aortic stenosis.

25. Although there have been no reports of the interaction between chlorpromazine, cloprothion or trifluoropromazine and metoprolol, the combination of phenothiazines and -blockers can enhance each other, causing Hypotension and phenothiazine poisoning. The effect of both drugs should be monitored when combined and the dose reduced if necessary.

26. Zileuton can cause a significant increase in propranolol concentration. Although there is currently no report on the interaction between Zileuton and Metoprolol, caution should be exercised in conjunction with close monitoring.

27. It can aggravate the first dose response of alpha blockers. In addition to prazosin, other alpha receptor blockers are rare, but they should still be used with metoprolol.

28. Metoprolol can increase the blood concentration of lidocaine. When combined, the blood concentration of lidocaine should be closely monitored and the dose adjusted accordingly.

29. Combination with digoxin can lead to prolonged atrioventricular conduction time, and metoprolol can increase the blood concentration of digoxin. Careful monitoring of the electrocardiogram and blood concentration of digoxin should be performed when combined, and the dose should be adjusted accordingly.

30. It can enhance the efficacy of non-depolarizing muscle relaxants, such as cyproteronine chloride and oladium ammonium, and prolong the action time.

31. When combined with epinephrine, it can cause hypertension and bradycardia. Although metoprolol is a cardiac-selective beta-blocker and has a lesser stress response to adrenaline, it should still be avoided. If combined, blood pressure should be carefully monitored.

32. In combination therapy with metoprolol and clonidine, the sudden withdrawal of clonidine may exacerbate hypertension. Therefore, in order to withdraw cola, we should first remove metoprolol, closely monitor blood pressure, and then gradually reduce clonidine in a few days. Caution should be taken when using Mosulidine in combination with sudden withdrawal of Mosulidine.

33. In combination with methyldopa, very few patients may have abnormal reactions to endogenous or exogenous catecholamines, such as hypertension, tachycardia, or arrhythmia.

34. Combination with non-steroidal anti-inflammatory drugs can cause blood pressure to rise. If combined, the patient's blood pressure should be monitored and the metoprolol dose adjusted accordingly.

35. Rifampicin and rifabutin can induce liver cytochromease, accelerate the metabolism of metoprolol, and reduce the efficacy. If combined, increase the dose of metoprolol.

36. Phenobarbital or pentobarbital can induce liver microsomal enzyme system, which can reduce blood concentration, bioavailability and efficacy of metoprolol. The efficacy should be monitored when necessary, and the dose should be adjusted if necessary, or a -blocker drug that does not rely on liver metabolism, such as atenolol and timolol, should be used.

37. Metoprolol can antagonize the bronchiectasis caused by inhalation of norepinephrine.

38. Beta-blockers can antagonize the effects of ritodrine, so the combination of metoprolol and ritodrine should be avoided.

39. Metoprolol can reduce the efficacy of isoprenaline or xanthine.

40. Abutamine has -receptor agonistic effect, and if metoprolol is used in combination, the effect is weakened. Therefore, metoprolol should be discontinued for at least 48 hours before the use of acetamidine.

41. Heart-selective beta-blockers are less likely to cause impaired glucose tolerance in patients with type 2 diabetes, but diabetic patients should still be aware of the combination of metoprolol and hypoglycemic agents.

42. Ephedra contains ephedrine and pseudoephedrine, which can reduce the efficacy of antihypertensive drugs. Patients with hypertension treated with metoprolol should avoid using ephedra-containing preparations.

43. Metoprolol and acenocoumarol, phenprocoumon, procainamide, acetylcholine, antacids, bromazepam, laurazepam, coleseran, isosorbide mononitrate, Nizatidine, pantoprazole, omeprazole, rizatriptan, and sevelamer did not interact significantly.

44. Eating can increase metoprolol concentration and the area under the curve.

Metoprolol poisoning

Metoprolol (Metoprolol, Metoprolol, Betaloc [1] [Question] Another name for Metoprolol, Methoxymolol) is a beta adrenal blocker, which is selected for beta1 receptors Stronger, so it has a lighter effect on increasing airway resistance, but it also has effects on 2 receptors in blood vessels and bronchial smooth muscle at higher doses, and is used to treat angina, hypertension and arrhythmias.

Oral 25 50mg, 2 / d, can increase to 100 150mg / d, intravenous injection for arrhythmia, start 5mg (1 2mg / min), repeat injection every 5min until it takes effect, generally total 10 ~ 15mg. Effective blood concentration is 0.05 0.1ng / ml. The oral LD50 of the mice was (2193.8 ± 166) mg / kg.

Clinical manifestation

See related content of propranolol:

Adverse reaction

Such as bradycardia, hypotension, dizziness, headache, dry mouth, gastrointestinal discomfort, nausea, lack of appetite, rash, etc.

2. Poisoning performance

(1) Cardiovascular system performance: Congestive heart failure, heart failure can occur suddenly or slowly, bradycardia, hypotension, and cardiac arrest.

(2) Respiratory system performance: bronchospasm, asthma, cough, dyspnea, and tidal breathing.

(3) Nervous system performance: burnout, weakness, insomnia or drowsiness, hearing impairment, paresthesia, etc.

(4) Digestive system performance: abdominal pain, diarrhea, bloating, constipation, etc.

(5) Hematological manifestations: thrombocytopenic purpura, agranulocytosis, and eosinophilia.

treatment

The main points of treatment for metoprolol poisoning are:

1. Discontinue the drug when there are adverse reactions or poisoning manifestations, lavage the stomach with lukewarm 0.45% saline, reduce diarrhea, and inject 10% glucose solution intravenously to promote the excretion of the drug from the body.

2. Bradycardia: intramuscular or intravenous injection of 0.5 to 1 mg of atropine; or slow intravenous infusion of 200 to 300 ml of 5% glucose solution with isoproterenol 0.5 to 1 mg. If it is ineffective, a pacemaker can be given.

3. Blood pressure drops given booster drugs.

4. Improve heart function, can use glucagon 0.5 ~ 1mg, intramuscular injection, subcutaneous injection or intravenous injection. Or 60% to 80ml of 50% glucose solution, intravenous injection.

5. Bronchial spasm, inhaling oxygen, giving aminophylline, scopolamine or isoproterenol.

6. Other symptomatic treatments ^[2] .

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