Metoprolol

• (±) -1 - ( isopropylamino ) -3 - [ 4 - (2 -methoxyethyl) - phenoxy] propan- 2-ol
• Latin: Metoprololum

• 37350-58-6
• 56392-17-7 ( tartrate 2:1)
• 80274-67-5 ( fumarate 2:1)
• 98418-47-4 ( succinate 2:1)

C07AB02

β -adrenergic receptor blocker

Selective blockade of β1 - receptors

121-124 ° C ( tartrate)

• 3470 mg · kg -1 ( LD50, rat, oral)
• 2090 mg · kg -1 ( LD50, Mouse, oral, tartrate )

Template: Infobox chemical / molecular formula search available

Metoprolol is a drug from the group of selective β1 - adrenergic receptor ( beta-blockers ) and is used to treat high blood pressure, coronary heart disease, use of cardiac arrhythmias and acute treatment of myocardial infarction. Another field of application is the migraine prophylaxis.

• 2.1 Mechanism of action ( pharmacodynamics )
• 2.2 Absorption and distribution in the body ( pharmacokinetics )

• 3.1 Chemical Information
• 3.2 dosage forms
• 3.3 Market importance

Clinical information

Areas of application (indications )

Metoprolol can be used in the treatment of heart attack, high blood pressure, coronary heart disease, heart failure and certain cardiac arrhythmias. In addition, metoprolol is used in migraine patients for seizure prophylaxis, if certain criteria are met.

Contraindications ( contraindications)

Metoprolol is contraindicated in congestive heart failure (NYHA IV), atrioventricular block second or third degree, bradycardia ( resting heart rate less than 50 beats per minute at baseline ), hypotension ( systolic blood pressure less than 90 mmHg) and bronchial hyperresponsiveness ( inter alia about be applied in conjunction with bronchial asthma). In patients with peripheral circulatory disturbances of the amplification is possible complaints.

Interactions with other drugs

Intravenous administration of metoprolol in patients already receiving therapy with calcium antagonists ( verapamil and diltiazem on ) or other antiarrhythmic drugs (such as disopyramide ) may lead to severe bradycardia arrhythmia and is therefore contraindicated; as well as the iv administration of the above calcium antagonists and antiarrhythmic therapy with metoprolol ( except Intensive Care Medicine ).

Use during pregnancy and lactation

Metoprolol should be used during pregnancy and lactation only under strict medical supervision. In animal models (mouse and rat) there was evidence of a reduction in the placenta and consequently fetal growth disorders. Also, the risk of childhood cardiac arrhythmias can not be excluded.

Special populations (diabetes, kidney disease )

With simultaneous use of metoprolol and insulin or oral hypoglycemic agents whose effect can be enhanced or extended, which increases the risk of hypoglycemia. At the same warning signs of hypoglycaemia ( tachycardia and tremor ) are disguised or mitigated. Therefore, regular blood sugar checks are required in diabetic patients under treatment with metoprolol.

Adverse effects (side effects)

In addition to occasional hypersensitivity reactions related side effects such as ringing in the ears and dizziness may be observed through the reduction of blood pressure. More rarely occur on central nervous changes ( fatigue, hallucinations), bronchospasm, potency and Harnentleerungsstörungen. The ability to actively participate in road traffic, use machines or work without safe stop can be affected by metoprolol. Especially at the beginning of treatment, dose increase or additional alcohol consumption is to be expected with a change of reaction. In predisposed persons can (anaphylactic shock) under beta-blocker therapy reactions to allergens more severe to anaphylactic reactions. MAOIs prevent the breakdown of metoprolol in the body and thus lead to its enrichment. In addition, metoprolol enhances the effect glucose-lowering drugs such as insulin and sulfonylureas. In the application of glucose-lowering agents metoprolol may mask the warning symptoms, in particular tremor and tachycardia. Metoprolol strengthened further the effects of other antihypertensive drugs ( indication of the severe drops in blood pressure with the use of β - blockers with calcium antagonists of the verapamil and diltiazem type). Also effective reinforcing effects with other heart rhythm affecting drugs are known. Beta-blockers can activate psoriasis in individual cases.

Overdose

The degree of poisoning depends on the applied amount of substance and is expressed in the form of severe falls in blood pressure, low heart rate to cardiac arrest with corresponding functional failures of the institutions. An overdose requires intensive medical treatment and supervision.

Pharmacological properties

Mechanism of action ( pharmacodynamics )

Metoprolol blocked β - adrenergic receptors, notably β1 -adrenoceptors, mainly in the excitement of education and conduction tissue of the heart ( sinus node, atria, AV node, ventricular muscle ) and are located in the coronary arteries. This reduces the metoprolol conduction velocity, the impact frequency and force of contraction of the heart. β2 -adrenoceptors are not in heart tissue, but, on the bronchial muscle located vessels and other organs such as the bladder, liver and muscles, and can be blocked by metoprolol little or only at a higher dose. It follows that metoprolol may be used more in patients with chronic respiratory diseases (such as with asthma ) or with peripheral circulatory disorders as β - blockers, which block both non-selective β1 - and β2 -adrenoceptors. From the distribution of receptors is also the spectrum of side effects can be partly explained.

Metoprolol stimulates the β -adrenoceptors not ( no intrinsic sympathomimetic activity, ISA) and has only weak membrane-stabilizing properties. The relative potency of metoprolol to propranolol is 1

Uptake and distribution in the body ( pharmacokinetics )

Metoprolol is taken after oral administration in the gastrointestinal tract almost completely ( about 95 %) and mainly metabolized by oxidation in the liver by the CYP2D6 isoenzyme. Two of the three major metabolites also show weak beta -blocking properties, but are not clinically relevant. In cirrhosis of the liver can be expected of unchanged metoprolol because of the reduced metabolic rate then with increased plasma levels.

Due to the high first- pass effect about 50 % of the original dose is systemically available. Peak plasma levels are reached after 1.5-2 hours. The plasma protein binding is 12% and the relative volume of distribution was 5.6 l / kg. Metoprolol and its metabolites are eliminated renally to about 95 %. The plasma half-life is 3-5 hours. After prolonged use the Metoprololeinnahme must not abruptly interrupted or the medication should be discontinued completely. The dose should be reduced slowly ( tapering off treatment ) to avoid excessive cardiovascular reactions.

Other Information

Chemical information

Virtually all β -blockers have structural similarities. This includes Propanolaminseitenkette with isopropyl or tertiary butyl substituents on the nitrogen. The aliphatic hydroxyl group is essential for the beta- blocking effect.

Metoprolol is chiral, the active stereoisomer ( eutomer ) is the ( S) form of metoprolol. Is used medicinally, the racemate, the enantiomers of drugs usually have different pharmacological properties and effects.

Dosage forms

The active substance metoprolol is offered as metoprolol succinate (salt of succinic acid ) than metoprolol tartrate ( tartaric acid salt ) or metoprolol (salt of fumaric acid ) in the form of tablets or prolonged-release tablets in different strengths; either as a single agent or in combination with the diuretic hydrochlorothiazide. Also a preparation for intravenous administration of 5 mg metoprolol tartrate per 5 ml solution for injection is available.

The sustained-release formulations are characterized in part by a special release kinetics from: the drug is released at a constant rate, which should lead to more uniform plasma levels. This is made possible by modern Retardierungstechnologien as the Osmotic Release Oral System ( OROS ) or multiple unit pellet system ( MUPS ). These dosage forms are ( zero-order kinetics zero order kinetics, ) characterized by additions such as name ZOK, NOK, or ZOT Zero.

Market significance

With around 900 million average daily doses of metoprolol was in 2012, the beta blocker most commonly used in Germany. In order Metoprolol is the leading representatives of the selective β1 - adrenergic receptor. The regulation of these increased by almost 50 % over the last 10 years. The non-selective substances, however, are declining.