Bisoprolol fumarate

Description

Bisoprolol fumarate is a β1-selective adrenergic blocker useful in the treatment of essential hypertension.

Originator

E. Merck (W. Germany)

The Uses of Bisoprolol fumarate

Bisoprolol fumarate is the active ingredient in bisoprolol, a drug that belongs to a group of beta-blockers. These drugs work by affecting the body's response to certain nerve impulses, particularly heart impulses. As a result, bisoprolol slows down the heart rate, allowing the heart to pump blood around the body more efficiently. At the same time, it reduces the amount of blood required by the heart and its consumption of oxygen. Bisoprolol fumarate is used to treat heart pain (ischaemic heart disease, angina pectoris) caused by high blood pressure and impaired perfusion of the coronary blood vessels.

The Uses of Bisoprolol fumarate

Labeled Bisoprolol, intended for use as an internal standard for the quantification of Bisoprolol by GC- or LC-mass spectrometry.

What are the applications of Application

(±)-Bisoprolol hemifumarate is a selective β1-AR antagonist

Manufacturing Process

A solution of 10 g of 1-(p-2-isopropoxyethoxymethylphenoxy)-3-isopropylideneamino-propan-2-ol [obtainable by reacting 1-(p-2- isopropoxyethoxymethylphenoxy)-2,3-epoxy propane with ammonia to give 1- (p-2-isopropoxyethoxymethylphenoxy)-3-amino-propan-2-ol and subsequently reacting this with acetone] in 250 ml of ethanol was hydrogenated on 0.5 g of Raney nickel at 25°C under 1 atmosphere of pressure until 1 equivalent of H2 had been absorbed. The mixture was filtered and the filtrate evaporated to give 1-(p-2-iso-propoxyethoxymethyl-phenoxy)-3-isopropylamino-propan-2-ol, fumarate, m.p. 100°C (after addition of equimolecular quantity of fumaric acid).

brand name

Zebeta (Duramed);CONCOR.

Therapeutic Function

Beta-adrenergic blocker

Biological Activity

A selective β 1 -adrenergic antagonist. Has a K d of 2-3 nM at the β 1 receptor and a β 1 / β 2 selectivity of approximately 100-fold.

Biochem/physiol Actions

Bisoprolol hemifumarate is useful in oral formulations due to its high bioavailability. It also shows long elimination half-life.

Clinical Use

Beta-1 adrenoceptor blocker:

Hypertension

Angina

Adjunctive treatment for heart failure

Drug interactions

Potentially hazardous interactions with other drugs
Anaesthetics: enhanced hypotensive effect. Analgesics: NSAIDs antagonise hypotensive effect. Anti-arrhythmics: increased risk of myocardial depression and bradycardia; increased risk of bradycardia, myocardial depression and AV block with amiodarone; increased risk of myocardial depression and bradycardia with flecainide. Antibacterials: concentration reduced by rifampicin. Antidepressants: enhanced hypotensive effect with MAOIs.
Antihypertensives; enhanced hypotensive effect; increased risk of withdrawal hypertension with clonidine; increased risk of first dose hypotensive effect with post-synaptic alpha-blockers such as prazosin.
Antimalarials: increased risk of bradycardia with mefloquine.
Antipsychotics enhanced hypotensive effect with phenothiazines.
Calcium-channel blockers: increased risk of bradycardia and AV block with diltiazem; hypotension and heart failure possible with nifedipine and nisoldipine; asystole, severe hypotension and heart failure with verapamil.
Cytotoxics: possible increased risk of bradycardia with crizotinib.
Diuretics: enhanced hypotensive effect.
Fingolimod: possibly increased risk of bradycardia.
Moxisylyte: possible severe postural hypotension.
Sympathomimetics: severe hypertension with adrenaline and noradrenaline, and possibly with dobutamine.

Metabolism

Bisoprolol is excreted from the body by two routes. 50% is metabolised by the liver to inactive metabolites which are then excreted by the kidneys. The remaining 50% is excreted by the kidneys in an unmetabolised form.

Side Effects

Common side effects of Bisoprolol fumarate include: tiredness, feeling weak (in patients with chronic heart failure), dizziness, headache, feeling cold or numbness in the hands or feet, low blood pressure, stomach or intestinal problems such as nausea, vomiting, diarrhoea or constipation. They are usually slight and usually go away within 1 to 2 weeks of starting treatment. Uncommon or rare side effects include: sleep disorders, depression, dizziness when standing, breathing problems in people with asthma or chronic lung disease, muscle weakness, muscle spasms, hearing problems, allergic runny nose, liver problems, impaired erection, fainting and severe allergic reactions.