|Trade names||Zebeta, Concor, others|
|Metabolism||50% liver, CYP2D6, CYP3A4|
|Biological half-life||10–12 hours|
|Chemical and physical data|
|Molar mass||325.443 g/mol|
|3D model (JSmol)|
Bisoprolol, marketed under the tradename Zebeta among others, is a medication most commonly used for heart diseases. This specifically includes high blood pressure, chest pain from not enough blood flow to the heart, and heart failure. It is taken by mouth.
Common side effects include headache, feeling tired, diarrhea, and swelling in the legs. More severe side effects include worsening asthma, blocking the ability to recognize low blood sugar, and worsening heart failure. There are concerns that use during pregnancy may be harmful to the baby. Bisoprolol is in the Beta blocker family of medications and is of the β1 selective type.
Bisoprolol was patented in 1976 and approved for medical use in 1986. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Bisoprolol is available as a generic medication. The wholesale cost in the developing world is about 2.98 to 4.94 USD per month. In the United States, as of 2015, it costs about 25 to 50 USD a month.
Bisoprolol is beneficial in treatment for high blood pressure (hypertension), reduced blood flow to the heart (cardiac ischemia); congestive heart failure, and preventive treatment before and primary treatment after heart attacks, decreasing the chances of recurrence. Bisoprolol targets hypertension (elevated blood pressure). In cardiac ischemia, the drug is used to reduce the activity of the heart muscle, so reduces oxygen and nutrient demand, and reduced blood supply can still transport sufficient amounts of oxygen and nutrients.
Bisoprolol can be used to treat cardiovascular diseases such as hypertension, coronary heart disease, arrhythmias, ischemic heart diseases, and myocardial infarction after the acute event. Patients with compensated congestive heart failure may be treated with bisoprolol as a comedication (usually with an ACE inhibitor, a diuretic, and a digitalis-glycosid, if indicated). In patients with congestive heart failure, it reduces the need for and the consumption of oxygen of the heart muscle. It is very important to start with low doses, as bisoprolol reduces also the muscular power of the heart, which is an undesired effect in congestive heart failure.[medical citation needed]
Overdose of bisoprolol leads to fatigue, hypotension, low blood sugar, bronchospasms, and bradycardia. Bronchospasms and low blood sugar because at high doses drug can be an antagonist for β2 adrenergic receptors located in lung and in liver. Bronchospasm is due to blockage in lungs of β2 receptor and low blood sugar because of decreased stimulation of glycogenolysis and gluconeogenesis in the liver via β2 receptor.
Beta-blockers should generally be avoided in people with a history of asthma or bronchospasm as they may make the disease worse. A beta 1 selective beta blocker like bisoprolol may be tried in those in whom other options are not available.
Mechanism of action
Bisoprolol is cardioprotective because it selectively and competitively blocks catecholamine (adrenalin) stimulation of β1 adrenergic receptors (adrenoreceptors), which are mainly found in the heart muscle cells and heart conduction tissue (cardiospecific), but also found in juxtaglomerular cells in the kidney. Normally, adrenalin and noradrenalin stimulation of the β1 adrenoreceptor activates a signalling cascade (Gs protein and cAMP) which ultimately leads to increased contractility and increased heart rate of the heart muscle and heart pacemaker, respectively. Bisoprolol competitively blocks the activation of this cascade, so decreases the adrenergic tone/stimulation of the heart muscle and pacemaker cells. Decreased adrenergic tone shows less contractility of heart muscle and lowered heart rate of pacemakers.
Pharmacology and biochemistry
Bisoprolol has both lipid- and water-soluble properties, making it a prime candidate over other β-blockers and even over other β1-blockers, being water-soluble, it has decreased incidence of central nervous system side effects (inability to diffuse into brain) compared to purely lipophilic compounds. Bisoprolol has an approximate half-life of 10–12 hours, and when ingested has nearly complete absorption into the blood stream. The high absorption is indicative of high bioavailability (approx. 90%). When being eliminated, the body evenly distributes it (50–50) between kidney excretion and liver biotransformation (then excreted). These factors make it a convenient once/day dosage when administered.
Bisoprolol β1-selectivity is especially important in comparison to other nonselective beta blockers. The effects of the drug are limited to areas containing β1 adrenoreceptors, which is mainly the heart and part of the kidney. Bisoprolol minimizes the side effects that might occur from administration of a nonspecific beta blocker where blockage of the other adrenoreceptors (β2, β3, α1, α2) occurs. The other receptors elicit a variety of responses in the body, and their blockage could cause a wide range of reactions, but β1 adrenoreceptors are cardiospecific for the most part, making bisoprolol ideal for treatment of cardiac events.
Bisoprolol has a higher degree of β1-selectivity compared to other β1-selective β-blockers such as atenolol, metoprolol, and betaxolol. However nebivolol is approximately 3.5 times more β1-selective.
Bisoprolol inhibits renin secretion by about 65% and tachycardia by about 30%.
Society and culture
Bisoprolol is available as a generic medication and has been approved by the FDA for manufacture by Teva, Mylan, Sandoz, Aurobino, and Unichem.
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