Bisoprolol, sold under the brand name Zebeta among others, is a

beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage cardiac arrhythmia, abnormal heart rhythms, and to protect the heart from a second myocardial infarction, heart attack after a first heart ...

medication used for

heart disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...

s. This includes

tachyarrhythmias Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (s ...

high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

, chest pain from not enough blood flow to the heart, and

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

. It is taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

. Common side effects include headache, feeling tired, diarrhea, and swelling in the legs. More severe side effects include worsening

asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, cou ...

, blocking the ability to recognize

low blood sugar Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...

, and worsening

. There are concerns that use during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

may be harmful to the baby. Bisoprolol is in the

family of medications and is of the β₁ selective type. Bisoprolol is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...

. Bisoprolol is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. In 2020, it was the 267th most commonly prescribed medication in the United States, with more than 1million prescriptions.

Medical uses

Bisoprolol is currently used for prevention of cardiovascular events following a heart attack in patients with risk factors for disease progression, in the management of congestive heart failure with reduced ejection fraction, and as a second-line agent for hypertension. Bisoprolol may be beneficial in the treatment of high blood pressure, but it is not recommended as a first-line anti-hypertensive agent without an accompanying

comorbid In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity (as if - several sicknesses together) - is the presence of one or more additional conditions often co-occurring (that is, concomitant or concurrent) with a primary ...

condition, for example, congestive heart failure. In

cardiac ischemia Coronary ischemia, myocardial ischemia, or cardiac ischemia,Potochny, Evy. "Cardiac Ischemia Symptoms." LiveStrong. Demand Media, 9 March 2010. Web. 6 Nov. 2010. is a medical term for a reduced blood flow in the coronary circulation through the ...

, the drug is used to reduce the activity of the heart muscle, thereby reducing its oxygen and nutrient demands and allowing its reduced blood supply to still transport sufficient amounts of oxygen and nutrients to meet its needs.

Side effects

An overdose of bisoprolol can lead to fatigue,

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...

hypoglycemia Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...

bronchospasm Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release (degranulation) of substances from mast cells or basophils under the influence of anaphylatoxins. It causes di ...

s, and

bradycardia Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...

. Bronchospasms and hypoglycemia occur because at high doses, the drug can be an antagonist for β₂ adrenergic receptors located in the lungs and liver. Bronchospasm occurs due to the blockage of β₂ receptors in the lungs. Hypoglycemia occurs due to decreased stimulation of

glycogenolysis Glycogenolysis is the breakdown of glycogen (n) to glucose-1-phosphate and glycogen (n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase. Mechanism The ...

and

gluconeogenesis Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrat ...

in the liver via β₂ receptors.

Cautions

Non-selective beta-blockers should be avoided in people with asthma or bronchospasm as they may cause exacerbations and worsening of symptoms. A β₁ selective beta-blocker like bisoprolol may be cautiously tried in those with controlled, mild-to-moderate asthma with cardiac comorbidities. A 2014 meta-analysis found that cardioselective beta-blockers may cause detrimental changes in lung function and partially blunts β₂-agonist response. However, a 2017 control study found no significant association with asthma exacerbations by dose and exposure duration while a 2020 clinical trial found bisoprolol being non-inferior to

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...

in bronchodilator response to

salbutamol Salbutamol, also known as albuterol and sold under the brand name Ventolin among others, is a medication that opens up the medium and large airways in the lungs. It is a short-acting β2 adrenergic receptor agonist which works by causing rel ...

Pharmacology

Mechanism of action

Bisoprolol is cardioprotective because it selectively and competitively blocks

catecholamine A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Catechol can be either a free molecule or a subst ...

(

adrenaline Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...

) 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 Juxtaglomerular cells (JG cells), also known as juxtaglomerular granular cells are cells in the kidney that synthesize, store, and secrete the enzyme renin. They are specialized smooth muscle cells mainly in the walls of the afferent arteriol ...

in the kidney. Normally, adrenaline and noradrenaline stimulation of the β₁ adrenoreceptor activates a

signalling cascade A biochemical cascade, also known as a signaling cascade or signaling pathway, is a series of chemical reactions that occur within a biological cell when initiated by a stimulus. This stimulus, known as a first messenger, acts on a receptor that ...

(

Gs protein The Gs alpha subunit (Gαs, Gsα) is a subunit of the heterotrimeric G protein Gs that stimulates the cAMP-dependent pathway by activating adenylyl cyclase. Gsα is a GTPase that functions as a cellular signaling protein. Gsα is the founding ...

and

cAMP Camp may refer to: Outdoor accommodation and recreation * Campsite or campground, a recreational outdoor sleeping and eating site * a temporary settlement for nomads * Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...

) which ultimately leads to increased

myocardial contractility Myocardial contractility represents the innate ability of the heart muscle (cardiac muscle or myocardium) to contract. The ability to produce changes in force during contraction result from incremental degrees of binding between different types of t ...

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.

β₁-selectivity

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, whilst β₁ adrenoceptor selective can help patients to avoid certain side-effects associated with non-selective beta-blocker activity at additional adrenoceptors (α₁ and β₂), it does not signify its superiority in treating beta-blocker indicated cardiac conditions such as heart failure but could prove beneficial to patients with specific comorbidities. Bisoprolol has a higher degree of β₁-selectivity compared to

atenolol Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Atenolol, however, does not seem to improve mortality in those with high blood pressure. Other uses include the prevention of mi ...

metoprolol Metoprolol, sold under the brand name Lopressor, among others, is a selective β1 receptor blocker medication. 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 a ...

and

betaxolol Betaxolol is a selective beta1 receptor blocker used in the treatment of hypertension and angina. Being selective for beta1 receptors, it typically has fewer systemic side effects than non-selective beta-blockers, for example, not causing bronc ...

. With a selectivity ranging from being 11-15 times more selective for β₁over β₂ However

nebivolol Nebivolol is a beta blocker used to treat high blood pressure and heart failure. As with other β-blockers, it is generally a less preferred treatment for high blood pressure. It may be used by itself or with other blood pressure medication. I ...

is approximately 3.5 times more β₁-selective.

Renin-angiotensin system

Bisoprolol inhibits

renin Renin (etymology and pronunciation), also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin–angiotensin–aldosterone system (RAAS)—also known as the r ...

secretion by about 65% and

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...

by about 30%.

Pharmacokinetics

After ingestion, bisoprolol is absorbed and has a high bioavailability of approximately 90% with plasma half-life of 10-12 hours. When being eliminated, the body evenly distributes it (50–50) between kidney excretion and liver biotransformation (then excreted). Bisoprolol has both lipid- and water-soluble properties. The plasma protein binding of bisoprolol is approximately 35%, the volume of distribution is 3.5 L/kg and the total clearance is approximately 15 L/h. Bisoprolol is eliminated from the body in two ways - 50% of the substance is converted in the liver to inactive metabolites, which are then excreted in the kidneys. The remaining 50% is eliminated unchanged via the kidneys. Since elimination is equal in liver and kidney, no dose adjustment is required in patients with hepatic or renal impairment. The pharmacokinetics of bisoprolol are linear and independent of age. In patients with chronic heart failure (NYHA stage III), the plasma level of bisoprolol is higher and the half-life is longer than in healthy subjects. At a daily dose of 10 mg, the steady-state peak plasma concentration is 64±21 ng/mL and the half-life is 17±5 hours.

History

Bisoprolol was

patent A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an enabling disclosure of the invention."A p ...

ed in 1976 and approved for medical use in 1986. It was approved for medical use in the United States in 1992.

Brand names

In India, it is sold under trade name Bisotab and is available in 2 strengths of 2.5 mg and 5 mg. In Italy, it is sold under trade name Congescor and is available in 6 strengths of 1.25 mg, 2.5 mg, 3.75 mg, 5 mg, 7.5 mg and 10 mg. In Germany and Eastern Europe bisoprolol is marketed as Bisoprolol-ratiopharm by

Ratiopharm Ratiopharm is a German pharmaceutical company that is Europe's leading generics brand. Ratiopharm was owned by Adolf Merckle and makes generic pharmaceuticals. They are based in Ulm, Germany, with products being distributed in over 35 countries ...

( Teva).

References

External links

* {{Authority control Beta blockers N-isopropyl-phenoxypropanolamines Peripherally selective drugs Merck brands World Health Organization essential medicines Wikipedia medicine articles ready to translate