Bisoprolol, sold under the brand names Bisotab, Concor, Corbis and Zebeta among others, is a

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

which is selective for the beta-1 receptor and used for

cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...

s, including

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 ...

high blood pressure Hypertension, also known as high blood pressure, 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 itself. It is, however, a major ri ...

angina Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typically the result of parti ...

, and

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

. It is taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

. Common side effects include

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

, feeling tired,

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

, and swelling in the legs. More severe side effects include worsening

asthma Asthma is a common 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 wh ...

, blocking the ability to recognize

low blood sugar Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes 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 tria ...

, and worsening

. There are concerns that use during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

may be harmful to the baby. 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 sufficiency of disclosure, enabling discl ...

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

and 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 2022, it was the 249th most commonly prescribed medication in the United States, with more than 1million prescriptions.

Medical uses

Bisoprolol is 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 antihypertensive agent. It can be an adjunct to first-line antihypertensive agents in patients with accompanying comorbidities, for example, congestive heart failure, where selected beta blockers can be added in patients who remain mildly to moderately symptomatic despite appropriate doses of an angiotensin-converting-enzyme inhibitor. 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 abnormally reduced blood flow in the coronary circulation thro ...

, 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, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

hypoglycemia Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes 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 tria ...

bronchospasm Bronchospasm or a bronchial spasm is a sudden bronchoconstriction, 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 anaphylat ...

s, and

bradycardia Bradycardia, also called bradyarrhythmia, is a resting heart rate under 60 beats per minute (BPM). While bradycardia can result from various pathological processes, it is commonly a physiological response to cardiovascular conditioning or due ...

. 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. Mechanis ...

and

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

in the liver via β₂ receptors. There have been no reported cases of clinically evident drug-induced liver injury associated with bisoprolol.

Cautions

Non-selective beta-blockers should be avoided in people with asthma or bronchospasm as they may cause exacerbations and worsening of symptoms. β₁ selective beta-blockers like bisoprolol have not been shown to cause an increase in asthma exacerbations, and may be cautiously tried in those with controlled, mild-to-moderate asthma with cardiac comorbidities. A 2014 meta-analysis found that unlike non-selective beta-blockers, β₁ selective beta-blockers (bisoprolol) showed only a small impact on lung function, with patients remaining responsive 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 that causes relaxation of ...

(β₂ -agonist) rescue therapy and endorses the use of bisoprolol in select patients with controlled asthma. This was supported by a 2020 clinical trial where bisoprolol had no significant impact on bronchodilation post salbutamol administration.

Pharmacology

Mechanism of action

Bisoprolol is cardioprotective because it selectively and competitively blocks

catecholamine A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, 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. Cate ...

(

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 a ...

) 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 cell 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 arteri ...

s 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 GS may stand for: Businesses and organizations * Goldman Sachs, one of the world's largest global investment banks * Global Star Software, a former Canadian video game publisher * GS (Swedish union), a trade union in Sweden * GS Group, a Korea ...

and

cAMP Camp may refer to: Areas of confinement, imprisonment, or for execution * Concentration camp, an internment camp for political prisoners or politically targeted demographics, such as members of national or minority ethnic groups * Extermination ...

) which ultimately leads to increased

myocardial contractility Myocardial contractility represents the innate ability of the heart muscle ( cardiac muscle or myocardium) to contract. It is the maximum attainable value for the force of contraction of a given heart. The ability to produce changes in force during ...

and increased heart rate of the heart muscle and

heart pacemaker A pacemaker, also known as an artificial cardiac pacemaker, is an implanted medical device that generates electrical pulses delivered by electrodes to one or more of the chambers of the heart. Each pulse causes the targeted chamber(s) to co ...

, 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 are 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 angina, heart-associated chest pain. Although used to treat high blood pressure, it does not seem to improve mortality rate, mortality in those with the condi ...

metoprolol Metoprolol, sold under the brand name Lopressor among others, is a medication used to treat angina, high blood pressure and a number of conditions involving an abnormally fast heart rate. It is also used to prevent further heart problems afte ...

and

betaxolol Betaxolol is a beta blocker used in the treatment of hypertension and angina. It acts as a selective β1-adrenergic receptor antagonist. The drug was patented in 1975 and approved for medical use in 1983. Medical uses Hypertension Betaxol ...

. With a selectivity ranging from being 11 to 15 times more selective for β₁ over 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. ...

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 reni ...

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 ...

by about 30%.

Pharmacokinetics

After ingestion, bisoprolol is absorbed and has a high

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

of approximately 90% with a plasma half-life of 10–12 hours. Typically, half the circulating bisoprolol is

metabolized Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

by the liver, the rest passing unchanged through the kidneys before elimination; less than 2% may be

excreted Excretion is elimination of metabolic waste, which is an essential process in all organisms. In vertebrates, this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific ...

in the

feces Feces (also known as faeces American and British English spelling differences#ae and oe, or fæces; : faex) are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the ...

. Bisoprolol is soluble in both lipids and water. It is classified as a beta blocker with moderate

lipophilicity Lipophilicity (from Greek λίπος "fat" and φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are called lipophilic (translated ...

and hence intermediate potential for crossing the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

. This in turn may result in fewer effects in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

as well as a lower risk of

neuropsychiatric Neuropsychiatry is a branch of medicine that deals with psychiatry as it relates to neurology, in an effort to understand and attribute behavior to the interaction of neurobiology and social psychology factors. Within neuropsychiatry, the mind i ...

side effects than highly lipophilic beta blockers like

propranolol Propranolol is a medication of the beta blocker class. It is used to treat hypertension, high blood pressure, some types of cardiac dysrhythmia, irregular heart rate, thyrotoxicosis, capillary hemangiomas, akathisia, performance anxiety, and ...

but greater such effects than beta blockers with low lipophilicity like

. 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, the plasma level of bisoprolol is higher and the half-life is longer than in healthy subjects when compared across studies. There is a lack of evidence directly comparing bisoprolol pharmacokinetics between healthy subjects and chronic heart failure subjects.

References

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