Bisoprolol
Encyclopedia
Bisoprolol is a drug belonging to the group of beta blocker
s, a class of drugs used primarily in cardiovascular disease
s. More specifically, it is a selective type β1 adrenergic receptor
blocker. The FDA approved Duramed Pharmaceutical's application for Zebeta Oral Tablets (Bisoprolol Fumarate) as a new molecular entity on July 31, 1992. It has since been approved by the FDA for manufacture by Teva, Mylan, Sandoz, and Mutual Pharmaceutical Company.
Many beta-blockers are now available and in general they are all equally effective. There are, however, differences between them which may affect choice in treating particular diseases or individual patients.
Beta-blockers with a relatively short duration of action have to be given two or three times daily. Many of these are, however, available in modified-release formulations so that administration once daily is adequate for hypertension. For angina twice-daily treatment may sometimes be needed even with a modified-release formulation. Some beta-blockers such as atenolol, bisoprolol, carvedilol, celiprolol, and nadolol have an intrinsically longer duration of action and need to be given only once daily.
These are the favourable factors that are decreased and treat hypertension, heart attacks and ischemia. The decreases in contractility and heart rate are beneficial for hypertension because they reduce blood pressure[27] but for preventative measures for heart attacks and cardiac ischemia these decreases in heart rate and contraction decrease the hearts demand for oxygen and nutrients; primary treatment post heart attacks is to prevent recurrence of the infarction [27][30].
, coronary heart disease
, arrhythmias, ischemic heart diseases and treatment of myocardial infarction
after the acute event. Patients with compensated congestive heart failure
may be treated with Bisoprolol as a comedication (usually together 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.
The drug is also used to treat other conditions, including dysautonomia
, anxiety
and hyperthyroidism
(over active thyroid
gland).
Bisoprolol will give a positive result in doping tests.
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.
Beta blocker
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...
s, a class of drugs used primarily in cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
s. More specifically, it is a selective type β1 adrenergic receptor
Adrenergic receptor
The adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....
blocker. The FDA approved Duramed Pharmaceutical's application for Zebeta Oral Tablets (Bisoprolol Fumarate) as a new molecular entity on July 31, 1992. It has since been approved by the FDA for manufacture by Teva, Mylan, Sandoz, and Mutual Pharmaceutical Company.
Clinical use
Bisoprolol is beneficial in treatment for: high blood pressure (hypertension), reduced blood flow to the heart (cardiac ischemia); preventative treatment before and primary treatment after heart attacks decreasing the chances of recurrence. During hypertension there is an elevated blood pressure, which is what Bisoprolol targets. While in cardiac ischemia the drug is used to reduce the activity of the heart muscle and therefore reduce oxygen and nutrient demand, so reduced blood supply can still transport sufficient amounts of oxygen and nutrients. [24][27][30]Many beta-blockers are now available and in general they are all equally effective. There are, however, differences between them which may affect choice in treating particular diseases or individual patients.
Beta-blockers with a relatively short duration of action have to be given two or three times daily. Many of these are, however, available in modified-release formulations so that administration once daily is adequate for hypertension. For angina twice-daily treatment may sometimes be needed even with a modified-release formulation. Some beta-blockers such as atenolol, bisoprolol, carvedilol, celiprolol, and nadolol have an intrinsically longer duration of action and need to be given only once daily.
Mechanism of Action
Bisoprolol is cardioprotective because it selectively and competitively blocks catecholamine (adrenalin) stimulation of beta-1 adrenergic receptors (β1 adrenoreceptor) mainly found in the heart muscle cells and heart conduction tissue (cardio specific) but also found in juxtaglomerular cells in the kidney [24]. Normally adrenalin and noradrenalin stimulation of the β1 adrenoreceptor activates a signalling cascade (Gs protein and cAMP) which ultimately lead to increased contractility and increased heart rate of the heart muscle and heart pacemaker respectively [23]. Bisoprolol competitively blocks the activation of this cascade and therefore 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 heart pacemaker [25][28][29].These are the favourable factors that are decreased and treat hypertension, heart attacks and ischemia. The decreases in contractility and heart rate are beneficial for hypertension because they reduce blood pressure[27] but for preventative measures for heart attacks and cardiac ischemia these decreases in heart rate and contraction decrease the hearts demand for oxygen and nutrients; primary treatment post heart attacks is to prevent recurrence of the infarction [27][30].
Cautions
Beta-blockers can precipitate asthma and this effect can be dangerous. Beta-blockers should be avoided in patients with a history of asthma or bronchospasm; if there is no alternative, a cardioselective beta-blocker can be used with extreme caution under specialist supervision. Atenolol, bisoprolol, metoprolol, nebivolol, and (to a lesser extent) acebutolol, have less effect on the beta2 (bronchial) receptors and are, therefore, relatively cardioselective, but they are not cardiospecific. They have a lesser effect on airways resistance but are not free of this side effect.Side effects
Overdose of Bisoprolol leads to fatigue, hypotension[27], low blood sugar [29], bronchospasms and bradycardia [27]. Bronchospasms and low blood sugar because at high doses drug can be an antagonist for β2 adrenergic receptors located in lung and in liver. Bronchspasm 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.[24][26][27]Indications
Bisoprolol (Concor, Zebeta, Concore, Monocor) can be used to treat cardiovascular diseases such as hypertensionHypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, coronary heart disease
Coronary heart disease
Coronary artery disease is the end result of the accumulation of atheromatous plaques within the walls of the coronary arteries that supply the myocardium with oxygen and nutrients. It is sometimes also called coronary heart disease...
, arrhythmias, ischemic heart diseases and treatment of myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
after the acute event. Patients with compensated congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
may be treated with Bisoprolol as a comedication (usually together with an ACE inhibitor
ACE inhibitor
ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
, a diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
and a digitalis
Digitalis
Digitalis is a genus of about 20 species of herbaceous perennials, shrubs, and biennials that are commonly called foxgloves. This genus was traditionally placed in the figwort family Scrophulariaceae, but recent reviews of phylogenetic research have placed it in the much enlarged family...
-glycosid, if indicated). In patients with congestive heart failure, it reduces the need for and the consumption of oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
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.
The drug is also used to treat other conditions, including dysautonomia
Dysautonomia
Dysautonomia is a broad term that describes any disease or malfunction of the autonomic nervous system. This includes postural orthostatic tachycardia syndrome , inappropriate sinus tachycardia , vasovagal syncope, mitral valve prolapse dysautonomia, pure autonomic failure, neurocardiogenic...
, anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
and hyperthyroidism
Hyperthyroidism
Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...
(over active thyroid
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
gland).
Bisoprolol will give a positive result in doping tests.
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 will have decreased incidence of central nervous system side effects (inability to diffuse into brain) compared to purely lipophilic compounds [25][28]. Bisoprolol has an approximate half-life of 10-12 hours and when ingested has nearly complete absorption into the blood stream[28][29]. The high absorption is indicative of high bioavailability (approx. 90%)[28][29]. When being eliminated, the body evenly distributes it (50-50) between kidney excretion and liver biotransformation (then excreted) [25][28][29]. These factors make it a convenient once/day dosage when it’s being administered. [28][29]β1 Selectivity
Bisoprolol beta 1-selectivity is especially important in comparison to other non-selective beta blockers. The effects of the drug are limited to areas containing β1 adrenoreceptors which is mainly the heart and a little bit of the kidney [25][28]. Bisoprolol minimizes the side effects that might occur from administration of a non-specific 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 blockage of them could cause a wide range of reactions; but β1 adrenoreceptors are cardio specific for the most part, making Bisoprolol ideal for treatment of cardiac events [25][29].Bisoprolol has a higher degree of β1-selectivity compared to other β1-selective β-blockers such as atenolol, metoprolol
Metoprolol
Metoprolol is a selective β1 receptor blocker used in treatment of several diseases of the cardiovascular system, especially hypertension. The active substance metoprolol is employed either as metoprolol succinate or metoprolol tartrate...
and betaxolol
Betaxolol
Betaxolol is a selective beta1 receptor blocker used in the treatment of hypertension and glaucoma. Being selective for beta1 receptors, it typically has fewer systemic side effects than non-selective beta-blockers, for example, not causing bronchospasm as timolol may...
. However Nebivolol
Nebivolol
Nebivolol is a β1 receptor blocker with nitric oxide-potentiating vasodilatory effect used in treatment of hypertension and, in Europe, also for left ventricular failure...
is approximately 3.5 times more β1-selective.