|Systematic (IUPAC) name|
|Licence data||US FDA:|
|Pregnancy cat.||C (AU) C (US)|
|Legal status||℞ Prescription only|
|Mol. mass||325.443 g/mol|
|(what is this?)|
Bisoprolol is a drug belonging to the group of beta blockers, a class of medicines used primarily in cardiovascular diseases. More specifically, it is a selective type β1 adrenergic receptor blocker. The U.S. Food and Drug Administration (FDA) approved an application by Duramed Pharmaceutical 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, Aurobino, and Unichem.
Bisoprolol is beneficial in treatment for: high blood pressure (hypertension), reduced blood flow to the heart (cardiac ischemia); congestive heart failure, 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. 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.
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 β1 adrenergic receptors (adrenoreceptors), which are mainly found in the heart muscle cells and heart conduction tissue (cardio specific) 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 lead to increased contractility and increased heart rate of the heart muscle and heart pacemaker respectively. 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.
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 but for preventive 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.
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. Bisoprolol, metoprolol, nebivolol, and (to a lesser extent) acebutolol, have less effect on the β2 (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.
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. 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.
Bisoprolol (Concor, Zebeta, Concore, Monocor) can be used to treat cardiovascular diseases such as hypertension, 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.
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. 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 it’s being administered.
Bisoprolol β1-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. 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.
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 in animal models has been shown to be cardioprotective.
Bisoprolol inhibits renin secretion by about 65% and tachycardia by about 30%.
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