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|Metabolism||50% Hepatic, CYP2D6, CYP3A4|
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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.
It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.
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.
Beta-blockers with a relatively short duration of action must be given two or three times daily. Many of these are, however, available in modified-release formulations so 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 intrinsically longer durations of action and must be given only once daily.
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.
Beta-blockers can precipitate asthma and this effect can be dangerous. They should be avoided in patients with a history of asthma or bronchospasm; if no alternative is available, 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 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.
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.
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 heart's demand for oxygen and nutrients; primary treatment after heart attacks is to prevent recurrence of the infarction.
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 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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