For this reason, beta blockers that selectively block β1 adrenergic receptors (termed cardioselective or β1-selective beta blockers) produce fewer adverse effects (for instance, bronchoconstriction) than those drugs that non-selectively block both β1 and β2 receptors. In a laboratory experiment conducted on biopsied heart tissue, nebivolol proved to be the most β1-selective of the β-blockers tested, being approximately 3.5 times more β1-selective than bisoprolol. However, the drugs receptor selectivity in humans is more complex and depends on the drug dose and the genetic profile of the patient taking the medication. The drug is highly cardioselective at 5 mg. In addition, at doses above 10 mg, nebivolol loses its cardioselectivity and blocks both β1 and β2 receptors, while the recommended starting dose of nebivolol is 5 mg, sufficient control of blood pressure may require doses up to 40 mg. Furthermore, nebivolol is also not cardioselective when taken by patients with a genetic makeup that makes them "poor metabolizers" of nebivolol (and other drugs) or with CYP2D6 inhibitors. As many as 1 in 10 Caucasian people and even more black people are poor CYP2D6 metabolizers and therefore might benefit less from nebivolols cardioselectivity although currently there are no directly comparable studies.Nebivolol while selectively blocking beta(1) receptor acts as a beta(3)-agonist. β3 receptors are found in the gallbladder, urinary bladder, and in brown adipose tissue. Their role in gallbladder physiology is unknown, but they are thought to play a role in lipolysis and thermogenesis in brown fat.
In the urinary bladder it is thought to cause relaxation of the bladder and prevention of urination.Due to enzymatic inhibition, fluvoxamine increases the exposure to nebivolol and its active hydroxylated metabolite (4-OH-nebivolol) in healthy volunteers. Vasodilator action
Nebivolol is unique as a beta-blocker. Unlike carvedilol, it has a nitric oxide (NO)-potentiating, vasodilatory effect via stimulation of β3 receptors. Along with labetalol, celiprolol and carvedilol, it is one of four beta blockers to cause dilation of blood vessels in addition to effects on the heart. Antihypertensive effect
Nebivolol lowers blood pressure (BP) by reducing peripheral vascular resistance, and significantly increases stroke volume with preservation of cardiac output. The net hemodynamic effect of nebivolol is the result of a balance between the depressant effects of beta-blockade and an action that maintains cardiac output. Antihypertensive responses were significantly higher with nebivolol than with placebo in trials enrolling patient groups considered representative of the U.S. hypertensive population, in black people, and in those receiving concurrent treatment with other antihypertensive drugs. Pharmacokinetics
Nebivolol plasma protein binding is approximately 98%, mostly to albumin and its half-life of low doses is 12 hours in extensive CYP2D6 metabolizers and 19 hours in poor metabolizers. Contraindications
Severe bradycardia
Heart block greater than first degree
Patients with cardiogenic shock
Decompensated cardiac failure
Sick sinus syndrome (unless a permanent pacemaker is in place)
Patients with severe hepatic impairment (Child-Pugh class B)
Patients who are hypersensitive to any component of this product. Side effects
Side effects might include headache, tiredness, dizziness, lightheadedness, reduced blood flow to extremities, bradycardia.