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 nebivolol's 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. Controversies Pharmacology of side-effects Several studies have suggested that nebivolol has reduced typical beta-blocker-related side effects, such as fatigue, clinical depression, bradycardia, or impotence. However, according to the FDABystolic is associated with a number of serious risks. Bystolic is contraindicated in patients with severe bradycardia, heart block greater than first degree, cardiogenic shock, decompensated cardiac