Nebivolol

Nebivolol belongs to the beta-blocker family. At doses of 10 mg or less, in people who metabolize it quickly, it selectively blocks the beta-1 adrenergic receptors, those found mainly on the heart. By occupying them, it slows the action of adrenaline and noradrenaline on the heart muscle: the heart beats more slowly and with less force, which lowers blood pressure. This selectivity for beta-1 receptors weakens as the dose rises.

Nebivolol stands out for a second mechanism, one that goes beyond simple beta-1 blockade. It produces an endothelium-dependent vasodilation, the endothelium being the inner lining of the vessels, by stimulating the L-arginine / nitric oxide pathway. The nitric oxide released in this way relaxes the muscle of the arteries, which widen and offer less resistance to blood flow. This dilation adds to the slowing of the heart to bring pressure down.

Nebivolol is indicated for the treatment of high blood pressure, to lower the pressure. Pressure that stays too high over time forces the heart to work against increased resistance and relentlessly strains the walls of the arteries. By slowing the heart and dilating the vessels, nebivolol reduces this double load. A systematic review with meta-analysis confirmed its efficacy in essential arterial hypertension.

The goal of treatment is not to relieve a symptom, since high blood pressure is rarely felt, but to keep pressure within a safer range over time. This is why it is taken daily, even on days when everything seems fine. The benefit builds through continuity, as the load placed on the heart and the arteries decreases day after day.

Nebivolol is taken once a day. The half-life of its active isomer, d-nebivolol, is about 12 hours in fast metabolizers and about 19 hours in slow metabolizers of CYP2D6, which is enough to cover the day with a single dose. Food does not change its absorption: it can be swallowed with or without a meal. Taking it at a set time simply helps to avoid forgetting it.

Nebivolol is processed by the liver, through glucuronidation and through hydroxylation via the CYP2D6 enzyme. People who metabolize CYP2D6 slowly show an exposure to d-nebivolol roughly ten times higher, which is part of the reason the dose is adjusted individually. A beta-blocker should not be stopped on one’s own initiative, nor changed from one day to the next: adjusting the dose is up to the prescriber, who proceeds in steps.

In placebo-controlled trials, headache is the most frequently reported effect: 9 % of people at 5 mg, compared with 6 % on placebo. Fatigue reaches up to 5 % at doses of 20 to 40 mg, compared with 1 % on placebo. Dizziness affects up to 4 % of people, compared with 2 %. These effects most often remain mild and appear mainly at the start of treatment or after a dose increase.

Digestive complaints are rarer: diarrhea up to 3 % compared with 2 %, nausea up to 3 % compared with 0 %. Insomnia affects 1 % of people compared with 0 % on placebo. Slowing of the heart, or bradycardia, occurs in about 1 % of patients at doses of 20 to 40 mg, compared with 0 % on placebo: this is the expected extension of the molecule’s action on heart rhythm, and not a side effect.

Because nebivolol depends on CYP2D6, any medicine that slows this enzyme increases its exposure. Fluoxetine, an antidepressant, multiplies the area under the curve eightfold and the peak concentration of d-nebivolol threefold. Quinidine, propafenone and paroxetine call for the same caution. It is therefore useful to report all of one’s treatment to the doctor and the pharmacist before adding a new molecule.

Beta-blockers can mask the early signs of low blood sugar, in particular the quickening of the heart, which matters above all in people with diabetes: monitoring blood glucose keeps its full value in this context. On the laboratory side, nebivolol has been associated with a rise in blood urea, uric acid and triglycerides, as well as a fall in HDL cholesterol and platelet count. These are the parameters that monitoring checks over the course of treatment.

The best-documented point of contact between this treatment and the plate concerns sleep. The synthesis of melatonin by the pineal gland is commanded by the beta-1 adrenergic receptors, the very ones that nebivolol occupies. As a result, beta-1 beta-blockers reduce the nighttime secretion of melatonin, the hormone that signals night to the body; atenolol, for example, suppresses this nighttime production. In hypertensive patients treated with a beta-blocker, a melatonin intake over three weeks improved sleep quality in a randomized controlled trial.

Food provides melatonin, but in tiny amounts, and the body makes most of it from tryptophan, an amino acid present in eggs, walnuts, seeds and legumes. A banana or a bowl of oats supplies this kind of raw material. When beta-1 receptor blockade lowers nighttime production, the plate alone does not close this gap, and this is where a targeted intake makes sense. On top of your treatment, never in its place.