DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

330 and possibly papaverine-like relaxant effects on smooth
muscle (including bronchial). It also has been reported
to antagonize peripheral α 2
adrenergic receptor activity,
to promote NO production, and to inhibit oxidative
stress. There is evidence for intrinsic sympathomimetic
activity at the β 2
receptor. Celiprolol is devoid of
membrane-stabilizing activity. Weak α 2
antagonistic
properties are present, but are not considered clinically
significant at therapeutic doses (Toda, 2003).
SECTION II
NEUROPHARMACOLOGY
Celiprolol reduces heart rate and blood pressure and can
increase the functional refractory period of the atrioventricular node.
Oral bioavailability ranges from 30-70%, and peak plasma levels are
seen at 2-4 hours. It is largely unmetabolized and is excreted
unchanged in the urine and feces. Celiprolol does not undergo firstpass
metabolism. The predominant mode of excretion is renal.
Celiprolol is used for treatment of hypertension and angina (Felix
et al., 2001; Witchitz et al., 2000).
Nebivolol
Nebivolol (BYSTOLIC) is a third-generation selective
β 1
receptor antagonist with endothelial NO-mediated
vasodilator activity. In addition, nebivolol has antioxidant
properties and neutral to favorable effects on both
carbohydrate and lipid metabolism. Nebivolol lowers
blood pressure by reducing peripheral vascular resistance
and significantly increases stroke volume with
preservation of cardiac output and maintains systemic
flow and blood flow to target organs. Nebivolol generally
does not negatively affect serum lipids and may
increase insulin sensitivity. These benefits are also
observed in the presence of metabolic syndrome, which
is often present in hypertensive patients (Gielen et al.,
2006; Ignarro, 2008). Nebivolol has been approved for
treatment of hypertension.
Nebivolol is administered as the racemate containing equal
amounts of the d and l-enantiomers. The d-isomer is the active β
blocking component; the l-isomer is responsible for enhancing production
of NO. Nebivolol is devoid of intrinsic sympathomimetic
effects as well as membrane stabilizing activity and α 1
receptor
blocking properties. It is lipophilic, and concomitant administration
of chlorthalidone, hydrochlorothiazide, theophylline, or
digoxin with nebivolol may reduce its extent of absorption. The
NO-dependent vasodilating action of nebivolol and its high β 1
adrenergic
receptor selectivity likely contribute to the drug’s efficacy and
improved tolerability (e.g., less fatigue and sexual dysfunction) as an
antihypertensive agent (deBoer et al., 2007; Gupta and Wright, 2008;
Moen and Wagstaff, 2006; Rosei and Rizzoni, 2007). Metabolism
occurs via CYP2D6, and the influence of polymorphisms in the
CYP2D6 gene on the bioavailability and duration of nebivolol’s
actions is being evaluated (Lefebvre et al., 2006), as is the influence
of plasma concentration of receptor selectivity.
Other β Adrenergic Receptor Antagonists. There are numerous
β adrenergic receptor antagonists on the market as ophthalmologic
preparations for the treatment of glaucoma or other causes of high
blood pressure inside the eye (Chapter 64). These include carteolol
(OCUPRESS, others), metipranolol (OPTIPRANOLOL), nipradilol (HYPADIL;
not available in the U.S.), levobunolol (BETAGAN, LIQUIFILM, others),
betaxolol (BETOPTIC, others), and timolol (TIMOPTIC, others) (Henness
et al., 2007). The use of β adrenergic receptor antagonists in glaucoma
is contraindicated in patients with asthma, COPD, sympathomatic
sinus bradycardia, and cardiogenic shock.
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