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

drugs have additional cardiovascular properties (especially vasodilation)
that seem unrelated to β blockade. Table 12–3 summarizes
important pharmacological and pharmacokinetic properties of β
receptor antagonists.
Cardiovascular System. The major therapeutic effects
of β receptor antagonists are on the cardiovascular
system. It is important to distinguish these effects in
normal subjects from those in subjects with cardiovascular
disease such as hypertension or myocardial
ischemia.
Since catecholamines have positive chronotropic
and inotropic actions, β receptor antagonists slow the
heart rate and decrease myocardial contractility. When
tonic stimulation of β receptors is low, this effect is correspondingly
modest. However, when the sympathetic
nervous system is activated, as during exercise or stress,
β receptor antagonists attenuate the expected rise in
heart rate. Short-term administration of β receptor
antagonists such as propranolol decreases cardiac output;
peripheral resistance increases in proportion to
maintain blood pressure as a result of blockade of vascular
β 2
receptors and compensatory reflexes, such as
increased sympathetic nervous system activity, leading
to activation of vascular α receptors. However, with
long-term use of β antagonists, total peripheral resistance
returns to initial values (Mimran and Ducailar,
1988) or decreases in patients with hypertension (Man
in’t Veld et al., 1988). With β antagonists that also are α 1
receptor antagonists, such as labetalol, carvedilol, and
bucindolol, cardiac output is maintained with a greater
fall in peripheral resistance. This also is seen with β
receptor antagonists that are direct vasodilators.
β Receptor antagonists have significant effects on cardiac
rhythm and automaticity. Although it had been thought that these
effects were due exclusively to blockade of β 1
receptors, β 2
receptors
likely also regulate heart rate in humans (Altschuld and
Table 12–3
Pharmacological/Pharmacokinetic Properties of β Adrenergic Receptor Blocking Agents
MEMBRANE INTRINSIC EXTENT OF ORAL PROTEIN
STABILIZING AGONIST LIPID ABSORPTION AVAI- PLASMA BINDING
DRUG ACTIVITY ACTIVITY SOLUBILITY (%) LABILITY (%) t 1/2
(HOURS) (%)
Classical non-selective β blockers: First generation
Nadolol 0 0 Low 30 30-50 20-24 30
Penbutolol 0 + High ~100 ~100 ~5 80-98
Pindolol + +++ Low >95 ~100 3-4 40
Propranolol ++ 0 High <90 30 3-5 90
Timolol 0 0 Low to 90 75 4 <10
moderate
β 1
-Selective β blockers: Second generation
Acebutolol + + Low 90 20-60 3-4 26
Atenolol 0 0 Low 90 50-60 6-7 6-16
Bisoprolol 0 0 Low ≤90 80 9-12 ~30
Esmolol 0 0 Low NA NA 0.15 55
Metoprolol + * 0 Moderate ~100 40-50 3-7 12
Non-selective β blockers with additional actions: Third generation
Carteolol 0 ++ Low 85 85 6 23-30
Carvedilol ++ 0 Moderate >90 ~30 7-10 98
Labetalol + + Low >90 ~33 3-4 ~50
β 1
-selective β blockers with additional actions: Third generation
Betaxolol + 0 Moderate >90 ~80 15 50
Celiprolol 0 + Low ~74 30-70 5 4-5
Nebivolol 0 0 Low NA NA 11-30
*Detectable only at doses much greater than required for β blockade.