CHAPTER 20

p-Blockers

257

TABLE 20-1 1Indications for the f5-Blocl<ers

Category

Drug

NONSELECTIVE

propranolol (Inderal)
nadolol (Corgard)
penbutolol (Levatol)
pindolol (Visken)
sotalol (Betapace, Betapace AF)

Hypertension

Angina

CHF

/
/

Arrhythmias

ISA

Other Uses

Migraineprophylaxis, essen

tialtremor, hypertrophic
subaortic stenosis, pheo-

chromocytoma, Graves'
disease. Ml prophylaxis

/
/

Glaucoma, migraine prophy

laxis, Ml prophylaxis

timolol (Blocadren)

Migraine prophylaxis
p,-SELECTIVE

atenolol (Tenormin)

metoprolol (Lopressor,
Toprol XL)

acebutolol (Sectral)
betaxolol (Kerlone)

/ (extended-

releaseonly)

Acute Ml, Ml prophylaxis

Acute Ml, Ml prophylaxis

Glaucoma

bisoprolol (Zebeta)
esmolol (Brevibloc) (IV

only)
a-p-BLOCKER

nebivolol (Bystolic)

labetalol (Normodyne,

/
/

Ml prophylaxis, acute Ml

Ml prophylaxis, acute Ml

Trandate)

carvedilol (Coreg)

Comparison of Adrenergic Receptors

TABLE 20-2

Receptor
a,

Site

Effect of Stimulation

Smooth muscle in blood

Vasoconstriction

vessels

0.2

Stomach, intestine

Decreased motility and tone

Kidney

Increased renin secretion

Liver

Gluconeogenesis

Smooth muscle in blood

Vasodilation

vessels

Pi

Cardiac

Increased rate and force of

contraction

P2

Kidney

Increased renin secretion

Bronchial, vascular, coro

naryarteriole, uterine

Vasodilation

smooth muscle, skeletal

muscle
Pancreas

Decreased secretion

Liver

Gluconeogenesis

P'blockers reduce the heart rate-blood pressure product dur

ing exercise, symptoms of angina or the ischemic threshold
during exercise are delayed or avoided.
CHF is perpetuated by an active renin-angiotensin sys
tem coupled with increased tone of the sympathetic ner
vous system; thus, decreasing catecholamine levels reduce

cardiac congestion and left ventricular hypertrophy (LVH).

|3-Blockers may increase Pi-Receptor sensitivity and restore
inotropic response. p2'P-6ceptors promote peripheral
vasodilation.

P-Blockers prevent arrhythmia by blocking abnormal

cardiac pacemaker potentials, decreasing myocardial oxygen
demand, prolonging ventricular filling time, and decreasing
microvascular damage of the myocardium.
Clinically significant differences between P-blockers
have been noted. These agents are classified by their
P-blocking selectivity (Pi- or P2-a [p-blocking ability]),
membrane-stabilizing activity (MSA), ISA, and pharmacokinetics. See Table 20-3 for characteristics of individual
agents.

metabolic (glycogenolytic, lipolytic), myocardial stimulant,

vasodilator, and bronchodilator actions of catecholamines,
and they suppress renin release (Table 20-2).

As a result of ^-blockade, cardiac output and heart rate

are decreased. Slowing of the AV conduction system pre
vents an increase in cardiac automaticity and prolongs the
refractory period. Decreased sympathetic peripheral out
flow blocks the release of renin (carteolol, labetalol, and

pindolol do not consistently inhibit renin release). BP

is lowered by the action of P-blockers in decreasing car
diac output, peripheral vascular resistance, venous return,
plasma volume, and renin release. The intrinsic sympathomimetic activity (ISA)-active |3-blockers do not reduce
renin release.

P-Blockers relieve the symptoms of angina by com

petitively inhibiting sympathetic stimulation of the heart,
thereby reducing both heart rate and contractility. Because

Selectivity (or cardioselectivity) refers to the ability of

the drug to preferentially block the Pi-receptors. Cardioselective P-blockers will inhibit Pi-receptors while producing
less inhibition of the P2-receptors that mediate bronchodi-

lation or peripheral vasodilation. However, cardioselectiv

ity is dose dependent, and substantial P2-blockade occurs
in patients with angina for whom higher doses are used.
Thus, the advantage of using Pi-selectivity to reduce bronchospasm and decrease peripheral resistance may be dimin
ished with a high-dose regimen. Most providers use selective
P-blockers. Cardioselectivity is a clinically important feature
of P-blockers.
Intrinsic sympathomimetic activity, or ISA, is another
characteristic of P-blockers. Also known as partial agonist
activity (PAA), ISA simultaneously blocks natural catechol
amine while only partially activating P-receptors. Therefore,
side effects such as bradycardia, bronchoconstriction, and
resting peripheral vascular resistance may be minimized. ISA