Lecture 9 Adrenoceptor blockers: alpha and beta blockers

Adrenoceptor Blockers
( Adrenergic Antagonists)
lecture 9

 Alpha- and beta-adrenoceptor-blocking agents
are divided into primary subgroups on the basis
of their receptor selectivity.
 All of these agents are pharmacologic
antagonists or partial agonists.
 Because α and β blockers differ markedly in their
effects and clinical applications, these drugs are
considered separately in the following
discussion.

ALPHA-BLOCKING DRUGS
Classification
 Subdivisions of the α blockers are based on selective affinity for α1 versus
α2 receptors or a lack thereof.
 Other features used to classify the α-blocking drugs are their reversibility
and duration of action.
 Irreversible, long-acting—Phenoxybenzamine is the prototypical long-
acting, irreversible α blocker. It is only slightly α1-selective.
 Reversible, shorter-acting—Phentolamine is a competitive, reversible
blocking agent that does not distinguish between α1 and α2 receptors.
 Alpha1-selective—Prazosin is a highly selective, reversible pharmacologic
α1 blocker. Doxazosin, terazosin, and tamsulosin are similar drugs.
 Alpha2-selective— Yohimbine and rauwolscine are α2-selective
competitive pharmacologic antagonists.
 They are used primarily in research applications.

Mechanism of Action
 Phenoxybenzamine binds covalently to the α
receptor, thereby producing an irreversible
(insurmountable) blockade.
 The other agents are competitive antagonists, and
their effects can be surmounted by increased
concentrations of agonist.
 This difference may be important in the treatment
of pheochromocytoma because a massive release of
catecholamines from the tumor may overcome a
reversible blockade.

Clinical Uses
 1. Nonselective α blockers—Nonselective α blockers
have limited clinical applications.
 The best-documented application is in the presurgical
management of pheochromocytoma.
 Such patients may have severe hypertension and
reduced blood volume, which should be corrected
before subjecting the patient to the stress of surgery.
 Phenoxybenzamine is usually used during this
preparatory phase; phentolamine is sometimes used
during surgery.

 2. Selective α blockers—Prazosin, doxazosin, and terazosin
are used in hypertension .
 These α1 blockers, tamsulosin, and silodosin are also used to
reduce urinary hesitancy and prevent urinary retention in
men with benign prostatic hyperplasia.
Toxicity
 The most important toxicities of the α blockers are simple
extensions of their α-blocking effects.
 The main manifestations are orthostatic hypotension and, in
the case of the nonselective agents, marked reflex
tachycardia.
 Tachycardia is less common and less severe with α1-
selective blockers.

BETA-BLOCKING DRUGS
A. Classification, Subgroups, and Mechanisms
 All of the β blockers used clinically are
competitive pharmacologic antagonists.
 Propranolol is the prototype.
 Drugs in this group are usually classified into
subgroups on the basis of β1 selectivity, partial
agonist activity, local anesthetic action, and lipid-
solubility.

1. Receptor selectivity
 Beta1-receptor selectivity (β1 block > β2 block) is a
property of acebutolol, atenolol, esmolol, metoprolol,
and several other β blockers. This property may be an
advantage when treating patients with asthma.
 Nadolol, propranolol, and timolol are typical
nonselective β blockers.
 Labetalol and carvedilol have combined α- and β-
blocking actions.
 Nebivolol has vasodilating action in addition to β1-
selective antagonism.

2. Partial agonist activity
 Partial agonist activity (“intrinsic
sympathomimetic activity”) may be an
advantage in treating patients with asthma
because these drugs (eg, pindolol, acebutolol)—
at least in theory—are less likely to cause
bronchospasm.
 In contrast, full antagonists such as propranolol
are more likely to cause severe bronchospasm in
patients with airway disease.

Effects and Clinical Uses
 Most of the organ-level effects of β blockers are
predictable from blockade of the β-receptor–
mediated effects of sympathetic discharge.
 The cardiovascular applications of β blockers—
especially in hypertension, angina, and
arrhythmias—are extremely important.

 Treatment of chronic (not acute) heart failure has
become an important application of β blockers.
Several large clinical trials have shown that some,
but not all, β blockers can reduce morbidity and
mortality when used properly in heart failure .
 Labetalol, carvedilol, and metoprolol appear to be
beneficial in this application.
 Pheochromocytoma is sometimes treated with
combined α- and β-blocking agents (eg, labetalol),
especially if the tumor is producing large amounts
of epinephrine as well as norepinephrine.

Toxicity
 Cardiovascular adverse effects, which are extensions of
the β blockade induced by these agents, include
bradycardia, atrioventricular blockade, and heart
failure. Patients with airway disease may suffer severe
asthma attacks.
 Beta blockers have been shown experimentally to reduce
insulin secretion, but this does not appear to be a
clinically important effect.
 However, premonitory symptoms of hypoglycemia from
insulin overdosage (tachycardia, tremor, and anxiety)
may be masked by β blockers

Lecture 9 Adrenoceptor blockers: alpha and beta blockers

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