Chapter 18
Adrenergic Antagonists
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Adrenergic Antagonists
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Cause direct blockade of adrenergic
receptors
With one exception, all produce reversible
(competitive) blockade
Most adrenergic antagonists are more
selective than the adrenergic agonists.
Two major groups
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Alpha-adrenergic blocking agents
Beta-adrenergic blocking agents
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Adrenergic Antagonists
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Alpha-adrenergic antagonists I: therapeutic
and adverse response to alpha blockade
Alpha-adrenergic antagonists II: properties of
individual alpha blockers
Beta-adrenergic antagonists I: therapeutic
and adverse responses to beta blockade
Beta-adrenergic antagonists II: properties of
individual beta blockers
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Therapeutic Applications of
Alpha Blockade
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Essential hypertension
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Lowers blood pressure by blocking alpha1
receptors on arterioles and veins, causing
vasodilation
Reversal of toxicity from alpha1 agonists
Benign prostatic hyperplasia

Reduced contraction of smooth muscle in the
bladder neck and prostatic capsule
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Therapeutic Applications of
Alpha Blockade
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Pheochromocytoma
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Catecholamine-secreting tumor
Usually located in adrenal medulla
Principal cause of hypertension is usually
activation of alpha1 receptors, but beta1 receptors
can also contribute
Treatment: best option is surgery
• Inoperable tumor: alpha1 antagonists suppress
hypertension
• Surgery: before surgery, manipulation of tumor can
cause massive catecholamine release
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Therapeutic Applications of
Alpha Blockade
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Raynaud’s disease
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Peripheral vascular disorder
Vasospasms in the toes and fingers
Suppress symptoms by preventing alphamediated vasoconstriction
Ineffective against other peripheral vascular
disorders that involve inappropriate
vasoconstriction
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Adverse Effects of Alpha1 Blockade
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Detrimental effects result from blockade of
alpha1 receptors
Effects from alpha2 receptors are minor
Orthostatic hypotension
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Blockade of alpha receptors on veins
Reduced muscle tone in the venous wall
Upon standing, blood pools in the veins
Return of blood to the heart reduced
Cardiac output decreased: blood pressure drops
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Adverse Effects of Alpha1 Blockade
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Reflex tachycardia
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Nasal congestion
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Dilates the blood vessels of the nasal mucosa
Inhibition of ejaculation
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Reflex to increase heart rate via the autonomic nervous
system (ANS)
Alpha1 activation required for ejaculation
Impotence is reversible; resolves when drug is discontinued
Sodium retention and increased blood volume
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Reduced BP promotes renal retention of sodium and water
Usually combined with diuretic when used for hypertension
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Adverse Effects of Alpha2 Blockade

The most significant adverse effect
associated with alpha2 blockade—
potentiation of the reflex tachycardia
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Alpha-Adrenergic Antagonists II
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Prazosin
Terazosin
Doxazosin
Tamsulosin
Alfuzosin
Phentolamine
Phenoxybenzamine
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Prazosin

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
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Actions and uses
Pharmacokinetics
Adverse effects
Preparations, dosage, and administration
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Terazosin
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
Actions and uses
Pharmacokinetics
Adverse effects
Preparations, dosage, and administration
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Doxazosin
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Actions and uses
Pharmacokinetics
Adverse effects
Preparations, dosage, and administration
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Tamsulosin
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
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
Actions and uses
Pharmacokinetics
Adverse effects
Drug interactions
Preparations, dosage, and administration
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Alfuzosin


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
Actions and uses
Pharmacokinetics
Adverse effects
Drug interactions
Preparations, dosage, and administration
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Phentolamine
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
Actions and uses
Adverse effects
Preparations, dosage, and administration
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Phenoxybenzamine
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

Actions and uses
Adverse effects
Preparations, dosage, and administration
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Beta-Adrenergic Antagonists I

Therapeutic applications of beta blockade
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Angina pectoris
Hypertension
Cardiac dysrhythmias
 Myocardial infarction
 Heart failure
 Hyperthyroidism
 Migraine
 Stage fright
 Pheochromocytoma
 Glaucoma
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Beta-Adrenergic Antagonists I

Adverse effects of beta blockade

Adverse effects involve both beta1 and beta2
blockade.
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Beta-Adrenergic Antagonists I

Adverse effects of beta1 blockade
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Bradycardia
Reduced cardiac output
Precipitation of heart failure
AV heart block
Rebound cardiac excitation
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Beta-Adrenergic Antagonists I

Adverse effects of beta2 blockade
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
Bronchoconstriction
Inhibition of glycogenolysis
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Beta-Adrenergic Antagonists II:
Propranolol
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Pharmacologic effects
Pharmacokinetics
Therapeutic uses
Adverse effects
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

Bradycardia
AV heart block
Heart failure
Rebound cardiac excitation
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Beta-Adrenergic Antagonists II:
Propranolol

Adverse effects (cont’d)
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Bronchoconstriction
Inhibition of glycogenolysis
CNS effects
Precautions, warnings, and contraindications



Severe allergy
Diabetes
Cardiac, respiratory, and psychiatric disorders
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Beta-Adrenergic Antagonists II:
Propranolol

Drug interactions

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Calcium channel blockers
Insulin
Preparations, dosage, and administration



General dosing considerations
Preparations
Dosage
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Beta-Adrenergic Antagonists II:
Metoprolol
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Pharmacologic effects
Pharmacokinetics
Therapeutic uses
Adverse effects
Precautions, warnings, and contraindications
Preparations, dosage, and administration
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Beta-Adrenergic Antagonists II:
Other Beta-Adrenergic Blockers
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Receptor specificity: selective blockade
Pharmacokinetics
Therapeutic uses
Adverse effects
Intrinsic sympathomimetic activity (partial
agonist activity)
Dosage and administration
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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