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Chapter 19
Indirect-Acting Antiadrenergic
Agents
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Indirect-Acting Antiadrenergic Agents
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Prevent stimulation of peripheral adrenergic
receptors
Two groups
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Adrenergic neuron-blocking agents
• Decrease norepinephrine release
Centrally acting alpha2 agonists
• Reduce impulses along the sympathetic nerves
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Centrally Acting Alpha2 Agonists
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Reduce the firing of sympathetic neurons
Used primarily for hypertension
Effects similar to those of the direct-acting
adrenergic receptor blockers
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Centrally Acting Alpha2 Agonists
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Clonidine
Guanabenz and guanfacine
Methyldopa and methyldopate
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Clonidine
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Mechanism of antihypertensive action
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Selective activation of alpha2 receptors in the CNS
Reduces sympathetic outflow to blood vessels and
the heart
Pharmacologic effects
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Bradycardia and a decrease in cardiac output
Minimal orthostatic hypotension
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Clonidine
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Pharmacokinetics
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Lipid-soluble
Readily absorbed following oral administration
Therapeutic uses
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Two approved applications
• Hypertension
• Severe pain
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Clonidine
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Adverse effects
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Drowsiness: 35% of patients
Xerostomia: 40% of patients
Rebound hypertension
• Withdraw slowly over 2 to 4 days
Use in pregnancy
• Not recommended
Other adverse effects
• Constipation, impotence, gynecomastia, and adverse
CNS effects
• Risk for abuse
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Clonidine
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Preparations, dosage, and administration
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Preparations
• Oral and transdermal
Dosage and administration
• Transdermal applied every 7 days
• Applied to hairless upper arm or torso
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Guanabenz and Guanfacine
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Pharmacology
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Adverse effects
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Very similar to that of clonidine
Xerostomia, sedation, rebound hypertension
if not weaned
Dosage and administration
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Methyldopa and Methyldopate
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Mechanism of action
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Lowers blood pressure (BP) by acting at sites
within the CNS
Causes alpha2 activation
Not an alpha2 agonist: taken up into brainstem and
converted into alpha2 agonist
Pharmacologic effects
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Vasodilation, not cardiosuppression
Lowers BP in supine and standing subjects
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Methyldopa and Methyldopate
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Therapeutic use
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Hypertension
One of the earliest drugs; no longer a first-line
drug
Adverse effects
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Positive Coombs’ test and hemolytic anemia
Hepatotoxicity
• Hepatitis, jaundice, and rarely fatal hepatic necrosis
Other adverse effects
• Xerostomia, sexual dysfunction, orthostatic hypotension,
and CNS effects
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Adrenergic Neuron-Blocking Agents
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Act presynaptically to reduce the release of
norepinephrine from sympathetic neurons
Very little effect on release of epinephrine
from adrenal medulla
Reserpine
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Reserpine
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Mechanism of action
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Depletion of NE from postganglionic sympathetic
neurons
Closely resembles alpha and beta blockade
Can cause depletion of transmitters (serotonin,
catecholamines)
Pharmacologic effects
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Peripheral effects
• Slows heart rate and reduces cardiac output
 CNS effects
• Sedation and state of indifference
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Reserpine
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Therapeutic uses
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Adverse effects
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Principal indication: hypertension (but not a
preferred drug)
Psychotic states (but not a preferred drug)
Depression
Bradycardia, orthostatic hypotension, nasal
congestion
GI involvement
Preparations, dosage, and administration
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Fig. 19-1. Mechanism of reserpine action.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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