Sympatholytic Agents

54
Yury Khelemsky, Karina Gritsenko,
and Christopher Curatolo

Overview of Sympatholytic Agents Adrenergic Receptor Antagonists

Sympatholytic drugs are agents that decrease Description and Mechanism of Action

the activity of the sympathetic nervous system
(SNS). This is accomplished via a variety of
mechanisms that most commonly include adren-
ergic receptor blockade (e.g., α and β adrenergic
receptor antagonism) as well as specific recep-
tor agonism (i.e., α2 adrenergic receptor ago-
nism) (1). The SNS signal, however, may be
blocked in other ways (e.g., peripheral gangli-
onic blockade) (2).
The most common sympatholytic agents block
adrenergic receptors via competitive antagonism
at peripheral α and β adrenergic receptors.
Examples
• β Adrenergic receptor (βAR) antagonists—
metoprolol, propranolol
• α Adrenergic receptor (αAR) antagonists—pra-
zosin, terazosin, doxazosin, phenoxy­benzamine

Y. Khelemsky, MD (*)
Department of Anesthesiology, Icahn School of
Medicine at Mount Sinai, One Gustave L. Levy
Place, KCC 8th Floor, Box 1010, New York,
NY 10029, USA
e-mail: yury.khelemsky@mountsinai.org
K. Gritsenko, MD
Department of Anesthesiology, Albert Einstein
College of Medicine, Montefiore Medical Center,
3400 Bainbridge Ave, LL400, Bronx,
NY 10128, USA
e-mail: kgritsen@montefiore.org
C. Curatolo, MD, MEM
Department of Anesthesiology, Icahn School of
Medicine at Mount Sinai, One Gustave L. Levy Pl,
KCC 8th Floor, Box 1010, New York,
NY 10029, USA
e-mail: cjcuratolo@gmail.com
Clinical Indications
Migraine headache prophylaxis—propranolol
and metoprolol. Not useful in acute migraine
attacks.
Complex regional pain syndrome (CRPS)—
recommended in SNS-mediated pain syndromes.
α1AR antagonists (esp. terazosin and phenoxy-
benzamine) are recommended.
Acute panic symptoms/performance anxiety
(e.g., public speaking)—βAR antagonists (esp. pro-
pranolol) are effective in controlling SNS-mediated
symptoms (e.g., sweating, tachycardia, etc.).

© Springer International Publishing Switzerland 2017 193

R.J. Yong et al. (eds.), Pain Medicine, DOI 10.1007/978-3-319-43133-8_54
194
Post-traumatic stress disorder (PTSD)—pra- E  xamples
zosin (αAR antagonist) is effective for PTSD-­
related nightmares. Clonidine (oral, transdermal, IV, intrathecal, epi-
dural), dexmedetomidine (Precedex), tizanidine
(Zanaflex), and epinephrine
Side Effects
αAR antagonists: orthostatic hypotension, dizzi-
ness, weakness, tachycardia
βAR antagonists: bronchospasm (esp. nonselec-
tive βAR antagonists), bradycardia, fatigue,
sleep disturbance, hypoglycemia
Interactions
Caution in patients with cardiac conduction
defects.
Caution in patients on medications that slow car-
diac conduction (e.g., calcium channel
blockers).
Beta receptor antagonists can interfere with the
clearance of lidocaine.
Weaning
Avoid abrupt discontinuation (esp. βAR
antagonists)
 lpha-2 Adrenergic Receptor
A
Agonists
Description and Mechanism of Action
α2AR agonists cause sedation, analgesia, and
hypotension in a dose-dependent fashion. The
effects of these agents are predominantly centrally
mediated. These agents decrease sympathetic dis-
charge via preganglionic fibers in the splanchnic
nerves and postganglionic fibers of cardiac nerves.
Additionally, these agents stimulate parasympa-
thetic outflow. The agents’ hypotensive effects
may result from activation of preganglionic α2ARs
causing a decrease in catecholamine release from
postganglionic sympathetic nerves (1).
Y. Khelemsky et al.
Clinical Indications
Adjunctive analgesia, especially periopera-
tive—clonidine, dexmedetomidine, epinephrine
• Clonidine is a potent adjuvant when added to
regional and intrathecal techniques.
–– Enhances the effects of epidural opioids
–– Prolongs and enhances the activity of intra-
thecal local anesthetics
• Clonidine may be an important adjuvant for
acute pain management.
• Dexmedetomidine reduces opioid requirements
and reduces postoperative nausea and vomiting
without increasing recovery time.
• Epinephrine enhances and prolongs the effects
of epidural local anesthetics.
Adjunctive anesthesia—reliably reduces the
minimum dosage of other anesthetics needed to
produce sedation and general anesthesia (esp. IV
dexmedetomidine)
Refractory CRPS—epidural clonidine
Restless leg syndrome—clonidine (esp. refrac-
tory cases)
Spasticity (cerebral and spinal cord
disorders)—tizanidine
Side Effects
Sedation, hypotension, bradycardia, fatigue, dry
mouth
Interactions
Caution with other drugs that may lower blood
pressure or heart rate
54  Sympatholytic Agents
Weaning
Abrupt discontinuation of long-term therapy may
cause rebound hypertension
Other Sympatholytics
Description and Mechanism of Action
A reduction in SNS activity may occur via
other mechanisms such as the blockade of gan-
glionic transmission (e.g., trimethaphan), the
reduction of neurotransmitter release (e.g.,
guanethidine), or the depletion of neurotrans-
mitters (e.g., reserpine) (2). These agents are
rarely employed today and are listed for his-
torical purposes only.
195
Other agents that contain some amount of sym-
patholytic activity include ergot alkaloids (e.g.,
dihydroergotamine), which are primarily used for
acute migraine treatment, and neuroleptics (e.g.,
chlorpromazine, haloperidol) that in addition to
their primary action as antidopaminergic agents
produce significant αAR antagonist (1).
Suggested Readings
1. Blaudszun G, Lysakowski C, Elia N, Tramer
MR. Effect of perioperative systemic alpha2 agonists
on postoperative morphine consumption and pain
intensity: systematic review and meta-analysis of ran-
domized controlled trials. Anesthesiology.
2012;116(6):1312–22.
2. Chan AK, Cheung CW, Chong YK. Alpha-2 agonists
in acute pain management. Expert Opin Pharmacother.
2010;11(17):2849–68.