Clonidine (Catapres, Duraclon) is an
imidazoline derivative with predominantly α2-adrenergic ago-nist activity. It is highly lipid
soluble and readily penetrates the blood–brain barrier and the placenta.
Studies indicate that binding of clonidine to recep-tors is highest in the
rostral ventrolateral medulla in the brainstem (the final common pathway for
sym-pathetic outflow) where it activates inhibitory neu-rons. The overall
effect is to decrease sympathetic activity, enhance parasympathetic tone, and reduce
circulating catecholamines. There is also evidence that much of clonidine’s
antihypertensive action occurs via binding to a nonadrenergic (imidazo-line)
receptor. In contrast, its analgesic effects, par-ticularly in the spinal cord,
are mediated entirely via pre- and possibly postsynaptic α2-adrenergic recep-tors that block
nociceptive transmission. Clonidine also has local anesthetic effects when
applied to peripheral nerves and is frequently added to local anesthetic
Clonidine is a commonly used
antihyper-tensive agent that reduces sympathetic tone,decreasing systemic
vascular resistance, heart rate, and blood pressure. In anesthesia, clonidine
is used as an adjunct for epidural, caudal, and peripheral nerve block
anesthesia and analgesia. It is often used in the management of patients with
chronic neuro-pathic pain to increase the efficacy of epidural opioid
infusions. When given epidurally, the analgesic effect of clonidine is
segmental, being localized to the level at which it is injected or infused.
When added to local anesthetics of intermediate duration (eg, mepi-vacaine or
lidocaine) administered for epidural or peripheral nerve block, clonidine will
markedly pro-long both the anesthetic and analgesic effects.
Unlabeled/investigational uses of
clonidine include serving as an adjunct in premedication, control of withdrawal
syndromes (nicotine, opioids, alcohol, and vasomotor symptoms of menopause),
and treatment of glaucoma as well as various psychi-atric disorders.
Sedation, dizziness, bradycardia, and
dry mouth are common side effects. Less commonly, bradycardia, orthostatic
hypotension, nausea, and diarrhea may be observed. Abrupt discontinuation of
clonidine following long-term administration (>1 mo) can produce a withdrawal
phenomenon characterized by rebound hypertension, agitation, and sympa-thetic
Epidural clonidine is usually started at
30 mcg/h in a mixture with an opioid or a local anesthetic. Oral clonidine is
readily absorbed, has a 30–60 min onset, and lasts 6–12 h. In the treatment of
acute hyperten-sion, 0.1 mg can be given orally every hour until the blood
pressure is controlled, or up to a maximum of 0.6 mg; the maintenance dose is
0.1–0.3 mg twice daily. Transdermal preparations of clonidine can also be used
for maintenance therapy. They are available as 0.1, 0.2, and 0.3 mg/d patches
that are replacedevery 7 days. Clonidine is metabolized by the liver and
excreted renally. Dosages should be reduced for patients with renal insufficiency.
Clonidine enhances and prolongs sensory
and motor blockade from local anesthetics. Additive effects with hypnotic
agents, general anesthetics, and sedatives can potentiate sedation,
hypotension, and bradycardia. The drug should be used cautiously, if at all, in
patients who take β-adrenergic blockers and in those with significant cardiac
conduction system abnormalities. Lastly, clonidine can mask the symp-toms of
hypoglycemia in diabetic patients.