Clonidine
Clonidine
is an imidazoline compound with potent alpha2-adrenergic agonist effects. At
high doses, it has been shown to act as a peripheral partial alpha-adrenergic
receptor agonist, resulting in stimulation of the peripheral post-synaptic
alpha2-receptors, thus temporarily increasing blood pressure and pulse rate.
Apart
from its utility in hypertension, clonidine is also used in the treatment of
attention deficit disorder, prophylaxis of migraine, and management of ethanol,
opiate, and nicotine withdrawal. It is well absorbed orally and demonstrates
peak effects at 2 to 3 hours. Excretion
as unchanged drug is mostly via the kidneys. Apraclonidine is a related drug
which is used as 0.5% or 1.0% ophthalmic solution in a sterile isotonic
solution for topical application to the eye. Guanfacine and guanabenz
are not popular in India, but share the same mode of action as clonidine.
· Dry mouth, drowsiness, orthostatic
hypotension, insomnia, agitation, myalgia, arrhythmias, and GI upset. Paralytic
ileus occurs rarely.
· Abrupt withdrawal of clonidine can
be life-threatening. Withdrawal effects include agitation, tremor,
palpitations, insomnia, severe hypertension, nausea, and vomiting. Even
otherwise, rebound hypertension is common.
· Usual therapeutic plasma level of
clonidine has been reported as less than or equal to 4 mcg/L. Toxic effects
generally occur within 30 minutes to 4 hours after overdose and usually resolve
within 24 to 72 hours.
· Overdose results in bradycardia
progressing to heart block, hypotension, hypothermia, CNS depression, miosis,
and periodic apnoea. Sometimes there is paradoxical hyperten-sion. Clonidine
poisoning is much more severe in children as compared to adults.
· Central adrenergic inhibitory
effects following clonidine overdose include impaired consciousness, hypotonia
and hyporeflexia, miosis, bradycardia, hypotension, respiratory depression and
apnoea, and hypothermia. Partial peripheral adrenergic stimulatory effects
include mild to moderate hypertension and tachycardia, which is usually
short-lived, and most often followed by hypotension and bradycardia.
· Large overdoses may result in
reversible cardiac conduction defects or arrhythmias.
· Hypothermia may occur within 1 hour
of the ingestion and may last as long as 48 hours, but is usually mild and
resolves spontaneously within 6 to 8 hours.
· Drowsiness, somnolence, ataxia,
impaired consciousness and coma are frequently seen. Seizures may rarely occur
following large overdoses.
· Toxic effects following ingestion of
apraclonidine ophthalmic drops are similar to those of clonidine overdose.
·
Clonidine levels are not readily available or useful for guiding
therapy.
·
No specific lab work (CBC, electrolytes, urinalysis) is
needed unless otherwise indicated.
·
Monitor for CNS and respiratory depression. Monitor vital
signs, continuous ECG, and pulse oximetry in symptomatic patients.
·
Endotracheal intubation and ventilation may be indicated in
the presence of apnoea, coma, depressed respirations, or hypotonia during the
first 24 hours following ingestion of clonidine.
·
All patients with an altered mental status, bradycardia,
hypo or hypertension require observation (frequent monitoring of vital signs
and ECG) for a minimum of 6 to 12 hours or until the patient remains
asymptomatic for a period of 4 hours.
·
Activated charcoal is beneficial if administered early.
Induc-tion of vomiting and gastric lavage are contraindicated.
·
Naloxone reverses the deleterious effects on respiration and
CVS function. Large doses may have to be admin-istered (upto 8 to 10 mg).
Naloxone is most effective at reversing respiratory depression, somewhat
helpful at lessening the “paradoxical hypertensive” effect, and least effective
against hypotension. The most frequently recommended initial naloxone dose for
opiate overdose is as follows: 0.4 to 2 mg intravenous bolus in both children
and adults, and may be repeated at 2 to 3 minutes intervals according to
desired patient response. Caution should be exercised when administering
naloxone to the paediatric patient. Severe hypertension requiring management
with phentolamine has followed the administration of naloxone in several
paediatric clonidine overdoses.
·
Atropine counteracts bradycardia. Bradycardia and
hypotension may respond to atropine alone in patients with heart rates below
60. Give 1 mg intravenously, and repeat in three to five minutes if asystolic
cardiac arrest persists. Three milligrams (0.04 mg/kg) intravenously is a fully
vagolytic dose in most adults.
·
For hypotension, infuse 10 to 20 ml/kg of isotonic fluid and
place in Trendelenburg position.If hypotension persists, administer dopamine or
noradrenaline. Consider central venous pressure monitoring to guide further
fluid therapy. Dopamine is effective for hypotension. Paradox-ical hypertension
responds well to sodium nitroprusside (intravenous infusion at a rate between
0.5 and 10 mcg/ kg/min, and adjusted based on the patient’s response).
·
Cardiac arrhythmias should be treated with standard
antiarrhythmic drugs, if necessary.
·
Alpha-adrenergic antagonists such as tolazoline may have
antidotal action in clonidine poisoning. The recom-mended dose is 5 to 10 mg as
IV infusion every 15 minutes (upto a maximum of 40 mg).
·
Yohimbine, a CNS alpha2-adrenergic antagonist, has been used
for treatment of clonidine overdose.
·
Haemodialysis, haemoperfusion and forced diuresis are not
likely to significantly enhance the elimination of this drug.
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