Clonidine is a sympatholytic medication used to treat high blood pressure, attention-deficit/hyperactivity
disorder, anxiety disorders, withdrawal, migraine, menopausal flushing, diarrhoea and certain
pain conditions. It is classified as a centrally acting α2 adrenergic agonist and imidazoline
receptor agonist that has been in clinical use for over 40 years.
Medical uses
Clonidine along with methylphenidate has been studied for treatment of ADHD. In 2010, the
Food and Drug Administration approved the use of clonidine either as an adjunct to traditional
stimulant therapy or as a monotherapy in the treatment of ADHD. In Australia, while ADHD
is an accepted use for clonidine it has not been approved by the TGA for this indication.
Clonidine can be used in the treatment of Tourette syndrome. Clonidine may be used to
ease withdrawal symptoms associated with the long-term use of narcotics, alcohol and nicotine.
It can alleviate opioid withdrawal symptoms by reducing the sympathetic nervous system
response such as tachycardia and hypertension, as well as reducing sweating, hot and cold
flashes, and general restlessness. It may also be helpful in aiding smokers to quit.
The sedation effect is also useful although its side effects can include insomnia, thus
exacerbating an already common feature of opioid withdrawal.
Clonidine also has several off-label uses, and has been prescribed to treat psychiatric
disorders including stress, sleep disorders, and hyperarousal caused by post-traumatic
stress disorder, borderline personality disorder, and other anxiety disorders. Clonidine is
also a mild sedative, and can be used as premedication before surgery or procedures. Its epidural
use for pain during heart attack, postoperative and intractable pain has also been studied
extensively. Clonidine has also been suggested as a treatment for rare instances of dexmedetomidine
withdrawal. Clonidine can be used in restless legs syndrome. It can also be used to treat
facial flushing and redness associated with rosacea. It has also been successfully used
topically in a clinical trial as a treatment for diabetic neuropathy. Clonidine can also
be used for migraine headaches and hot flashes associated with menopause.
Clonidine suppression test Clonidine's effect on reducing circulating
epinephrine by a central mechanism was used in the past as an investigatory test for phaeochromocytoma,
which is a catecholamine-synthesizing tumour, usually of the adrenal medulla. In a clonidine
suppression test plasma catecholamines levels are measured before and 3 hours after a 0.3 mg
oral test dose has been given to somebody. A positive test occurs if there is no decrease
in plasma levels. Pregnancy
Clonidine is classed by the FDA as pregnancy category C. It is classified by the TGA of
Australia as pregnancy category B3, which means that it has shown some detrimental effects
on foetal development in animal studies, although the relevance of this to human beings is unknown.
Additionally, clonidine can pass into breast milk and may harm a nursing baby. Therefore,
caution is warranted in women who are pregnant, planning to become pregnant, or are breastfeeding.
Adverse effects The principle adverse effects of clonidine
are dry mouth, dizziness, hypotension and drowsiness.
Adverse effects by frequency Very common:
Low blood pressure Common:
Uncommon:
Rare:
Withdrawal Clonidine suppresses sympathetic outflow resulting
in lower blood pressure, but sudden discontinuation can cause rebound hypertension due to a rebound
in sympathetic outflow. Clonidine therapy should generally be gradually
tapered off when discontinuing therapy to avoid rebound effects from occurring. Treatment
of clonidine withdrawal hypertension depends on the severity of the condition. Reintroduction
of clonidine for mild cases, alpha and beta blockers for more urgent situations. Beta
blockers never should be used alone to treat clonidine withdrawal as alpha vasoconstriction
would still continue. Mechanism of action
Clonidine treats high blood pressure by stimulating α2-receptors in the brain, which decreases
peripheral vascular resistance, lowering blood pressure. It has specificity towards the presynaptic
α2-receptors in the vasomotor center in the brainstem. This binding decreases presynaptic
calcium levels, thus inhibiting the release of norepinephrine. The net effect is a decrease
in sympathetic tone. It has also been proposed that the antihypertensive effect of clonidine
is due to agonism on the I1-receptor, which mediates the sympatho-inhibitory actions of
imidazolines to lower blood pressure. Its mechanism of action in the treatment of ADHD
is to increase noradrenergic tone in the prefrontal cortex directly by binding to postsynaptic
α2A adrenergic receptors and indirectly by increasing norepinephrine input from the locus
coeruleus. Synthesis
Clonidine, 2-(2,6-dichlorophenylamino)imidazoline, is synthesized from 2,6-dichloroaniline, the
reaction of which with ammonium thiocyanate gives N-(2,6- dichlorophenyl)thiourea. Methylation
of this product, followed by the subsequent reaction with ethylene diamine gives clonidine.
K. Zeile, H. Staehle, K. H. Hauotman, DE 1303141 . H. Stahle, K. Zeile, U.S. Patent 3,202,660.
K. Zeile, K. H. Hauotman, H. Stahle, U.S. Patent 3,236,857.
Boehringer Sohn Ingelheim, BE 653933 . Boehringer Sohn Ingelheim, GB 1016514 .
Boehringer Ingelheim GmbH, GB 1034938 .
US patent 3937717, Stahle, H.; Koppe, H.; Kummer, W.; Stockhaus, K., "2-Phenylamino-imidazolines-(2)",
issued 1976-02-10, assigned to Boehringer Ingelheim GmbH
References
External links U.S. National Library of Medicine: Drug Information
Portal - Clonidine