Clonidine (trade names Catapres, Kapvay, Nexiclon and others) is a sympatholytic medication used to treat high blood pressure, ADHD, anxiety/panic disorder, and certain pain conditions. It is classified as a centrally acting α2adrenergic agonist. An alternative hypothesis that has been proposed is that clonidine acts centrally as an imidazoline receptor agonist.
Clonidine XR has been approved by the FDA for the treatment of ADHD. In Australia, while ADHD is an accepted use for clonidine (which in Australia is only available in immediate release formulations) it has not been approved by the TGA for this indication.
Clonidine may be used to ease withdrawal symptoms associated with the long-term use of narcotics, alcohol and nicotine (smoking). 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. The sedation effect is also useful although its side effects can include insomnia, thus exacerbating an already common feature of opioid withdrawal.
Clonidine's effect on reducing circulating epinephrine by a central mechanism was used in the past as an investigatory test for pheochromocytoma, which is a catecholamine-synthesizing tumor, 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 a patient. A positive test occurs if there is no decrease in plasma levels.
Clonidine is classed by the FDA as pregnancy category C. It is not known whether clonidine is harmful to an unborn baby. 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.
The principle adverse effects of clonidine are dry mouth, dizziness, hypotension (low blood pressure) and drowsiness.
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.
Since ADHD drugs like amphetamine and methylphenidate tend to stimulate the sympathetic nervous system, missed doses of clonidine while under ADHD stimulant therapy might entail increased risks of a more severe rebound hypertension. This has not been evaluated.
It has also been proposed that the antihypertensive effect of clonidine is due to agonism on the I1-receptor (imidazoline receptor), which mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure.
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.
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