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Clonidine is a direct-acting α2 adrenergic agonist prescribed historically as an antihypertensive agent. It has found new uses, including treatment of some types of neuropathic pain, opioid detoxification, sleep hyperhidrosis, anaesthetic use, and off-label, to counter the side effects of stimulant medications such as methylphenidate or amphetamine. It is becoming a more accepted treatment for insomnia, as well as for relief of menopausal symptoms. Clonidine is increasingly used in conjunction with stimulants to treat attention-deficit hyperactivity disorder (ADHD), for which it is administered in late afternoon or evening for sleep, and because it sometimes helps moderate ADHD-associated impulsive and oppositional behavior, and may reduce tics. Clonidine can also be used in the treatment of Tourette syndrome.
Mechanism
The main use for this medication is to treat high blood pressure. It works by stimulating α2 receptors in the brain which decreases cardiac output and peripheral vascular resistance, lowering blood pressure. It has specificity towards the presynaptic alpha-2 receptors in the vasomotor center in the brainstem. This binding decreases presynaptic calcium levels, and inhibits the release of norepinephrine (NE). The net effect is a decrease in sympathetic tone.Indications & preparations
Clonidine is typically available as tablets (Catapres, Dixarit), as a transdermal patch (Catapres-TTS), or as an injectable form to be given epidurally, directly to the central nervous system.
FDA approved uses
This medication may also be used to ease withdrawal symptoms associated with the long-term use of narcotics, alcohol and nicotine (smoking). In addition, clonidine has also been used for migraine headaches, hot flashes associated with menopause, attention deficit hyperactivity disorder.Clonidine is regularly prescribed to opiate addicts to help alleviate their withdrawal symptomology. It is mainly used to combat the sympathetic nervous system response to opiate withdrawal, namely tachycardia and hypertension, in the first couple days of withdrawals. It helps take away the sweating, hot/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 opiate withdrawal.
Adverse effects
This drug may cause drowsiness, lightheadedness, dry mouth, dizziness, or constipation. Clonidine may also cause hypotension. It can also cause inhibition of orgasm in women. Sucking on sugarless hard candy or ice chips, chewing sugarless gum, drinking water, and using a saliva substitute may help relieve dry mouth.Pharmacodynamics
Clonidine is a centrally-acting α-adrenergic receptor agonist with more affinity for α2 than α1. It selectively stimulates receptors in the brain that monitor catecholamine levels in the blood. These receptors close a negative feedback loop that begins with descending sympathetic nerves from the brain that control the production of catecholamines (epinephrine, also known as adrenaline, and norepinephrine) in the adrenal medulla. By fooling the brain into believing that catecholamine levels are higher than they really are, clonidine causes the brain to reduce its signals to the adrenal medulla, which in turn lowers catecholamine production and blood levels. The result is a lowered heart rate and blood pressure, with side effects of dry mouth and fatigue. If clonidine is suddenly withdrawn the sympathetic nervous system will revert to producing high levels of epinephrine and norepinephrine, higher even than before treatment, causing rebound hypertension. Rebound hypertension can be avoided by slowly withdrawing treatment.Clonidine suppression test
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 µg/kg oral test dose has been given to a patient. A positive test occurs if there is no decrease in plasma levels.Footnotes
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Last updated on Tuesday October 07, 2008 at 19:39:34 PDT (GMT -0700)
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This article is licensed under the GNU Free Documentation License.
Last updated on Tuesday October 07, 2008 at 19:39:34 PDT (GMT -0700)
View this article at Wikipedia.org - Edit this article at Wikipedia.org - Donate to the Wikimedia Foundation
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