Clonidine (trade names Catapres, Kapvay, Nexiclon, Clophelin, and others) is a medication used to treat high blood pressure, attention deficit hyperactivity disorder, anxiety disorders, tic disorders, withdrawal (from either alcohol, opioids, or smoking), migraine, menopausal flushing, diarrhea, and certain pain conditions. It is classified as a centrally acting ?2 adrenergic agonist and imidazoline receptor agonist that has been in clinical use for over 40 years.
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Medical uses
The US Food and Drug Administration (FDA) has approved clonidine for the treatment of attention deficit hyperactivity disorder (ADHD), alone or with stimulants in 2010, for pediatric patients aged 6-17 years. It was later approved for adults. In Australia, clonidine is an accepted but not approved use for ADHD by the TGA. Clonidine along with methylphenidate has been studied for treatment of ADHD. According to the clinical trials submitted to FDA its effectiveness is comparable to stimulants commonly used for ADHD. When used alone it leads to ~35% improvement in symptoms, comparable to ~30% improvement when stimulants are used. Some studies show clonidine more sedating than guanfacine, which may be better at bed time along with an arousing stimulant at morning. Clonidine can be used in the treatment of Tourette syndrome (specifically for tics).
Clonidine may be used to ease withdrawal symptoms associated with the long-term use of narcotics, alcohol, benzodiazepine 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. It may also be helpful in aiding smokers to quit. The sedation effect is also useful. However, 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 has also been used to treat diarrhea associated with irritable bowel syndrome, fecal incontinence, diabetes, withdrawal-associated diarrhea, intestinal failure, neuroendocrine tumors and cholera.
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 fetal development in animal studies, although the relevance of this to human beings is unknown. Clonidine can pass into breast milk and may harm a nursing baby; caution is warranted in women who are pregnant, planning to become pregnant, or are breastfeeding.
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Adverse effects
The principal adverse effects of clonidine are sedation, dry mouth, and hypotension (low blood pressure).
Adverse effects by frequency
Very common (>10% frequency):
Common (1-10% frequency):
Uncommon (0.1-1% frequency):
Rare (<0.1% frequency):
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 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 ?2 receptors in the brain, which decreases peripheral vascular resistance, lowering blood pressure. It has specificity towards the presynaptic ?2 receptors in the vasomotor center in the brainstem. This binding decreases presynaptic calcium levels, thus inhibiting the release of norepinephrine (NE). 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 (imidazoline 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 (PFC) directly by binding to postsynaptic ?2A adrenergic receptors and indirectly by increasing norepinephrine input from the locus coeruleus.
Source of the article : Wikipedia
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