Trade names Catapres, Kapvay, Nexiclon
US FDA: link
epidural, IV, transdermal, topical
Bioavailability 75-95% (oral), 60-70% (transdermal)
Protein binding 20-40%
Hepatic to inactive metabolites, 2/3 [2 ] CYP2D6 
Half-life IR: 12-16 hours,
14 hours for repeated dosing [3 ] [1 ]
Excretion urine (72%)
C02 AC01 N02 , CX02 S01 EA04
C 9 H 9 Cl 2 N 3
Molecular mass 230.093 g/mol
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Clonidine (trade names Catapres, Kapvay, Nexiclon, Clophelin, and others) is a sympatholytic medication used to treat high blood pressure, attention deficit hyperactivity disorder, anxiety disorders, withdrawal (from either alcohol, opioids, or smoking), migraine, menopausal flushing, diarrhea, and certain pain conditions. It is classified as a centrally acting [4 ] α 2 adrenergic agonist and imidazoline receptor agonist that has been in clinical use for over 40 years. [5 ]
Medical uses [ edit ]
Clonidine tablets and transdermal patch
Food and Drug Administration (FDA) has approved clonidine, like guanfacine, for the treatment of attention deficit hyperactivity disorder (ADHD), alone or with stimulants in 2010, for pediatric patients aged 6–17 years. [2 ] It was later approved for adults. In [6 ] Australia, clonidine is an accepted but not approved use for ADHD by the TGA. Clonidine along with [7 ] methylphenidate has been studied for treatment of ADHD. [8 ] [9 ] Some studies show clonidine more sedating than [10 ] guanfacine -which may be better at bed time along with an arousing stimulant at morning. [11 ] Clonidine can be used in the treatment of [12 ] Tourette syndrome (specifically for tics). Clonidine may be used to ease withdrawal symptoms associated with the long-term use of [13 ] narcotics, alcohol, benzodiazepine and nicotine (smoking). It can alleviate [14 ] 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. [15 ] The sedation effect is also useful although its side effects can include insomnia, thus exacerbating an already common feature of opioid withdrawal. [16 ] [17 ]
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. [18 ] [19 ] [20 ] [21 ] [22 ] [23 ] [24 ] Clonidine is also a mild [25 ] 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. [26 ] Clonidine has also been suggested as a treatment for rare instances of [27 ] dexmedetomidine withdrawal. Clonidine can be used in [28 ] 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 [29 ] diabetic neuropathy. Clonidine can also be used for [30 ] migraine headaches and hot flashes associated with menopause. [31 ] [32 ]
Clonidine suppression test [ edit ]
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 [33 ] 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. [33 ]
Pregnancy [ edit ]
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.
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. [34 ] [35 ]
Adverse effects [ edit ]
The principle adverse effects of clonidine are sedation, dry mouth, and hypotension (low blood pressure).
Adverse effects by frequency [34 ] [36 ] [37 ]
Very common (>10% frequency):
Common (1-10% frequency):
Pain below the ear (from salivary gland)
Uncommon (0.1-1% frequency):
Rare (<0.1% frequency):
Withdrawal [ edit ]
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. [38 ] [39 ]
Mechanism of action [ edit ]
Clonidine treats high blood pressure by stimulating
α in the brain, which decreases 2-receptors peripheral vascular resistance, lowering blood pressure. It has specificity towards the presynaptic α 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 I [40 ] 1-receptor ( imidazoline receptor), which mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure. Its mechanism of action in the treatment of [41 ] ADHD is to increase noradrenergic tone in the prefrontal cortex (PFC) directly by binding to postsynaptic α and indirectly by increasing norepinephrine input from the 2A adrenergic receptors locus coeruleus. [42 ]
References [ edit ]
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^ Fitzgerald, PJ (October 2013). "Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine.". Substance Abuse 7: 171–83. doi: 10.4137/SART.S13019. PMC 3798293. PMID 24151426.
^ Giannini, AJ (1997). Drugs of Abuse (2nd ed.). Los Angeles: Practice Management Information.
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^ Boehnlein, JK; Kinzie, JD (March 2007). "Pharmacologic reduction of CNS noradrenergic activity in PTSD: the case for clonidine and prazosin.". Journal of Psychiatric Practice 13 (2): 72–8. doi: 10.1097/01.pra.0000265763.79753.c1. PMID 17414682.
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^ Najjar, F; Weller, RA; Weisbrot, J; Weller, EB (April 2008). "Post-traumatic stress disorder and its treatment in children and adolescents.". Current Psychiatry Reports 10 (2): 104–8. doi: 10.1007/s11920-008-0019-0. PMID 18474199.
^ Ziegenhorn, AA; Roepke, S; Schommer, NC; Merkl, A; Danker-Hopfe, H; Perschel, FH; Heuser, I; Anghelescu, IG; Lammers, CH (April 2009). "Clonidine improves hyperarousal in borderline personality disorder with or without comorbid posttraumatic stress disorder: a randomized, double-blind, placebo-controlled trial". Journal of Clinical Psychopharmacology 29 (2): 170–3. doi: 10.1097/JCP.0b013e31819a4bae. PMID 19512980.
^ Fazi, L; Jantzen, EC; Rose, JB; Kurth, CD; Watcha, MF (2001). "A comparison of oral clonidine and oral midazolam as preanesthetic medications in the pediatric tonsillectomy patient" (PDF). Anesthesia and Analgesia 92 (1): 56–61. doi: 10.1097/00000539-200101000-00011. PMID 11133600.
^ Patel, SS; Dunn, CJ; Bryson, HM (1996). "Epidural clonidine: a review of its pharmacology and efficacy in the management of pain during labour and postoperative and intractable pain". CNS Drugs 6 (6): 474–497. doi: 10.2165/00023210-199606060-00007.
^ Kukoyi, AT; Coker, SA; Lewis, LD; Nierenberg, DW (January 2013). "Two cases of acute dexmedetomidine withdrawal syndrome following prolonged infusion in the intensive care unit: Report of cases and review of the literature". Human and Experimental Toxicology 32 (1): 107–110. doi: 10.1177/0960327112454896. PMID 23111887 . Retrieved . 1 March 2013
^ Blount, BW; Pelletier, AL (2002). "Rosacea: A Common, Yet Commonly Overlooked, Condition". American Family Physician 66 (3): 435–441. PMID 12182520.
^ Campbell, CM; Kipnes, MS; Stouch, BC; Brady, KL; Kelly, M; Schmidt, WK; Petersen, KL; Rowbotham, MC; Campbell, JN (September 2012). "Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy" (PDF). Pain 153 (9): 1815–1823. doi: 10.1016/j.pain.2012.04.014. PMC 3413770. PMID 22683276.
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