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Clonidine: Difference between revisions
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'''Clonidine''' (known by the trade names '''Catapres''', '''Kapvay''', '''Nexiclon''', '''Clophelin''', and others) is a [[psychoactive class::depressant]] substance of the [[chemical class:: | '''Clonidine''' (known by the trade names '''Catapres''', '''Kapvay''', '''Nexiclon''', '''Clophelin''', and others) is a [[psychoactive class::depressant]] substance of the [[chemical class::arylaminoimidazoline]] class. It is primarily used to treat [[increased blood pressure|high blood pressure]], but can also be used for a variety of conditions that include attention deficit hyperactivity disorder, [[anxiety]] disorders, tic disorders, [[drug withdrawal|substance withdrawal]], migraine, [[diarrhea]], and certain pain conditions.<ref>{{cite journal | veditors=((Soni, H.)), ((Brayfield, A.)) | journal=Pharmaceutical Press | title=“Clonidine”. Martindale: The Complete Drug Reference | volume=22 | issue=5 | pages=12–12 | date=13 January 2014 | url=http://rcnpublishing.com/doi/abs/10.7748/en.22.5.12.s13 | issn=1354-5752| doi=10.7748/en.22.5.12.s13 | access-date=28 June 2014}}</ref> | ||
Developed by Boehringer Ingelheim for its blood pressure effects, clonidine first saw clinical use in 1966.<ref name="Stahle">Stähle, H. | Developed by Boehringer Ingelheim for its blood pressure effects, clonidine first saw clinical use in 1966.<ref name="Stahle">{{cite journal | vauthors=((Stähle, H.)) | journal=Best Practice & Research Clinical Anaesthesiology | title=A historical perspective: development of clonidine | volume=14 | issue=2 | pages=237–246 | date= June 2000 | url=https://linkinghub.elsevier.com/retrieve/pii/S152168960090079X | issn=15216896 | doi=10.1053/bean.2000.0079}}</ref> | ||
As the first anti-hypertensive agent with a clearly identifiable central site of action, clonidine has been an important pharmacological tool in discovering the role of central α-adrenoceptors in the physiology of central blood pressure regulation.<ref name="Stahle" /> | As the first anti-hypertensive agent with a clearly identifiable central site of action, clonidine has been an important pharmacological tool in discovering the role of central α-adrenoceptors in the physiology of central blood pressure regulation.<ref name="Stahle" /> | ||
Clonidine is classified as a centrally acting α<sub>2</sub> [[adrenergic]] [[agonist]] and imidazoline [[receptor]] [[agonist]].<ref name="Neil">Neil, | Clonidine is classified as a centrally acting α<sub>2</sub> [[adrenergic]] [[agonist]] and imidazoline [[receptor]] [[agonist]].<ref name="Stahle" /><ref name="Neil">{{cite journal | vauthors=((Neil, M. J.)) | journal=Current Clinical Pharmacology | title=Clonidine: clinical pharmacology and therapeutic use in pain management | volume=6 | issue=4 | pages=280–287 | date= November 2011 | issn=2212-3938 | doi=10.2174/157488411798375886}}</ref> | ||
Its activity on the α<sub>2</sub> receptors in the brainstem inhibits the release of [[norepinephrine]] (NE), resulting in decreased sympathetic nervous system tone.<ref>Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 12. ISBN 1-59541-101-1.</ref> | Its activity on the α<sub>2</sub> receptors in the brainstem inhibits the release of [[norepinephrine]] (NE), resulting in decreased sympathetic nervous system tone.<ref>Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 12. ISBN 1-59541-101-1.</ref> | ||
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With the discovery of clonidine, the central a-adrenergic receptors first became known to chemists, pharmacologists and physicians. It has been an important pharmacological tool in researching the role of central α-adrenoceptors in the physiology of central blood pressure regulation and nervous system function.<ref name="Stahle" /> | With the discovery of clonidine, the central a-adrenergic receptors first became known to chemists, pharmacologists and physicians. It has been an important pharmacological tool in researching the role of central α-adrenoceptors in the physiology of central blood pressure regulation and nervous system function.<ref name="Stahle" /> | ||
In the 2010s, the US Food and Drug Administration (FDA) approved clonidine, both alone or with [[stimulants]], for the treatment of attention deficit hyperactivity disorder (ADHD) in pediatric and adult patients. In Australia, clonidine is an accepted but not approved use for ADHD by the TGA.<ref>Rossi, S, | In the 2010s, the US Food and Drug Administration (FDA) approved clonidine, both alone or with [[stimulants]], for the treatment of attention deficit hyperactivity disorder (ADHD) in pediatric and adult patients. In Australia, clonidine is an accepted but not approved use for ADHD by the TGA.<ref>{{cite book | vauthors=((Rossi, S.)), ((Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists)), ((Pharmaceutical Society of Australia)), ((Royal Australian College of General Practitioners)) | date= 2013 | title=Australian medicines handbook 2013. | publisher=Australian Medicines Handbook | isbn=9780980579093}}</ref> | ||
==Chemistry== | ==Chemistry== | ||
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==Pharmacology== | ==Pharmacology== | ||
===Pharmacodynamics=== | ===Pharmacodynamics=== | ||
Clonidine is an [[agonist]] for the α<sub>2</sub> [[adrenaline|adrenergic]] [[receptor]]. When α<sub>2</sub> receptors in the brain are stimulated, peripheral vascular resistance decreases, resulting in lowered blood pressure. It has specificity towards the presynaptic α<sub>2</sub> 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 nervous system tone.<ref>Sullivan, P. A., De Quattro, V., Foti, A. | Clonidine is an [[agonist]] for the α<sub>2</sub> [[adrenaline|adrenergic]] [[receptor]]. When α<sub>2</sub> receptors in the brain are stimulated, peripheral vascular resistance decreases, resulting in lowered blood pressure. It has specificity towards the presynaptic α<sub>2</sub> 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 nervous system tone.<ref>{{cite journal | vauthors=((Sullivan, P. A.)), ((De Quattro, V.)), ((Foti, A.)), ((Curzon, G.)) | journal=Hypertension (Dallas, Tex.: 1979) | title=Effects of clonidine on central and peripheral nerve tone in primary hypertension | volume=8 | issue=7 | pages=611–617 | date= July 1986 | issn=0194-911X | doi=10.1161/01.hyp.8.7.611}}</ref> | ||
Three G-protein coupled α2-receptor subtypes have been identified: α<sub>2A</sub>, α<sub>2B</sub>, and α<sub>2C</sub>. Each subtype has a unique pattern of tissue distribution in the central nervous system and peripheral tissues. The α2A-receptor is widely distributed throughout the central nervous system; it is found in the locus coeruleus, brain stem nuclei, cerebral cortex, septum, hypothalamus, and hippocampus. α<sub>2A</sub> receptors are also expressed in the kidneys, spleen, thymus, lung and salivary glands. The α<sub>2C</sub>-receptor is primarily expressed in the central nervous system, including the striatum, olfactory tubercle, hippocampus and cerebral cortex. The α<sub>2B</sub> receptor is located primarily in the periphery (kidney, liver, lung and heart).{{citation needed}} | Three G-protein coupled α2-receptor subtypes have been identified: α<sub>2A</sub>, α<sub>2B</sub>, and α<sub>2C</sub>. Each subtype has a unique pattern of tissue distribution in the central nervous system and peripheral tissues. The α2A-receptor is widely distributed throughout the central nervous system; it is found in the locus coeruleus, brain stem nuclei, cerebral cortex, septum, hypothalamus, and hippocampus. α<sub>2A</sub> receptors are also expressed in the kidneys, spleen, thymus, lung and salivary glands. The α<sub>2C</sub>-receptor is primarily expressed in the central nervous system, including the striatum, olfactory tubercle, hippocampus and cerebral cortex. The α<sub>2B</sub> receptor is located primarily in the periphery (kidney, liver, lung and heart).{{citation needed}} | ||
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Clonidine also has peripheral α<sub>1</sub> agonist activity.{{citation needed}} | Clonidine also has peripheral α<sub>1</sub> agonist activity.{{citation needed}} | ||
Clonidine is also an agonist for the imidazoline I<sub>1</sub> receptor.<ref>Bricca, G., Greney, H., Zhang, J., Dontenwill, M., Stutzmann, J., Belcourt, A., | Clonidine is also an agonist for the imidazoline I<sub>1</sub> receptor.<ref>{{cite journal | vauthors=((Bricca, G.)), ((Greney, H.)), ((Zhang, J.)), ((Dontenwill, M.)), ((Stutzmann, J.)), ((Belcourt, A.)), ((Bousquet, P.)) | journal=European Journal of Pharmacology: Molecular Pharmacology | title=Human brain imidazoline receptors: further characterization with [3H]clonidine | volume=266 | issue=1 | pages=25–33 | date= January 1994 | url=https://linkinghub.elsevier.com/retrieve/pii/0922410694902054 | issn=09224106 | doi=10.1016/0922-4106(94)90205-4}}</ref> This has been proposed to be responsible for the antihypertensive effects.<ref>{{cite journal | vauthors=((Reis, D. J.)), ((Piletz, J. E.)) | journal=The American Journal of Physiology | title=The imidazoline receptor in control of blood pressure by clonidine and allied drugs | volume=273 | issue=5 | pages=R1569-1571 | date= November 1997 | issn=0002-9513 | doi=10.1152/ajpregu.1997.273.5.R1569}}</ref> | ||
{| class="wikitable" | {| class="wikitable" | ||
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|{{effects/physical| | |{{effects/physical| | ||
*'''[[Effect::Sedation]]''' - Clonidine can produce a strong sedative effect, which has been compared to that of [[benzodiazepines]]. Users can become very tired and sleep through prompts to awake. | *'''[[Effect::Sedation]]''' - Clonidine can produce a strong sedative effect, which has been compared to that of [[benzodiazepines]]. Users can become very tired and sleep through prompts to awake. | ||
*'''[[Effect::Decreased heart rate]]'''<ref>Anderson, R. J., Hart, G. R., Crumpler, C. P., | *'''[[Effect::Decreased heart rate]]'''<ref>{{cite journal | vauthors=((Anderson, R. J.)), ((Hart, G. R.)), ((Crumpler, C. P.)), ((Lerman, M. J.)) | journal=Annals of Emergency Medicine | title=Clonidine overdose: report of six cases and review of the literature | volume=10 | issue=2 | pages=107–112 | date= February 1981 | issn=0196-0644 | doi=10.1016/s0196-0644(81)80350-2}}</ref> - In normal use as well as overdose, heartrate is lowered and is directly affected by how much is taken. | ||
*'''[[Effect::Decreased blood pressure]]''' - Clonidine's sympatholytic effects quickly and effectively | *'''[[Effect::Decreased blood pressure]]''' - Clonidine's sympatholytic effects quickly and effectively lower blood pressure.<ref>{{cite journal | vauthors=((Mitchell, A.)), ((Bührmann, S.)), ((Opazo Saez, A.)), ((Rushentsova, U.)), ((Schäfers, R. F.)), ((Philipp, T.)), ((Nürnberger, J.)) | journal=Cardiovascular Drugs and Therapy | title=Clonidine lowers blood pressure by reducing vascular resistance and cardiac output in young, healthy males | volume=19 | issue=1 | pages=49–55 | date= January 2005 | issn=0920-3206 | doi=10.1007/s10557-005-6890-6}}</ref> Users should take care to avoid standing up too quickly to avoid an overwhelming light-headedness and possible fainting spell. | ||
*'''[[Effect::Abnormal heartbeat]]''' - This effect has a low likelihood. Caution should be taken if clonidine is taken with other substances that affect heartbeat. Intense physical activity should be avoided while on this substance. | *'''[[Effect::Abnormal heartbeat]]''' - This effect has a low likelihood. Caution should be taken if clonidine is taken with other substances that affect heartbeat. Intense physical activity should be avoided while on this substance. | ||
*'''[[Effect::Dry mouth]]''' | *'''[[Effect::Dry mouth]]''' | ||
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|{{effects/cognitive| | |{{effects/cognitive| | ||
*'''[[Effect::Cognitive fatigue]]''' | *'''[[Effect::Cognitive fatigue]]''' | ||
*'''[[Effect::Addiction suppression]]''' - Clonidine has shown efficacy as a treatment for alcohol, opioid, and nicotine substance use disorders.{{citation needed}} It has been shown to block opiate withdrawal symptoms.<ref>Gold, | *'''[[Effect::Addiction suppression]]''' - Clonidine has shown efficacy as a treatment for alcohol, opioid, and nicotine substance use disorders.{{citation needed}} It has been shown to block opiate withdrawal symptoms.<ref>{{cite journal | vauthors=((Gold, MarkS.)), ((Redmond, D. E.)), ((Kleber, HerbertD.)) | journal=The Lancet | title=CLONIDINE BLOCKS ACUTE OPIATE-WITHDRAWAL SYMPTOMS | volume=312 | issue=8090 | pages=599–602 | date= September 1978 | url=https://linkinghub.elsevier.com/retrieve/pii/S0140673678928234 | issn=01406736 | doi=10.1016/S0140-6736(78)92823-4}}</ref> | ||
*'''[[Effect::Anxiety suppression]]''' - Clonidine has mild to moderate anxiolytic effects and is sometimes used clinically to treat anxiety.<ref>Hoehn-Saric R | *'''[[Effect::Anxiety suppression]]''' - Clonidine has mild to moderate anxiolytic effects and is sometimes used clinically to treat anxiety.<ref>{{cite journal | vauthors=((Hoehn-Saric, R.)) | journal=Archives of General Psychiatry | title=Effects of Clonidine on Anxiety Disorders | volume=38 | issue=11 | pages=1278 | date=1 November 1981 | url=http://archpsyc.jamanetwork.com/article.aspx?doi=10.1001/archpsyc.1981.01780360094011 | issn=0003-990X | doi=10.1001/archpsyc.1981.01780360094011}}</ref> | ||
*'''[[Effect::Focus enhancement]]''' - This effect usually occurs at lower doses which are sometimes prescribed for the treatment of ADHD. | *'''[[Effect::Focus enhancement]]''' - This effect usually occurs at lower doses which are sometimes prescribed for the treatment of ADHD. | ||
*'''[[Effect::Focus suppression]]''' - This effect usually occurs at higher doses. | *'''[[Effect::Focus suppression]]''' - This effect usually occurs at higher doses. | ||
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Symptoms of clonidine overdose include constriction of pupils of the eye, drowsiness, high blood pressure followed by a drop in pressure, irritability, low body temperature, slowed breathing, slowed heartbeat, slowed reflexes, and weakness.{{citation needed}} | Symptoms of clonidine overdose include constriction of pupils of the eye, drowsiness, high blood pressure followed by a drop in pressure, irritability, low body temperature, slowed breathing, slowed heartbeat, slowed reflexes, and weakness.{{citation needed}} | ||
There are case reports that show [[naloxone]] may be a useful antidote in treating clonidine overdoses. However, this is not in widespread clinical use.<ref> | There are case reports that show [[naloxone]] may be a useful antidote in treating clonidine overdoses. However, this is not in widespread clinical use.<ref>{{cite journal | vauthors=((Niemann, J. T.)), ((Getzug, T.)), ((Murphy, W.)) | journal=Annals of Emergency Medicine | title=Reversal of clonidine toxicity by naloxone | volume=15 | issue=10 | pages=1229–1231 | date= October 1986 | url=https://linkinghub.elsevier.com/retrieve/pii/S0196064486808745 | issn=01960644 | doi=10.1016/S0196-0644(86)80874-5}}</ref> | ||
===Tolerance and addiction potential=== | ===Tolerance and addiction potential=== | ||
Clonidine is [[Addiction potential::not addictive and has a low potential for abuse]]. The chronic use of clonidine can produce physical dependence and withdrawal symptoms if one suddenly stops their usage. Clonidine therapy should generally be gradually tapered when discontinuing therapy to avoid rebound hypertension from occurring. | Clonidine is [[Addiction potential::not addictive and has a low potential for abuse]]. The chronic use of clonidine can produce physical dependence and withdrawal symptoms if one suddenly stops their usage. Clonidine therapy should generally be gradually tapered when discontinuing therapy to avoid rebound hypertension from occurring. | ||
Although clonidine is not considered to be addictive, cases of misuse have been documented among certain groups with pre-existing substance use disorders. It is sometimes used in combination with [[opiates]] to extend and potentiate their effects.<ref>Dennison, S. J. | Although clonidine is not considered to be addictive, cases of misuse have been documented among certain groups with pre-existing substance use disorders. It is sometimes used in combination with [[opiates]] to extend and potentiate their effects.<ref>{{cite journal | vauthors=((Dennison, S. J.)) | journal=The Psychiatric Quarterly | title=Clonidine abuse among opiate addicts | volume=72 | issue=2 | pages=191–195 | date= 2001 | issn=0033-2720 | doi=10.1023/a:1010375727768}}</ref> This practice may increase the risk of oversedation and respiratory depression associated with opioid use. | ||
===Dangerous interactions=== | ===Dangerous interactions=== | ||
{{DangerousInteractions/Intro}} | {{DangerousInteractions/Intro}} | ||
{{DangerousInteractions/Depressants}} | |||
==Legal status== | ==Legal status== | ||
{{LegalStub}} | {{LegalStub}} | ||
'''United States:''' Clonidine is only available with a prescription.<ref>CLONIDINE HYDROCHLORIDE TABLETS, USP | * '''Germany:''' Clonidine is prescription medicine, according to Anlage 1 AMVV.<ref>{{Citation | title=AMVV - Verordnung über die Verschreibungspflicht von Arzneimitteln | url=https://www.gesetze-im-internet.de/amvv/BJNR363210005.html}}</ref> | ||
*'''Switzerland:''' Clonidine is listed as a "Abgabekategorie B" pharmaceutical, which requires a prescription.{{citation needed}} | |||
* '''United States:''' Clonidine is only available with a prescription.<ref>{{Citation | title=CLONIDINE HYDROCHLORIDE TABLETS, USP Rx only | url=https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=091a191f-4380-4960-834c-0618da738403&type=display}}</ref> | |||
==See also== | ==See also== | ||
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==External links== | ==External links== | ||
*[https://en.wikipedia.org/wiki/Clonidine Clonidine (Wikipedia)] | *[https://en.wikipedia.org/wiki/Clonidine Clonidine (Wikipedia)] | ||
*[https://www.erowid.org/pharms/clonidine/ Clonidine (Erowid Vault)] | |||
*[https://isomerdesign.com/PiHKAL/explore.php?id=3717 Clonidine (Isomer Design)] | |||
*[https://drugs-forum.com/wiki/Clonidine Clonidine (Drugs-Forum)] | |||
==Literature== | ==Literature== | ||
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[[Category:Psychoactive substance]] | [[Category:Psychoactive substance]] | ||
[[Category:Depressant]] | [[Category:Depressant]] | ||
[[Category:Arylaminoimidazoline]] | |||