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Clonidine: Difference between revisions

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'''Clonidine''' (also known by the trade names '''Catapres''', '''Kapvay''', '''Nexiclon''', '''Clophelin''', and others) is a medication used to treat [[increased blood pressure|high blood pressure]], attention deficit hyperactivity disorder, [[anxiety]] disorders, tic disorders, [[drug withdrawal|substance withdrawal]] (from either [[alcohol]], [[opioids]], or smoking tobacco), migraine, menopausal flushing, [[diarrhea]], and certain pain conditions.<ref>Brayfield, A, ed. (13 January 2014). "Clonidine". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 28 June 2014.</ref> It is classified as a centrally acting α2 [[adrenergic]] [[agonist]] and imidazoline [[receptor]] [[agonist]]. It has been in clinical use for over 40 years.<ref>Neil, MJ (November 2011). "Clonidine: clinical pharmacology and therapeutic use in pain management.". Current Clinical Pharmacology. 6 (4): 280–7. PMID 21827389.</ref>
'''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">{{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" />
 
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>
 
Clonidine has several off-label uses. It 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.<ref>{{cite journal|last1=van der Kolk|first1=BA|title=The drug treatment of post-traumatic stress disorder.|journal=Journal of Affective Disorders|date=September–October 1987|volume=13|issue=2|pages=203–13|doi=10.1016/0165-0327(87)90024-3|pmid=2960712}}</ref><ref>{{cite journal|last1=Sutherland|first1=SM|last2=Davidson|first2=JR|title=Pharmacotherapy for post-traumatic stress disorder.|journal=The Psychiatric Clinics of North America|date=June 1994|volume=17|issue=2|pages=409–23|pmid=7937367}}</ref><ref>{{cite journal|last1=Southwick|first1=SM|last2=Bremner|first2=JD|last3=Rasmusson|first3=A|last4=Morgan CA|first4=3rd|last5=Arnsten|first5=A|last6=Charney|first6=DS|title=Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder.|journal=Biological Psychiatry|date=November 1999|volume=46|issue=9|pages=1192–204|doi=10.1016/S0006-3223(99)00219-X|pmid=10560025}}</ref><ref>{{cite journal|last1=Strawn|first1=JR|last2=Geracioti|first2=TD, Jr|title=Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder.|journal=Depression and Anxiety|date=2008|volume=25|issue=3|pages=260–71|doi=10.1002/da.20292|pmid=17354267}}</ref><ref>{{cite journal|last1=Boehnlein|first1=JK|last2=Kinzie|first2=JD|title=Pharmacologic reduction of CNS noradrenergic activity in PTSD: the case for clonidine and prazosin.|journal=Journal of Psychiatric Practice|date=March 2007|volume=13|issue=2|pages=72–8|doi=10.1097/01.pra.0000265763.79753.c1|pmid=17414682}}</ref><ref>{{cite journal|last1=Huffman|first1=JC|last2=Stern|first2=TA|title=Neuropsychiatric consequences of cardiovascular medications.|journal=Dialogues in Clinical Neuroscience|date=2007|volume=9|issue=1|pages=29–45|pmid=17506224|pmc=3181843}}</ref><ref>{{cite journal|last1=Najjar|first1=F|last2=Weller|first2=RA|last3=Weisbrot|first3=J|last4=Weller|first4=EB|title=Post-traumatic stress disorder and its treatment in children and adolescents.|journal=Current Psychiatry Reports|date=April 2008|volume=10|issue=2|pages=104–8|doi=10.1007/s11920-008-0019-0|pmid=18474199}}</ref><ref>{{cite journal|last1=Ziegenhorn|first1=AA|last2=Roepke|first2=S|last3=Schommer|first3=NC|last4=Merkl|first4=A|last5=Danker-Hopfe|first5=H|last6=Perschel|first6=FH|last7=Heuser|first7=I|last8=Anghelescu|first8=IG|last9=Lammers|first9=CH|title=Clonidine improves hyperarousal in borderline personality disorder with or without comorbid posttraumatic stress disorder: a randomized, double-blind, placebo-controlled trial|journal=Journal of Clinical Psychopharmacology|date=April 2009|volume=29|issue=2|pages=170–3|doi=10.1097/JCP.0b013e31819a4bae|pmid=19512980}}</ref>
 
==History and culture==
In the early 1960s, the medicinal chemist Helmut Stähle was tasked by Boehringer Ingelheim with synthesizing a peripherally active a-adrenergic compound that would be useful for nasal decongestion as simple nose drops. A locally acting a-adrenergic vasoconstrictor agent was expected to provide relief from the symptoms of the common cold by shrinking the swollen nasal membranes and producing an unobstructed air passage.<ref name="Stahle" />
 
The synthetic design of clonidine was achieved when Stähle had the idea of substituting two chlorine groups on the phenyl group of the imidazoline structure, which most of the newer decongestive agents at the time were derived from. At that time, a double halogen substitution was still unusual for pharmaceuticals, and the prevailing opinion was that compounds with several halogen atoms would at best be useful as pesticides. Despite this, clonidine was pursued and discovered to have a remarkably high vasoconstrictive and decongestive effect at an unusually low dosage level.<ref name="Stahle" />
 
The decongestive effects were then determined by nasal cavity tests on anesthetized dogs. After the first trial in humans, it became clear that clonidine's decongestant properties were far less interesting than its potent anti-hypertensive effects. The compound was then developed for this new indication and was introduced into therapy in 1966 under the trade name '''Catapres''', where it saw widespread use.<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>{{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==
Clonidine is an imdiazoline compound, meaning that its main chemistry is of an imidazole ring. A nitrogen bonded to the imidazole and chlorinated phenyl group makes an amine.
Clonidine, or 2-[(2,6-Dichlorophenyl)imino]imidazoline, is a compound of the imidazoline chemical class. Imidazolines are substituted amidines in which the amidine function is incorporated into an imidazoline ring. This portion is connected to an aromatic nucleus by way of a methylene bridge.
 
Additionally, two chlorine atoms are substituted in the 2- and 6-positions of the phenyl ring. This addition has the critical effect of making the molecule sufficiently lipophilic to penetrate the blood-brain barrier.{{citation needed}}
 
Other compounds of this class include the a-adrenergic agents tolazoline, naphazoline, and phentolamine. The a-adrenergic effects of clonidine and other imidazolidine compounds may be explained on the basis of a structural overlap between clonidine and [[norepinephrine]].
 
==Pharmacology==
==Pharmacology==
{{pharmacology}}
===Pharmacodynamics===
Binding affinities:
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>
Clonidine shows agonism at the following receptors, namely the alpha (α) receptors. It lowers blood pressure by stimulating the α<sub>2</sub> receptors in the brain.<ref>Isaac L., "Clonidine in the central nervous system: site and mechanism of hypotensive action." (1980) https://www.ncbi.nlm.nih.gov/pubmed/6154837</ref>
 
*α<sub>1A</sub> receptor: 316.23 nM
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}}
*α<sub>1B</sub> receptor: 316.23 nM
 
*α<sub>1D</sub> receptor: 125.89 nM
The α<sub>2A</sub>- and α<sub>2C</sub> receptors are located presynaptically and inhibit the released of noradrenaline from sympathetic nerves. Stimulation of these receptors decreases sympathetic tone, resulting in decreases in blood pressure and heart rate. Sedation and analgesia is mediated by centrally located α<sub>2A</sub> receptors, while peripheral α<sub>2B</sub> receptors mediate constriction of vascular smooth muscle. α<sub>2A</sub> receptors also mediate essential components of the analgesic effect of nitrous oxide in the spinal cord. Clonidine stimulates all three α<sub>2</sub> receptor subtypes with similar potency.{{citation needed}}
*α<sub>2A</sub> receptor: 42.92 nM
 
*α<sub>2B</sub> receptor: 106.31 nM
Clonidine also has peripheral α<sub>1</sub> agonist activity.{{citation needed}}
*α<sub>2C</sub> receptor: 233.1 nM
 
Clonidine also binds to the Imidazoline I<sub>1</sub> receptor as an agonist.
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"
|-
! Binding Sites
! Binding Affinity K<sub>i</sub> (nM)<ref>Roth, BL; Driscol, J (12 January 2011). "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Archived from the original on 8 November 2013. Retrieved 25 November 2013.</ref>
|-
| α<sub>1A</sub>
| 316.23
|-
| α<sub>1B</sub>
| 316.23
|-
| α<sub>1D</sub>
| 125.89
|-
| α<sub>2A</sub>
| 42.92
|-
| α<sub>2B</sub>
| 106.31
|-
| α<sub>2C</sub>
| 233.1
|}
 
===Pharmacokinetics===
Clonidine is rapidly absorbed from the gastrointestinal tract and has excellent CNS penetration because of lipid solubility.{{citation needed}} Peak plasma concentrations are reached 3-5 hours after a single oral dose.{{citation needed}} No known pharmacologically active metabolites exist.{{citation needed}} Plasma half-life is 12-16 hours, with the antihypertensive effects occurring within 30-60 minutes of ingestion. Clonidine is excreted unchanged in the urine and is metabolized by the liver.{{citation needed}}


Some studies suggest that clonidine in low doses can boost growth hormone levels.<ref>Effect of clonidine on growth hormone, prolactin, luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone in the serum of normal men. (1990). Lal S, Tolis G, Martin SB, Brown GM, Guyda H. https://www.ncbi.nlm.nih.gov/pubmed/1184719</ref>
==Subjective effects==
==Subjective effects==
{{EffectStub}}
 
''{{Preamble/SubjectiveEffects}}''                                                             
''{{Preamble/SubjectiveEffects}}''                                                             
{{effects/base
{{effects/base


|{{effects/physical|
|{{effects/physical|
*'''[[Effect::Sedation]]''' - Clonidine can be strong in its sedating effect.
*'''[[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.
** This can lead to atypical walking gait from decreased locomotion coordination. The effect can look similar to the "Thorazine shuffle," an effect caused by chlorpromazine (Thorazine) due to its sedating effect.
*'''[[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 heart rate]]'''
*'''[[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::Decreased blood pressure]]''' - Clonidine's sympatholytic effects lower blood pressure and is commonly used to treat hypertension.<ref>Mitchell A, Bührmann S, Opazo Saez A, Rushentsova U, Schäfers RF, Philipp T, et al. Clonidine lowers blood pressure by reducing vascular resistance and cardiac output in young, healthy males. Cardiovasc Drugs Ther 2005;19:49–55. pmid:15883756</ref>
*'''[[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]]''' - Clonidine's chance of causing this is relatively low, but caution ''should'' be taken if clonidine is taken with other drugs that can cause this. Intense physical activity should be avoided.
*'''[[Effect::Dry mouth]]'''
*'''[[Effect::Dry mouth]]'''
*'''[[Effect::Constipation]]'''
*'''[[Effect::Constipation]]'''
*'''Decreased blood pressure upon standing''' - This effect may be overwhelming at higher doses and can be described as a "head rush" or feeling of lightheadedness.
*'''[[Effect::Physical fatigue]]'''  
*'''[[Effect::Physical fatigue]]''' - This general feeling of decreased movement and tiredness is from sedation.
*'''[[Effect::Pupil constriction]]'''
*'''[[Effect::Dizziness]]''' - Clonidine can lead to an increased chance of falls due to this. This effect gets stronger with the dose increasing.
*'''[[Effect::Dizziness]]''' - This effect can increase the likelihood of falling and injuring oneself.
*'''Skin reactions''' - This can happen if clonidine is given in a patch, such as in Catapres-TTS.
*'''Raynaud's Phenomenon''' - Raynaud's Phenomenon occurs when the spasm of arteries results in reduced blood flow to the extremities, causing a pale tone, tingling, coldness, and numbness.
*'''[[Effect::Anxiety]]'''
*'''Raynaud's Phenomenon''' - Raynaud's Phenomenon occurs when the spasm of arteries results in reduced flood flow to the extremities, causing a pale tone, tingling, coldness, and numbness.
*'''[[Effect::Auditory suppression]]''' - According to anecdotal reports, this effect is likely due to very low blood pressure. It has been described as a "hollow" type distortion or loss of hearing.
}}
}}
|{{effects/cognitive|
|{{effects/cognitive|
*'''[[Effect::Cognitive fatigue]]'''
*'''[[Effect::Cognitive fatigue]]'''
*'''[[Effect::Anxiety suppression]]''' - Clonidine has relatively strong anxiolytic effects and is sometimes used clinically to treat anxiety.<ref>Hoehn-Saric R, Merchant AF, Keyser ML, Smith NVK. Effects of Clonidine on Anxiety Disorders. Arch Gen Psychiatry.</ref>
*'''[[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::Irritability]]''' - One can feel very agitated and annoyed at things. This especially happens when the medicine is suddenly stopped, which is an incorrect practice; clonidine should be [[tapering|tapered]] off of the user.
*'''[[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 suppression]]''' - This usually occurs at higher doses. The effect is also usually from the sedated state.
*'''[[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::Memory enhancement]]'''
*'''[[Effect::Thought deceleration]]'''
*'''[[Effect::Thought deceleration]]'''
}}
{{effects/auditory|
*'''[[Effect::Auditory suppression]]''' - Reports describe this effect as a "hollow" loss of hearing. It is believed to be a result of lowered blood pressure.
}}
{{effects/aftereffects|
*'''[[Effect::Irritability]]''' - One can feel very agitated and annoyed, especially with more ease. This especially happens when the medicine is suddenly stopped, which is an incorrect practice; clonidine should be [[tapering|tapered]] off of the user.
*'''[[Effect::Increased heart rate]]''' - This occurs as a rebound effect to clonidine's antihypertensive effects and is typically only prominent following sustained use.
*'''[[Effect::Increased blood pressure]]''' - This occurs as a rebound effect to clonidine's antihypertensive effects and is typically only prominent following sustained use.
}}
}}
}}
}}
===Experience reports===
There are currently {{#ask:[[Category:Clonidine]][[Category:Experience]] | format=count}} anecdotal reports which describe the effects of this compound within our [[experience index]].
{{#ask: [[Category:Clonidine]][[Category:Experience]]|format=ul|Columns=1}}
Additional experience reports can be found here:
* [https://erowid.org/experiences/subs/exp_Pharms_Clonidine.shtml Erowid Experience Vaults: Clonidine]


==Toxicity and harm potential==
==Toxicity and harm potential==
It is strongly recommended that one use [[responsible use|harm reduction practices]] when using this drug, especially concurrently with other [[depressants]]. According to drugs.com, clonidine's maximum medical dose for hypotension is 2.4 miligrams in divided doses.  
 
At therapeutic doses (0.2-0.9 mg/d), clonidine is commonly associated with adverse effects such as dry mouth, sedation, dizziness, and constipation. While generally safe, at toxic doses clonidine can cause serious cardiopulmonary instability and central nervous system (CNS) depression in children and adults. Caution should be used when clonidine is taken with other [[depressants]].
 
It is strongly recommended that one use [[responsible use|harm reduction practices]] when using this substance.  


===Lethal dosage===
===Lethal dosage===
According to dailymed.nlm.nih.gov's prescribing information page for clonidine, clonidine's oral [[LD50|LD<sub>50</sub>]] in mice is 206 mg/kg and for rats, 465 mg/kg.  
The oral [[LD50|LD<sub>50</sub>]] for clonidine in mice is 206 mg/kg and for rats, 465 mg/kg.{{citation needed}} In humans, lethality is rare with a small number of reported deaths. Morbidity, in terms of cardiorespiratory and CNS dysfunction, generally tends to be more severe in young persons than in adults.{{citation needed}}
 
===Overdose===
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 studies that show [[naloxone]] may be a useful antidote in treating clonidine overdoses. However, this is not in widespread clinical use.<ref> Reversal of clonidine toxicity by naloxone. Niemann, James T et al. Annals of Emergency Medicine, Volume 15, Issue 10, 1229 - 1231</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 seems to be able to cause addiction and can be tolerated over periods of time. It is used concurrently with prescription pain-killers ([[opioids]]) recreationally because it might have potentiating effects, but this has not been studied and is dangerous due to concurrent use of depressants.
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>{{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}}
*'''[[Depressants]]''' (''[[1,4-Butanediol]], [[2M2B]], [[alcohol]],<ref>Koski, A., Ojanperä, I., & Vuori, E. (2002). Alcohol and benzodiazepines in fatal poisonings. Alcoholism: Clinical and Experimental Research, 26(7), 956-959.</ref> [[benzodiazepines]], [[barbiturates]], [[GHB]]/[[GBL]], [[methaqualone]], [[opioids]]'') - This combination can result in dangerous or even fatal levels of [[respiratory depression]]. These substances potentiate the [[muscle relaxation]], [[sedation]] and [[amnesia]] caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the [[recovery position]] or have a friend move them into it.
{{DangerousInteractions/Depressants}}


==Legality==
==Legal status==
{{LegalStub}}
{{LegalStub}}
'''United States:''' In the US, clonidine is only available through prescription.{{citation needed}}
* '''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==
*[[Responsible use]]
*[[Responsible use]]
*[[Depressant]]
*[[Depressant]]
*[[Adrenaline]] (Epinephrine)
*[[Noradrenaline]] (Norpinephrine)
==External links==
*[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==
* Stähle, H. (2000). A historical perspective: development of clonidine. Best Practice & Research Clinical Anaesthesiology, 14(2), 237-246. https://doi.org/10.1053/bean.2000.007
==References==
==References==
<references />
<references />
{{references}}
 
[[Category:Substance]][[Category:Psychoactive substance]][[Category:Proofread]]
[[Category:Psychoactive substance]]
[[Category:Depressant]]
[[Category:Arylaminoimidazoline]]
Retrieved from "http://psy.st/wiki/Clonidine"