Clonidine Explained

Watchedfields:changed
Verifiedrevid:456485213
Width:175
Width2:200
Tradename:Catapres, Kapvay, Nexiclon, others
Dailymedid:Clonidine
Pregnancy Au:B3
Routes Of Administration:Oral, epidural, intravenous (IV), transdermal, topical
Class:Centrally acting α2A-agonist hypotensive agent
Atc Prefix:C02
Atc Suffix:AC01
Legal Au:S4
Legal Ca:Rx-only
Legal Uk:POM
Legal Us:Rx-only
Bioavailability:70–80% (oral),[1] 60–70% (transdermal)[2]
Protein Bound:20–40%
Metabolism:Liver to inactive metabolites, 2/3 CYP2D6[3]
Elimination Half-Life:IR: 12–16 hours; 41 hours in kidney failure,[4] [5] 48 hours for repeated dosing
Excretion:Urine (72%)[6]
Onset:IR: 30–60 minutes after an oral dose[7]
Cas Number:4205-90-7
Pubchem:2803
Iuphar Ligand:516
Drugbank:DB00575
Chemspiderid:2701
Unii:MN3L5RMN02
Kegg:D00281
Chebi:3757
Chembl:134
Iupac Name:N-(2,6-Dichlorophenyl)-4,5--1H-imidazol-2-amine
C:9
H:9
Cl:2
N:3
Smiles:Clc1cccc(Cl)c1N/C2=N/CCN2
Stdinchi:1S/C9H9Cl2N3/c10-6-2-1-3-7(11)8(6)14-9-12-4-5-13-9/h1-3H,4-5H2,(H2,12,13,14)
Stdinchikey:GJSURZIOUXUGAL-UHFFFAOYSA-N

Clonidine, sold under the brand name Catapres among others, is an α2A-adrenergic agonist[8] medication used to treat high blood pressure, ADHD, drug withdrawal (alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, and certain pain conditions.[9] The drug is often prescribed off-label for tics. It is used orally (by mouth), by injection, or as a transdermal skin patch.[9] Onset of action is typically within an hour with the effects on blood pressure lasting for up to eight hours.[9]

Common side effects include dry mouth, dizziness, headaches, hypotension, and sleepiness.[9] Severe side effects may include hallucinations, heart arrhythmias, and confusion.[10] If rapidly stopped, withdrawal effects may occur, such as a dangerous rise in blood pressure.[9] Use during pregnancy or breastfeeding is not recommended.[10] Clonidine lowers blood pressure by stimulating α2 receptors in the brain, which results in relaxation of many arteries.[9]

Clonidine was patented in 1961 and came into medical use in 1966.[11] [12] [13] It is available as a generic medication.[9] In 2021, it was the 80th most commonly prescribed medication in the United States, with more than 8million prescriptions.[14] [15]

Medical uses

Clonidine is used to treat high blood pressure, attention deficit hyperactivity disorder (ADHD), drug withdrawal (alcohol, opioids, or smoking), menopausal flushing, diarrhea, and certain pain conditions. It also sees some use off-label for episodic insomnia, restless-legs syndrome, and anxiety, among other uses.[9]

Resistant hypertension

Clonidine may be effective for lowering blood pressure in people with resistant hypertension.[16]

Clonidine works by slowing the pulse rate and exerts a reduction of serum concentrations of renin, aldosterone, and catecholamines.[17]

Attention deficit hyperactivity disorder

Clonidine may improve symptoms of attention deficit hyperactivity disorder in some people but causes many adverse effects and the beneficial effect is modest.[18] In Australia, clonidine is an accepted but not approved use for ADHD by the TGA.[19] Clonidine, along with methylphenidate, has been studied for treatment of ADHD.[20] [21] [22] While not as effective as methylphenidate in treating ADHD, clonidine does offer some benefit;[20] it can also be useful in combination with stimulant medications.[23] Some studies show clonidine to be more sedating than guanfacine, which may be better at bedtime along with an arousing stimulant in the morning.[24] [25] Clonidine has been used to reduce sleep disturbances in ADHD, including to help offset stimulant-associated insomnia.[26] [27] [28] [29] Unlike stimulant medications, clonidine is regarded as having no abuse potential, and may even be used to reduce abuse of drugs including nicotine and cocaine.[30]

In the US, only the extended-release form of clonidine is approved for ADHD treatment.[31]

Drug withdrawal

Clonidine may be used to ease drug withdrawal symptoms associated with abruptly stopping the long-term use of opioids, alcohol, benzodiazepines and nicotine.[32] It can alleviate opioid withdrawal symptoms by reducing the sympathetic nervous system response such as tachycardia and hypertension, hyperhidrosis (excessive sweating), hot and cold flashes, and akathisia.[33] It may also be helpful in aiding smokers to quit.[34] The sedation effect can also be useful. Clonidine may also reduce severity of neonatal abstinence syndrome in infants born to mothers that are using certain drugs, particularly opioids.[35] In infants with neonatal withdrawal syndrome, clonidine may improve the neonatal intensive care unit Network Neurobehavioral Score.[36]

Clonidine has also been suggested as a treatment for rare instances of dexmedetomidine withdrawal.[37]

Spasticity

Clonidine has some role in the treatment of spasticity, acting principally by inhibiting excessive sensory transmission . Its use, however, is mainly as a second or third line agent, due to side effects such as hypotension, bradycardia, and drowsiness.[38] Clonidine can be administered intrathecally,[39] which confers various benefits, including a reduction or prevention of the blood pressure lowering effects and increased effectiveness against spasticity.[40] The effectiveness of intrathecal clonidine is comparable to that of intrathecal baclofen for spasticity.[40]

Clonidine suppression test

The reduction in circulating norepinephrine by clonidine was used in the past as an investigatory test for phaeochromocytoma, which is a catecholamine-synthesizing tumor, usually found in the adrenal medulla.[41] In a clonidine suppression test, plasma catecholamine levels are measured before and 3 hours after a 0.3 mg oral test dose has been given to the patient. A positive test occurs if there is no decrease in plasma levels.[41]

Other uses

Clonidine also has several off-label uses, and has been prescribed to treat psychiatric disorders including stress, sleep disorders, hyperarousal caused by post-traumatic stress disorder, borderline personality disorder, and other anxiety disorders.[42] [43] [44] [45] [46] [47] [48] [49] Clonidine is also a mild sedative, and can be used as premedication before surgery or procedures.[50] It has also been studied as a way to calm acute manic episodes.[51] Its epidural use for pain during heart attack, and postoperative and intractable pain has also been studied extensively.[52] Clonidine can be used in restless legs syndrome.[53] It can also be used to treat facial flushing and redness associated with rosacea.[54] It has also been successfully used topically in a clinical trial as a treatment for diabetic neuropathy.[55] Clonidine can also be used for migraine headaches and hot flashes associated with menopause.[56] [57] Clonidine has also been used to treat refractory diarrhea associated with irritable bowel syndrome, fecal incontinence, diabetes, diarrhea associated with opioid withdrawal, intestinal failure, neuroendocrine tumors, and cholera.[58] Clonidine can be used in the treatment of Tourette syndrome (specifically for tics).[59] Clonidine has also had some success in clinical trials for helping to remove or ameliorate the symptoms of hallucinogen persisting perception disorder (HPPD).[60]

Injection of α2 receptor agonists into the knee joint space, including clonidine, may reduce the severity of knee pain after arthroscopic knee surgery.[61]

Light-activated derivatives of clonidine (adrenoswitches) have been developed for research purposes and shown to control pupillary reflex with light in blind mice by topical application.[62]

Pregnancy and breastfeeding

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 appears in high concentration in breast milk; a nursing infant's serum clonidine concentration is approximately 2/3 of the mother's.[63] Caution is warranted in women who are pregnant, planning to become pregnant, or are breastfeeding.[64]

Adverse effects

The principal adverse effects of clonidine are sedation, dry mouth, and hypotension (low blood pressure).[6]

By frequency[65] [66]

Very common (>10% frequency):

Common (1–10% frequency):

Uncommon (0.1–1% frequency):

Rare (<0.1% frequency):

Withdrawal

Because clonidine suppresses sympathetic outflow, resulting in lower blood pressure, sudden discontinuation can result in acute hypertension due to a rebound in sympathetic outflow. In extreme cases, this can result in a hypertensive crisis, which is a medical emergency.[67]

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.[68] [69]

Pharmacology

Clonidine[70]
Site Ki (nM) Species Ref
>1,000 Human
>10,000 Rat [71]
>10,000 Human
316.23Human [72]
316.23 Human
125.89 Human
35.48  - 61.65 Human [73]
69.18  - 309.0 Human
134.89  - 501.2Human
> 10,000 Rat [74]
31.62Bovine
I2 (cortex) >1,000 Rat
>1,000 Rat
>1,000 Rat
>10,000 Guinea Pig [75]
The Ki refers to a drug's affinity for a receptor. The smaller the Ki, the higher the affinity for that receptor.[76] Reported imidazoline-2 binding is measured in the cortex - I2 receptor bindings measured in stomach membranes are much lower.[77]

Mechanism of action

Clonidine crosses the blood–brain barrier.[4]

High blood pressure

Clonidine treats high blood pressure by stimulating α2 receptors in the brainstem, which decreases peripheral vascular resistance, lowering blood pressure. It has specificity towards the presynaptic α2 receptors in the vasomotor center in the brainstem. This binding has a sympatholytic effect, suppresses release of norepinephrine, ATP, renin, and neuropeptide Y which if released would increase vascular resistance.[8]

Clonidine also acts as an agonist at imidazoline-1 (I1) receptors in the brain, and it is hypothesized that this effect may contribute to reducing blood pressure by reducing signaling in the sympathetic nervous system; this effect acts upstream of the central α2 agonist effect of clonidine.[8] [78]

Clonidine may also cause bradycardia, theoretically by increasing signaling through the vagus nerve. When given intravenously, clonidine can temporarily increase blood pressure by stimulating α1 receptors in smooth muscles in blood vessels.[79] This hypertensive effect is not usual when clonidine is given orally or by the transdermal route.[8]

Plasma concentration of clonidine exceeding 2.0 ng/mL does not provide further blood pressure reduction.[80]

Attention deficit hyperactivity disorder

In the setting of attention deficit hyperactivity disorder (ADHD), clonidine's molecular mechanism of action occurs due to its agonism at the α2A adrenergic receptor, the subtype of the adrenergic receptor that is most principally found in the brain. Within the brain, the α2A adrenergic receptors are found within the prefrontal cortex (PFC), among other areas. The α2A adrenergic receptors are found on the presynaptic cleft of a given neuron, and, when activated by an agonist, the effect on downstream neurons is inhibitory. The inhibition is accomplished by preventing the secretion of the neurotransmitter norepinephrine. Thus, clonidine's agonism on α2A adrenergic receptors in the PFC inhibits the action of downstream neurons by preventing the secretion of norepinephrine.[81]

This mechanism is similar to the brain's physiological inhibition of PFC neurons by the locus ceruleus (LC), which secretes norepinephrine into the PFC. Although norepinephrine can also bind to target adrenergic receptors on the downstream neuron (otherwise inducing a stimulatory effect), norepinephrine also binds to α2A adrenergic receptors (akin to clonidine's mechanism of action), inhibiting the release of norepinephrine by that neuron and inducing an inhibitory effect. Because the PFC is required for working memory and attention, it is thought that clonidine's inhibition of PFC neurons helps to eliminate irrelevant attention (and subsequent behaviors), improving the person's focus and correcting deficits in attention.

Growth hormone test

Clonidine stimulates release of GHRH hormone from the hypothalamus, which in turn stimulates pituitary release of growth hormone.[82] This effect has been used as part of a "growth hormone test," which can assist with diagnosing growth hormone deficiency in children.[83]

Pharmacokinetics

After being ingested, clonidine is absorbed into the blood stream rapidly with an overall bioavailability around 70–80%.[84] Peak concentrations in human plasma occur within 60–90 minutes for the "immediate release" (IR) version of the drug, which is shorter than the "extended release" (ER/XR) version.[85] Clonidine is fairly lipid soluble with the logarithm of its partition coefficient (log P) equal to 1.6;[86] to compare, the optimal log P to allow a drug that is active in the human central nervous system to penetrate the blood brain barrier is 2.0.[87] Less than half of the absorbed portion of an orally administered dose will be metabolized by the liver into inactive metabolites, with roughly the other half being excreted unchanged by the kidneys. About one-fifth of an oral dose will not be absorbed, and is thus excreted in the feces. Work with liver microsomes shows in the liver clonidine is primarily metabolized by CYP2D6 (66%), CYP1A2 (10–20%), and CYP3A (0–20%) with negligible contributions from the less abundant enzymes CYP3A5, CYP1A1, and CYP3A4.[3] 4-hydroxyclonidine, the main metabolite of clonidine, is also an α2A agonist but is non lipophilic and is not believed to contribute to the effects of clonidine since it does not cross the blood–brain barrier.[88] [89]

Measurements of the half-life of clonidine vary widely, between 6 and 23 hours, with the half-life being greatly affected by and prolonged in the setting of poor kidney function. Variations in half-life may be partially attributable to CYP2D6 genetics.[3] Some research has suggested the half-life of clonidine is dose dependent and approximately doubles upon chronic dosing,[90] while other work contradicts this.[2] Following a 0.3 mg oral dose, a small study of five patients by Dollery et al. (1976) found half-lives ranging between 6.3 and 23.4 hours (mean 12.7).[91] A similar N=5 study by Davies et al. (1977) found a narrower range of half-lives, between 6.7 and 13 hours (average 8.6 hours),[84] while an N=8 study by Keraäen et al. that included younger patients found a somewhat shorter average half-life of 7.5 hours.[92]

History

Clonidine was introduced in 1966.[93] It was first used as a hypertension treatment under the trade name of Catapres.[94]

Society and culture

Brand names

As of June 2017, clonidine was marketed under many brand names worldwide: Arkamin, Aruclonin, Atensina, Catapin, Catapres, Catapresan, Catapressan, Chianda, Chlofazoline, Chlophazolin, Clonid-Ophtal, Clonidin, Clonidina, Clonidinã, Clonidine, Clonidine hydrochloride, Clonidinhydrochlorid, Clonidini, Clonidinum, Clonigen, Clonistada, Clonnirit, Clophelinum, Dixarit, Duraclon, Edolglau, Haemiton, Hypodine, Hypolax, Iporel, Isoglaucon, Jenloga, Kapvay, Klofelino, Kochaniin, Lonid, Melzin, Menograine, Normopresan, Paracefan, Pinsanidine, Run Rui, and Winpress.[95] It was marketed as a combination drug with chlortalidone as Arkamin-H, Bemplas, Catapres-DIU, and Clorpres, and in combination with bendroflumethiazide as Pertenso.[95]

External links

Notes and References

  1. Web site: Catapres- clonidine hydrochloride tablet . DailyMed . 6 September 2016 . 21 December 2019 . The pharmacokinetics of clonidine is dose-proportional in the range of 100 to 600 µg.The absolute bioavailability of clonidine on oral administration is 70% to 80%. Peak plasma clonidine levels are attained in approximately 1 to 3 hours. . 4 August 2020 . https://web.archive.org/web/20200804180055/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7f569dc-6bed-42dc-9bec-940a9e6b090d . live .
  2. Lowenthal DT, Matzek KM, MacGregor TR . Clinical pharmacokinetics of clonidine . Clinical Pharmacokinetics . 14 . 5 . 287–310 . May 1988 . 3293868 . 10.2165/00003088-198814050-00002 . 24783447 .
  3. Claessens AJ, Risler LJ, Eyal S, Shen DD, Easterling TR, Hebert MF . CYP2D6 mediates 4-hydroxylation of clonidine in vitro: implication for pregnancy-induced changes in clonidine clearance . Drug Metabolism and Disposition . 38 . 9 . 1393–1396 . September 2010 . 20570945 . 10.1124/dmd.110.033878 . 2939473 .
  4. Web site: Catapres- clonidine hydrochloride tablet . DailyMed . 6 September 2016 . 21 December 2019 . Following intravenous administration, clonidine displays biphasic disposition with a distribution half-life of about 20 minutes and an elimination half-life ranging from 12 to 16 hours. The half-life increases up to 41 hours in patients with severe impairment of renal function. Clonidine crosses the placental barrier. It has been shown to cross the blood–brain barrier in rats. . 4 August 2020 . https://web.archive.org/web/20200804180055/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7f569dc-6bed-42dc-9bec-940a9e6b090d . live .
  5. Web site: Kapvay . RxList . 30 October 2014 . 12 October 2017 . https://web.archive.org/web/20171012000817/https://www.ncbi.nlm.nih.gov/pubmed/20570945 . live .
  6. Web site: clonidine (Rx) - Catapres, Catapres-TTS, more... Medscape Reference. WebMD. 10 November 2013. 4 December 2020. https://web.archive.org/web/20201204171104/https://reference.medscape.com/drug/catapres-tts-clonidine-342382. live.
  7. Web site: Catapres- clonidine hydrochloride tablet . DailyMed . 6 September 2016 . 21 December 2019 . Catapres tablets act relatively rapidly. The patient’s blood pressure declines within 30 to 60 minutes after an oral dose, the maximum decrease occurring within 2 to 4 hours. . 4 August 2020 . https://web.archive.org/web/20200804180055/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7f569dc-6bed-42dc-9bec-940a9e6b090d . live .
  8. Book: Westfall TC, Macarthur H, Westfall DP . Goodman and Gilman's The Pharmacological Basis of Therapeutics. 2017. McGraw-Hill Education / Medical. 9781259584732 . Brunton L, Knollmann B, Hilal-Dandan R . 13th. en. Chapter 12:Adrenergic Agonists and Antagonists.
  9. Web site: Clonidine Monograph for Professionals . Drugs.com . American Society of Health-System Pharmacists . 2 February 2019 . en . 3 February 2019 . https://web.archive.org/web/20190203030724/https://www.drugs.com/monograph/clonidine.html . live .
  10. Book: British national formulary : BNF 76. 2018. Pharmaceutical Press. 9780857113382. 144. 76.
  11. Neil MJ . Clonidine: clinical pharmacology and therapeutic use in pain management . Current Clinical Pharmacology . 6 . 4 . 280–287 . November 2011 . 21827389 . 10.2174/157488411798375886 . 40756251 .
  12. Stähle H . A historical perspective: development of clonidine. Best Practice & Research Clinical Anaesthesiology. June 2000. 14. 2. 237–246. 10.1053/bean.2000.0079.
  13. Book: Fischer J, Ganellin CR . Analogue-based Drug Discovery . 2006 . John Wiley & Sons . 9783527607495 . 550 . en . 12 September 2020 . 29 April 2023 . https://web.archive.org/web/20230429051619/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA550 . live .
  14. Web site: The Top 300 of 2021 . ClinCalc . 14 January 2024 . 15 January 2024 . https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx . live .
  15. Web site: Clonidine - Drug Usage Statistics . ClinCalc . 14 January 2024.
  16. Viera AJ . Hypertension Update: Resistant Hypertension . FP Essent . 469 . 20–25 . June 2018 . 29863319 .
  17. Web site: CATAPRES- clonidine hydrochloride tablet . DailyMed . 6 September 2016 . 21 December 2019 . Slowing of the pulse rate has been observed in most patients given clonidine, but the drug does not alter normal hemodynamic response to exercise. Other studies in patients have provided evidence of a reduction in plasma renin activity and in the excretion of aldosterone and catecholamines. . 4 August 2020 . https://web.archive.org/web/20200804180055/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7f569dc-6bed-42dc-9bec-940a9e6b090d . live .
  18. Connor DF, Fletcher KE, Swanson JM . A meta-analysis of clonidine for symptoms of attention-deficit hyperactivity disorder . Journal of the American Academy of Child and Adolescent Psychiatry . 38 . 12 . 1551–1559 . December 1999 . 10596256 . 10.1097/00004583-199912000-00017 .
  19. Book: Rossi, S . 978-0-9805790-9-3 . Australian Medicines Handbook . Adelaide . The Australian Medicines Handbook Unit Trust . 2013 . 2013 .
  20. Palumbo DR, Sallee FR, Pelham WE, Bukstein OG, Daviss WB, McDERMOTT MP . Clonidine for attention-deficit/hyperactivity disorder: I. Efficacy and tolerability outcomes . Journal of the American Academy of Child and Adolescent Psychiatry . 47 . 2 . 180–188 . February 2008 . 18182963 . 10.1097/chi.0b013e31815d9af7 .
  21. Daviss WB, Patel NC, Robb AS, McDERMOTT MP, Bukstein OG, Pelham WE, Palumbo D, Harris P, Sallee FR . Clonidine for attention-deficit/hyperactivity disorder: II. ECG changes and adverse events analysis . Journal of the American Academy of Child and Adolescent Psychiatry . 47 . 2 . 189–198 . February 2008 . 18182964 . 10.1097/chi.0b013e31815d9ae4 .
  22. Kornfield R, Watson S, Higashi AS, Conti RM, Dusetzina SB, Garfield CF, Dorsey ER, Huskamp HA, Alexander GC . Effects of FDA advisories on the pharmacologic treatment of ADHD, 2004-2008 . Psychiatric Services . 64 . 4 . 339–346 . April 2013 . 23318985 . 4023684 . 10.1176/appi.ps.201200147 .
  23. Kollins SH, Jain R, Brams M, Segal S, Findling RL, Wigal SB, Khayrallah M . Clonidine extended-release tablets as add-on therapy to psychostimulants in children and adolescents with ADHD . Pediatrics . 127 . 6 . e1406–e1413 . June 2011 . 21555501 . 3387872 . 10.1542/peds.2010-1260 .
  24. Jäkälä P, Riekkinen M, Sirviö J, Koivisto E, Kejonen K, Vanhanen M, Riekkinen P . Guanfacine, but not clonidine, improves planning and working memory performance in humans . Neuropsychopharmacology . 20 . 5 . 460–470 . May 1999 . 10192826 . 10.1016/S0893-133X(98)00127-4 . free .
  25. Clonidine and Guanfacine IR vs ER: Old Drugs With "New" Formulations . 1 August 2014 . Mental Health Clinician . 2014 . 10.9740/mhc.n186955 . Freeland K, Turner A, Gormley L . 4 . 22–26 . free . 9 August 2014 . https://web.archive.org/web/20140809181310/http://cpnp.org/resource/mhc/2014/01/clonidine-and-guanfacine-ir-vs-er-old-drugs-new-formulations . live .
  26. Nguyen M, Tharani S, Rahmani M, Shapiro M . A review of the use of clonidine as a sleep aid in the child and adolescent population . Clinical Pediatrics . 53 . 3 . 211–216 . March 2014 . 24027233 . 10.1177/0009922813502123 . 742140 .
  27. Hoban TF . Assessment and treatment of disturbed sleep in attention deficit hyperactivity disorder . Expert Review of Neurotherapeutics . 4 . 2 . 307–316 . March 2004 . 15853572 . 10.1586/14737175.4.2.307 . 35000868 .
  28. Book: Handbook of Disruptive Behavior Disorders . Schachar R, Ickowicz A . Pharmacological Treatment of Attention-Deficit/HyperactivityDisorder . 1999 . 221–254 . Springer US . 10.1007/978-1-4615-4881-2_10 . 978-1-4613-7214-1.
  29. Wilens TE, Biederman J, Spencer T . Clonidine for sleep disturbances associated with attention-deficit hyperactivity disorder . Journal of the American Academy of Child and Adolescent Psychiatry . 33 . 3 . 424–426 . 1994 . 8169189 . 10.1097/00004583-199403000-00018 .
  30. Clemow DB, Walker DJ . The potential for misuse and abuse of medications in ADHD: a review . Postgraduate Medicine . 126 . 5 . 64–81 . September 2014 . 25295651 . 10.3810/pgm.2014.09.2801 . 207580823 .
  31. Web site: Highlights of Prescribing Information: Kapvay . US FDA . 31 March 2024.
  32. Fitzgerald PJ . 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 . 171–183 . October 2013 . 24151426 . 3798293 . 10.4137/SART.S13019 .
  33. Book: Giannini AJ . Drugs of Abuse . 2nd . Los Angeles . Practice Management Information . 1997 .
  34. Gourlay SG, Stead LF, Benowitz NL . Clonidine for smoking cessation . The Cochrane Database of Systematic Reviews . 2008 . 3 . CD000058 . 2004 . 15266422 . 7038651 . 10.1002/14651858.CD000058.pub2 .
  35. Streetz VN, Gildon BL, Thompson DF . Role of Clonidine in Neonatal Abstinence Syndrome: A Systematic Review . The Annals of Pharmacotherapy . 50 . 4 . 301–310 . April 2016 . 26783353 . 10.1177/1060028015626438 . 40652097 .
  36. Disher T, Gullickson C, Singh B, Cameron C, Boulos L, Beaubien L, Campbell-Yeo M . Pharmacological Treatments for Neonatal Abstinence Syndrome: A Systematic Review and Network Meta-analysis . JAMA Pediatrics . 173 . 3 . 234–243 . March 2019 . 30667476 . 6439896 . 10.1001/jamapediatrics.2018.5044 .
  37. Kukoyi A, Coker S, Lewis L, Nierenberg D . Two cases of acute dexmedetomidine withdrawal syndrome following prolonged infusion in the intensive care unit: Report of cases and review of the literature . Human & Experimental Toxicology . January 2013 . 32 . 1 . 107–110 . 10.1177/0960327112454896 . 23111887 . 31570614 .
  38. Chang E, Ghosh N, Yanni D, Lee S, Alexandru D, Mozaffar T . A Review of Spasticity Treatments: Pharmacological and Interventional Approaches . Critical Reviews in Physical and Rehabilitation Medicine . 25 . 1–2 . 11–22 . 2013 . 25750484 . 4349402 . 10.1615/CritRevPhysRehabilMed.2013007945 .
  39. Smith HS, Deer TR, Staats PS, Singh V, Sehgal N, Cordner H . Intrathecal drug delivery . Pain Physician . 11 . 2 Suppl . S89–S104 . March 2008 . 10.36076/ppj.2008/11/S89 . 18443642 .
  40. Rémy-Néris O, Denys P, Bussel B . Intrathecal clonidine for controlling spastic hypertonia . Physical Medicine and Rehabilitation Clinics of North America . 12 . 4 . 939–51, ix . November 2001 . 10.1016/S1047-9651(18)30040-8 . 11723871 .
  41. Eisenhofer G, Goldstein DS, Walther MM, Friberg P, Lenders JW, Keiser HR, Pacak K . Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results . The Journal of Clinical Endocrinology and Metabolism . 88 . 6 . 2656–2666 . June 2003 . 12788870 . 10.1210/jc.2002-030005 . free .
  42. van der Kolk BA . The drug treatment of post-traumatic stress disorder . Journal of Affective Disorders . 13 . 2 . 203–213 . September–October 1987 . 2960712 . 10.1016/0165-0327(87)90024-3 .
  43. Sutherland SM, Davidson JR . Pharmacotherapy for post-traumatic stress disorder . The Psychiatric Clinics of North America . 17 . 2 . 409–423 . June 1994 . 7937367 . 10.1016/S0193-953X(18)30122-9 .
  44. Southwick SM, Bremner JD, Rasmusson A, Morgan CA, Arnsten A, Charney DS . Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder . Biological Psychiatry . 46 . 9 . 1192–1204 . November 1999 . 10560025 . 10.1016/S0006-3223(99)00219-X . 32148292 . free .
  45. Strawn JR, Geracioti TD . Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder . Depression and Anxiety . 25 . 3 . 260–271 . 2008 . 17354267 . 10.1002/da.20292 . 33940152 . free .
  46. Boehnlein JK, Kinzie JD . Pharmacologic reduction of CNS noradrenergic activity in PTSD: the case for clonidine and prazosin . Journal of Psychiatric Practice . 13 . 2 . 72–78 . March 2007 . 17414682 . 10.1097/01.pra.0000265763.79753.c1 . 1607064 .
  47. Huffman JC, Stern TA . Neuropsychiatric consequences of cardiovascular medications . Dialogues in Clinical Neuroscience . 9 . 1 . 29–45 . 2007 . 17506224 . 3181843 . 10.31887/DCNS.2007.9.1/jchuffman .
  48. Najjar F, Weller RA, Weisbrot J, Weller EB . Post-traumatic stress disorder and its treatment in children and adolescents . Current Psychiatry Reports . 10 . 2 . 104–108 . April 2008 . 18474199 . 10.1007/s11920-008-0019-0 . 23494905 .
  49. Ziegenhorn AA, Roepke S, Schommer NC, Merkl A, Danker-Hopfe H, Perschel FH, Heuser I, Anghelescu IG, Lammers CH . 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 . 170–173 . April 2009 . 19512980 . 10.1097/JCP.0b013e31819a4bae . 31292297 .
  50. Fazi L, Jantzen EC, Rose JB, Kurth CD, Watcha MF . A comparison of oral clonidine and oral midazolam as preanesthetic medications in the pediatric tonsillectomy patient . Anesthesia and Analgesia . 92 . 1 . 56–61 . January 2001 . 11133600 . 10.1097/00000539-200101000-00011 . 18885497 . free .
  51. Giannini AJ, Extein I, Gold MS, Pottash AL, Castellani S . Clonidine in mania . Drug Development Research . 3 . 1 . 101–105 . 1983 . 10.1002/ddr.430030112 . 85093127 .
  52. Patel SS, Dunn CJ, Bryson HM . Epidural clonidine: a review of its pharmacology and efficacy in the management of pain during labour and postoperative and intractable pain . CNS Drugs . 1996 . 6 . 6 . 474–497 . 10.2165/00023210-199606060-00007 . 72544106 .
  53. Web site: Treatment and Management of RLS . www.medscape.org . WebMD LLC . 3 October 2018 . 29 September 2017 . https://web.archive.org/web/20170929042337/http://www.medscape.org/viewarticle/522010_6 . live .
  54. Blount BW, Pelletier AL . Rosacea: a common, yet commonly overlooked, condition . American Family Physician . 66 . 3 . 435–440 . August 2002 . 12182520 . 12 February 2012 . 26 July 2011 . https://web.archive.org/web/20110726103851/http://www.aafp.org/afp/2002/0801/p435.html . live .
  55. Campbell CM, Kipnes MS, Stouch BC, Brady KL, Kelly M, Schmidt WK, Petersen KL, Rowbotham MC, Campbell JN . Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy . Pain . 153 . 9 . 1815–1823 . September 2012 . 22683276 . 3413770 . 10.1016/j.pain.2012.04.014 .
  56. Web site: Clonidine Oral Uses . . 30 May 2007 . 25 October 2007 . https://web.archive.org/web/20071025030547/http://www.webmd.com/drugs/drug-11754-Clonidine.aspx?drugid=11754&drugname=Clonidine . live .
  57. Web site: Clonidine . Drugs.com . 25 May 2017 . 14 April 2017 . https://web.archive.org/web/20170414001745/https://www.drugs.com/clonidine.html . live .
  58. Fragkos KC, Zárate-Lopez N, Frangos CC . What about clonidine for diarrhoea? A systematic review and meta-analysis of its effect in humans . Therapeutic Advances in Gastroenterology . 9 . 3 . 282–301 . May 2016 . 27134659 . 4830099 . 10.1177/1756283X15625586 .
  59. Egolf A, Coffey BJ . Current pharmacotherapeutic approaches for the treatment of Tourette syndrome . Drugs of Today . 50 . 2 . 159–179 . February 2014 . 24619591 . 10.1358/dot.2014.50.2.2097801 .
  60. Martinotti G, Santacroce R, Pettorruso M, Montemitro C, Spano MC, Lorusso M, di Giannantonio M, Lerner AG . Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives . Brain Sciences . 8 . 3 . 47 . March 2018 . 29547576 . 5870365 . 10.3390/brainsci8030047 . free .
  61. Ryan TJ, Holyoak R, Vlok R, Melhuish T, Hodge A, Binks M, Hurtado G, White L . Intra-articular Alpha-2 Agonists as an Adjunct to Local Anesthetic in Knee Arthroscopy: A Systematic Review and Meta-Analysis . J Knee Surg . 32 . 2 . 138–145 . February 2019 . 29534270 . 10.1055/s-0038-1636909 . 3861878 .
  62. Prischich D, Gomila AM, Milla-Navarro S, Sangüesa G, Diez-Alarcia R, Preda B, Matera C, Batlle M, Ramírez L, Giralt E, Hernando J, Guasch E, Meana JJ, de la Villa P, Gorostiza P . Adrenergic Modulation With Photochromic Ligands . Angewandte Chemie . 60 . 7 . 3625–3631 . February 2021 . 33103317 . 10.1002/anie.202010553 . Wiley . free . 2434/778579 .
  63. Book: Drugs and Lactation Database (LactMed) . 2006 . National Library of Medicine (US) . https://www.ncbi.nlm.nih.gov/books/NBK501628/ . 5 January 2019 . Clonidine . 30000689 . 5 December 2020 . https://web.archive.org/web/20201205111454/https://www.ncbi.nlm.nih.gov/books/NBK501628/ . live .
  64. Web site: Clonidine . Prescription Marketed Drugs . www.drugsdb.eu . 2 August 2011 . 28 March 2012 . https://web.archive.org/web/20120328060203/http://drugsdb.eu/drug.php?d=Clonidine&m=Physicians%20Total%20Care,%20Inc.&id=b65742b7-5db5-41cf-bf69-41700cdd2c59.xml . dead .
  65. Web site: CATAPRES® 150 TABLETS CATAPRES® AMPOULES. TGA eBusiness Services. Boehringer Ingelheim Pty Limited. 28 February 2013. 27 November 2013. PDF. 16 January 2017. https://web.archive.org/web/20170116171140/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-02400-3. live.
  66. Web site: Clonidine 25 mcg Tablets BP - Summary of Product Characteristics (SPC). electronic Medicines Compendium. Sandoz Limited. 2 August 2012. 27 November 2013. 2 December 2013. https://web.archive.org/web/20131202235526/http://www.medicines.org.uk/emc/medicine/21711/SPC/Clonidine+25mcg+Tablets+BP/. live.
  67. Web site: Clonidine. Martindale: The Complete Drug Reference. Pharmaceutical Press. 13 January 2014. 28 June 2014. Brayfield, A. London, UK. 28 August 2021. https://web.archive.org/web/20210828041402/https://about.medicinescomplete.com/wp-content/plugins/revslider/public/assets/js/extensions/revolution.extension.layeranimation.min.js?version=5.4.5. live.
  68. Book: Parker K, Brunton L, Goodman LS, Lazo JS, Gilman A . Goodman & Gilman's - the pharmacological basis of therapeutics . limited . McGraw-Hill . New York . 2006 . 854–855 . 978-0-07-142280-2 .
  69. Vitiello B . Understanding the Risk of Using Medications for ADHD with Respect to Physical Growth and Cardiovascular Function . Child Adolesc Psychiatr Clin N Am . 17 . 2 . 459–474, xi . 2008 . 18295156 . 2408826 . 10.1016/j.chc.2007.11.010 .
  70. Web site: PDSP Ki Database . Psychoactive Drug Screening Program (PDSP) . Bryan Roth . Roth BL, Driscol J . University of North Carolina at Chapel Hill and the United States National Institute of Mental Health . 14 August 2017 . 14 November 2022 . https://web.archive.org/web/20221114224224/https://pdsp.unc.edu/databases/pdsp.php?receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=Clonidine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query . live .
  71. Matsumoto I, Combs MR, Jones DJ . Characterization of 5-hydroxytryptamine1B receptors in rat spinal cord via [125I]iodocyanopindolol binding and inhibition of [3H]-5-hydroxytryptamine release . The Journal of Pharmacology and Experimental Therapeutics . 260 . 2 . 614–626 . February 1992 . 1738111 .
  72. Millan MJ, Dekeyne A, Newman-Tancredi A, Cussac D, Audinot V, Milligan G, Duqueyroix D, Girardon S, Mullot J, Boutin JA, Nicolas JP, Renouard-Try A, Lacoste JM, Cordi A . S18616, a highly potent, spiroimidazoline agonist at alpha(2)-adrenoceptors: I. Receptor profile, antinociceptive and hypothermic actions in comparison with dexmedetomidine and clonidine . The Journal of Pharmacology and Experimental Therapeutics . 295 . 3 . 1192–1205 . December 2000 . 11082457 .
  73. Jasper JR, Lesnick JD, Chang LK, Yamanishi SS, Chang TK, Hsu SA, Daunt DA, Bonhaus DW, Eglen RM . Ligand efficacy and potency at recombinant alpha2 adrenergic receptors: agonist-mediated [35S]GTPgammaS binding . Biochemical Pharmacology . 55 . 7 . 1035–1043 . April 1998 . 9605427 . 10.1016/s0006-2952(97)00631-x .
  74. Neve KA, Henningsen RA, Kinzie JM, De Paulis T, Schmidt DE, Kessler RM, Janowsky A . Sodium-dependent isomerization of dopamine D-2 receptors characterized using [125I]epidepride, a high-affinity substituted benzamide ligand . The Journal of Pharmacology and Experimental Therapeutics . 252 . 3 . 1108–1116 . March 1990 . 2138666 .
  75. Weber E, Sonders M, Quarum M, McLean S, Pou S, Keana JF . 1,3-Di(2-[5-3H]tolyl)guanidine: a selective ligand that labels sigma-type receptors for psychotomimetic opiates and antipsychotic drugs . Proceedings of the National Academy of Sciences of the United States of America . 83 . 22 . 8784–8788 . November 1986 . 2877462 . 10.1073/pnas.83.22.8784 . 387016 . 1986PNAS...83.8784W . free .
  76. Book: Kenakin T. Hacker M, Messer W, Bachmann K . Pharmacology . limited . 2009 . Elsevier . 9780123695215. 65 . en . Ligand-Receptor Binding and Tissue Response.
  77. Molderings GJ, Donecker K, Burian M, Simon WA, Schröder DW, Göthert M . Characterization of I2 imidazoline and sigma binding sites in the rat and human stomach . The Journal of Pharmacology and Experimental Therapeutics . 285 . 1 . 170–177 . April 1998 . 9536007 .
  78. Reis DJ, Piletz JE . The imidazoline receptor in control of blood pressure by clonidine and drugs . American Journal of Physiology . 1997 . 273 . 5 . R1569–R1571 . 9374795 . 10.1152/ajpregu.1997.273.5.R1569 .
  79. Giovannitti JA, Thoms SM, Crawford JJ . Alpha-2 adrenergic receptor agonists: a review of current clinical applications . en-US . Anesthesia Progress . 62 . 1 . 31–39 . 2015 . 25849473 . 4389556 . 10.2344/0003-3006-62.1.31 .
  80. Web site: CATAPRES- clonidine hydrochloride tablet . DailyMed . 6 September 2016 . 21 December 2019 . The antihypertensive effect is reached at plasma concentrations between about 0.2 and 2.0 ng/mL in patients with normal excretory function. A further rise in the plasma levels will not enhance the antihypertensive effect. . 4 August 2020 . https://web.archive.org/web/20200804180055/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7f569dc-6bed-42dc-9bec-940a9e6b090d . live .
  81. Cinnamon Bidwell L, Dew RE, Kollins SH . Alpha-2 adrenergic receptors and attention-deficit/hyperactivity disorder . Current Psychiatry Reports . 12 . 5 . 366–373 . October 2010 . 20652773 . 3676929 . 10.1007/s11920-010-0136-4 .
  82. Low LC . Growth hormone-releasing hormone: clinical studies and therapeutic aspects . Neuroendocrinology . 53 . Suppl 1 . 37–40 . 1991 . 1901390 . 10.1159/000125793 .
  83. Web site: Growth Hormone Test . www.cincinnatichildrens.org . Cincinnati Children's Hospital Medical Center . 13 October 2018 . en . 14 October 2018 . https://web.archive.org/web/20181014010221/https://www.cincinnatichildrens.org/health/g/growth-hormone . live .
  84. Davies DS, Wing AM, Reid JL, Neill DM, Tippett P, Dollery CT . Pharmacokinetics and concentration-effect relationships of intervenous and oral clonidine . Clinical Pharmacology and Therapeutics . 21 . 5 . 593–601 . May 1977 . 870272 . 10.1002/cpt1977215593 . 5566079 .
  85. Khan ZP, Ferguson CN, Jones RM . alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role . Anaesthesia . 54 . 2 . 146–165 . February 1999 . 10215710 . 10.1046/j.1365-2044.1999.00659.x . 28405271 .
  86. Book: Foye's principles of medicinal chemistry . limited . 2008 . Lippincott Williams & Wilkins . Philadelphia . 9780781768795 . 403 . 6th .
  87. Pajouhesh H, Lenz GR . Medicinal chemical properties of successful central nervous system drugs . NeuroRx . 2 . 4 . 541–553 . October 2005 . 16489364 . 1201314 . 10.1602/neurorx.2.4.541 .
  88. Skingle M, Hayes AG, Tyers MB . Antinociceptive activity of clonidine in the mouse, rat and dog . Life Sciences . 31 . 11 . 1123–1132 . September 1982 . 6128647 . 10.1016/0024-3205(82)90086-8 .
  89. Curtis AL, Marwah J . Alpha adrenoceptor modulation of the jaw-opening reflex . Neuropharmacology . 26 . 7A . 649–655 . July 1987 . 2819761 . 10.1016/0028-3908(87)90224-3 . 41743285 .
  90. Frisk-Holmberg M, Paalzow L, Edlund PO . Clonidine kinetics in man--evidence for dose dependency and changed pharmacokinetics during chronic therapy . British Journal of Clinical Pharmacology . 12 . 5 . 653–658 . November 1981 . 7332729 . 10.1111/j.1365-2125.1981.tb01284.x . 1401969 .
  91. Dollery CT, Davies DS, Draffan GH, Dargie HJ, Dean CR, Reid JL, Clare RA, Murray S . Clinical pharmacology and pharmacokinetics of clonidine . Clinical Pharmacology and Therapeutics . 19 . 1 . 11–17 . January 1976 . 1245090 . 10.1002/cpt197619111 . 39473828 .
  92. Keränen A, Nykänen S, Taskinen J . Pharmacokinetics and side-effects of clonidine . European Journal of Clinical Pharmacology . 13 . 2 . 97–101 . May 1978 . 658114 . 10.1007/BF00609752 . 24702183 .
  93. Stähle H . A historical perspective: development of clonidine . Best Practice & Research Clinical Anaesthesiology . June 2000 . 14 . 2 . 237–246 . 10.1053/bean.2000.0079 .
  94. News: Clonidine: Drug Uses, Dosage & Side Effects - Drugs.com. Drugs.com. 10 December 2017. en-US. 14 April 2017. https://web.archive.org/web/20170414001745/https://www.drugs.com/clonidine.html. live.
  95. Web site: Clonidine brand names. Drugs.com. 16 June 2017. 6 August 2017. https://web.archive.org/web/20170806101340/https://www.drugs.com/international/clonidine.html. live.

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Clonidine".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.