Clonidine

Clonidine, sold as the brand name Catapres among others, is a medication used to treat high blood pressure, attention deficit hyperactivity disorder, drug withdrawal (alcohol, opioids, or smoking), menopausal flushing, diarrhea, spasticity and certain pain conditions.[7] It is used by mouth, by injection, or as a skin patch.[7] Onset of action is typically within an hour with the effects on blood pressure lasting for up to eight hours.[7]

Clonidine
Clinical data
Pronunciation/ˈklɒnədiːn/
Trade namesCatapres, Kapvay, Nexiclon, others
AHFS/Drugs.comMonograph
MedlinePlusa682243
License data
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth, epidural, intravenous (IV), transdermal, topical
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability70–80% (oral),[1] 60–70% (transdermal)[2]
Protein binding20–40%[3]
MetabolismLiver to inactive metabolites,[3] 2/3 CYP2D6
Onset of actionIR:30-60 minutes after a dose by mouth[4]
Elimination half-lifeIR: 12–16 hours; 41 hours in kidney failure,[5][6] 48 hours for repeated dosing[2]
ExcretionUrine (72%)[3]
Identifiers
CAS Number
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.021.928
Chemical and physical data
FormulaC9H9Cl2N3
Molar mass230.09 g·mol−1
3D model (JSmol)
  (verify)

Common side effect include dry mouth, dizziness, headaches, and sleepiness.[7] Severe side effects may include hallucinations, heart arrhythmias, and confusion.[8] If rapidly stopped, withdrawal effects may occur.[7] Use during pregnancy or breastfeeding is not recommended.[8] Clonidine lowers blood pressure by stimulating α2 receptors in the brain, which results in relaxation of many arteries.[7]

Clonidine was patented in 1961 and came into medical use in 1966.[9][10][11] It is available as a generic medication.[7] In 2017, it was the 79th most commonly prescribed medication in the United States, with more than ten million prescriptions.[12][13]

Medical uses
Clonidine tablets and transdermal patch

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.[7]

Resistant hypertension

Clonidine may be effective for lowering blood pressure in people with resistant hypertension.[14]

Clonidine works by slowing the pulse rate and exert a reduction of serum concentrations of renin, aldosterone and catecholamines.[15]

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.[16] In Australia, clonidine is an accepted but not approved use for ADHD by the TGA.[17] Clonidine along with methylphenidate has been studied for treatment of ADHD.[18][19][20] While not as effective as methylphenidate in treating ADHD, clonidine does offer some benefit;[21] it can also be useful in combination with stimulant medications.[22] Some studies show clonidine to be more sedating than guanfacine, which may be better at bed time along with an arousing stimulant at morning.[23][24]

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 (smoking).[25] It can alleviate opioid withdrawal symptoms by reducing the sympathetic nervous system response such as tachycardia and hypertension, as well as reducing sweating, hot and cold flashes, and general restlessness.[26] It may also be helpful in aiding smokers to quit.[27] The sedation effect is also useful. However, its side effects can include insomnia, thus exacerbating an already common feature of opioid withdrawal.[28] Clonidine may also reduce severity of neonatal abstinence syndrome in infants born to mothers that are using certain drugs, particularly opioids.[29] In infants with neonatal withdrawal syndrome, clonidine may improve the neonatal intensive care unit Network Neurobehavioral Score.[30]

Clonidine has also been suggested as a treatment for rare instances of dexmedetomidine withdrawal.[31]

Spasticity

Clonidine has some role in the treatment of spasticity, acting principally by inhibiting excessive sensory transmission below the level of injury. Its use however is mainly as a second or third line agent, due to side effects such as hypotension, bradycardia and drowsiness.[32]

Other

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.[33][34][35][36][37][38][39][40] Clonidine is also a mild sedative, and can be used as premedication before surgery or procedures.[41] Its epidural use for pain during heart attack, postoperative and intractable pain has also been studied extensively.[42] Clonidine can be used in restless legs syndrome.[43] It can also be used to treat facial flushing and redness associated with rosacea.[44] It has also been successfully used topically in a clinical trial as a treatment for diabetic neuropathy.[45] Clonidine can also be used for migraine headaches and hot flashes associated with menopause.[46][47] 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.[48] Clonidine can be used in the treatment of Tourette syndrome (specifically for tics).[49] Clonidine has also had some success in clinical trials for helping to remove or ameliorate the symptoms of Hallucinogen persisting perception disorder (HPPD). [50]

Injection into the knee joint space of α2 receptor agonists, including clonidine, may reduce the severity of knee pain after arthroscopic knee surgery.[51]

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 tumour, usually found in the adrenal medulla.[52] 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.[52]

Pregnancy and breastfeeding

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.[53] Clonidine appears in high concentration in breast milk and nursing infants have approximately 2/3 of serum clonidine concentrations as the mother.[54] Caution is warranted in women who are pregnant, planning to become pregnant, or are breastfeeding.[55]

Adverse effects

The principal adverse effects of clonidine are sedation, dry mouth, and hypotension (low blood pressure).[3]

By frequency[53][56]

Very common (>10% frequency):

Common (1-10% frequency):

  • Anxiety
  • Constipation
  • Sedation (dose-dependent)
  • Nausea/vomiting
  • Malaise
  • Abnormal LFTs
  • Rash
  • Weight gain/loss
  • Pain below the ear (from salivary gland)
  • Erectile dysfunction

Uncommon (0.1-1% frequency):

Rare (<0.1% frequency):

Withdrawal

While clonidine suppresses sympathetic outflow resulting in lower blood pressure, the sudden discontinuation can cause rebound hypertension due to a rebound in sympathetic outflow.[57]

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.[58][59]

Pharmacology

Mechanism of action
ReceptorKi (nM)[60]
Alpha-1A adrenergic receptor316.23
Alpha-1B adrenergic receptor316.23
Alpha-1D adrenergic receptor125.89
Alpha-2A adrenergic receptor42.92
Alpha-2B adrenergic receptor106.31
Alpha-2C adrenergic receptor233.1
The Ki refers to a drug's affinity for a receptor. The smaller the Ki, the higher the affinity for that receptor.[61]

Clonidine crosses the blood-brain barrier.[5]

High blood pressure

Clonidine treats high blood pressure by stimulating α2 receptors in the brain stem, 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.[62]:201–203

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, but this effect acts upstream of the central α2 agonist effect of clonidine.[62]:201–203[63]

Clonidine also may cause bradycardia, probably 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.[64] This hypertensive effect is not usual when clonidine is given by mouth or by the transdermal route.[62]:201–203

Plasma concentration of clonidine exceeding 2.0 ng/mL does not provide further blood pressure reduction.[65]

Attention deficit hyperactivity disorder
Structural comparison between the neurotransmitter norepinephrine and the drug clonidine. Both drugs bind to alpha-2 adrenergic receptors.[66] Similarities between the two structures are shown highlighted in red.

In the setting of attention deficit hyperactivity disorder (ADHD), clonidine's molecular mechanism of action occurs due to its agonism at the alpha-2A adrenergic receptor, the subtype of the alpha-2 adrenergic receptor that is most principally found in the brain. Within the brain, the alpha-2A adrenergic receptors are found within the prefrontal cortex (PFC), among other areas. The alpha-2A 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 alpha-2A adrenergic receptors in the PFC inhibits the action of downstream neurons by preventing the secretion of norepinephrine.[66]

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 alpha-2A 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.[66]

Growth hormone test

Clonidine stimulates release of growth hormone releasing hormone from the hypothalamus, which in turn stimulates pituitary release of growth hormone.[67] This effect has been used as part of a "growth hormone test," which can assist with diagnosing growth hormone deficiency in children.[68]

Pharmacokinetics

After being ingested, clonidine is absorbed into the blood stream rapidly and nearly completely, with peak concentrations in human plasma occurring within 60–90 minutes.[69] Clonidine is fairly lipid soluble with the logarithm of its partition coefficient (log P) equal to 1.6;[70][69] 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.[71] 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.[69] About one-fifth of an oral dose will not be absorbed, and is thus excreted in the feces.[69] The half-life of clonidine varies widely, with estimates between 6 and 23 hours, and is greatly affected by and prolonged in the setting of poor kidney function.[69]

History

Clonidine was introduced in 1966.[72] It was first used as a hypertension treatment under the trade name of Catapres.[73]

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, Melzin, Menograine, Normopresan, Paracefan, Pinsanidine, Run Rui, and Winpress.[74] It was marketed as a combination drug with chlortalidone as Arkamin-H, Bemplas, Catapres-DIU, and Clorpres, and in combination with bendroflumethiazide as Pertenso.[74]

References
  1. "Catapres- clonidine hydrochloride tablet". DailyMed. 2016-09-06. Retrieved 2019-12-21. 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.
  2. Lowenthal, DT; Matzek, KM; MacGregor, TR (May 1988). "Clinical pharmacokinetics of clonidine". Clinical Pharmacokinetics. 14 (5): 287–310. doi:10.2165/00003088-198814050-00002. PMID 3293868. S2CID 24783447.
  3. "clonidine (Rx) - Catapres, Catapres-TTS, more." Medscape Reference. WebMD. Retrieved 10 November 2013.
  4. "Catapres- clonidine hydrochloride tablet". DailyMed. 2016-09-06. Retrieved 2019-12-21. 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.
  5. "Catapres- clonidine hydrochloride tablet". DailyMed. 2016-09-06. Retrieved 2019-12-21. 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.
  6. "Kapvay". RxList.
  7. "Clonidine Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 2 February 2019.
  8. British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 144. ISBN 9780857113382.
  9. Neil, MJ (November 2011). "Clonidine: clinical pharmacology and therapeutic use in pain management". Current Clinical Pharmacology. 6 (4): 280–7. doi:10.2174/157488411798375886. PMID 21827389. S2CID 40756251.
  10. Stähle, Helmut (June 2000). "A historical perspective: development of clonidine". Best Practice & Research Clinical Anaesthesiology. 14 (2): 237–246. doi:10.1053/bean.2000.0079.
  11. Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 550. ISBN 9783527607495.
  12. "The Top 300 of 2020". ClinCalc. Retrieved 11 April 2020.
  13. "Clonidine - Drug Usage Statistics". ClinCalc. Retrieved 11 April 2020.
  14. Viera AJ (June 2018). "Hypertension Update: Resistant Hypertension". FP Essent. 469: 20–25. PMID 29863319.
  15. "CATAPRES- clonidine hydrochloride tablet". DailyMed. 2016-09-06. Retrieved 2019-12-21. 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.
  16. Connor DF, Fletcher KE, Swanson JM (December 1999). "A meta-analysis of clonidine for symptoms of attention-deficit hyperactivity disorder". J Am Acad Child Adolesc Psychiatry. 38 (12): 1551–9. doi:10.1097/00004583-199912000-00017. PMID 10596256.
  17. Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
  18. Palumbo, DR; Sallee, FR; Pelham WE, Jr; Bukstein, OG; Daviss, WB; McDermott, MP (February 2008). "Clonidine for attention-deficit/hyperactivity disorder: I. Efficacy and tolerability outcomes". Journal of the American Academy of Child and Adolescent Psychiatry. 47 (2): 180–8. doi:10.1097/chi.0b013e31815d9af7. PMID 18182963.
  19. Daviss, WB; Patel, NC; Robb, AS; McDermott, MP; Bukstein, OG; Pelham WE, Jr; Palumbo, D; Harris, P; Sallee, FR (February 2008). "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): 189–98. doi:10.1097/chi.0b013e31815d9ae4. PMID 18182964.
  20. Kornfield R, Watson S, Higashi AS, Conti RM, Dusetzina SB, Garfield CF, Dorsey ER, Huskamp HA, Alexander GC (April 2013). "Impact of FDA Advisories on Pharmacologic Treatment of Attention Deficit Hyperactivity Disorder". Psychiatric Services. 64 (4): 339–46. doi:10.1176/appi.ps.201200147. PMC 4023684. PMID 23318985.
  21. PALUMBO, DONNA R.; SALLEE, FLOYD R.; PELHAM, WILLIAM E.; BUKSTEIN, OSCAR G.; DAVISS, W. BURLESON; McDERMOTT, MICHAEL P. (February 2008). "Clonidine for Attention-Deficit/Hyperactivity Disorder: I. Efficacy and Tolerability Outcomes". Journal of the American Academy of Child & Adolescent Psychiatry. 47 (2): 180–188. doi:10.1097/chi.0b013e31815d9af7. PMID 18182963.
  22. Kollins, Scott H.; Jain, Rakesh; Brams, Matthew; Segal, Scott; Findling, Robert L.; Wigal, Sharon B.; Khayrallah, Moise (2011-06-01). "Clonidine Extended-Release Tablets as Add-on Therapy to Psychostimulants in Children and Adolescents With ADHD". Pediatrics. 127 (6): e1406–e1413. doi:10.1542/peds.2010-1260. ISSN 0031-4005. PMC 3387872. PMID 21555501.
  23. Jäkälä, P.; Riekkinen, M.; Sirviö, J.; Koivisto, E.; Kejonen, K.; Vanhanen, M.; Riekkinen Jr, P. (1999). "Guanfacine, But Not Clonidine, Improves Planning and Working Memory Performance in Humans". Neuropsychopharmacology. 20 (5): 460–470. doi:10.1016/S0893-133X(98)00127-4. PMID 10192826.
  24. "Clonidine and Guanfacine IR vs ER: Old Drugs With "New" Formulations". Mental Health Clinician. Retrieved August 1, 2014.
  25. 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.
  26. Giannini, AJ (1997). Drugs of Abuse (2nd ed.). Los Angeles: Practice Management Information.
  27. Gourlay, SG; Stead, LF; Benowitz, NL (2004). "Clonidine for smoking cessation". The Cochrane Database of Systematic Reviews (3). CD000058. doi:10.1002/14651858.CD000058.pub2. PMC 7038651. PMID 15266422.
  28. Giannini, AJ; Extein, I; Gold, MS; Pottash, ALC; Castellani, S (1983). "Clonidine in mania". Drug Development Research. 3 (1): 101–105. doi:10.1002/ddr.430030112. S2CID 85093127.
  29. Streetz VN, Gildon BL, Thompson DF (April 2016). "Role of Clonidine in Neonatal Abstinence Syndrome: A Systematic Review". Ann Pharmacother. 50 (4): 301–10. doi:10.1177/1060028015626438. PMID 26783353. S2CID 40652097.
  30. Disher T, Gullickson C, Singh B, Cameron C, Boulos L, Beaubien L, Campbell-Yeo M (January 2019). "Pharmacological Treatments for Neonatal Abstinence Syndrome: A Systematic Review and Network Meta-analysis". JAMA Pediatr. 173 (3): 234–243. doi:10.1001/jamapediatrics.2018.5044. PMC 6439896. PMID 30667476.
  31. Kukoyi A, Coker S, Lewis L, Nierenberg D (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 & Experimental Toxicology. 32 (1): 107–110. doi:10.1177/0960327112454896. PMID 23111887. S2CID 31570614.
  32. Chang, Eric; Ghosh, Nilasha; Yanni, Daniel; Lee, Sujin; Alexandru, Daniela; Mozaffar, Tahseen (2013). "A Review of Spasticity Treatments: Pharmacological and Interventional Approaches". Critical Reviews in Physical and Rehabilitation Medicine. 25 (1–2): 11–22. doi:10.1615/CritRevPhysRehabilMed.2013007945. ISSN 0896-2960. PMC 4349402. PMID 25750484.
  33. van der Kolk, BA (September–October 1987). "The drug treatment of post-traumatic stress disorder". Journal of Affective Disorders. 13 (2): 203–13. doi:10.1016/0165-0327(87)90024-3. PMID 2960712.
  34. Sutherland, SM; Davidson, JR (June 1994). "Pharmacotherapy for post-traumatic stress disorder". The Psychiatric Clinics of North America. 17 (2): 409–23. doi:10.1016/S0193-953X(18)30122-9. PMID 7937367.
  35. Southwick, SM; Bremner, JD; Rasmusson, A; Morgan CA, 3rd; Arnsten, A; Charney, DS (November 1999). "Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder". Biological Psychiatry. 46 (9): 1192–204. doi:10.1016/S0006-3223(99)00219-X. PMID 10560025. S2CID 32148292.
  36. Strawn, JR; Geracioti, TD, Jr (2008). "Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder". Depression and Anxiety. 25 (3): 260–71. doi:10.1002/da.20292. PMID 17354267. S2CID 33940152.
  37. 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. S2CID 1607064.
  38. Huffman, JC; Stern, TA (2007). "Neuropsychiatric consequences of cardiovascular medications". Dialogues in Clinical Neuroscience. 9 (1): 29–45. PMC 3181843. PMID 17506224.
  39. 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. S2CID 23494905.
  40. 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. S2CID 31292297.
  41. 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. S2CID 18885497.
  42. 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. S2CID 72544106.
  43. "Treatment and Management of RLS". www.medscape.org. WebMD LLC. Retrieved 3 October 2018.
  44. Blount, BW; Pelletier, AL (2002). "Rosacea: A Common, Yet Commonly Overlooked, Condition". American Family Physician. 66 (3): 435–441. PMID 12182520.
  45. 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". Pain. 153 (9): 1815–1823. doi:10.1016/j.pain.2012.04.014. PMC 3413770. PMID 22683276.
  46. "Clonidine Oral Uses". WebMD.
  47. "Clonidine". Drugs.com.
  48. Fragkos, Konstantinos C.; Zárate-Lopez, Natalia; Frangos, Christos C. (2016-01-25). "What about clonidine for diarrhoea? A systematic review and meta-analysis of its effect in humans". Therapeutic Advances in Gastroenterology. 9 (3). 1756283X15625586. doi:10.1177/1756283X15625586. ISSN 1756-283X. PMC 4830099. PMID 27134659.
  49. Egolf, A; Coffey, BJ (February 2014). "Current pharmacotherapeutic approaches for the treatment of Tourette syndrome". Drugs of Today. 50 (2): 159–79. doi:10.1358/dot.2014.50.2.2097801. PMID 24619591.
  50. Martinotti, Giovanni; Santacroce, Rita; Pettorruso, Mauro; Montemitro, Chiara; Spano, Maria Chiara; Lorusso, Marco; di Giannantonio, Massimo; Lerner, Arturo G. (2018-03-16). "Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives". Brain Sciences. 8 (3). doi:10.3390/brainsci8030047. ISSN 2076-3425. PMC 5870365. PMID 29547576.
  51. Ryan TJ, Holyoak R, Vlok R, Melhuish T, Hodge A, Binks M, Hurtado G, White L (February 2019). "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. doi:10.1055/s-0038-1636909. PMID 29534270. S2CID 3861878.
  52. Eisenhofer, G; Goldstein, DS; Walther, MM; et al. (2003). "Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results". Journal of Clinical Endocrinology & Metabolism. 88 (6): 2656–2666. doi:10.1210/jc.2002-030005. PMID 12788870.
  53. "CATAPRES® 150 TABLETS CATAPRES® AMPOULES" (PDF). TGA eBusiness Services. Boehringer Ingelheim Pty Limited. 28 February 2013. Retrieved 27 November 2013.
  54. "Clonidine". Drugs and Lactation Database (LactMed). National Library of Medicine (US). 2006. Retrieved 5 January 2019.
  55. "Clonidine". Prescription Marketed Drugs. www.drugsdb.eu.
  56. "Clonidine 25 mcg Tablets BP - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Sandoz Limited. 2 August 2012. Retrieved 27 November 2013.
  57. Brayfield, A, ed. (13 January 2014). "Clonidine". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 28 June 2014.
  58. Parker, K; Brunton, L; Goodman, LS; Lazo, JS; Gilman, A (2006). Goodman & Gilman's - the pharmacological basis of therapeutics. New York: McGraw-Hill. pp. 854–855. ISBN 978-0-07-142280-2.
  59. Vitiello, B. (2008). "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. doi:10.1016/j.chc.2007.11.010. PMC 2408826. PMID 18295156.
  60. 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.
  61. Terry Kenakin (2009). "Ligand-Receptor Binding and Tissue Response". In Hacker, Miles; Messer, William; Bachmann, Kenneth (eds.). Pharmacology. Elsevier. p. 65. ISBN 9780123695215.
  62. Westfall, Thomas C.; Macarthur, Heather; Westfall, David P (2017). "Chapter 12:Adrenergic Agonists and Antagonists". In Brunton, Laurence; Knollmann, Bjorn; Hilal-Dandan, Randa (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education / Medical. ISBN 9781259584732.
  63. Reis, D. J.; Piletz, J. E. (1997). "The imidazoline receptor in control of blood pressure by clonidine and drugs". American Journal of Physiology. 273 (5): R1569–R1571. doi:10.1152/ajpregu.1997.273.5.R1569. PMID 9374795.
  64. Giovannitti, Joseph A.; Thoms, Sean M.; Crawford, James J. (2015). "Alpha-2 Adrenergic Receptor Agonists: A Review of Current Clinical Applications". Anesthesia Progress. 62 (1): 31–38. doi:10.2344/0003-3006-62.1.31. ISSN 0003-3006. PMC 4389556. PMID 25849473.
  65. "CATAPRES- clonidine hydrochloride tablet". DailyMed. 2016-09-06. Retrieved 2019-12-21. 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.
  66. Cinnamon Bidwell, L; Dew, RE; Kollins, SH (October 2010). "Alpha-2 adrenergic receptors and attention-deficit/hyperactivity disorder". Current Psychiatry Reports. 12 (5): 366–73. doi:10.1007/s11920-010-0136-4. PMC 3676929. PMID 20652773.
  67. Low LC (1991). "Growth hormone-releasing hormone: clinical studies and therapeutic aspects". Neuroendocrinology. 53 Suppl 1: 37–40. doi:10.1159/000125793. PMID 1901390.
  68. "Growth Hormone Test". www.cincinnatichildrens.org. Cincinnati Children's Hospital Medical Center. Retrieved 13 October 2018.
  69. Khan, ZP; Ferguson, CN; Jones, RM (February 1999). "alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role". Anaesthesia. 54 (2): 146–65. doi:10.1046/j.1365-2044.1999.00659.x. PMID 10215710. S2CID 28405271.
  70. Foye's principles of medicinal chemistry (6th ed.). Philadelphia: Lippincott Williams & Wilkins. 2008. p. 403. ISBN 9780781768795.
  71. Pajouhesh, H; Lenz, GR (October 2005). "Medicinal chemical properties of successful central nervous system drugs". NeuroRx. 2 (4): 541–53. doi:10.1602/neurorx.2.4.541. PMC 1201314. PMID 16489364.
  72. Stähle, Helmut (June 2000). "A historical perspective: development of clonidine". Best Practice & Research Clinical Anaesthesiology. 14 (2): 237–246. doi:10.1053/bean.2000.0079.
  73. "Clonidine: Drug Uses, Dosage & Side Effects - Drugs.com". Drugs.com. Retrieved 2017-12-10.
  74. "Clonidine brand names". Drugs.com. Retrieved 16 June 2017.
  • "Clonidine". Drug Information Portal. U.S. National Library of Medicine.
  • Alpha-2 agonists in ADHD
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.