Ogled vira Metilfenidat

{{Infopolje učinkovina
| Watchedfields = changed
| verifiedrevid = 464371569
| IUPAC_name = metil 2-fenil-2-(piperidin-2-il)acetat
| image = Methylphenidate-2D-skeletal.svg
| width = 200
| image2 = Methylphenidate-enantiomers-3D-balls.png
| width2 = 225

<!--Clinical data-->
| tradename = Concerta, Methylin, Ritalin, Medikinet, Equasym XL, Quillivant XR, Metadate
| Drugs.com = {{drugs.com|monograph|methylphenidate-hydrochloride}}
| MedlinePlus = a682188
| licence_US = Methylphenidate
| pregnancy_AU = B3
| pregnancy_US = C
| legal_AU = S8
| legal_CA = Schedule III
| legal_UK = Class B
| legal_US = Schedule II
| legal_DE = Anlage II
| legal_status = Rx-only
| dependency_liability = telesna: je ni<br />psihološka: zmerna
| addiction_liability = Moderate
| routes_of_administration = peroralno, intravensko, transdermalno, inhalacijsko

<!--Pharmacokinetic data-->
| bioavailability = okoli 30 % (od 11 do 52 %)
| protein_bound = 10–33 %
| metabolism = [[jetra|jetrna]] (80 %), predvsem z encimom [[karboksilesteraza 1|CES1A1]]
| elimination_half-life = 2–3 h<ref name="pmid10628897">{{cite journal|last1=Kimko|first1=HC|last2=Cross|first2=JT|last3=Abernethy|first3=DR|title=Pharmacokinetics and clinical effectiveness of methylphenidate.|journal=Clinical pharmacokinetics|date=December 1999|volume=37|issue=6|pages=457–70|pmid=10628897|doi=10.2165/00003088-199937060-00002}}</ref>
| excretion = s [[seč]]em (90 %)

<!--Identifiers-->
| IUPHAR_ligand = 7236
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 113-45-1
| ATC_prefix = N06
| ATC_suffix = BA04
| PubChem = 4158
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00422
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4015
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 207ZZ9QZ49
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D04999
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 6887
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 796

<!--Chemical data-->
| C=14 | H=19 | N=1 | O=2
| molecular_weight = 233,31 g/mol
| smiles = O=C(OC)C(C1CCCCN1)C2=CC=CC=C2
| InChI = 1/C14H19NO2/c1-17-14(16)13(11-7-3-2-4-8-11)12-9-5-6-10-15-12/h2-4,7-8,12-13,15H,5-6,9-10H2,1H3
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C14H19NO2/c1-17-14(16)13(11-7-3-2-4-8-11)12-9-5-6-10-15-12/h2-4,7-8,12-13,15H,5-6,9-10H2,1H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = DUGOZIWVEXMGBE-UHFFFAOYSA-N
| melting_point = 74
| melting_notes = <ref name="Pubchem properties">{{cite encyclopedia|title=Methylphenidate|section-url=http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4158#x27|website=Pubchem Compound|publisher=National Center for Biotechnology Information|accessdate=24 June 2014|section=Chemical and Physical Properties}}</ref>
| boiling_point = 136
| boiling_notes = <ref name="Pubchem properties" />
}}
'''Metílfenidát''' je [[psihostimulans]], ki deluje kot [[zaviralec ponovnega privzema dopamina in noradrenalina]] in se uporablja pri zdravljenju [[motnja aktivnosti in pozornosti|motnje aktivnosti in pozornosti]]<ref>http://www.termania.net/slovarji/slovenski-medicinski-slovar/5526712/metilfenidat?dictionaries=95&query=metilfenidat&SearchIn=All, Slovenski medicinski e-slovar, vpogled: 29. 12. 2015.</ref> in [[narkolepsija|narkolepsije]]. Učinkovino preučujejo v [[klinična študija|kliničnih študijah]] že več kot 50 let in za zdravljenje motnje aktivnosti in pozornosti obstajajo številni dokazi o varnosti in učinkovitosti.<ref>http://www.patient.info/health/attention-deficit-hyperactivity-disorder-leaflet</ref> 

V Evropski uniji je na tržišču od leta 1950 pod različnimi imeni ('''Ritalin''', '''Concerta''', '''Equasim''', '''Medikinet''', '''Rubifen''' ...).<ref name=jazmp2009>http://www.jazmp.si/fileadmin/datoteke/dokumenti/SRZH/Arhiv_starejsih_objav/Metilfenidat_Objava2009-02-09.pdf Sporočilo za javnost glede zdravil, ki vsebujejo metilfenidat, JAZMP, 5. 2. 2009, vpogled: 3. 1. 2016.</ref> Njegova uporaba se je razširila v 90. letih dvajsetega stoletja, ko se je uveljavila diagnoza motnje aktivnosti in pozornosti.<ref>{{navedi knjigo|isbn=978-0553379068|first=Lawrence |last=Diller|title=Running on Ritalin|year= 1999}}</ref><ref>{{cite journal |author1=Lange KW |author2=Reichl S |author3=Lange KM |author4=Tucha L |author5=Tucha O | title = The history of attention deficit hyperactivity disorder | journal = ADHD Attention Deficit and Hyperactivity Disorders | volume = 2 | issue = 4 | pages = 241–255 | year = 2010 | pmid = 21258430 | pmc = 3000907 | doi = 10.1007/s12402-010-0045-8 }}</ref> Med letoma 2007 in 2012 se je predpisovanje metilfenidata v Veliki Britaniji na primer povečalo za 50 % in v letu 2013 se je uporaba tega zdravila na svetovni ravni povečala na 2,4 milijonov odmerkov, kar predstavlja 66-odstotno povečanje v primerjavi s predhodnim letom. 80 % svetovne porabe doprinesejo Združene države Amerike.<ref>http://www.bbc.com/news/health-23674235</ref><ref>{{Navedi splet |url=http://www.pharmaceutical-journal.com/news-and-analysis/news-in-brief/narcotics-monitoring-board-reports-66-increase-in-global-consumption-of-methylphenidate/20068042.article |title=arhivska kopija |accessdate=2015-12-29 |archive-date=2017-09-21 |archive-url=https://web.archive.org/web/20170921050031/http://www.pharmaceutical-journal.com/news-and-analysis/news-in-brief/narcotics-monitoring-board-reports-66-increase-in-global-consumption-of-methylphenidate/20068042.article |url-status=dead }}</ref>

Za motnjo aktivnosti in pozornosti in sorodne motnje povezujejo s premajhno dejavnostjo [[dopamin]]a in [[noradrenalin]]a v možganih, predvsem v [[prefrontalna skorja|prefrontalni skorji]], ki sodeluje med drugim pri besednem sklepanju, reševanju problemov, načrtovanju, kognitivni inhibiciji ...<ref name='cortex'>{{navedi splet | url = http://www.medscape.org/viewarticle/523887_4 | title = Functional Roles of Norepinephrine and Dopamine in ADHD: Dopamine in ADHD | accessdate = 8. 10. 2013 | year = 2006 | work = Medscape|quote=}}</ref><ref>{{cite journal | author1 = Arnsten AF |author2=Li BM | title = Neurobiology of Executive Functions: Catecholamine Influences on Prefrontal Cortical Functions | journal = Biological Psychiatry | volume = 57 | issue = 11 | pages = 1377–84 | year = 2005 | pmid = 15950011 | doi = 10.1016/j.biopsych.2004.08.019 }}</ref> Mehanizem delovanja metilfenidata temelji na zaviranju ponovnega privzema kateholaminov, zlasti dopamina, nazaj v živčne končiče. Zavira namreč prenašalne beljakovine za dopamin in noradrenalin, kar poveča njuno koncentracijo v [[sinaptična špranja|sinaptični špranji]] in s tem delovanje obeh [[živčni prenašalec|živčnih prenašalcev]]. Hkrati pa metilfenidat deluje tudi kot [[agonist]] na [[serotoninski receptor|serotoninskih receptorjih  5-HT<sub>1A</sub>]].<ref>{{cite journal |pmid=19322953 | volume=64 | title=The psychostimulant d-threo-(R,R)-methylphenidate binds as an agonist to the 5HT(1A) receptor. | date=Feb 2009 | journal=Pharmazie | pages=123–5}}</ref>

== Mehanizem delovanja ==
Delovanje metilfenidata je povezano z zaviranjem ponovnega privzema [[dopamin]]a in [[noradrenalin]]a v presinaptične nevrone v prefrontalnem korteksu, zato je posledično povečana koncentracija monoaminov (dopamina in noradrenalina) v zunajnevronskem prostoru (sinaptični špranji).<ref> Štuhec, M.: Hiperkinetični sindrom: Od epidemiologije do zdravljenja z zdravili. Farmacevtski vestnik, številka 2, 2015 : 177-184.</ref> 

== Uporaba ==
Metilfenidat je [[psihostimulans]], ki deluje tako, da povečuje aktivnost osrednjega živčevja.<ref name="pmid10440465">{{cite journal | author1 = Markowitz JS |author2=Logan BK |author3=Diamond F |author4=Patrick KS | title = Detection of the novel metabolite ethylphenidate after methylphenidate overdose with alcohol coingestion | journal = Journal of Clinical Psychopharmacology | volume = 19 | issue = 4 | pages = 362–6 | year = 1999 | pmid = 10440465 | doi = 10.1097/00004714-199908000-00013 }}</ref> Povzroča povečano budnost in pozornost ter zmanjša utrujenost.<ref name="steele">{{cite journal | author1 = Steele M | author2 = Weiss M | author3 = Swanson J | author4 = Wang J | author5 = Prinzo RS | author6 = Binder CE | title = A randomized, controlled effectiveness trial of OROS-methylphenidate compared to usual care with immediate-release methylphenidate in attention deficit-hyperactivity disorder | journal = Can J Clin Pharmacol | volume = 13 | issue = 1 | pages = e50–62 | year = 2006 | pmid = 16456216 | url = http://www.cjcp.ca/pdf/CJCP_05-012_e50.pdf | format = PDF | access-date = 2016-01-03 | archive-date = 2011-12-15 | archive-url = http://webarchive.nationalarchives.gov.uk/20111215210932/http%3A//www.cjcp.ca/CJCP_05%2D012_e50%2Dr101628 | url-status = dead }}</ref> Kratkoročne koristi zdravljenja in [[stroškovna učinkovitost]] so izkazane.<ref>{{cite journal | author1= Gilmore A |author2=Milne R | title = Methylphenidate in children with hyperactivity: review and cost-utility analysis | journal = Pharmacoepidemiol Drug Saf | volume = 10 | issue = 2 | pages = 85–94 | year = 2001 | pmid = 11499858 | doi = 10.1002/pds.564 }}</ref><ref>{{cite journal | author1= Mott TF |author2=Leach L |author3=Johnson L | title = Clinical inquiries. Is methylphenidate useful for treating adolescents with ADHD? | journal = The Journal of Family Practice | volume = 53 | issue = 8 | pages = 659–61 | year = 2004 | pmid = 15298843 | url = http://www.jfponline.com/Pages.asp?AID=1753 }}</ref> Uporablja se za zdravljenje motnje aktivnosti in pozornosti pri otrocih, starih šest let ali več. Uporablja se kot del celovitega programa zdravljenja motnje, kadar samo korektivni ukepi ne zadostujejo. Celovit program običajno vključuje še psihološke, izobraževalne in socialne ukrepe.<ref>http://www.cbz.si/cbz/bazazdr2.nsf/o/3F2F82EA55C3AF9BC12579C2003F6709/$File/s-012372.pdf{{Slepa povezava|date=oktober 2022 |bot=InternetArchiveBot |fix-attempted=yes }} Povzetek glavnih značilnosti zdravila Concerta 18 mg tablete s podaljšanim sproščanjem, vpogled: 3. 1. 2016.</ref> [[Nenamenska uporaba|Nenamensko]] se uporablja tudi za zdravljenje [[bipolarna motnja|bipolarne motnje]] in [[huda depresivna motnja|hude depresivne motnje]], ki se ne odzivata na druge oblike zdravljenja.<ref>{{cite journal | first1= Bernardo |last1=Dell’Osso |first2=Cristina |last2=Dobrea |first3=Laura |last3=Cremaschi |first4=Chiara |last4=Arici |first5=A. Carlo |last5=Altamura | title = Wake-Promoting Pharmacotherapy for Psychiatric Disorders | journal = Current Psychiatry Reports | volume = 16 | issue = 12 | pages = 524 | year = 2014 | pmid = 25312027 | doi = 10.1007/s11920-014-0524-2 }}</ref>

[[Metaanaliza|Metaanalize]] in sistemski pregledi slik z magnetno resonanco, so pokazali tudi na dolgoročne učinke zdravljenja motnje aktivnosti in pozornosti s psihostimulansi, kot so [[amfetamin]]i in metilfenidat. Zmanjšajo se namreč anomalije v strukturi in delovanju možganov, značilne za bolnike s to boleznijo.<ref name="Neuroplasticity 1">{{cite journal |author1=Hart H |author2=Radua J |author3=Nakao T |author4=Mataix-Cols D |author5=Rubia K |title=Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects |journal=JAMA Psychiatry |volume=70 |issue=2 |pages=185–198 |date=February 2013 |pmid=23247506 |doi=10.1001/jamapsychiatry.2013.277 |url=https://archive.org/details/sim_jama-psychiatry_2013-02_70_2/page/185}}</ref><ref name="Neuroplasticity 2">{{cite journal |author1=Spencer TJ |author2=Brown A |author3=Seidman LJ |author4=Valera EM |author5=Makris N |author6=Lomedico A |author7=Faraone SV |author8=Biederman J |title=Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies |journal=J. Clin. Psychiatry |volume=74 |issue=9 |pages=902–917 |date=September 2013 |pmid=24107764 |doi=10.4088/JCP.12r08287 |url=https://archive.org/details/sim_journal-of-clinical-psychiatry_2013-09_74_9/page/902|pmc=3801446}}</ref><ref name="Neuroplasticity 3">{{cite journal | title=Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects. | journal=Acta psychiatrica Scand. | date=February 2012 | volume=125 | issue=2 | pages=114–126 | pmid=22118249 | author1=Frodl T |author2=Skokauskas N | quote=Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non-treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure. | doi=10.1111/j.1600-0447.2011.01786.x}}</ref> Pregledi raziskav so nadalje ugotovili varnost in učinkovitost dolgotrajne uporabe psihostimulansov pri motnji aktivnosti in pozornosti.<ref name="Millichap_3">{{navedi knjigo | author = Millichap, JG |  editor = Millichap, JG | title = Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD | url = https://archive.org/details/attentiondeficit00mill | year = 2010 | publisher = Springer | location = New York | isbn = 9781441913968 | pages = [https://archive.org/details/attentiondeficit00mill/page/n121 111]–113 | edition=2. | chapter = Chapter 3: Medications for ADHD}}</ref><ref name="Long-Term Outcomes Medications">{{cite journal | author1= Huang YS |author2=Tsai MH | title = Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge | journal = CNS Drugs | volume = 25 | issue = 7 | pages = 539–554 |date=July 2011  | pmid = 21699268 | doi = 10.2165/11589380-000000000-00000 | url = }}</ref>  V nadzorovanih [[klinična študija|kliničnih raziskavah]] je uporaba amfetaminov in metilfenidata pokazala učinkovitost in varnost tudi pri neprekinjeni večletni uporabi zdravila.<ref name="Long-Term Outcomes Medications" /><ref name="Millichap">{{navedi knjigo | author = Millichap, JG |  editor = Millichap, JG | title = Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD | url = https://archive.org/details/attentiondeficit00mill | year = 2010 | publisher = Springer | location = New York | isbn = 9781441913968 | pages = [https://archive.org/details/attentiondeficit00mill/page/n131 121]–123 | edition=2. | chapter = Chapter 3: Medications for ADHD}}</ref> 

Metilfenidat je izkazal tudi učinkovitost pri [[narkolepsija|narkolepsiji]], ki spada med kronične motnje spanca. Učinkovito poveča budnost, pozornost in zmogljivost.<ref name="pmid9484423">{{cite journal | author = Fry JM | title = Treatment modalities for narcolepsy | journal = Neurology | volume = 50 | issue = 2 Suppl 1 | pages = S43–8 | year = 1998 | pmid = 9484423 | doi = 10.1212/WNL.50.2_Suppl_1.S43 }}</ref> Kljub učinkovitosti pa zmogljivosti bolnikov ne poveča na raven posameznikov, ki nimajo narkolepsije.<ref name="pmid7701190">{{cite journal | author = Mitler MM | title = Evaluation of treatment with stimulants in narcolepsy | journal = Sleep | volume = 17 | issue = 8 Suppl | pages = S103–6 | year = 1994 | pmid = 7701190 }}</ref>

== Neželeni učinki ==
Pogosti kratkotrajni [[neželeni učinek|neželeni učinki]] metilfenidata so  [[motnja spanja|motnje spanja]], pomanjkanje teka, [[neješčnost]] (anoreksija) ter zmanjšanje telesne teže, manj pogosti pa [[tahikardija]], [[povišan krvni tlak|povečanje krvnega tlaka]],
[[glavobol]] in [[prebavne motnje]]. Pri bolnikih s srčno-žilnimi boleznimi se uporaba stimulansov ne priporoča, razen v primerih, kadar korist presega tveganje.<ref>Štuhec, Matej (2013). Pregled zdravil za zdravljenje motnje pozornosti s hiperaktivnostjo. Zdravniški vestnik, letnik 82, številka 4, str. 243-254.</ref> Metilfenidat lahko poslabša tudi nekatere psihiatrične motnje, na primer [[depresija (razpoloženje)|depresijo]], [[samomorilskost|samomorilne misli]], sovražnost, [[psihoza|psihoze]] in [[manija|manijo]].<ref name=jazmp2009/>

== Sklici ==
{{sklici}}
{{normativna kontrola}}

[[Kategorija:Evforiki]]
[[Kategorija:Karboksilatni estri]]
[[Kategorija:Metilni estri]]
[[Kategorija:Nootropiki]]
[[Kategorija:Simpatikomimetični amini]]
[[Kategorija:Zaviralci ponovnega privzema dopamina in noradrenalina]]
[[Kategorija:Zdravila z delovanjem na kardiovaskularni sistem]]