Klopidogrel

Klopidogrel
(IUPAC) ime
	(+)-(S)-metil 2-(2-hlorofenil)-2-(6,7-dihidrotieno[3,2-c]piridin-5(4H)-il)acetat
Klinički podaci
Robne marke	Plaviks
AHFS/Drugs.com	Monografija
MedlinePlus	a601040
Identifikatori
CAS broj	113665-84-2
ATC kod	B01AC04
PubChem	60606
DrugBank	APRD00444
ChemSpider	54632
UNII	A74586SNO7
KEGG	D07729
ChEBI	CHEBI:37941
ChEMBL	CHEMBL1771
Hemijski podaci
Formula	C16H16ClNO2S
Mol. masa	321.82 g/mol
SMILES	eMolekuli & PubHem
InChI
	InChI=1S/C16H16ClNO2S/c1-20-16(19)15(12-4-2-3-5-13(12)17)18-8-6-14-11(10-18)7-9-21-14/h2-5,7,9,15H,6,8,10H2,1H3/t15-/m0/s1 ; Key: GKTWGGQPFAXNFI-HNNXBMFYSA-N
Farmakokinetički podaci
Bioraspoloživost	>50%
Vezivanje za proteine plazme	94–98%
Metabolizam	Hepatički
Poluvreme eliminacije	7–8 sati (neaktivni metabolit)
Izlučivanje	50% renalno; 46% biliharno
Farmakoinformacioni podaci
Trudnoća	B1(AU) B(US)
Pravni status	Samo na recept (S4) (AU) POM (UK) ℞-only (SAD)
Način primene	Oralno

Klopidogrel (INN) je oralni, antitrombotski agens iz tienopiridinske klase, koji se koristi za inhibiranje formiranja krvnih ugrušaka pri lečenju koronarne arterijske bolesti, periferne vaskularne bolesti, i cerebrovaskularne bolesti. Njega su izvele na tržište kompanije Bristol-Majers Skvib i Sanofi pod imenom Plaviks. Ovaj lek deluje putem ireverzibilne inhibicije P2Y₁₂ receptora na ćelijskoj membrani trombocita. Endogeni agonist tog receptora je adenozin difosfat (ADP).^[6] Nepoželjna dejstva su krvarenje, jaka neutropenija, i trombocitička trombocitopenična purpura (TTP).^[7]

Farmakologija uredi

Klopidogrel je prolek koji deluje na ADP receptor na ćelijskoj membrani trombocita. Ovaj lek specifično i ireverzibilno inhibira P2Y₁₂ receptor, koji je značajan za agregaciju trombocita i umrežavanje proteina fibrina.^[8] Blokada ovog receptora inhibira agregaciju trombocita putem blokiranja aktivacije glikoprotein IIb/IIIa puta. IIb/IIIa kompleks deluje kao receptor uglavnom za fibrinogen i vitronektin, ali i za fibronektin i fon Vilebrandov faktor. Aktivacija tog kompleksa je "finalni zajednički put" agregacije trombocita.

Inhibicija trombocita počinje dva sata nakon oralne doze klopidogrela. Početak dejstva je spor, tako da se početna doza od 300–600 mg obično primenjuje.

Reference uredi

↑ Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit
↑ Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.
↑ Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit
↑ Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.
↑ Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit
↑ Thomas L. Lemke, David A. Williams, ur. (2007). Foye's Principles of Medicinal Chemistry (6 izd.). Baltimore: Lippincott Willams & Wilkins. ISBN 0-7817-6879-9.
↑ Hardman JG, Limbird LE, Gilman AG. (2001). Goodman & Gilman's The Pharmacological Basis of Therapeutics (10 izd.). New York: McGraw-Hill. DOI:10.1036/0071422803. ISBN 0-07-135469-7.
↑ Savi P, Zachayus JL, Delesque-Touchard N et al. (July 2006). „The active metabolite of Clopidogrel disrupts P2Y12 receptor oligomers and partitions them out of lipid rafts”. Proceedings of the National Academy of Sciences of the USA 103 (29): 11069–11074. DOI:10.1073/pnas.0510446103. PMC 1635153. PMID 16835302.

Literatura uredi

Spoljašnje veze uredi

	Portal Medicina
	Portal Hemija

Plaviks zvanični vebsajt Arhivirano 2009-08-04 na Wayback Machine-u
Plaviks informacije o doziranju

[1] Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit

[2] Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.

[3] Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit

[4] Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.

[5] Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit

[Foye-6] Thomas L. Lemke, David A. Williams, ur. (2007). Foye's Principles of Medicinal Chemistry (6 izd.). Baltimore: Lippincott Willams & Wilkins. ISBN 0-7817-6879-9.

[Goodman_Gilman-7] Hardman JG, Limbird LE, Gilman AG. (2001). Goodman & Gilman's The Pharmacological Basis of Therapeutics (10 izd.). New York: McGraw-Hill. DOI:10.1036/0071422803. ISBN 0-07-135469-7.

[Savi-8] Savi P, Zachayus JL, Delesque-Touchard N et al. (July 2006). „The active metabolite of Clopidogrel disrupts P2Y12 receptor oligomers and partitions them out of lipid rafts”. Proceedings of the National Academy of Sciences of the USA 103 (29): 11069–11074. DOI:10.1073/pnas.0510446103. PMC 1635153. PMID 16835302.

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