Ihe ọmụma
Clopidogrel ntụ ntụ, ụdị prodrug nke ọgwụ antiplatelet Clopidogrel, aghọwo isi nkuku na mgbochi nke ihe omume thrombotic arterial. Dị ka onye otu thienopyridine klas nke adenosine diphosphate (ADP) antagonists, Clopidogrel na-arụ ọrụ dị mkpa na ahụike obi site na igbochi nchịkọta platelet. Isiokwu a na-achọ ime ka a ghọtakwuo ihe mejupụtara kemịkalụ na nhazi nke ntụ ntụ Clopidogrel, usoro ya na ngwa ya na omume ahụike, mgbe ọ na-ewepụ mkparịta ụka banyere mmetụta ndị ọzọ.
Kedu ihe na-eme ka Clopidogrel dị irè?
Ịdị irè Clopidogrel sitere na kemịkalụ ya pụrụ iche. Ihe na-arụ ọrụ na Clopidogrel ntụ ntụ bụ Clopidogrel besylate, nke sitere na thiophene. Usoro kemịkal ya bụ C16H16ClNO2S·C7H7O2S, na-egosipụta ịdị arọ nke molekụla ihe dịka 555.3. Ọnụnọ nke mgbanaka thiophene na chlorine atom bụ isi ihe na-arụ ọrụ ọgwụ ya. Mgbe ị risịrị nri, Clopidogrel na- metabolized n'ime imeju ka ọ mepụta metabolite na-arụ ọrụ nke na-ahọrọ na enweghị ike ijikọ ya na onye na-anabata platelet P2Y12, na-egbochi ịgbalite mgbasa ozi ADP na mkpokọta.
Njem Clopidogrel site na prodrug na-adịghị arụ ọrụ ruo n'ụdị ya na-arụ ọrụ bụ usoro mgbagwoju anya nke gụnyere ọtụtụ usoro nke metabolism imeju. Ntughari a bụ nke sistemu enzyme cytochrome P450 (CYP), ọkachasị CYP2C19 isoenzyme. Metabolism ịgbalite Clopidogrel bụ usoro oxidation nke ụzọ abụọ. Na nzọụkwụ mbụ, mgbanaka thiophene nke Clopidogrel bụ oxidized iji mepụta 2-oxo-clopidogrel. Ngwakọta etiti a na-enwetakwu oxidation na hydrolysis iji mepụta metabolite na-arụ ọrụ, nke nwere otu thiol.
Otu thiol nke metabolite na-arụ ọrụ dị mkpa maka ọrụ antiplatelet ya. Ọ na-etolite akwa mmiri disulfide yana ihe fọdụrụ na cysteine na onye nnabata P2Y12, na-egbochi saịtị njikọ maka ADP nke ọma. Ngbanwe a na-enweghị mgbagha nke onye na-anabata ya na-egbochi ADP ka ọ rụọ ọrụ platelet, si otú a na-egbochi nchịkọta platelet ma belata ihe ize ndụ nke ihe omume thrombotic.
Na-enyocha Ọdịdị Molecular nke Clopidogrel na ihe ọ pụtara
Ọdịdị molekụla nke Clopidogrel dị mgbagwoju anya ma nwee mmetụta dị ukwuu maka akụrụngwa ọgwụ ya. Ngwakọta ahụ nwere mgbanaka thienopyridine jikọtara ya na mgbanaka pyridine, yana eriri akụkụ carboxymethyl nke etinyere na otu benzenesulfonate. Ihe owuwu a na-enye ohere ka Clopidogrel bụrụ lipophilic, na-eme ka nnabata ya dị na eriri afọ ma na-agafe ihe mgbochi ụbụrụ ọbara. Nhazi molekul na-ekerekwa òkè na metabolism ya, yana enzymes pụrụ iche n'ime imeju, dị ka CYP2C19, na-atụgharị Clopidogrel n'ụdị ọrụ ya.
Mgbanaka thienopyridine bụ isi ihe eji arụ ọrụ nke na-eme ka Clopidogrel dị iche na ndị nnọchi anya antiplatelet ndị ọzọ. Usoro mgbanaka a bụ maka ikike ọgwụ na-emekọrịta ihe na enzymes CYP450 na imeju, na-enye ohere maka ntụgharị ya na metabolite na-arụ ọrụ. Atọm chlorine nke etinyere na mgbanaka thiophene na-enye aka na nkwụsi ike nke molekul ahụ n'ozuzu ya ma na-ekerekwa òkè na njirimara ọgwụ.
Agbụ akụkụ carboxymethyl nke Clopidogrel bụ ihe ọzọ dị mkpa nhazi. N'ụdị prodrug, a na-eme ka agbụ a dị n'akụkụ, nke na-eme ka lipophilicity nke molecule dịkwuo mma ma na-eme ka ọ dị mfe. N'oge usoro ịgbalite metabolic, a na-agbaji ester bond, na-ekpughe otu carboxylic acid nke dị mkpa maka ịmepụta metabolite na-arụ ọrụ.
Otu benzenesulfonate dị na Clopidogrel besylate na-eje ozi dị ka onye na-emepụta nnu, na-eme ka ọ dịkwuo mfe na nkwụsi ike nke ogige ahụ. Nke a dị mkpa karịsịa maka imepụta Clopidogrel n'ụdị usoro ọgwụgwọ dị iche iche, gụnyere mbadamba na ngwọta maka nchịkwa intravenous.
Ọdịdị akụkụ atọ nke Clopidogrel na-arụkwa ọrụ dị mkpa na mmekọrịta ya na onye na-anabata P2Y12. Nhazi oghere nke atọm na metabolite na-arụ ọrụ na-enye ohere maka njikọ ziri ezi na onye na-anabata ya, na-eme ka nkọwapụta dị elu na ike dị na ọrụ antiplatelet ya.
Ịghọta mmekọrịta dị n'usoro-ọrụ nke Clopidogrel edugala n'ịzụlite ihe ọhụrụ antiplatelet nwere profaịlụ ọgwụ ka mma. Dịka ọmụmaatụ, prasugrel na ticagrelor, ndị bụkwa P2Y12 antagonists ndị na-anabata ya, bụ ndị e mere dabere na nghọta enwetara site n'ịmụ usoro na usoro omume nke Clopidogrel.
Kedu ka esi eji ntụ ntụ Clopidogrel mee ihe na ọgwụgwọ ahụike?
N'ihe gbasara ahụike, Clopidogrel ntụ ntụ A na-emegharịkarị ma jiri ya mee ihe n'ụdị dị iche iche, gụnyere mbadamba nkume na ngwọta intravenous. A na-edekarị ya maka ndị ọrịa nwere akụkọ ihe mere eme nke myocardial infarction, ọrịa strok, ma ọ bụ ọrịa akwara dị n'akụkụ guzosiri ike. Ojiji Clopidogrel na-agbatị ruo ndị a na-eme ihe dị ka stent nke akwara obi, ebe ọ na-enyere aka igbochi mkpụkọta mkpụkọ gburugburu stent. A na-edekọ nchekwa na ịdị irè nke Clopidogrel nke ọma n'ọtụtụ ule ụlọ ọgwụ, na-egosipụta ike ya iji belata ihe ize ndụ nke ọrịa obi na-enweghị itinye uche na-enweghị isi na mmetụta ndị nwere ike ime.
Usoro ọnụ nke Clopidogrel maka ọtụtụ ihe ngosi bụ 75 mg kwa ụbọchị. Agbanyeghị, na nnukwu ọrịa akwara obi ma ọ bụ tupu itinye aka na akwara akwara, a na-enyekarị dose 300-600 mg iji nweta mgbochi platelet ngwa ngwa. Usoro ntinye ihe a na-eji ohere nke Clopidogrel's pharmacokinetics, na-enye ohere ịmalite ime ngwa ngwa na ọnọdụ ụlọ ọgwụ ngwa ngwa.
A na-ejikarị clopidogrel na-ejikọta ya na aspirin, usoro a maara dị ka ọgwụgwọ antiplatelet dual (DAPT). Nchikota a egosila ịdị mma dị elu n'igbochi ihe omume thrombotic ma e jiri ya tụnyere onye ọrụ ọ bụla, karịsịa na ndị ọrịa nwere nnukwu ọrịa obi na-arịa ọrịa obi ma ọ bụ ndị na-agbanye stent nke akwara obi. Ogologo oge DAPT nwere ike ịdịgasị iche dabere na ọnọdụ ahụike, sitere na ọtụtụ ọnwa ruo ihe karịrị otu afọ n'ọnọdụ ụfọdụ.
N'ime ndị ọrịa na-ahọrọ ịwa ahụ na-abụghị nke obi, a na-akwụsịkarị Clopidogrel ụbọchị 5-7 tupu usoro ahụ iji belata ohere nke ọbara ọgbụgba. Otú ọ dị, n'ime ndị ọrịa nwere ọrịa obi na-adịbeghị anya ma ọ bụ nnukwu ihe ize ndụ thrombotic, ekwesịrị iji nlezianya tụlee mkpebi ịkwụsị Clopidogrel megide ihe ize ndụ nke stent thrombosis ma ọ bụ ihe omume obi ndị ọzọ.
Ojiji nke Clopidogrel n'ime ndị ọrịa chọrọ nlebara anya nke ọma. Dịka ọmụmaatụ, n'ime ndị ọrịa nwere polymorphisms mkpụrụ ndụ ihe nketa na-emetụta ọrụ CYP2C19, ọkachasị ndị nwere ọrụ enzyme belatara, mgbanwe nke Clopidogrel na metabolite na-arụ ọrụ nwere ike imebi. Nke a nwere ike ibute mmetụta antiplatelet belata yana enwere ike ịbawanye ihe egwu nke ihe omume obi. N'ọnọdụ ndị dị otú a, enwere ike ịtụle ọgwụ antiplatelet ọzọ ma ọ bụ doses dị elu nke Clopidogrel.
Clopidogrel ahụtakwala ngwa karịa ọrịa akwara obi. A na-eji ya na njikwa ọrịa akwara dị n'akụkụ, ebe o gosipụtara ịdị irè n'ibelata ihe ize ndụ nke infarction myocardial, ọrịa strok, na ọnwụ vaskụla. N'ime ndị ọrịa nwere ọrịa strok ma ọ bụ ọgụ ischemic na-adịru nwa oge, a na-eji Clopidogrel, ma ọ bụ naanị ya ma ọ bụ yana yana aspirin, maka mgbochi nke abụọ nke ihe omume cerebrovascular ugboro ugboro.
Mmepe nke nleba anya nleba anya ọrụ platelet enyela ohere maka ọgwụgwọ antiplatelet ahaziri iche. Nnwale ndị a nwere ike nyochaa nzaghachi onye ọrịa na Clopidogrel, nwere ike ịchọpụta ndị nwere ike irite uru na atụmatụ antiplatelet ọzọ. Otú ọ dị, iji ule ndị dị otú ahụ eme ihe mgbe nile na omume ụlọ ọgwụ ka bụ isiokwu nke nyocha na arụmụka na-aga n'ihu.
Nnyocha e mere n'oge na-adịbeghị anya enyochala uru Clopidogrel nwere na ọnọdụ ahụike ndị ọzọ. Dịka ọmụmaatụ, ọmụmụ ihe enyochala iji ya na-egbochi nephropathy dị iche iche na ndị ọrịa na-anata angiography nke akwara obi. Ụfọdụ nnyocha egosiwokwa na ọ ga-arụ ọrụ Clopidogrel na ụfọdụ ọrịa neurodegenerative, dabere na ihe ndị na-egbochi mkpali ya, n'agbanyeghị na nke a ka bụ mpaghara nyocha.
mmechi
Clopidogrel ntụ ntụ, ya na ihe mejupụtara kemịkalụ ya na ihe owuwu molekụla, guzo dị ka ihe akaebe maka mmepụta ọgwụ ọgbara ọhụrụ. Ọrụ ya na igbochi ihe omume thrombotic arterial bụ nke ọma, na ngwa ya na omume ahụike na-aga n'ihu. Ka anyị na-aga n'ihu na-enyocha oke nlekọta ahụike obi, nghọta nke akụrụngwa na usoro nke Clopidogrel ka dị mkpa.
Njem nke Clopidogrel site na nchọpụta ya ruo na ọnọdụ ọ dị ugbu a dị ka isi ihe na ọgwụgwọ antiplatelet na-egosi mkpa ọ dị ịghọta mmekọrịta dị mgbagwoju anya n'etiti usoro kemịkalụ, ọgwụ ọgwụ, na nrụpụta ụlọ ọgwụ. Usoro thienopyridine nke Clopidogrel, ụdị ọgwụ ya na mmekọrịta ya na onye na-anabata P2Y12 abụghị naanị ịgbanwegharị njikwa nke ọrịa obi mana emeghewokwa ụzọ maka mmepe nke ndị nnọchi anya antiplatelet ọhụrụ.
Ka nghọta anyị banyere ọgwụ ahaziri onwe ya na-aga n'ihu, ojiji nke Clopidogrel nwere ike ịchacha nke ọma. Nnwale mkpụrụ ndụ ihe nketa maka CYP2C19 polymorphisms na nyocha ọrụ platelet nwere ike inye ohere maka atụmatụ antiplatelet ahaziri ahazi karị, na-ebuli ịdị irè ma na-ebelata ihe egwu. Ọzọkwa, nyocha na-aga n'ihu n'ime mmetụta pleiotropic nke Clopidogrel, gafere ọrụ antiplatelet guzosiri ike, nwere ike ikpughe ngwa ọgwụgwọ ọhụrụ n'ọdịnihu.
Ihe ịga nke ọma nke Clopidogrel na-egosikwa mkpa ọ dị ịnọgide na-eme nyocha na mmepe na ngalaba ọgwụgwọ antithrombotic. Ọ bụ ezie na Clopidogrel ewepụtala ụkpụrụ dị elu na ọgwụgwọ antiplatelet, nchụso ndị ọrụ na-amalite ngwa ngwa, mmetụta antiplatelet na-agbanwe agbanwe, yana profaịlụ nchekwa ka mma ka bụ mpaghara nyocha.
N'ikpeazụ, chemical mejupụtara na Ọdịdị nke Clopidogrel ntụ ntụ na-anọchi anya ọganiru dị ịrịba ama na kemistri ọgwụ na ọgwụ. Ojiji a na-ejikarị eme ihe na ụlọ ọgwụ emewo ka nsonaazụ ka mma maka ọtụtụ nde ndị ọrịa nwere ọrịa obi. Ka anyị na-ele anya n'ọdịnihu, ihe mmụta ndị a mụtara na Clopidogrel ga-aga n'ihu na-agwa ma na-akpali mmepe nke usoro ọgwụgwọ ọhụrụ, na-eme ka anyị nwee ike ịlụso ọrịa thrombotic ọgụ ma melite ahụike obi n'ụwa nile.
Ọ bụrụ na ị nwekwara mmasị na ngwaahịa a ma chọọ ịmatakwu nkọwa ngwaahịa, ma ọ bụ chọọ ịmata maka ngwaahịa ndị ọzọ metụtara, biko nweere onwe gị ịkpọtụrụ. iceyqiang@aliyun.com.
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