Teriparatid 750mg

Imiterere ya Teriparatid Structure

Research bwa Teriparatid Ubushakashatsi

Teriparatid isobanura iki?

Teriparatid ni igereranya ryimisemburo ya parathiyide yumuntu (PTH) igizwe na acide 34 yambere ya amino ya hormone ya parathiyide yumuntu. Igenga amagufwa yo mu magufwa yigana ibikorwa bya physiologique ya hormone ya parathiyide ya endogenous. Teriparatid niwo muti wambere wa sintetike ya anabolike yemewe kuri osteoporose ikabije. Imiterere yacyo yerekana homologiya nini hamwe na PTH ya endogenous, ituma ibikorwa bya reseptor ya PTH bihindura ibikorwa bya metabolike osteoclast.

Nubuhe buryo bwo gukora kuri Teriparatid?

Ingaruka kuri osteoblasts:

Itera ikwirakwizwa rya osteoblast: Teriparatid itera ikwirakwizwa rya selile osteoblast precursor selile, ikongera umubare wa osteoblast. Mu bushakashatsi bw’inyamaswa, imiyoborere rimwe na rimwe ya teriparatide yihutishije cyane ikwirakwizwa ry’ingirabuzimafatizo ya mesenchymal ishobora gutandukanya osteoblasts mu magufa. Ibi byafashaga selile nyinshi gutandukanya osteoblasts ikuze, itanga ibikoresho byinshi bya selile yo gukora amagufwa. Mu bushakashatsi bw’umuco wa vitro bwerekanye ko igabanywa ry’ingirabuzimafatizo ya osteoblast iri mu itsinda ryavuwe na Teriparatide ryari hejuru cyane ugereranije n’itsinda rishinzwe kugenzura, byerekana ko Teriparatid itera mu buryo butaziguye ikwirakwizwa ry’utugingo ngengabuzima twa osteoblast ^[1,2].

Kongera ibikorwa bya Osteoblast: Teriparatid ntabwo yongera umubare wa osteoblast gusa ahubwo inazamura ibikorwa byabo. Igenzura imvugo ya genes ijyanye no guhuza amagufwa ya matrix muri osteoblasts, nka izo kodegisi yo mu bwoko bwa I collagen na osteocalcine, byerekana kwiyongera kurwego rwo kwerekana. Ubwoko bwa I kolagen, ibice byibanze bigize matrike yamagufa, bigira uruhare mugushiraho urwego rukomeye rwa matrix binyuze muri synthesis. Osteocalcine igira uruhare runini mu kwangiza amagufwa mu guteza imbere calcium ion muri matrix, bityo bigatuma amagufwa yiyongera. Binyuze muri ubwo buryo, osteoblasts ikomatanya kandi ikarekura matrike yamagufwa neza, byorohereza amagufwa mashya ^[2,3].

Kubuza osteocyte apoptose: Mugihe gisanzwe cyimiterere yumubiri, osteocytes ikorerwa apoptose nyuma yo kurangiza imirimo yihariye yo gukora amagufwa. Teriparatid ihagarika iyi nzira ya apoptotique, ikongerera igihe cya osteocyte. Teriparatid ikora inzira ya selile yerekana inzira, nka PI3K / Akt inzira. Iyo ukora, iyi nzira ihagarika imvugo ya poroteyine zifitanye isano na apoptose, bigatuma osteoblasts ikomeza imirimo yabo ikora amagufwa kandi igakomeza gukomeza no gukomera kw'amagufwa ^[1,3].

Ingaruka kuri Osteoclasts: Ingaruka za Teriparatid kuri osteoclasts ziragoye. Mugihe cyo kunywa rimwe na rimwe, bigira ingaruka kuri osteoclasts hakoreshejwe uburyo butaziguye. Itera osteoblast gusohora kwa osteoprotegerin (OPG), cytokine ihuza amarushanwa ihuza reseptor ikora ibintu bya kirimbuzi κB ligand (RANKL). RANKL ni urufunguzo rwingenzi rwo gutandukanya osteoclast no gukora. Iyo OPG ihujwe na RANKL, RANKL ntishobora guhuza reseptor ya RANK hejuru ya selile osteoclast precursor selile, bityo ikabuza gutandukanya osteoclast no gukura no kugabanya amagufwa. Mu barwayi ba osteoporose, aho resorption igufa irenze kwibumbira mu magufa, teriparatide igabanya ibikorwa bya osteoclast ikoresheje ubu buryo. Ibi bigarura uburinganire hagati ya resorption no kwibumbira hamwe, biteza imbere amagufwa ^[2,3].

Igishushanyo 1 Imbuga zikorwa kumurongo wa mbere wo kuvura osteoporose. Teriparatid, agace ka recombinant gormone ya parathiyide, itera amagufwa yongera ibikorwa bya osteoblast kandi, ku rugero ruto, ikabuza kwinjiza osteoclast ^[4].

Guhindura Amagufwa ya Metabolism Bifitanye isano n'inzira zerekana ibimenyetso:

Inzira ya Wnt / β-Catenin: Inzira ya Wnt / β-catenin yerekana inzira igira uruhare runini mugutezimbere amagufwa no kubungabunga amagufwa homeostasis. Teriparatid ikora iyi nzira, iteza imbere kwirundanya kwimitsi no guhinduranya nucleaire ya cat-catenin. Nucleaire β-catenin ihuza ibintu bifitanye isano no kwandukura, gutangira kwandukura amagufwa ajyanye no gukora amagufwa no kongera imvugo ya osteoblast yihariye yo kwandukura Runx2. Runx2 irongera igenga itandukaniro rya osteoblast n'imikorere, bityo igatera amagufwa. Gukora iyi nzira kandi birabuza gutandukanya osteoblast kuri adipocytes, bigatuma habaho itandukaniro ryinshi ryingirabuzimafatizo ya mesenchymal stem selile igana kumurongo wa osteoblast, bityo ukongera amagufwa ^[1,3].

Inzira ya PTH / PTHrP Ibimenyetso byerekana inzira: Teriparatid, igereranya imisemburo ya parathiyide (PTH), cyane cyane itanga ingaruka zayo muguhuza reseptor ya PTH / PTHrP. Iyo uhambiriye, Teriparatid ikora inzira yerekana ibimenyetso nkinzira ya cAMP / PKA n'inzira ya PLC / PKC. Gukora izi nzira bigenga imikorere ya osteoblast na osteoclast, biteza imbere amagufwa. Inzira ya cAMP / PKA yongerera imbaraga genes zijyanye na osteoblast muguhindura ibikorwa byo kwandukura ibintu, mugihe inzira ya PLC / PKC igira uruhare muburyo bwo kuvugurura imikorere ya cytoskeletal hamwe ningirabuzimafatizo, bigira ingaruka kumyuka ya osteoblast no mumikorere ^[2,5].

Ni ubuhe buryo bukoreshwa na Teriparatid?

Umuti wa Osteoporose

Osteoporose ya Postmenopaose: Teriparatid niwo muti wa mbere wa sintetike ya anabolike yemewe yo kuvura abagore batangiye gucura bafite ostéoporose ikabije. Mugukangura amagufwa, byongera amagufwa, bityo bikagabanya ibyago byo kuvunika. Ku bagore nyuma yo gucura, gukoresha teriparatide ya buri munsi byongera ubwinshi bwamagufwa yamagufa, bikagabanya ibyago byo kuvunika kwurugingo ku kigero cya 65% naho kuvunika kwa vertebral ku 53% ugereranije na placebo. Meta-isesengura ryamakuru yihariye yo murwego rwabarwayi yerekanaga igabanuka rya 56% ibyago byo kuvunika ikibuno ugereranije no kugenzura. Byongeye kandi, ugereranije na risedronate, Teriparatid yagabanije ibyago byo kuvunika inshyashya n’ubuvuzi ku gipimo cya 56% na 52%, ku bagore barwaye osteoporose ikabije ^[3,6,7].

Osteoporose y'abagabo: Biremewe kandi kuvura osteoporose y'abagabo. Quattrocchi E n'abandi. yerekanye ko mu barwayi ba osteoporose y'abagabo, Teriparatide (inshinge 20μg na 40μg buri munsi) byatanze ubwiyongere bugaragara mu mibare y’ubwinshi bw’amagufwa y’umugongo: 5.9% mu itsinda rya 20μg na 9.0% mu itsinda rya 40μg (byombi P <0.001). Ku ijosi ry'umugore, ubwinshi bw'amagufwa bwiyongereyeho 1.5% mu itsinda rya 20μg (P = 0.021) na 0,9% mu itsinda rya 40μg (P <0.001) ^[7].

Glucocorticoid-Associated Osteoporose: Teriparatid ikoreshwa kandi mu kuvura osteoporose iterwa na glucocorticoid iterwa na osteoporose ku barwayi b'igitsina gabo n'abagore bafite imvune, ifasha aba barwayi kongera amagufwa no kugabanya amagufwa ndetse n'ingaruka zo kuvunika ziterwa no gukoresha glucocorticoid ^[8].

Inkunga yo gukiza kuvunika: Ku barwayi bavunitse, kongera igihe gito amagufwa ahavunitse ni ngombwa mugusana, uruhare teriparatide irashobora gusohoza. Yakozweho ubushakashatsi mubyitegererezo by'inyamaswa ndetse n'abarwayi nk'igikoresho gishobora kuzamura imvune. Mugihe hakenewe ubundi bushakashatsi, ubushakashatsi buriho bwerekana ubushobozi bwabwo mugutezimbere gukira kuvunika ^[3].

Kuvugurura amagufwa ya Alveolar: Ubushakashatsi bujyanye na bwo bwerekana ko Teriparatide ishobora gukoreshwa mu kuvugurura amagufwa ya alveolar mu bihe nka jawbone necrosis, chronique periodontitis, amenyo yatewe amenyo osseointegration, hamwe n’amenyo ya ortodontique, aho byongera amagufwa ya alveolar. Icyakora, hakenewe ubundi bushakashatsi bw’amavuriro y’abantu kugira ngo hemezwe uburyo bukoreshwa n’ingaruka mbi ku ndwara zitandukanye zo mu kanwa ^[9].

Gutwita- no Kwonsa Bifitanye isano na Osteoporose: Ku barwayi bafite ostéoporose itwite- na amashereka (PLO), kuvura hamwe na Teriparatid (20μg / kumunsi) bifatanije na calcium na vitamine D byatumye ubwiyongere bukabije bw’imyunyu ngugu y’amagufwa y’amezi 12 na 24 ugereranije na calcium na vitamine D yonyine. Ku mezi 12, ubwiyongere buringaniye bwuruti rwumugongo amagufwa yubucucike bwa 20.9 ± 11.9% mumatsinda ya teriparatide na 6.2 ± 4.8% mumatsinda yo kugenzura (P <0.001). Ku mezi 24, kwiyongera hagati y’umugongo w’amagufwa y’amagufwa yari 32.9 ± 13.4% ku barwayi 7 bavuwe na Teriparatid na 12.2 ± 4.2% mu barwayi 6 bagenzura (P = 0.001). Nta kuvunika kwa muganga kwabayeho mu gihe cyo kuvura ^[10].

Porogaramu zidasanzwe: Teriparatid yavuzwe mubushakashatsi bwakozwe kubibazo byamagufwa yihariye, nka hypoparathyroidism ifitanye isano na osteodystrophy (ABD) hamwe na hypercalcemia. Umugore w'imyaka 51 utunzwe na dialyse yarwaye hypercalcemia nyuma ya parathiyideectomy, byemejwe na biopsy yamagufa nka ABD. Nyuma y'amezi 12 yo kuvura Teriparatide, urugero rwa calcium ya calcium yarasanzwe, byerekana ikibazo cya mbere cyanditse cya Teriparatid gikemura hypercalcemia ifitanye isano na ABD ^[11].

Umwanzuro

Teriparatide ifite akamaro kanini osteoporose ifite ibyago byinshi byo kuvunika. Yerekanwa ku barwayi bafite amateka y’imvune nyinshi za osteoporotique, ubwinshi bw’amagufwa y’amagufwa make, hamwe n’igisubizo gike ku buvuzi busanzwe bwa osteoporose.

Ibyerekeye Umwanditsi

Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.

Umwanditsi w'ikinyamakuru

Susan V. Bukata ni umushakashatsi mu Ishuri Rikuru ry’Ubuvuzi n’amenyo ya kaminuza ya Rochester, inzobere mu bijyanye n’amagufwa n’indwara zifata imitsi. Yanditse ibitabo byinshi byibanda ku binyabuzima by’amagufwa, gukiza kuvunika, hamwe n’ubuvuzi bw’imiti ya anabolike nka teriparatide mu myitozo ngororamubiri. Ibikorwa bye byagize uruhare mu gusobanukirwa ingamba zo kuvura zo kunoza amagufwa no kuvugurura. Susan V. Bukata yanditse ku rutonde rwerekana [1].

bifatikaIbitekerezo

[1] Bukata SV, Puzas JE. Gukoresha orthopedic ya teriparatide. Raporo ya Osteoporose y'ubu 2010; 8(1): 28-33.DOI: 10.1007 / s11914-010-0006-3.

[2] Hasegawa T, Miyamoto Y, Yamamoto T, Amizuka N. [Igikorwa cya Anabolic ya teriparatide kubarwayi ba osteoporotic]. Nihon Yakurigaku Zasshi 2019; 153(1): 16-21.DOI: 10.1254 / fpj.153.16.

[3] Marin F, Ma YL. Ivunika rya Osteoporotic hamwe na sisitemu yo mu bwoko bwa skeletale: Mechanism, Assessment, and Treatment. Muri: Takahashi HE, Burr DB, Yamamoto N, ed. Teriparatid. Singapore: Springer Singapore; 2022: 339-359.DOI: 10.1007 / 978-981-16-5613-2_22.

[4] Hanley D, Adachi J, Bell A, Brown V. Denosumab: Uburyo bwibikorwa nibisubizo byubuvuzi. Ikinyamakuru mpuzamahanga cy’ubuvuzi bwa 2012; 66.DOI: 10.1111 / ijcp.12022.

[5] Kim S. Mechanism hamwe nubushobozi bwa hormone parathiyide muri osteoporose. Ikinyamakuru cy’ishyirahamwe ry’ubuvuzi rya Koreya 2022; 65: 361-365.DOI: 10.5124 / jkma.2022.65.6.361.

[6] Itsinda JS, Depite Kane, Abu-Baker A. Teriparatid mu kuvura osteoporose. Ikinyamakuru cyo muri Amerika cyubuzima-Sisitemu Farumasi: Ajhp: Ikinyamakuru cyemewe cyumuryango wabanyamerika wubuzima-Sisitemu ya Farumasi 2008; 65 6: 532-539. https://api.semanticscholar.org/CorpusID:207290777.

[7] Quattrocchi E, Kourlas H. Teriparatid: isubiramo. Ubuvuzi bwa Clinical 2004; 26 6: 841-854. https://api.semanticscholar.org/CorpusID:20011673.

[8] Minisola S, Cipriani C, Grotta GD, n'abandi. Kuvugurura kumutekano no gukora neza bya teriparatide mukuvura osteoporose. Iterambere ryubuvuzi mu ndwara ya Musculoskeletal 2019; DOI: 10.1177 / 1759720X19877994.

[9] Agnihotri R, Gaur S. Porogaramu ya Teriparatid yo kuvugurura amagufwa ya Alveolar: Isubiramo rifatika. Ikinyamakuru cyumuryango mpuzamahanga wo gukumira no kuvura amenyo yabaturage 2021; 11 (6): 639-643.DOI: 10.4103 / jispcd.JISPCD_169_21.

[10] Lampropoulou-Adamidou K, Trovas G, Triantafyllopoulos IK, n'abandi. Umuti wa Teriparatid mu barwayi bafite Inda- na Lactation-Associated Osteoporose. Kubara Tissue International 2021; 109(5): 554-562.DOI: 10.1007 / s00223-021-00871-y.

[11] Peugh J, Khalil A, Chan MR, Hansen KE. Ubuvuzi bwa Teriparatide kuri Hypercalcemia Ifitanye isano n'indwara ya Adynamic. Jbmr Plus 2019; 3(7): e10176.DOI: 10.1002 / jbm4.10176.

INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Z'UBUREZI.  

Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorerwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.