Isihloko
I-methylene blue ye-encephalopathy ebangelwa yi-ifosfamide: lokho okuboniswa yimibiko yeziguli, nalokho engakubonisi
I-ifosfamide iwumuthi ofaka amaqembu e-alkyl osetshenziswa kakhulu ekwelapheni umdlavuza, kuhlanganise ne-sarcoma, i-lymphoma, umdlavuza womlomo wesibeletho, nomdlavuza wamaphaphu. Engxenyeni encane yeziguli, ibangela into ethusayo: emahoreni kuya ezinsukwini ngemva kokuqala kokufakwa komuthi ngomthambo, isiguli siyadideka, siyaluza, siyozela, futhi ngezinye izikhathi silahlekelwa ngokuphelele ukuqonda okungokoqobo noma singasabeli. Izithombe zokuhlola ngokuvamile azibonisi okungavamile. Ezimweni eziningi, lesi simo siyaphela phakathi nezinsuku ezimbalwa uma umuthi usumisiwe. Odokotela abangochwepheshe bomdlavuza bakubiza ngokuthi i-encephalopathy ebangelwa yi-ifosfamide, futhi ukungabikezeleki kwayo yisizathu esenza umbiko wango-1990s wokuthi udayi oluhlaza okwesibhakabhaka wayibuyisela emuva usaxoxwa eminyangweni yezibhedlela nanamuhla.
Umbuzo ophendulwa yilesi sihloko ucacile futhi unomkhawulo. Ingabe i-methylene blue iyayelapha noma iyayivimbela le encephalopathy, futhi buqine kangakanani ubufakazi? Impendulo emfushane iwukuthi imibiko yokwelapha okuphuthumayo iyamangalisa kodwa ubufakazi bubuthaka, kanti obokuvimbela bubuthaka nakakhulu. Lo mehluko ubalulekile ngoba lesi yisinqumo sasesibhedlela esenziwa ngaphansi kwengcindezi, hhayi isinqumo sesengezo esenziwa ekhaya.
Indlela i-encephalopathy ebonakala ngayo
Izimpawu ngokuvamile ziqala ngesikhathi sokufakwa kwe-ifosfamide ngomthambo noma ngokushesha ngemva kwalokho: ukungazi ukuthi ukuphi noma yisiphi isikhathi, ukungahlaliseki, ukubona noma ukuzwa izinto ezingekho, ukozela, futhi ngezinye izikhathi ukuquleka noma ikhoma. I-EEG ivame ukubonisa ukwehla kwejubane lomsebenzi kagesi wobuchopho ezindaweni eziningi. Ingozi iyanda uma imithamo iphezulu, umuthi ufakwa ngokushesha, izinso zingasebenzi kahle, i-albumin iphansi, kunomlando wesifo sobuchopho, noma kusetshenziswa ngesikhathi esifanayo imithi edambisa umuntu. Iziqephu eziningi ziyaphela ngokunakekelwa okusekelayo kuphela ngosuku olulodwa kuya kwezintathu, nakuba kuba khona izimo ezinzima noma ezithatha isikhathi eside, futhi ukuphinde kunikezwe i-ifosfamide kungabangela ukuphindeka kwesigameko.
Leyo ndlela yemvelo isifo esiqhubeka ngayo yiyona okufanele uyiqonde ngaphambi kokufunda noma yimuphi umbiko we-methylene blue. Umuthi onikezwe ngosuku lwesibili lokudideka, okulandelwa ukululama ngosuku lwesithathu, kungenzeka ukuthi awenzanga lutho nhlobo. Zonke izimangalo ezingezansi kufanele zikalwe ngokubheka ukuthi isiguli singalulama ngokwaso.
Lapho kwavela khona umqondo we-methylene blue
Ngo-1994, iqembu laseBern labika imiphumela yomchamo ezigulini ezithola i-ifosfamide eyayifana nesifo esingavamile esitholwa ngofuzo sokudluliselwa kwama-electron kuma-mitochondria, lapho kwakukhona khona i-glutaric acid ne-sarcosine ngokweqile. Labuye lachaza ukubuyiselwa emuva ngokushesha kwe-encephalopathy ngemva kokunikezwa kwe-methylene blue embikweni omfushane we-Lancet. Ukubuyekezwa kwendlela yokusebenza okwalandela akuzange kuphakamise indlela eyodwa, kodwa ezintathu ezisebenza ndawonye.
Okokuqala, i-ifosfamide iyahlakazwa esibindini ibe yizinga elikhulu le-chloroethylamine, elihlangana ne-cysteine lakhe inhlanganisela eyindilinga equkethe isibabule ebizwa ngokuthi i-thialysine ketimine. Leyo nhlanganisela ivimba ama-flavoprotein ochungechungeni lokuphefumula lwama-mitochondria, ivimbele ukufakwa kwe-oxygen ku-NADH ngendlela evamile. I-methylene blue, njengomamukeli ohlukile wama-electron, ingathatha indawo yesinyathelo esivinjiwe; lo mqondo ususelwa ekusetshenzisweni kwayo kwakudala kwezinye izinhlobo ze-glutaric aciduria.
Okwesibili, uchungechunge lwe-redox oluvinjiwe kanye nomthwalo owedlulele wama-aldehyde ovela ekuhlakazweni kwe-ifosfamide kwehlisa isilinganiso se-NAD uma iqhathaniswa ne-NADH, okuphazamisa ukukhishwa kwama-aldehyde nokukhiqizwa kwe-glucose. I-methylene blue iphinde iguqule i-NADH ngokuyifaka ku-oxidation ukuze iye ku-NAD, ibuyisele ingxenye yalokho kulinganisa. Indlela efanayo yokuhambisa ama-electron ku-redox iyisisekelo seminye imiphumela yayo eminingi ehlongozwayo emangqamuzaneni, futhi isimiso esijwayelekile sendlela i-methylene blue ehambisa ngayo ama-electron kufanelekile ukuba siqondwe ngokwehlukana nalokhu kusetshenziswa kwayo okukhethekile kwezokwelapha.
Okwesithathu, i-methylene blue ivimba ama-enzyme e-amine oxidase abengaguqula i-chloroethylamine ibe yi-chloroacetaldehyde, okuwumkhiqizo wokuhlakazwa komuthi onobuthi obuqondile ezinzwaneni nasezinso, otholakala ungaboshiwe ku-plasma yeziguli ezithola i-ifosfamide. Ukuncipha kwe-chloroacetaldehyde kusho ukuncipha kokulimala okulandelayo, kuhlanganise nokuncipha kokuphazamiseka kwe-oxidation yama-fatty acid okuboniswe kuma-mitochondria ahlukanisiwe.
Le ndlela yokusebenza iyakholakala futhi ichazwe ngemininingwane engavamile. Ukukholakala akusho ukufakazelwa, kodwa kuchaza ukuthi kungani odokotela bomdlavuza bayithatha ngokungathi sína imibiko yokuqala.
Imibiko yokwelapha okuphuthumayo: kuyashesha, kodwa akukho maqembu okuqhathanisa
Umbiko ocashunwa kakhulu usengowango-1995 wowesifazane oneminyaka engu-68 owayenomdlavuza womlomo wesibeletho, owadideka futhi wayaluza ngemva kokuthola i-ifosfamide engu-5 g ngemitha eyisikwele phakathi namahora angu-24. I-CT yakhe yayingabonisi okungavamile, kanti i-EEG yakhe yabonisa ukwehla kwejubane lomsebenzi kagesi wobuchopho ezindaweni eziningi. Wanikezwa i-methylene blue engu-50 mg ngomthambo phakathi kwemizuzu emihlanu, kwathiwa wayesephapheme futhi ekhuluma ngokuqondakalayo phakathi kwemizuzu eyishumi. Imizuzu eyishumi ishesha kakhulu kunendlela yemvelo yokululama, okuyisizathu esenza leli cala elilodwa laba nesisindo esikhulu kangaka.
Uchungechunge lwemibiko eyalandela aluzange lumangalise kangako. Ochungechungeni olwahlola amarekhodi esikhathi esedlule eziguli ezingu-52 ezathola i-ifosfamide, ezingu-12 zaba ne-encephalopathy yezinga lesi-2 noma elibi kakhulu; kuzo, eziyisishiyagalombili zathola i-methylene blue engu-50 mg ngomthambo izikhathi eziyisithupha ngosuku. Ezine zalulama ngokuphelele phakathi namahora angu-24, kuhlanganise nesinye esasisesimweni esinzima esalulama cishe phakathi nehora; ezinye ezimbili zalulama kungakapheli amahora angu-48, nezinye ezimbili kungakapheli amahora angu-72. Kodwa zonke iziguli ezine ezingazange zelashwe nazo zalulama phakathi namahora angu-48, njengoba ababhali ngokwabo babika. Uchungechunge lwezigameko ezingu-15 ezinganeni lwathola inzuzo ebonakalayo enganeni eyodwa kuphela kwezinhlanu ezelashwa. Imibiko yeziguli ezimbili ezindala eyashicilelwa ngo-2018, ezelashwa ngo-50 mg njalo emahoreni amane, yabonisa ukuthi zaqala ukuba ngcono ngemva kwamahora angu-12 kuya kwangu-16 kuphela, futhi zabuyela esimweni sazo sangaphambili ngemva kwezinsuku ezimbili kuya kwezintathu; lokhu akuhlukanga esikhathini sokululama ngokunakekelwa okusekelayo.
Ukubuyekezwa kwemibhalo yango-2020 kwabala iziguli ezingu-38 ezelashwa nge-methylene blue ezazisemibikweni eshicilelwe, futhi cishe izingxenye ezintathu kwezine zazo zachazwa njengeziphendule kahle. Lelo nani lizwakala liqinisekisa uze ukhumbule ukuthi ukululama okusheshayo kuyabhalwa kushicilelwe, kanti okuthatha isikhathi eside ngokuvamile akwenziwa kanjalo. Ukuchema ekushicilelweni kwenza amaqoqo emibiko yeziguli abukeke engcono kunesimo sangempela.
Ithebula lobufakazi: hlukanisa izindlela zocwaningo
Ithebula elingezansi liwumgogodla walokhu kubuyekezwa. Imibiko yeziguli ingaphakamisa kuphela; uchungechunge olungenawo amaqembu okuqhathanisa lungachaza kuphela; futhi kulo mbuzo azikho izivivinyo zokusebenza ezabiwe ngokungahleliwe.
| Izinga lobufakazi | Ucwaningo | Indlela yocwaningo neziguli | Uhlelo lokunikezwa kwe-methylene blue | Okwenzekile |
|---|---|---|---|---|
| Umbiko wesiguli | Kupfer et al., Lancet 1994 | Icala lokuqala lokwelashwa kanye nelilodwa lokuvimbela; umphumela wokuhlolwa kwamakhemikhali omzimba onephethini efana ne-glutaric aciduria | Ukwelashwa: 50 mg IV; ukuvimbela: ngomlomo | Kwabikwa ukubuyiselwa emuva ngokushesha; isiguli sesibili asizange siphinde sibe nesimo lapho siphinde sinikezwa umuthi |
| Umbiko wesiguli | Zulian et al., N Engl J Med 1995 | Owesifazane oneminyaka engu-68, umdlavuza womlomo wesibeletho, ukudideka ngemva kwe-ifosfamide engu-5 g/m2 phakathi no-24 h | 50 mg IV phakathi no-5 min, isixazululo esingu-1 percent | Waphaphama futhi wakhuluma ngokuqondakalayo phakathi no-10 min |
| Uchungechunge lweziguli, ukuhlolwa kwamarekhodi esikhathi esedlule nokuqhathaniswa nabangelashwanga | Pelgrims et al., Br J Cancer 2000 | Iziguli ezingu-52 ezathola i-ifosfamide; ezingu-12 ezine-encephalopathy yezinga lesi-2 noma elibi kakhulu; ezingu-8 zelashwa, ezingu-4 azelashwanga | Ukwelashwa: 50 mg IV izikhathi eziyisithupha ngosuku; ukuvimbela: 50 mg izikhathi ezine ngosuku ezigulini ezingu-3 | Ezelashwa: ezingu-4 kwezingu-8 zalulama phakathi no-24 h, zonke phakathi no-72 h. Ezingelashwanga: zonke ezingu-4 zalulama phakathi no-48 h |
| Uchungechunge lweziguli | Turner et al., Clin Oncol 2003 | Izigameko ezingu-4 zesimo esiqale ngokushesha, ezingu-2 kamuva zanikezwa umuthi wokuvimbela | Ngokuvamile 50 mg ngomlomo izikhathi ezintathu ngosuku | Kwabikwa ukuthuthuka okukhulu phakathi no-24 h; isimo saba buthakathaka lapho umuthi uphinde unikezwa kanye nokuvimbela |
| Uchungechunge lweziguli, izingane | Dufour et al., Arch Pediatr 2006 | Izigameko ze-encephalopathy ezingu-15 ezinganeni | Ukwelashwa: 50 mg IV njalo ngo-4 h; ukuvimbela njalo ngo-6 h | Kwabonwa inzuzo kwesisodwa kwezingu-5 ezelashwa; akukho ukuphindeka kuzo zombili ezingu-2 ezanikwa umuthi wokuvimbela |
| Ucwaningo lokuhamba nokucutshungulwa komuthi emzimbeni, alukho iqembu lokuqhathanisa ukusebenza | Aeschlimann et al., Drug Metab Dispos 1998 | Iziguli ezingu-9 ezinomdlavuza wamaphaphu ezithola i-ifosfamide, i-mesna, ne-etoposide | 50 mg ngomlomo izikhathi ezintathu ngosuku kusukela kusihlwa ngaphambi kokwelashwa ngamakhemikhali | Yabekezeleleka; alukho ushintsho olubalulekile ekwenziweni kwe-ifosfamide isebenze; kwathiwa ivikela isimiso sezinzwa kodwa alikho iqembu lokuqhathanisa |
| Ukuhlolwa kwamarekhodi esikhathi esedlule, kugxilwe ekuvimbeleni | Sweiss et al., Drug Safety 2008 | Iziguli ezingu-19 ezithola i-ifosfamide ngemithamo ephezulu; ezingu-8 ezine-encephalopathy; ezingu-5 zaphinde zanikezwa umuthi kanye nokuvimbela | I-methylene blue yokuvimbela, izinhlelo zokuyinikeza zazihlukene | Zonke ezingu-5 ezaphinde zanikezwa umuthi kanye nokuvimbela zaphinde zaba ne-encephalopathy |
| Ukuqhathaniswa kwemijikelezo kusetshenziswa amarekhodi esikhathi esedlule | Richards et al., J Oncol Pharm Pract 2011 | Imijikelezo engu-166 ene-methylene blue, i-thiamine, noma i-albumin yokuvimbela, iqhathaniswa nengenakho ukuvimbela | Izindlela ezihlukahlukene zokuvimbela | I-encephalopathy ku-21.1 percent wemijikelezo enokuvimbela uma iqhathaniswa no-8.4 percent ngaphandle kokuvimbela; kungenzeka ukuthi imiphumela yaphazanyiswa izizathu zokukhetha ukunikeza ukuvimbela |
| Uchungechunge lwamarekhodi esikhathi esedlule | Uchungechunge lwezingane nabantu abadala abasebasha lwase-MD Anderson, 2025 | Iziguli ezingu-24 ezine-encephalopathy; ezingu-20 zathola i-methylene blue | Ngokuvamile 50 mg IV njalo ngo-6 h, imithamo engu-5 iyinani eliphakathi | Ezingu-19 kwezingu-20 zalulama phakathi no-24 kuya ku-120 h, kungekho ukuqhathaniswa nabangelashwanga; isimo saphindeka kwezingu-3 kwezingu-5 ezaphinde zanikezwa umuthi kanye nokuvimbela |
Uma ufunda ikholomu yemiphumela uye phansi, iphethini iyafana: imibiko yokuqala emangalisayo, bese kuba nemiphumela ehamba kancane kakhulu futhi exubile njengoba inani leziguli likhula kuvela namaqembu okuqhathanisa. Lokho kuwuphawu lwendlela yokwelapha umphumela wayo wangempela, uma ukhona, uncane.
Ubufakazi bokuvimbela abuqinile
Isimangalo sokuvimbela sidinga isiphetho saso ngoba sithonya ukunikezwa kwemithi kwangempela. Ngemva kokuhlangenwe nakho kokuqala kwaseBern nge-ifosfamide yomlomo kanye no-50 mg izikhathi ezintathu ngosuku, lapho kungazange kubonwe ukulimala kwesimiso sezinzwa, izikhungo eziningana zazama ukuvimbela nge-methylene blue lapho kuphinde kunikezwa i-ifosfamide. Imiphumela iyahlukahluka. Ezinye iziguli ezaphinde zanikezwa umuthi zaba neziqephu ezibuthakathaka noma azibanga nazo nhlobo; kolunye uchungechunge, wonke umuntu owanikezwa ukuvimbela lapho ephinda ethola umuthi wayesaba ne-encephalopathy. Ukuqhathanisa okukodwa kwamarekhodi esikhathi esedlule kwathola i-encephalopathy eningi emijikelezweni enokuvimbela kunengenakho, cishe ngokuqinisekile ngenxa yokuthi iziguli ezazisengozini enkulu kakhulu zazikhethelwe ukuvimbela.
Ababhali bemihlahlandlela bakubonile lokhu. Umhlahlandlela ohlanganyelwe wokulimala kwesimiso sezinzwa wezinhlangano zaseYurophu zezokwelapha umdlavuza nezesimiso sezinzwa waphetha ngokuthi azikho izivivinyo ezinamaqembu okuqhathanisa, nokuthi i-methylene blue ayinakutuswa ekuvimbeleni noma ekwelapheni ngokusekelwe ebufakazini obukhona. Ulwazi lokunikezwa komuthi nezinye izinqubo zezikhungo zithatha isimo esithambile, zithi ingacatshangelwa ku-encephalopathy emaphakathi noma enzima. Zombili lezi zimo zichaza idatha efanayo; zihluka kuphela esisindweni esinikezwa imibiko yeziguli lapho kungekho enye indlela engcono.
Umongo wochwepheshe okufanele waziwe ngumuntu ongeyena udokotela womdlavuza
Amaphuzu amathathu asebenzayo abeka umongo waso sonke isinqumo esenziwa eceleni kombhede wesiguli. Okokuqala, lapha i-methylene blue isetshenziswa ngaphandle kokusetshenziswa okugunyazwe ngokusemthethweni, inikezwa ngomthambo esibhedlela, ngokuvamile ngo-50 mg njalo emahoreni amane kuya kwayisishiyagalombili kuze kuphele izimpawu. Ayilona ikhambi lasekhaya futhi lesi sihloko asiyona imihlahlandlela yemithamo.
Okwesibili, i-methylene blue ivimba i-monoamine oxidase A futhi inesexwayiso esibiyelwe ebhokisini mayelana ne-serotonin syndrome uma ihlanganiswa nemithi yokucindezeleka ethinta i-serotonin kanye nama-opioid athile. I-serotonin syndrome iye yabikwa ngokukhethekile ngesikhathi sokwelashwa kwe-encephalopathy ebangelwa yi-ifosfamide. Futhi akufanele isetshenziswe uma kukhona ukushoda kwe-glucose-6-phosphate dehydrogenase ngenxa yengozi yokuhlakazeka kwamangqamuzana abomvu egazi. Ulwazi lokuphepha nokusebenzisana neminye imithi kanye nombuzo obanzi wokuthi ukusetshenziswa kwe-methylene blue kuphephile yini esigulini esithile kufanele kube yingxenye yesinqumo ngaphambi kokuvulwa kwanoma yiliphi ibhodlela lomuthi oluhlaza okwesibhakabhaka.
Okwesithathu, ukumisa i-ifosfamide, ukunikeza uketshezi, ukulungisa ama-electrolyte neminye imithi ehambisana nayo, nokukhipha ezinye izimbangela zokudideka kuseyisisekelo. Lapho isetshenziswa khona, i-methylene blue yengezwa kuleso sisekelo, ayithathi indawo yaso. Ukufunda indlela yokufunda ucwaningo lwe-methylene blue kuyasiza lapha: buza ukuthi umbiko wawuneqembu lokuqhathanisa yini, ukuthi ubukhulu be-encephalopathy bahlukaniswa kanjani, yini enye eyashintsha ngesikhathi esifanayo, nokuthi isikhathi sokululama sihlukile yini endleleni yemvelo eyaziwayo yosuku olulodwa kuya kwezintathu.
Isiphetho
Ukusetshenziswa kwe-methylene blue ku-encephalopathy ebangelwa yi-ifosfamide kusekelwe endleleni yokusebenza yama-mitochondria enengqondo, emibikweni embalwa yokwelapha okuphuthumayo eholele ekululameni okusheshayo futhi emangalisa ngempela, nasochungechungeni oluningi lweziguli lapho ezelashwa nezingelashwanga zilulama ngezikhathi ezifanayo. Njengokwelashwa okuphuthumayo kwe-encephalopathy enzima noma ethatha isikhathi eside, abanye odokotela bomdlavuza bakubona kunengqondo ngenxa yokungabikho kwezinye izindlela. Njengendlela yokuvimbela esetshenziswa njalo, ubufakazi abukusekeli. Noma ubani ohlangana nalo mbuzo, kungaba isiguli, umnakekeli, noma uchwepheshe wezokwelapha, kufanele awubheke njengesinqumo sochwepheshe esenziwa esibhedlela ngesiguli ngasinye, futhi abheke ukululama okusheshayo njengomqondo odinga ukuhlolwa kunokuba kube ubufakazi.