Ingabe i-buprenorphine ikusasa lokuphathwa kabuhlungu okungapheli?
Ngenkinga yobuso, izinkinga ze-opioid nobuhlungu obungapheli ziphikisana ngokuqondile. Yize i-CDC ibonisa ukuthi "ubufakazi obulinganesikhathi eside lwe-opioid therapy for ubuhlungu obungapheli ngaphandle kokunakekelwa kokuphela kokuphila buhlala bukhawulelwe, ngaphandle kobufakazi obanele bokunquma izinzuzo zesikhathi eside ngaphandle kokutheleleka kwe-opioid," iqiniso lihlala ukuthi i-opioids yiyona ukungenela okuyinhloko ekwelapheni ubuhlungu obungapheli.
Nakuba abahlinzeki bokunakekelwa okuyinhloko bangabeka i-opioids yobuhlungu obungapheli, bayanqikaza ukwenza kanjalo ngenxa yokwesaba ukudlula ngokweqile noma ukuthembela. Odokotela abaningi abanakekelwa ngokuyisisekelo bathola ithuba lokunikeza iziguli i-opioids isikhathi eside kakhulu futhi bacindezela ngokushesha lezi ziguli kubachwepheshe bezinhlungu.
Naphezu kokungafuni ukuphatha, ubuhlungu obungapheli buya ngokuya njalo. Ngo-2010, amaphesenti angu-31 aseMelika azwa ubuhlungu obungapheli, okuchazwe njengobuhlungu obuhlala ngaphezu kwezinyanga ezintathu kuya kweziyisithupha. Ngenxa yokuthi iningi labantu abanezinhlungu ezingapheli zikhona odokotela bokunakekelwa okuyinhloko, kungaba ukuphumelela uma sinezinye izindlela eziphephile futhi eziphumelelayo kuma-opioids-imithi ethile abadokotela abazozizwa bekhululekile ukuyibeka. Imithi ebizwa ngokuthi i-buprenorphine ngelinye ilanga ingasiza ukulingana nalo mthethosivivinywa.
Kuyini i-Buprenorphine?
I-Buprenorphine ingokwezigaba zezidakamizwa ezibizwa ngokuthi i-opioid partial agonist-antagonists.
Ngaphandle kwesinye isidakamizwa esihlanganisa i-buprenorphine ne-naloxone (i-Suboxone), i-buprenorphine isetshenziswa njenge-opioid substitution therapy ukuphatha ukuxhomeka kwe-opioid (ukuxhomeka ku-heroin noma izidakamizwa zemithi). Lezi zidakamizwa zisebenza ngokuvimbela izimpawu zokuhoxiswa uma umuntu oncike kuma-opioids eyeka ukuthatha i-opioids.
I-Buprenorphine isisetshenziswa se-opioid semisynthetic ye-opium alkaloid thebaine, etholakala opium poppy ( Papaver somniferum ). Ngempela kuthatha amashumi eminyaka ukuba abacwaningi bakwazi ukukhiqiza izidakamizwa, futhi kwakukhona imizamo eminingi ehlulekile ngaphambi kokuba inkampani yesiNgisi ishicilele imithi ngo-1966. Ngo-1978, kwasungulwa ukuguqulwa kwe-buprenorphine ngokulandelana, kulandelwa isichazamazwi (esetshenziswa ngaphansi kolimi) iteration ngo-1982. Ngo-1985, i-buprenorphine yasungulwa e-United States njenge-analgesic ye-opioid.
Indlela Esebenza ngayo
I-Buprenorphine inezinqubo eziqondile kakhulu zesenzo ezenza kube nomphumela wokwelapha ukuxhomeka kwe-opioid kodwa mhlawumbe ubuhlungu obungapheli, futhi.
Okokuqala, i-buprenorphine ine-affinity ehlanganisiwe ephezulu ye-μ-opioid receptor, eyabangela ukukhululeka kobuhlungu. Ngaphezu kwalokho, i-buprenorphine inezinga eliphansi lokuhlukanisa kusukela ku-μ-opioid receptor, okusho ukuthi lihlala lihlanganiswe isikhathi eside kumamukeli, futhi liye lenza umphumela wesikhathi eside.
Okwesibili, nakuba i-buprenorphine ithanda i-μ-opioid receptor kancane, isebenza njenge-μ-opioid receptor agonist, okusho ukuthi ngenkathi i-buprenorphine ivimbela ukuhoxiswa kwe-opioid, izenzo zayo zingaphansi kwama-opioid.
Okwesithathu, i-buprenorphine ingumphikisi we-κ-opioid receptor ogcwele.
Ukusetshenziselwa imiphumela ye-κ-opioid receptor imiphumela ye-euphoric neyengqondo ye-opioids. Ngamanye amazwi, i-buprenorphine ngeke ikwenze "phezulu."
Ukuphatha
Njengoba kushiwo ngaphambili, i-naloxone ivame ukuhlanganiswa ne-buprenorphine ngendlela ye-Suboxone. I-Naloxone iyinhlangano yokuphikisana ne-opioid receptor. Uma kuhlangene emithini ephansi ne-buprenorphine, i-naloxone ingamelana nemiphumela emibi ye-opioid-kuhlanganise nokucindezeleka okuphefumulayo, ukugujwa nokuxilonga-ngaphandle kokunciphisa i-analgesia, noma ukukhululeka kobuhlungu. Ngaphezu kwalokho, ukwengezwa kwe-naloxone kuya ku-buprenorphine kusebenza njengesivimbela ukusetshenziswa kabi kwezidakamizwa.
Ngokusho kwe-NIH:
I-Buprenorphine ifika njengethebhulethi yokulinganisa. Ukuhlanganiswa kwe-buprenorphine ne-naloxone kufana nethebhulethi yokulinganisa (i-Zubsolv) kanye nefilimu engezansi (i-Suboxone) ukuthatha ngaphansi kolimi kanye ne-buccal [cheek] ifilimu (i-Bunavail) ukusebenzisa phakathi kwegamu nesigama.
I-Buprenorphine iphinda ifike ku-patch transdermal, ukubunjwa kwangaphakathi, futhi, kamuva nje, i-spray spray. Ngo-December 2017, kwamenyezelwa ukuthi i-FDA ibukezela ukuhlunga okuncane okuyizinhlamvu eziyisikhombisa ukuze ukwelashwa ubuhlungu obukhulu.
Okuqhamuka uma udla imishanguzo
Nakuba kungenasidingo njenge-opioids, kokubili buprenorphine ne-Suboxone kungaba nemiphumela emibi emibi kufaka okulandelayo:
- Ukuhlungu obusemhlane
- Umbono ophundlekile
- Ukuqokwa
- Kunzima ngokulala
- Ukuphefumula komlomo
- Izinwele
- Ubuhlungu besisu
- Ubuhlungu belimi
Imiphumela emibi kakhulu, njengokwalukhuni ukuphefumula noma ukuvuvukala komlomo noma ulimi, kudinga ukwelashwa ngokushesha. Okubalulekile, ukuxuba i-buprenorphine nezinye izidakamizwa ezifana ne-benzodiazepines kungabulala.
Buprenorphine for Pain Chronic
Ekubukezweni okuhlelekile okushicilelwe ngoDisemba 2017, i-Aiyer kanye nabobhali be-co-author bahlola ukusebenza kwe-buprenorphine ekuphatheni ubuhlungu obungapheli. Abacwaningi bahlaziya izilingo ezingama-25 ezilawulwa ngokungahleliwe ezihilela ama-buprenorphine amahlanu:
- Buprenorphine engathandeki
- Buprenorphine engezansi
- I-buprenorphine engezansi / i-naloxone (i-Suboxone)
- Buccal buprenorphine
- Buprenorphine edluliswayo
Ngokuvamile, abacwaningi bathole ukuthi izifundo ezingu-14 kwezingu-25 zaphakamisa ukuthi i-buprenorphine kunoma yikuphi ukuklama kwakuphumelela ekwelapheni ubuhlungu obungapheli. Ngokuqondile, izifundo ezingu-10 kwezingu-15 zabonisa ukuthi i-transdermal buprenorphine yayiphumelele, kanti izifundo ezimbili kwabathathu zibonisa ukuthi ibhakalini buprenorphine yayisebenza kahle. Ucwaningo olulodwa kuphela lwesithupha lwabonisa ukuthi i-buprenorphine eyingqayizivele noma eyengaphakathi yayiyasebenza ekwelapheni ubuhlungu obungapheli. Okubalulekile, akukho miphumela emibi kakhulu eyabika kunoma yiziphi izifundo, okubonisa ukuthi buprenorphine iphephile.
Ngo-2014, abalobi be-Cote nabambisene nabo babhicilele ukubuyekezwa okuhleliwe okuhlola ukusebenza kwe-buprenorphine eyingqayizivele ekwelapheni ubuhlungu obungapheli. Nakuba iningi lezifundo abazihlolisayo zazingabonwa futhi zingaphansi kwekhwalithi, abacwaningi bathola ukuthi i-buprenorphine yokulinganisa yayiphumelele ekuphatheni ubuhlungu obungapheli. Ngokuphawulekayo, ama-Cote nabambhali abambisene nabo bahlanganisa uhlu olulandelayo lwezinzuzo ezikhona ze-buprenorphine:
- Ukuphumelela kakhudlwana ebuhlungu be-neuropathic ngenxa yephrofayli yayo ehlukile yokwelapha.
- Ukusebenziseka kalula kulaba asebekhulile nasengozini yokulahlekelwa yinhlamba ngenxa yomphumela wayo omncane kokuphila kwengxenye kanye nemetabolites.
- Ukunciphisa umzimba okuncane okuqhathaniswa ne-morphine kanye ne-fentanyl ngokusekelwe ebufakazini obuncane kakhulu kusuka emsebenzini wokuthobela kanye nomtholampilo.
- Umphumela wokufakelwa wokucindezeleka ukuphefumula uma usetshenziselwa ngaphandle kwezinye izidakamizwa zesistimu zenzwa, mhlawumbe ngoba umsebenzi wangaphakathi wokukhiqiza i-analgesia ungase ube ngaphansi kokucindezeleka kokuphefumula.
- Umthelela omncane ku-hypogonadism, njengoba kuboniswe ekwelashweni kwesondlo.
- Ukuthuthukiswa okuncane kokubekezelelana, mhlawumbe nge-kappa receptor antagonism noma i-opioid-receptor-like (ORL-1) i-agonism.
- I-antihyperalgesic effect, mhlawumbe ngenxa yokuphikisana kwe-kappa receptor noma i-ORL-1 agonism.
- Umthelela wokucindezela iziguli ezingaphenduli ekwelashweni okuvamile.
Ngokuthakazelisayo, kukhishwa ngokuthi ngenxa yezindawo zayo ezibophezelayo, i-buprenorphine ingakwazi ukusiza abantu abathola ama-hyperalgesia anikwe i-opioid.
Ku-athikili okuthiwa "Ukubuyekezwa okuphelele kwe-hyperalgesia eyenziwe ngama-opioid," u-Lee nabobhali be-opioid-hyperlagesia abanjwe opioid njengalokhu okulandelayo:
I-hyperalgesia eyenziwe ngama-opioid (OIH) ichazwa njengesizwe sokuzwela kwe-nociceptive okubangelwa ukuvezwa kwama-opioid. Lesi simo sibonakala ngempendulo ephikisanayo lapho isiguli esithola ama-opioid ekwelapheni ubuhlungu empeleni singase sizwele ngokwengeziwe into ethile ebuhlungu. Uhlobo lobuhlungu obhekana nalo lungase lufane nobuhlungu obunzima noma bungase buhluke ebuhlungu obuqala bokuqala. I-OIH ibonakala iyinto ehlukile, ecacile, futhi ephawulekayo engachaza ukulahlekelwa kwe-opioid ngempumelelo kwezinye iziguli.
Okuphawulayo, ubuhlungu obunama-nociceptive ubuhlungu obubuhlungu obubangelwa umonakalo oyingxenye yomzimba. Kucatshangelwa ukuthi i-buprenorphine inezakhiwo ze-antinociceptive.
Ku-athikili ka-2014 eyanyatheliswa ku- Anesthesiology , uKhen kanye nabalobi ababhalisile bhala lokhu okulandelayo:
I-Buprenorphine iye yaboniswa ukuguqula i-hyperalgesia eyakhiwe ama-opioid ngokusebenzisa 'u-antinociception olwenziwe yi-buprenorphine.' Ngaphezu kwalokho, i-buprenorphine ingumphikisi we-κ-receptor futhi ingaqhudelana nomphumela we-spinal dynorphin, i-κ-receptor agonist engapheliyo. Ngenxa yokuthi i-dynorphin yomgogodla iyanda emva kokuvezwa kwe-opioid futhi inomthelela ku-OIH, lo mphumela wokuncintisana we-buprenorphine kwisayithi yokubopha i-κ-receptor inganciphisa umphumela we-spin dynorphin obangela ukwehla kwe-OIH.
Ukuchaza iBuprenorphine
Elinganiselwe, e-United States, buprenorphine isivele isetshenziselwa ukuphatha ubuhlungu obungapheli. I-Suboxone inqunywe off-ilebula yokuphathwa ubuhlungu obungapheliyo. Ngaphezu kwalokho, i-transdermal buprenorphine patch iyatholakala ekwelapheni ubuhlungu obungapheliyo e-United States.
Kodwa-ke, ayikho imibono yokuvumelana mayelana nokusebenza kokusebenzisa i-buprenorphine ngale njongo. Njengamanje, izifundo ezimbalwa ezihlola umphumela we-buprenorphine ebuhlungu obungapheli azifani kakhulu nezindlela zabo, ngakho-ke kunzima kakhulu ukuziqhathanisa nomunye.
Ngaphambi kokuba i-buprenorphine isetshenziselwe ukuphathwa ubuhlungu obungapheli kuba umkhuba osekelwe ebufakazini, izinkinga ezihlukahlukene kuzodingeka zixazululwe. Isibonelo, izifundo zamanje zisebenzisa izilinganiso ezihlukahlukene zokuhlukunyezwa lapho zihlola ukuphumelela ngaleyo ndlela zinikeza ukuhlaziywa okungahambisani. Izilinganiso zokulinganisa ubuhlungu ezifundweni zokuhlola i-buprenorphine kuzodingeka zilungiswe. Ngaphezu kwalokho, amasu okuqapha kanye nomzila wokuphatha kuzodingeka ahlolwe ngezinkulumo ezehlukene zobuhlungu obungapheli.
Uma umuthi we-buprenorphine wezinhlungu ezingapheliyo owake waba yibo ubufakazi obusekelwe, odokotela bokunakekelwa okuyisisekelo ngokuqinisekile babezobongwa ngale mkhuba. Ngo-2000, umthetho we-US Drug Addiction Treatment Act wenza kube ngokomthetho odokotela bokunakekelwa okuyinhloko ukuhlinzeka ngemithi yokwelapha i-opioid ngokusebenzisa i-Schedule III, IV, neV imithi. Ngo-2002, i-FDA ivume ukwelashwa okukodwa ngesiguli nge-buprenorphine, ukuyibeka njengesidakamizwa seSheduli III.
Konke lokho udokotela oyinhloko okunakekelwa okudingeka akwenze ukuze akwazi ukuhlinzekela i-buprenorphine kwisilungiselelo sangaphandle-isiguli ukugcwalisa amahora ayisishiyagalombili wokuqeqesha. Noma kunjalo, bambalwa abahlinzeki bokunakekelwa okuyisisekelo abafanelekile ukubeka i-buprenorphine.
Nakuba odokotela abaningi bokunakekelwa okuyinhloko bangase bakhonce ngokusikisela, ngeke kube nzima kakhulu ukucabanga ukuthi odokotela bokunakekelwa okuyinhloko ngelinye ilanga bangaphatha ubuhlungu obungapheli esimweni sokuphulukisa iziguli besebenzisa i-buprenorphine. Ngaphandle kokunakekelwa okuyinhloko odokotela abanamandla okubeka i-buprenorphine, i-CDC nayo ineziqondiso endaweni yokunakekelwa odokotela bokuqala ukuphatha ubuhlungu obungapheli ngama-opioids.
Ngokuyinhloko, iziqondiso ze-CDC zincoma ukuthi odokotela bokunakekelwa okuyinhloko banikeze ama-opioids ngobuhlungu obungapheliyo kuphela uma ukwelapha okungenayo i-opioid kunganele, futhi ukubeka i-opioids esenzweni esincane kunazo zonke. Kulo mongo, i-buprenorphine ingase ibhekwe njengendlela ehlukile ye-opioid.
> Imithombo:
> Aiyer R, et al. Ukwelashwa Kwezinhlungu Eziphuthumayo Nge-Buprenorphine Ehlukahlukene Ukubunjwa: Ukubuyekezwa Okuhlelekile Kwezifundo Zemitholampilo. Anesthesia & Analgesia. 2017. [i-epub ngaphambi kokuphrinta]
> Chen KY, Chen L, i-Mao J. Buprenorphine-Naloxone Therapy ekulawuleni izinhlungu. Anesthesiology. 2014; 120 (5): 1262-74.
> I-Cote J, i-Montgomery L. I-Buprenorphine eyingqayizivele njenge-Analgesic ku-Pain Chronicle: Ukubuyekeza Okuhlelekile. Imithi Yezinhlungu. 2014; 15: 1171-1178.
> Dowell D, Haegerich TM, i-Chou R. i-CDC Guideline yokuchaza ama-opioid for Pain Chronic - United States, 2016. I-MMWR. 2016; 65 (1): 1-49.
> Lee M, et al. Ukubuyekezwa Okuphelele Kwe-Hyperalgesia E-opioid-Induced. Udokotela Wezinhlungu. 2011; 14 (2): 145-61.