Ubururu bwa metilene n'indwara ya bipolar: Gusuzuma ubushakashatsi bwo kwa muganga

Mu magambo make

Ubururu bwa metilene bumaze igihe bwigwa ku ndwara ya bipolar kiruta icyo abantu benshi batekereza, guhera mu myaka ya 1970 ubwo abashakashatsi bashakaga ibyakoreshwa mu mwanya wa litiyumu cyangwa byayongerwaho. Ibimenyetso byose bihari ni bike: ubushakashatsi bumwe bwakurikiranye itsinda ry'abarwayi nta guhisha ubuvuzi bahabwaga, amagerageza abiri ya kera afite amatsinda yo kugereranya, n'ubushakashatsi bumwe bwa vuba bwagabanyije abitabiriye mu buryo bwa tombola, bagahinduranya ubuvuzi. Icyagaragaye mu buryo buhoraho muri ubwo bushakashatsi ni ukugabanuka kw'ibimenyetso by'agahinda gakabije n'ibimenyetso byasigaye igihe ubururu bwa metilene bwongerwaga ku buvuzi bwari busanzwe butangwa. Nta bushakashatsi bwagaragaje ko bwagabanyaga maniya, kandi nta bwatanze ikimenyetso gisobanutse cyo guhindukira muri maniya, nubwo umubare w'abitabiriye wari muto cyane ku buryo utashoboraga gutanga igisubizo gihamye kuri icyo kibazo. Umuntu wese usuzuma iki kinyabutabire akwiye gusoma ubwo bushakashatsi nk'ubwiga ubuvuzi bw'inyongera, atari ibimenyetso byo kubukoresha bwonyine, kandi akabanza gusuzuma imiburo yerekeye imikoranire yabwo n'indi miti mbere yo gufata imyanzuro ijyanye n'ikoreshwa.

Impamvu indwara ya bipolar yitabiriwe hakiri kare

Impamvu yo gukora ubwo bushakashatsi ntiyigeze iba uko ubururu bwa metilene bwasaga n'imiti isanzwe ituma amarangamutima adahindagurika. Imiterere yabwo isa n'iya fenotiyazine, kandi abashakashatsi ba mbere bakekaga ko bwashoboraga guhindura vanadate yo muri plasma ikajya mu buryo budakora cyane, bugahindura imikorere ya ATPase ya sodiyumu na potasiyumu ifitanye isano n'ihindagurika ry'amarangamutima. Mu kugerageza icyo gitekerezo, Naylor na bagenzi be bavurishije ubwo bururu abarwayi babiri bahoraga bahindagurika mu byiciro by'indwara, babona ko bamara igihe kirekire kurushaho bafite amarangamutima aringaniye, ari byo byashishikarije ibyakozwe nyuma byose. Inkuru ya Howland ku mateka y'ubururu bwa metilene mu buvuzi bwo mu mutwe ishyira uyu murimo mu rwego rw'amateka yawo, igakurikirana iki kinyabutabire kuva cyari intangiriro yo gukora fenotiyazine kugeza kibaye ikinyabutabire kigeragezwa mu guhindura imikorere yo mu mutwe.

Ubushakashatsi bwakurikiyeho ku buryo bukora bwongeye gusobanura impamvu zo kubwiga, bwibanda ku mikorere ya mitokondiriya no ku buringanire bw'imikoranire yo gutanga no kwakira elegitoroni. Imikorere mibi ya mitokondiriya yagiye ihuzwa n'indwara ya bipolar binyuze mu bushakashatsi ku miryango, ibyabonetse ku mikorere ya jene nyuma y'urupfu, no ku nyamaswa zikoreshwa nk'icyitegererezo, nk'imbeba ifite ihinduka rya jene POLG1, igaragaza imiterere isa n'indwara ya bipolar igira icyo ihindukaho kubera litiyumu. Isuzuma rya Alda ryo mu 2019 ku bururu bwa metilene mu ndwara z'imyakura n'izo mu mutwe rivuga ko ubushobozi bw'iki kinyabutabire bwo gutambutsa elegitoroni zikanyura ku bice byafunzwe mu ruhererekane rwo kuzitwara, bugabanya isohoka ry'ubwoko bwa ogisijeni bukora cyane, bugiha agaciro mu gushaka no kugerageza ibitekerezo ku bihindura imikorere ya mitokondiriya. Irindi suzuma ku bururu bwa metilene nk'ikinyabutabire gishobora kuvura agahinda gakabije ryongeraho kubuza MAO-A gukora, guhagarika synthase ya monogiside ya azote na guanylate cyclase, n'ingaruka zo kugabanya kubyimbirwa mu gusobanura uburyo bushobora gukora. Icyakora, ubwo buryo bwo gukora ni ibitekerezo bigomba kugeragezwa. Ikibazo cyo kwa muganga ni icyo amagerageza yapimye, n'imiterere yakorewemo.

Amagerageza, rimwe ku rindi

Itsinda ry'abarwayi ryakurikiranywe na Narsapur na Naylor: abarwayi batitabiraga ubuvuzi, ubuvuzi butahishwe

Raporo ya mbere yari iy'itsinda ry'abarwayi 24 bafite indwara imaze igihe kirekire cyangwa ikomeye, nta tsinda ryo kugereranya ryari rihari, bahawe ubururu bwa metilene nk'inyongera kuri 200 cyangwa 300 mg buri munsi, mu gihe cyari hagati y'iminsi mike n'ikirenga umwaka. Cumi n'icyenda bari bafite indwara ya bipolar (maniya n'agahinda gakabije), kandi 14 muri abo 19 bafashwe nk'abagaragaje neza ko bamerewe neza kurushaho, bingana na 74 ku ijana bitabiriye ubuvuzi. Abarwayi batatu isuzuma ryabo ry'indwara ya bipolar ryashidikanywagaho ntibitabiriye ubuvuzi.

Ibi mubifate nk'ibyabyara ibitekerezo byo kugerageza, atari amakuru ahamya ubushobozi bw'ubuvuzi. Nta kugabanya abitabiriye mu buryo bwa tombola kwabayeho, nta guhisha ubuvuzi bahabwaga, nta gipimo ngenderwaho kimwe cyakoreshejwe, kandi imiti bari basanzwe bafata ntiyatangajwe yose. Umubare wa 74 ku ijana wo mu itsinda ryakurikiranywe nta guhisha ubuvuzi, rigizwe n'abarwayi batitabiraga ubuvuzi, ugaragaza uko abakurikirana babibonaga n'uburyo abarwayi batoranyijwe, kimwe n'uko ugaragaza imikorere y'umuti.

Naylor na bagenzi be, 1986: imyaka ibiri yo gukumira ibihe by'indwara, hahinduranywa ubuvuzi hamwe na litiyumu

Ubu ni bwo bushakashatsi bwa mbere bwari bufite intego nini kurusha ubundi: igerageza ry'imyaka ibiri, ryakozwe ku barwayi 31 bafite indwara ya bipolar, bagabanyijwe mu buryo bwa tombola, bagahinduranya ubuvuzi, abarwayi n'ababakurikirana batazi ubuvuzi bwatanzwe. Buri wese yagombaga guhabwa 300 mg buri munsi mu mwaka umwe na 15 mg buri munsi mu wundi mwaka, hakoreshejwe tombola mu kugena icyabanza. Igipimo cya 15 mg cyakoreshejwe nk'icyo kugereranya, ahanini kubera ko guhinduka kw'ibara ry'inkari kwatumaga bidashoboka guhisha neza ikoreshwa ry'umuti w'igereranya udafite igikorwa na kimwe. Icy'ingenzi ni uko buri wese yakomeje gufata litiyumu mu gihe cyose, bityo kuva mu ntangiriro ubu bwari ubuvuzi bw'inyongera bwo gukumira ibihe by'indwara.

Cumi na barindwi muri 31 barangije iyo myaka yombi. Mu barangije, ibimenyetso by'agahinda gakabije byari byoroheje kurushaho ku buryo bufite ubusobanuro mu ibarurishamibare mu mwaka wa 300 mg ugereranyije n'umwaka wa 15 mg, naho ubukana bw'ibimenyetso bya maniya ntibwatandukanyaga ibyo bipimo. Byatangajwe ko kwinjizwa mu bitaro byagabanutse mu gihe cy'igerageza ugereranyije na mbere yaryo, nubwo isuzuma rya Alda ryakurikiyeho rivuga ko ibi byagaragaraga no mu bihe bya 15 mg, bikagora gusobanura ibyavuye mu bushakashatsi. Abashakashatsi ubwabo bagaragaje intege nke zabwo: umubare muto w'abitabiriye, 45 ku ijana bataburangije, ibipimo byoroheje byo gusuzuma ibimenyetso, gushidikanya ku guhisha ubuvuzi, no kutamenya neza niba 15 mg nta gikorwa cy'umuti yagiraga. Izo mpungenge za nyuma zaje kugaragara ko zari zifite ishingiro, nk'uko bisobanurwa hepfo.

Ubushakashatsi bwa Naylor ku gipimo gito mu gahinda gakabije: impamvu “umuti w'igereranya” ushobora kuba warakoraga

Igereranya ryakurikiyeho ryamaze ibyumweru bitatu, abarwayi n'ababakurikirana batazi ubuvuzi bwatanzwe, ryagerageje 15 mg buri munsi ugereranyije n'umuti w'igereranya udafite igikorwa ku barwayi 35 bafite agahinda gakabije gakomeye, maze risanga ubururu bwa metilene bwarushije uwo muti w'igereranya ku buryo bufite ubusobanuro mu ibarurishamibare. Iri tsinda ryiganjemo abafite agahinda gakabije katari ako mu ndwara ya bipolar, aho kuba igerageza ku ndwara ya bipolar, bityo ribarirwa mu bimenyetso rusange ku gahinda gakabije aho kubarirwa mu bimenyetso ku ndwara ya bipolar. Akamaro karyo ku basoma iby'indwara ya bipolar kari mu buryo ubushakashatsi bwakozwe: igipimo cya 15 mg cyakoreshejwe nk'icyo kugereranya muri ya magerageza yombi yo guhinduranya ubuvuzi cyari ubwacyo cyararushije umuti w'igereranya udafite igikorwa. Bityo, itandukaniro ryose ry'ubuvuzi ryapimwe ugereranyije na 15 mg rishobora kuba rigaragaza itandukaniro rito kurusha iryagaragara nta buvuzi na bumwe, kandi bivuze ko nta na rimwe muri ayo magerageza ya kera ryari rifite itsinda ryahawe umuti w'igereranya nyakuri udafite igikorwa.

Alda na bagenzi be, 2017: igerageza rya vuba ryo guhinduranya ubuvuzi bw'inyongera

Ubushakashatsi bukomeye kurusha ubundi bwakozwe kugeza ubu bwagabanyije mu buryo bwa tombola abantu bakuru 37 bafite indwara ya bipolar yo mu bwoko bwa I cyangwa II n'ibimenyetso byasigaye, bahabwa ubururu bwa metilene 195 mg buri munsi ugereranyije na 15 mg buri munsi, buri gipimo kigatangwa ibyumweru 13, hanyuma bagahinduranya. Byari byeruye ko ari ubuvuzi bw'inyongera: buri wese yari amaze nibura amezi atatu ameze neza ku miti ya lamotrigine kandi yarayikomeje; litiyumu, divalproex, imiti yo kuvura ibimenyetso byo gutakaza ubushobozi bwo kumenya ibiriho, n'imiti y'agahinda gakabije byari byemewe ku bipimo bidahinduka. Igerageza riboneka kuri PubMed 27284082. Ibimenyetso byo mu ntangiriro byari byoroheje kugeza ku biringaniye, impuzandengo y'amanota y'agahinda gakabije ku gipimo cya Hamilton iri hafi ya 7.6, naho ku cya Montgomery-Asberg iri hafi ya 12.7.

Ibyavuye mu bushakashatsi byagaragaje ko 195 mg yarushaga 15 mg ku bipimo by'agahinda gakabije n'amaganya. Mu barangije, ingano y'ingaruka yari hafi ya 0.71 ku gipimo cya Hamilton cy'agahinda gakabije, 0.80 ku gipimo cya Montgomery-Asberg, na 0.79 ku gipimo cya Hamilton cy'amaganya; buri imwe yari ifite ubusobanuro mu ibarurishamibare. Isesengura ry'abarwayi bose 37 ryakoresheje igipimo cya nyuma cyabonetse mu mwanya w'ibyaburaga nyuma yacyo na ryo ryatanze ibisubizo bisa, bifite ubusobanuro mu ibarurishamibare. Amanota ya maniya yagumye hasi kandi adahinduka, nta ngaruka z'ubuvuzi zagaragaye; uruhurirane rw'ibizamini by'ubushobozi bwo gutekereza ntirwagaragaje inyungu ifite ubusobanuro mu ibarurishamibare ku kwibuka amagambo, ubushobozi bwo gutegura no kuyobora ibikorwa, cyangwa ibipimo byo kwitondera ibintu. Abitabiriye icumi bavuye mu igerageza kubera impamvu zirimo gukomera kw'ibimenyetso by'indwara ya bipolar, amaganya, amazi yigumira mu mubiri, no kwisubiraho ku kwemera kwitabira. Ingaruka mbi zari ahanini kumva uburyaryate igihe cyo kwihagarika bwamaraga igihe gito, ibibazo by'igifu n'amara, no kubabara umutwe.

Imbonerahamwe y'amagerageza yo kwa muganga: icyageragejwe koko

Gusoma uko ibisubizo byerekeza nta kubikabiriza

Ibintu bitatu bikomeza kugira agaciro nubwo hari izo mbogamizi. Icya mbere, icyerekezo cy'ingaruka kirahuye: ibimenyetso by'agahinda gakabije n'ibimenyetso byasigaye byagabanutse ku gipimo kinini muri ya magerageza yombi afite amatsinda yo kugereranya ku ndwara ya bipolar, kandi ingano y'ingaruka yari iringaniye mu igerageza rya vuba. Icya kabiri, nta na kimwe muri ubu bushakashatsi gishyigikira ko ubu bururu bugabanya maniya. Igerageza ryibanze kuri maniya ntiryagaragaje inyungu, kandi ubushakashatsi bwo guhinduranya ubuvuzi ntibwabonye itandukaniro kuri maniya; ibyo ni ukutaboneka kw'ubushobozi bwo kugabanya maniya, si ibimenyetso byo gutuma amarangamutima aringanira mu mpande zombi z'indwara. Icya gatatu, nta kimenyetso cya maniya yatangiye bitewe n'ubuvuzi cyagaragaye, ariko ayo magambo afite agaciro gato. Amanota ya maniya yo mu ntangiriro yari hafi ya zeru, kandi abahawe ubuvuzi babarirwaga mu makumi, bityo ubu bushakashatsi ntibwashoboraga kubona ibyago byo guhindukira muri maniya ku rwego rufite akamaro mu buvuzi. Imvugo ikwiye ni uko nta kimenyetso cyo guhindukira muri maniya cyabonetse, atari uko ibyago byo guhindukira muri maniya byakuweho.

Ibibazo bibiri by'uburyo ubushakashatsi bwakozwe bikwiye gushimangirwa kuko bireba ibimenyetso byose bihari. Guhisha ubuvuzi ntibyari byizewe muri buri bushakashatsi bwo guhinduranya ubuvuzi kubera imiterere yabwo: ubururu bwa metilene buhindura ibara ry'inkari, kandi igipimo gito cyo kugereranya cyatoranyijwe neza neza kugira ngo cyigane iyo ngaruka, mu gihe cyafatwaga nk'ikidakora. Kandi icyo gitekerezo cyagaragaye ko atari cyo: igipimo gito cyarushije umuti w'igereranya udafite igikorwa mu gahinda gakabije, bivuze ko amagereranya y'ingenzi yari ay'ibipimo by'ubuvuzi bubiri bwombi bushobora gukora, aho kuba amagerageza agereranya umuti n'umuti w'igereranya udafite igikorwa. Ingano y'ingaruka yapimwe muri ubwo buryo iragoye gusobanura kandi ntishobora guhurizwa hamwe n'iyo mu magerageza asanzwe y'imiti y'agahinda gakabije afite itsinda rihabwa umuti w'igereranya udafite igikorwa.

Ni ngombwa kutarenga imbibi z'ibyo ubu bushakashatsi bwize. Aya ni amagerageza ku ndwara ya bipolar afite ibipimo by'ibisubizo bijyanye n'iyo ndwara, kandi ntakwiye kuvangwa n'ibimenyetso biva mu yandi matsinda y'abantu. Abasomyi bashaka ubushakashatsi ku ngingo zegeranye n'iyi bakwiye kureba ukwabyo ibyabonetse ku maganya, ubushakashatsi ku bushobozi bwo gutekereza, n'amakuru ku mutekano n'imikoranire n'indi miti, kuko buri ngingo ireba uburyo butandukanye bwo gukora ubushakashatsi n'ibintu bitandukanye byo kwitondera ku byago.

Umutekano mu gukoresha imiti myinshi ku ndwara ya bipolar

Imiburo ibiri ireba mu buryo butaziguye abarwayi ba bipolar, bakunze kwandikirwa imiti ikora kuri serotonine. Ubururu bwa metilene na Azure B, ikinyabutabire gikomoka ku itunganywa ryabwo mu mubiri, ni ibibuza MAO-A gukora bifite imbaraga kandi igikorwa cyabyo gishobora gusubira inyuma; kubikoresha icyarimwe n'imiti ya SSRIs, SNRIs, n'indi miti ikora kuri serotonine bishobora gutera sindorome ya serotonine. Hafi ya raporo zose zasohotse ku ngaruka z'uburozi zarebaga ubururu bwa metilene bwatanzwe mu mutsi, kandi igerageza rya vuba ku ndwara ya bipolar ryemereye 20 muri 37 kwitabiriye gukoresha imiti y'agahinda gakabije nta kibazo kijyanye na serotonine kibaye, ariko ibyo byabaye ku bantu bake ntibikuraho umuburo ku mikoranire y'imiti. Amakuru yemewe ari ku muti utangwa mu mutsi ubu afite umuburo uri mu kazu kuri iyi ngingo. Ikindi, kubura cyangwa kugira ubuke bwa anzime glucose-6-phosphate dehydrogenase ni impamvu ibuza gukoresha ubururu bwa metilene, kuko bushobora gutera isenyuka ry'insoro zitukura z'amaraso; kandi igerageza rya vuba ryakuye abo barwayi mu bashoboraga kwitabira. Umuntu wese ukoresha ibyo binyabutabire icyarimwe akeneye gukurikiranwa n'umuvuzi; iyi ni imikorere y'imiti ishobora guteza ibibazo nyakuri, si imikoranire y'inyunganiramirire idateye impungenge.

Aho ikibazo kigeze

Ubushakashatsi ku bururu bwa metilene mu ndwara ya bipolar ni buke, bwa kera, kandi butanga ibimenyetso byerekeza ku gitekerezo, hiyongeraho igerageza rimwe rya vuba ry'ibanze rifite ireme. Incamake itabikabiriza ni iyi: ubururu bwa metilene bwongerwa ku buvuzi, ku gipimo cya hafi ya 195 kugeza kuri 300 mg buri munsi, bwagiye bugabanya ibimenyetso by'agahinda gakabije n'ibimenyetso byasigaye mu matsinda mato, bugaragaza rimwe ikimenyetso cy'inyungu ku maganya, ntibwagaragaza inyungu ku bushobozi bwo gutekereza, ntibwagaragaza ingaruka zo kugabanya maniya, kandi ntibwagaragaza ikimenyetso cyo guhindukira muri maniya umubare w'abitabiriye washoboraga gutuma kigaragara. Amagerageza manini afite itsinda rihabwa umuti w'igereranya nyakuri udafite igikorwa, akorerwa ku bafite agahinda gakabije ko mu ndwara ya bipolar kari mu gihe cyako gikomeye, afite uburyo bwateganyijwe mbere bwo gukurikirana guhindukira muri maniya, n'uburyo buhagije bwo guhisha ubuvuzi, ntarakorwa. Kugeza akozwe, ubururu bwa metilene buracyari ubuvuzi bw'inyongera bukiri mu bushakashatsi muri uru rwego, bushimishije bihagije kugira ngo bwigwe kurushaho, ariko ibimenyetso biracyari bike cyane ku buryo bitashyigikira imyanzuro.