Ukwelapha kungasiza labo abanesifo sePasinson esasemva kwesikhathi
Ngo-Mashi 2017, i-FDA ivunyiwe i-safinamide (i-Xadago) ukuze isebenzise imitholampilo e-United States. I-Safinamide iyisidakamizwa sokuqala esamukeleka yi-FDA ukuphatha isifo sika-Parkinson eminyakeni engaphezu kwengu-10. Kuyindlela yokwazisa, noma yokwelashwa, okusetshenziselwa ukuhlanganiswa ne-levodopa.
Izifo zikaPasinson zichazwe
Isifo sikaParkinson yisifo sokunyakaza esithuthuka kancane kancane futhi siqala cishe eminyakeni engama-60.
Izimpawu zihlanganisa ukuthuthumela, ukuqina, ukuhamba kancane, nokulinganisela okungalungile. Lesi sifo siphelela ekuhluphekeni ngokuhamba, ukukhuluma, kanye neminye imisebenzi yokuphila yansuku zonke. E-United States, abantu abangaba ngu-50 000 batholakala benesifo sikaParkinson unyaka ngamunye.
Nakuba kungekho ukwelashwa kwesifo sikaParkinson, kunezindlela zokwelapha ezisiza ekulawuleni izibonakaliso, kuhlanganise okulandelayo:
- i-levodopa
- i-dopamine agonists (isib, apomorphine, bromocriptine, i-ropinirole ne-pramipexole)
- i-monoamine oxidase inhibitors noma i-MAO-B inhibitors (isb., i-selegeline ne-rasagaline)
- i-catechol-O-methyl-transferase (COMT) inhibitors (isb., i-entacapone ne-tolcapone)
- i-amantadine
- izidakamizwa ze-anticholinergic, ezifana no-Artane noCogentin (ngokuvamile abanikezwa abantu abasha abazama ukuzamazama kuzo)
Ngeshwa, azikho izindlela zokwelapha ezinciphisa noma eziyeka ukuqhubeka kwesifo sikaParkinson.
I-Levodopa iyisidakamizwa esiphezulu kakhulu futhi esivelele esisetshenziselwa ukuphatha isifo sikaParkinson; Kodwa-ke, umphumela wayo uvame ukuguga ngokuhamba kwesikhathi futhi kungaholela emiphumeleni emibi ehlanganisa i- dyskinesia .
Izidakamizwa ezibandakanya i-COMT inhibitors, i-dopamine agonists, kanye nezinqubo ezingekho-dopaminergic-njengezokwelapha ze-anticholinergic kanye ne-amantadine-zingasetshenziswa njengezinye izindlela kwi-levodopa, ngaphezu kwe-levodopa, noma ngokuhlanganisana.
Kubantu abanesifo esiphezulu se-Parkinson, lapho imithi ihluleka, ukukhushulwa kobuchopho obujulile (ukuhlinzeka ngobuchopho) kungacatshangwa ukuthi kusize ukunciphisa izimpawu.
Ngokuvamile, imishanguzo igcinelwe abantu abanezibonakaliso zabo eziye zaba nzima ngokwanele ukuphazamisa imisebenzi yokuphila kwansuku zonke. I-Levodopa ngokuvamile iyisidakamizwa esizikhethela kubantu abaneminyaka engama-65 nangaphezulu abaphila ngayo ngendlela engathà sina. Abantu abangaphansi kuka-65 bangaphathwa nge-dopamine agonist.
Izidakamizwa ziqaliswa ngomthamo ophansi kakhulu futhi ukwelashwa kuvame ukubambezeleka isikhathi eside ngangokunokwenzeka. Kodwa-ke, ucwaningo olusekela isiteji esiqondisayo sokuthi "qala kancane futhi uhambe kancane" ngemitha ye-levodopa ixutshwe. Ngokomlobi uPeter Jenner:
Ukwethulwa kwe-L-Dopa [levodopa] kulabo abanesifo eside isikhathi eside noma emithwalweni ephezulu kungaholela esikhathini esifushane somphumela omuhle ngaphambi kokuba kuvele izinkinga zezimoto. Kamuva nje, ukugcina umthamo we-L-dopa ngaphansi kuka-400 mg ngosuku ngosuku lokuqala lwe-PD kuboniswe ukunciphisa ingozi yokufakelwa kwe-dyskinesia.
Nokho, uJenner uyaqhubeka nokuphawula lokhu okulandelayo:
Ukusetshenziswa kweL-dopa kuqala kwaphinde kuboniswa ukuthi yindlela yokwelapha ephumelela kakhulu yezibonakaliso zezimoto nokungathinteki ingozi yesikhathi eside ye-dyskinesia.
Ngokuqinisekile, ubufakazi obunjalo obuphikisanayo bubonisa ukuthi kuncane kangakanani esikwaziyo mayelana nokugula nokuphathwa kwesifo sikaParkinson.
I-Safinamide: Isebenza Kanjani?
Kubantu abanesifo sikaPasinson, ubuchopho abukhiqizi ngokwanele i-neurotransmitter ebizwa ngokuthi i- dopamine .
Amaseli akhiqiza i-dopamine ayafa noma aphelelwe amandla. I-dopamine iyadingeka ukuze kulawulwe kahle imoto nokuhamba.
Ngokuqondile, i-dopamine idlulisela amasignali ebuchosheni obandakanyeka ekuhambeni okubushelelezi, okunenjongo njengokudla, ukubhala nokubhala. Njenga-selegeline ne-rasagaline, i-safinamide uhlobo lwe-MAO-B inhibitor, okuvimbela ukwehla kwe-dopamine futhi ngaleyo ndlela kwandisa amazinga ayo ebuchosheni.
Inothi, i-safinamide ibuye ihlise ukukhululwa kwe-glutamate; Kodwa-ke, umphumela othize walesi senzo ezenzweni zokwelapha izidakamizwa aziwa.
Ngokungafani namanye ama-inhibitors e-MAO-B, angabekwa yedwa kulabo abanesifo se- Parkinson esesisencane, i-safinamide ihloswe ukuba isetshenziswe ngokuhambisana nezinye izinhlobo zemithi ye-antiparkinson yezifo ezisemuva, ikakhulukazi i-levodopa kanye ne-dopamine agonists.
Lapho abantu beqala ukulashwa izimpawu zikaParkinson, izidakamizwa zivame ukusebenza kahle futhi izimpawu zilawulwa usuku lonke. Nokho, phakathi kweminyaka emihlanu nengu-10, ukusebenza kwezidakamizwa ezivamile zikaParkinson kuhlasela abantu abaningi, futhi ukulawula izimpawu kuba nzima ngokwengeziwe ukunciphisa.
Ngokuqondile, kubantu abaphakathi kwesifo se-Parkinson esesiphelile, ukuguquguquka kwezimoto noma ukunyakaza kwemisipha okungavumelani (i-dyskinesia ne- frozen ) baqala ukutshala.
I-Dyskinesia ibonakala kakhulu kubantu abathwala i- levodopa futhi kuba nomthelela omubi wokuphathwa kwezidakamizwa. Ukubonakaliswa kwe-dyskinesia kubhekana kabi ngokuphathelene nokubikezela futhi kufanele kube kuhle ukulibaziseka ngangokunokwenzeka. Ngaphezu kwalokho, izimpawu ezingezona izimoto, ezifana nokuwohloka komqondo , ukucindezeleka, nokucubungula, okungathinteki kakhulu uma kukhona izidakamizwa ze-dopaminergic, futhi kuyinkinga.
Lezi ziguli eziyekezela ngemuva kokwelashwa okwanele okuye kwadlula isikhathi kunzima ukuphatha ngendlela egcina ukuhamba kanye nekhwalithi yokuphila.
Ngamanye amazwi, uma i-levodopa iyeka ukusebenza futhi, ngenxa yokuthi asiqondi ukugula kwalesi sikhokhelo, kunzima ukubuyisela abantu esiteshini esisezingeni eliqinile kanye nekhwalithi yokuphila okuhlangenwe nakho ekuqaleni kwezifo lapho i-levodopa namanye ama-dopaminergic agents babesebenza.
Ngaphezu kwalokho, ngisho noma izinkinga zezimoto zihlanjululwa, izimpikiswano ezingezona izimoto ezinjengokuphazamiseka kwemizwa, ukuphazamiseka kokulala, nokudemeka kwengqondo kuba yinkinga kulabo abanesifo sePasinson esilandelayo.
Ngeshwa, asikwazi ukubikezela ukuthi yisiphi isifo se-Parkinson esilandelayo esizayo esizokwenza ukushintsha kwezimoto kanye nezinkinga zemoto. Konke, isikhathi sesifo, isigaba sesifo, ubude bokunakekelwa nge-levodopa, isisindo se-levodopa, ubulili, nesisindo somzimba bonke bakholelwa ukuthi badlala indima ekukhokhelweni kwemali ekugcineni.
ON Times ne-OFF Times
"NGESIKHATHI" kubhekisela esikhathini lapho imithi isebenza ngokwanele futhi izimpawu zesifo sikaParkinson zilawulwa.
"I-OFF isikhathi" ibhekisela ezikhathini lapho imishanguzo iphela futhi izimpawu zikaParkinson, ezifana nokuthuthumela, ukuqina nokuqina ukuhamba kuvela.
Ukwengezwa kwe-safinamide emiphakathini yezidakamizwa zabantu abanezifo eziphambili ze-Parkinson ezithatha i-levodopa kwandisa inani le-ON futhi liyancipha isikhathi.
Izivivinyo Zomtholampilo ze-Safinamide
Imiphumela evela ezivivinyweni ezimbili zomtholampilo ihlose ukuhlolisisa izinzuzo zokusebenzisa i-safinamide phakathi kwabantu abanesifo esiphezulu se-Parkinson. Laba bahlanganyeli babethole benesifo sikaParkinson eminyakeni emihlanu noma emihlanu.
Isivivinyo sokuqala somtholampilo sihlole abahlanganyeli abangu-669 abanezimoto eziguqukayo. Laba bahlanganyeli bathole i-safinamide ngaphezu kwamanye imithi ye-antiparkinson noma i-placebo (ayikho i-safinamide) nezinye izidakamizwa ze-antiparkinson.
Isilinganiso ON isikhathi sabathintekayo kwaba phakathi kwamahora angu-9.3 no-9.5. Ngemuva kwezinyanga eziyisithupha zokuhlolwa, izikhathi zikhuphuke kuzo zombili izigcawu zeziguli; Kodwa-ke, izikhathi ezithile zazingamaminithi angaba ngu-30 kulabo abathatha i-safinamide.
Ngemuva kweminyaka emibili yokwelashwa, isilinganiso se-ON isikhathi sihlale silingana nalabo abathatha i-safinamide kodwa kunciphise kulabo abathwala i-placebo. Ngakho-ke emva kweminyaka emibili ngokwesilinganiso, abahlanganyeli abathatha i-safinamide kanye ne-levodopa kanye neminye imithi ye-antiparkinson yabhekana nehora elilodwa lokuphathwa kahle kwezimpawu zikaHalinson.
Inothi, i-safinamide inciphise isikhathi NGAMINYAKA engama-35. Khumbula ukuthi izikhathi ezivuliwe zibhekisela ezinkathini lapho izidakamizwa ze-antiparkinson zigugile, futhi izimpawu ezifana nokuthuthumela ziphinde zikhukhumezeke.
Ngaphezu kokunweba ngezikhathi nokunciphisa izikhathi, i-safinamide iphinde ithuthukise ukunyakaza (amanqaku amoto) kulabo abayithathayo. Ngaphezu kwalokho, ngesilinganiso esiphezulu, i-safinamide nayo yasiza ngemisebenzi yokuphila kwansuku zonke kanye nekhwalithi yokuphila.
Ngokufanayo imiphumela yecala lesibili, elibandakanya abahlanganyeli abangu-549, liphakamisa ukwanda esikhathini esingaba nguhora elilodwa kulabo abathatha i-safinamide uma kuqhathaniswa nalabo abathatha indawo ye-placebo kanye nokunciphisa isikhathi esinikeziwe. Ukwengeza, ukuthuthukiswa kokusebenza kanye nekhwalithi yezikolo zokuphila nakho kwabonakala.
I-Safinamide Negative Side Effects
Ngenxa yemiphumela emibi, amaphesenti angu-3.7 abamba iqhaza athatha ama-safinamide aphelelwe izivivinyo zokwelashwa uma kuqhathaniswa namaphesenti angu-2.4 alabo abathatha i-placebo.
Imiphumela emibi evamile evezwe phakathi nalezi zivivinyo zemitholampilo yayihlanganisa okulandelayo:
- ama-jerky noma ahlukaniswe (ie, i-dyskinesia)
- uyawa
- isiyaluyalu
- ukulala
Kulezi zibonakaliso, i-dyskinesia yayivame ukuphindwe kabili kubantu abathatha i-safinamide uma kuqhathaniswa nalabo abangayithathi (okungukuthi, labo abathatha indawo ye-placebo).
Imiphumela engavamile engavamile kodwa eyingozi kakhulu ihlanganisa okulandelayo:
- ukwandisa ukucindezeleka kwegazi
- i-hallucinations ebonakalayo kanye nokuziphatha kwengqondo
- elele ubuthongo phakathi nosuku
- i-serotonin syndrome (uma isetshenziselwa nama-inhibitors we-MAO, ama-anti-depressants, nama-opioids)
- izinkinga zokulawula ukucindezela noma ukuziphatha okucindezelayo (cabanga i-OCD)
- umkhuhlane kanye nokudideka
- izinkinga zokubuyisela
Nazi ezinye izidakamizwa ongafanele uthathe uma uthatha i-safinamide:
- izidakamizwa ezithile (i-serotonin-norepinephrine reuptake inhibitors, i-tricyclics, ne-tetracyclic)
- cyclobenzaprine
- dextromorphan (etholakala eminye imithi yokukhwehlela)
- ama-opioid
- Wort St. John's Wort
Nakuba abantu abanezinkinga zezinso bangathatha i-safinamide, labo abanezinkinga ezinkulu zesibindi akufanele bathathe umuthi.
Ngaphansi
I-Safinamide iwusizo kakhulu kulabo abaphakathi kwesifo se-Parkinson esesiphezulu sezinyanga ezisedlule, abahlangabezana nokushintshashintsha kwezimoto (ie, i-dyskinesia) nokunciphisa ukusebenza kwemithi yabo (okungukuthi, izikhathi ezivaliwe). I-Safinamide ingaba ukwelapha okungcono kokwelashwa okuyisisekelo nge-levodopa kunamanye ukwelapha okungeziwe, kufaka phakathi amanye ama-inhibitors we-MAO-B kanye nama-inhibitors we-COMT. I-Safinamide ingasetshenziswa ngokuhambisana ne-levodopa nezinye izidakamizwa ze-antiparkinson. I-Safinamide ayisetshenziswanga yedwa.
Umphumela omubi kunawo wonke we-safinamide yi-dyskenesia, noma ukwanda kokunyakaza okungazibandakanyi. Abantu abanezinkinga ezinkulu zesibindi noma labo abathwala izidakamizwa ezithile noma ezinye imithi akufanele bathathe i-safinamide.
> Imithombo:
> Chaplin, S. Safinamide: Ukwelashwa Okungeziweko Kwezifo Ze-Parkinson. I-Prescriber. 2016.
> I-FDA ivumela izidakamizwa ukuphatha izifo zikaParkinson. Mashi 21, 2017. www.fda.gov.
> Jenner, P. Ukwelashwa Kwezingxenye Ezizayo Zezifo ZasePasinson - Ukufinyelela Kwemithi Manje Nesikhathi Esizayo. I-Neurodegeneneration yokuhumusha. 2015; 4: 3.
> Jankovic, J, no-Aguilar, i-LG. Izinyathelo Zamanje Zokuphathwa Kwezifo ZasePasinson. Izifo Neuropsychiatric and Treatment. 2008; 4 (4): 743-757.
> Schapira, AH, et al. Ukuhlolwa kwezokuphepha nokusebenza kweSafinamide njenge-Levodopa ehlangene neziguli ezine-Parkinson Izifo kanye neziMfucuza Zezimoto. I-JAMA Neurology. 2017; 74 (2): 216-224.