Unyango lunokunceda abo banesifo seParkinson esilandelayo
Ngo-Matshi 2017, i-FDA ivume i -finfinide (Xadago) ukuze isebenzise ukliniki e-United States. I-Safinamide yilisiza esitsha sokuqala esamkelwe yi-FDA ukuphatha isifo sika-Parkinson kwiminyaka engaphezu kwe-10. Yindlela yokwazisa, okanye ukongeza-unyango, esetyenziselwa ukudibanisa ne-levodopa.
Izifo zikaPasinson zichazwe
Isifo se-Parkinson sisifo sokunyakaza esenza ngokuthe ngcembe kwaye siqala ngokufikelela kwiminyaka engama-60.
Iimpawu zibandakanya ukuthuthumela, ukuqina, ukunyusa ukunyakaza, kunye nokulinganisela okungalunganga. Esi sifo ekugqibeleni kubangela ubunzima ngokuhamba, ukuthetha, kunye nezinye izinto eziqhelekileyo zokuphila kwansuku zonke. EUnited States, abantu abangaba ngu-50 000 bafumaneka ukuba banesifo se-Parkinson ngonyaka ngamnye.
Nangona kungekho nonyango kwisifo se-Parkinson, kukho unyango olunceda ekulawuleni izibonakaliso, kubandakanywa oku kulandelayo:
- levodopa
- i-dopamine agonists (umzekelo, i-apomorphine, i-bromocriptine, i-ropinirole kunye ne-pramipexole)
- i-monoamine oxidase inhibitors okanye ii-inhibitors ze-MAO-B (umzekelo, i-selegeline kunye ne-rasagaline)
- i-catechol-O-methyl-transferase (COMT) inhibitors (umzekelo, i-entacapone kunye ne-tolcapone)
- i-amantadine
- izidakamizwa zokulwa ne-anticholinergic, ezifana no-Artane noCogentin (ngokuqhelekileyo kunikwa abantu abancinci abakhuphayoyo uphawu oluphambili)
Ngelishwa, akukho zonyango ezityhutyha okanye eziyeke ukuqhubeka kwesifo sikaParkinson.
I-Levodopa yiyona nto isisigxina kunye nesigxina esasetyenziswayo ukuphatha isifo sikaParkinson; nangona kunjalo, isiphumo saso sithintela ixesha elide kwaye kunokukhokelela kwimiphumo emibi equka i- dyskinesia .
Izidakamizwa ezibandakanya i-COMT inhibitors, i-dopamine agonists, kunye neyeza ezingekho-dopaminergic-ezifana ne-anticholinergic unyango kunye ne-amantadine-zingasetyenziselwa iindlela zokungena kwi-levodopa, ngaphezu kwe-levodopa, okanye ngokudibanisana nomnye.
Kubantu abanesifo esiphezulu sePasinson, xa unyango luye lwahluleka, ukuvuselela ingqondo (ingqondo yobuchopho) ingaqwalaselwa ukunceda ekunciphiseni iimpawu.
Ngokuqhelekileyo, imithi igcinelwe abantu abaneempawu eziba nzima kakhulu ukuphazamisa imisebenzi yokuphila kwansuku zonke. I-Levodopa ngokuqhelekileyo isicatshulwa esikhethekileyo kubantu abaneminyaka engama-65 nangaphezulu ubudala abaphila ngayo. Abantu abangaphantsi kwama-65 banokuphathwa nge-dopamine agonist.
Iziyobisi ziqaliswe kwiqondo eliphantsi kakhulu kwaye unyango lulibaziseka ixesha elide kunokwenzeka. Nangona kunjalo, uphando oluxhasa isiqalo sokuthi "qala phantsi kwaye uhambe ngokukhawuleza" kunye nemilinganiselo ye-levodopa ixutywe. Ngokombhali uPeter Jenner:
Ukuqaliswa kwe-L-Dopa [levodopa] kulabo abanexesha elide lokugula okanye kwiqondo eliphezulu lingabangela ixesha elifutshane lokuphumelela ngaphambi kokuba kuvele iingxaki zeemoto. Ngoku kutshanje, ukugcina umthamo we-L-dopa engaphantsi kwe-400 mg ngosuku kwi-PD yokuqala kwaboniswa ukunciphisa umngcipheko wokufakelwa kwe-dyskinesia.
Nangona kunjalo, uJenner uyaqhubeka ephawula oku kulandelayo:
Ukusetyenziswa kwangaphambili kwe-L-dopa kwaboniswa ukuba yonyango oluphambili kwiimpawu zeemoto kwaye aluchaphazeli umngcipheko wesikhathi eside we-dyskinesia.
Ngokuqinisekileyo, ubungqina obunjalo obuphikisanayo bubonisa indlela esincinane esazi ngayo ngokugula kunye nokunyangwa kwesifo se-Parkinson.
I-Safinamide: Isebenza Kanjani?
Kubantu abanesifo sikaChinsinson, ingqondo ayivelisi ngokwaneleyo i-neurotransmitter ebizwa ngokuthi i- dopamine .
Iiseli ezivelisa i-dopamine zifa okanye zikhubazeke. I-Dopamine iyimfuneko yokulawula imoto eyiyo kunye nokunyakaza.
Ngokukodwa, i-dopamine idlulisela izibonakaliso kwingqondo echaphazelekayo ekuhambeni okugqithiseleyo, okunenjongo njengokutya, ukubhala nokubhala. Njenga-selegeline kunye ne-rasagaline, i-safinamide luhlobo lwe-MAO-B inhibitor, oluvimbela ukuphahlazeka kwe-dopamine kwaye ngaloo ndlela lwandisa amanqanaba alo engqondweni.
Ingqalelo, i-sfinamide iphinda ilandele ukukhululwa kwe-glutamate; Nangona kunjalo, umphumo othile wolu nyathelo kwizenzo zokwelapha izidakamizwa aziwa.
Ngokungafani nezinye ii-inhibitors ze-MAO-B, ezinokumiselwa zodwa kulabo abane-episitini yesifo se- Parkinson, i-safinamide ijoliswe ukuba isetyenziswe kunye nezinye iintlobo zemithi ye-antiparkinson yezifo ezisemva kwesigxina, ikakhulukazi i-levodopa kunye ne-dopamine agonists.
Xa abantu beqala kuqala unyango lweempawu zeParkinson, iziyobisi zivame ukusebenza kakuhle kwaye iimpawu zilawulwa yonke imihla. Nangona kunjalo, phakathi kweminyaka emihlanu ukuya kwe-10, kunjalo, ukusetyenziswa kweziyobisi zikaPasinson eziqhelekileyo kubangelwa ngabantu abaninzi, kwaye ukulawula impawu kunzima kunciphisa.
Ngokukodwa, kubantu abaphakathi kwesigaba sokugqibela se-Parkinson isifo, ukuguquguquka kweemoto okanye ukunyakaza kwama-muscle okungazibandakanya (i-dyskinesia kunye neqhwa ) kuqala ukulima.
I-Dyskinesia ibonakala kakhulu kubantu abathatha i- levodopa kwaye kuyimpembelelo embi yonyango lweziyobisi. Ukubonakaliswa kwe-dyskinesia kubangelwa kakubi ngokubhekiselele kwisiprofeto kwaye kufuneka ukuba kulungele ukulibaziseka kangangoko kunokwenzeka. Ukongezelela, iimpawu ezingezona iimoto, ezifana nokudemeka komzimba , ukudandatheka, kunye neengcamango, ezichaphazeleka kakhulu xa zikhona ngeziyobisi ze-dopaminergic, nazo ziba yingxaki.
Ezi zi gulane ezithintela emva kokunyanga okwaneleyo eziye zadlula ixesha kunzima ukuphatha ngendlela egcina ukuhamba kunye nomgangatho wobomi.
Ngamanye amazwi, xa i-levodopa iyeka ukusebenza ngokusemandleni, ngenxa yokuba asiyiqondi ukukhubazeka kwesi sihlomelo, kunzima ukubuyisela abantu kwisiseko esisisigxina kunye nempilo yobomi ngaphambili kwixesha lesifo xa i-levodopa nezinye i-dopaminergic agents be sebenza.
Ngaphezu koko, nangona ukuba iingxaki zeemoto zixhaswa kuzo, imiba engeyiyo imoto efana nokukhathazeka kwemizwelo, ukuphazamiseka kokulala, kunye nokugula komzimba kuya kuba yingxaki kubantu abanokugula kwesigxina seParkinson.
Ngelishwa, asikwazi ukuqikelela ukuba zeziphi iziganeko zesigxina seParkinson ziza kuhlakulela ukunyuka kweemeko kunye nezimo ezinzima. Ngokubanzi, ixesha lesifo, isigaba sesifo, ubude bonyango kunye ne-levodopa, i-levodopa dosages, ubulili kunye nesisindo somzimba bonke bakholelwa ukuba badlala indima ekuhlawulweni kokugqibela.
KWIMIQESHO NOKUPHAKHA KWIXESHA
"NGExesha" libhekisela kumaxesha xa amayeza asebenza ngokufanelekileyo kwaye iimpawu zesifo se-Parkinson zilawulwa.
"I-OFF time" ibhekisela kumaxesha apho amayeza enxiba kwaye iimpawu zikaParkinson, ezinjengokugubha, ukunyaniseka, nokuhamba nzima ukuhamba kwakhona.
Ukongezwa kwe-sfinamide kwizigulana zezilwanyana zabantu abanezifo eziphambili ze-Parkinson ezithatha i-levodopa zandisa inani le-ON kunye nokunciphisa i-OFF.
I-Safinamide Clinical Trials
Iziphumo ezivela kwizilingo ezibini zonyango ziye zakhangela izibonelelo ezinokusetyenziswa kwe-sfinamide phakathi kwabantu abanesifo esiphezulu sePacinson. Aba bathathi-nxaxheba bafumene ukuba banesifo se-Parkinson kwisithuba seminyaka emithathu okanye emihlanu.
Uvavanyo lokuqala lweklinikhi lwavandlakanya abachaphazelekayo abangama-669 abaneemoto eziguqukayo. Aba bathathi-nxaxheba bafumana i-shyamamide ngaphezu kweminye imithi ye-antiparkinson okanye indawo ye-placebo (ayikho i-safinamide) kunye nezinye izidakamizwa ze-antiparkinson.
Umyinge ngexesha lokuba abathathi-nxaxheba bephakathi kwama-9.3 no-9.5 iiyure. Emva kweenyanga ezintandathu zokuvavanywa, KWAKWENGEZIWE ukunyuka kwezi zimbini izigulane; Nangona kunjalo, KWAMAKHATHI amaxesha angaba malunga nemizuzu engama-30 kudala kwabo bathatha i-shyamamide.
Emva kweminyaka emibini yonyango, umyinge ngexesha elihlala ixesha elifanayo lihlala lifana nalabo bathatha i-shyamamide kodwa bancipha kulabo bathatha indawo ye-placebo. Ngaloo ndlela emva kweminyaka emibili ngokulinganayo, abathathi-nxaxheba bathatha i-shyamamide kunye ne-levodopa kunye namanye amayeza e-antiparkinson afunyenwe malunga neyure enye yonyango olululo lwezonyango ze-Parkinson.
Inqaku, i-sfinamide iyancitshiswe ixesha elingangange-35 imizuzu. Khumbula ukuba amaxesha akwi-OFF ayichaza kumaxesha apho izidakamizwa ze-antiparkinson zithinteka, kwaye iimpawu ezinjengezondlo ziphinda zixakeke.
Ukongezelela ukwandisa KWAMANZI kunye nokunciphisa amaxesha, i-safinamide iphinde iphucule ukuhamba (amanqaku emoto) kulabo bathabathayo. Ngaphezu koko kwi-dosage ephezulu, i-safinamide nayo yanceda ngemisebenzi yokuphila kwansuku zonke kunye nomgangatho wobomi.
Ngokufanayo neziphumo zetyala lesibini, ezibandakanya abathathi-nxaxheba abangama-549, zibonisa ukunyuka kwithuba kwixesha elilodwa malunga nalabo bathatha i-shyamamide xa kuthelekiswa nalabo bathatha indawo ye-placebo kunye nokunciphisa ixesha lokukhupha. Ukongezelela, ukuphuculwa kokusebenza kunye nemigangatho yobomi beempawu kwagqalwa kwakhona.
I-Safinamide Side Effects Side
Ngenxa yemiphumo emibi, i-3.7 ekhulwini yabathathi-nxaxheba bathatha i-shyamamide baphuma kwiimvavanyo zonyango xa kuthelekiswa nama-2.4 ekhulwini abo bathatha indawo.
Iimiphumo eziqhelekileyo ezibangelwa ngethuba lokuvavanywa kliniki zibandakanya oku kulandelayo:
- iingubo ezinje okanye eziqhekekileyo (okt, i-dyskinesia)
- kuwa
- isicaphulelo
- kulala
Kule miqondiso, i-dyskinesia yayingabini ngokuqhelekileyo kubantu abathatha i-shyamamide xa kuthelekiswa nabangayithathiyo (oko kukuthi, abo bathatha indawo ye-placebo).
Iziphumo eziqhelekileyo kodwa ezibi kakhulu zibandakanya oku kulandelayo:
- ukunyuka kwengcinezelo yegazi ephezulu
- i-hallucinations ebonakalayo kunye nokuziphatha kwengqondo
- ukulala ngexesha lomhla
- i-serotonin syndrome (xa isetyenziselwa i-MAO inhibitors, i-anti-depressants, ne-opioids)
- iingxaki ngokulawulwa komgudu okanye ukuziphatha okunyanzelekileyo (cinga i-OCD)
- umkhuhlane kunye nokudideka
- iingxaki zokubuyisela
Nazi ezinye iziyobisi ongafanele uthathe ukuba uthatha i-safinamide:
- izidakamizwa ezithile (i-serotonin-norepinephrine reuptake inhibitors, i-tricyclics, ne-tetracyclic)
- cyclobenzaprine
- dextromorphan (efunyenwe kwimithi ethile yokukhupha)
- opioids
- ISt John's Wort
Nangona abantu abanokukhubazeka kweengtso bangathatha i-shyamamide, abo baneengxaki ezinobindi ezinzulu abanokuthi bangathathi iyeza.
Okukwintsusa
I-Safinamide iyona iluncedo kulabo basesigxina sexesha lika-Parkinson yesifo esinexesha elide elifumana ukunyuka kweemoto (oko kukuthi, i-dyskinesia) kunye nokunciphisa ukuphumelela kwemithi yabo (oko kukuthi, iixesha ezikhuphayo). I-Safinamide ingaba yonyango elongezelelweyo yokonyango oluphambili kunye ne-levodopa kunamanye unyango olongezelelweyo, kuquka ezinye i-MAO-B inhibitors kunye ne-COMT inhibitors. I-Safinamide ingasetyenziselwa ukudibanisa ne-levodopa kunye nezinye izidakamizwa ze-antiparkinson. I-Safinamide ayisebenzisi yodwa.
Isiphumo esibi kakhulu sempembelelo ye-safinamide yi-dyskenesia, okanye ukwanda kwezinto ezizibandakanyekayo. Abantu abaneengxaki ezinzulu zesibindi okanye abo bathatha i-antidepressants okanye ezinye iyeza kufuneka bangathathi i-shyamide.
> Imithombo:
> Chaplin, S. Safinamide: Unyango olongezelelweyo lweZifo ze-Parkinson. I-Prescriber. 2016.
> I-FDA iyavuma iMichiza yokuphatha izifo zika-Parkinson. Matshi 21, 2017. www.fda.gov.
> Jenner, P. Ukwelashwa kweSigaba seSigxina seZifo zePacinson - Iindlela ze-Pharmacological Approaches Now nakwixesha elizayo. Ukuguquguquka kweentsholongwane. 2015; 4: 3.
> Jankovic, J, noAguilar, LG. Iindlela ezikhoyo zonyango lweZifo zeParkinson. Izifo Neuropsychiatric kunye neNyango. 2008; 4 (4): 743-757.
> Schapira, AH, et al. UVavanyo loKhuseleko kunye noPhuculo lweSafamamide njenge-Levodopa Abadibeneyo kwizigulane kunye ne-Parkinson Izifo kunye ne-Motor Fluctuations I-Trial Clinic Trial Trial. JAMA Neurology. 2017; 74 (2): 216-224.