Kalafo e ka thusa ba nang le lefu la Parkinson la kamorao ho nako
Ka March 2017, FDA e amohetse safinamide (Xadago) bakeng sa tšebeliso ea meriana United States. Safinamide ke eona moriana oa pele o amohelehang ke FDA ho tšoara lefu la Parkinson ka lilemo tse fetang 10. Ke mofuta oa adjunctive, kapa ho eketsa-kalafo, o sebelisitsoeng hammoho le levodopa.
Maloetse a Parkinson a hlalositsoe
Lefu la Parkinson ke boloetse bo tsamaeang butle-butle bo ntseng bo tsoela pele 'me hangata bo qala ho ba le lilemo tse ka bang 60.
Matšoao a kenyeletsa ho thothomela, ho tsitlella, ho lieha ho tsamaea, le ho leka-lekaneng ho leka-lekana. Lefu lena qetellong le baka mathata ka ho tsamaea, ho bua le mesebetsi e meng ea tloaelo ea bophelo ba letsatsi le leng le le leng. United States, batho ba ka bang 50 000 ba fumanoa ba e-na le lefu la Parkinson selemo se seng le se seng.
Le hoja ho se na pheko ea lefu la Parkinson, ho na le phekolo e thusang ka ho laola matšoao, ho akarelletsa le tse latelang:
- levodopa
- dopamine agonists (mohlala, apomorphine, bromocriptine, ropinirole le pramipexole)
- monoamine oxidase inhibitors kapa MAO-B inhibitors (mohlala, selegeline le rasagaline)
- catechol-O-methyl-transferase (COMT) inhibitors (mohlala, entacapone le tolcapone)
- amantadine
- lithethefatsi tsa anticholinergic, tse kang Artane le Cogentin (hangata li fuoe bacha bao ho thothometsoang ke bona matšoao a maholo)
Ka bomalimabe, ha ho na phekolo e fokolang kapa e emisang ho kula ha Parkinson.
Levodopa ke moriana o matla ka ho fetisisa le o hlaheletseng o sebelisetsoang ho tšoara lefu la Parkinson; leha ho le joalo, phello ea eona e atisa ho fela ka nako 'me e ka baka litla-morao tse mpe tse kang dyskinesia .
Lithethefatsi tse kenyelletsang COMT inhibitors, li-agonists le li-treat-non-dopaminergic-tse kang phekolo ea anticholinergic le amantadine-li ka sebelisoa e le mekhoa ea phekolo ea levodopa, ho phaella ho levodopa, kapa ka ho kopana.
Batho ba nang le lefu la Parkinson le tsoetseng pele, ha meriana e hlōleha, boko bo tebileng ba boko (ho buuoa ke boko) bo ka nkoa e le ho thusa ho fokotsa matšoao.
Ka tloaelo, meriana e boloketsoe batho bao matšoao a bona a leng a lekaneng ho kena-kenana le mesebetsi ea letsatsi le leng le le leng. Hangata Levodopa ke sethethefatsi sa khetho ho batho ba lilemo li 65 le ho feta bao mekhoa ea bona ea bophelo e kenyelletsoeng haholo. Batho ba ka tlase ho lilemo tse 65 ba ka phekoloa ka dopamine agonist.
Lithethefatsi li qalisoa ka tekanyo e tlase ka ho fetisisa ea meriana 'me kalafo e lieha ka nako e telele kamoo ho ka khonehang. Leha ho le joalo, lipatlisiso tse tšehetsang mohato o tataisang oa "qala fatše 'me o liehe" ka litekanyetso tsa levodopa li kopane. Ho ea ka mongoli Peter Jenner:
Ho kenyelletsoa ha L-Dopa [levodopa] ho ba nang le nako e telele ea ho kula kapa ka tekanyo e phahameng e ka lebisa nako e khutšoanyane ea phello e ntle pele likotsi tsa motlakase li hlaha. Haufinyane, ho boloka tekanyo ea L-dopa e ka tlaase ho 400 mg ka letsatsi ho PD e ile ea bontšoa ho fokotsa kotsi ea ho kenngoa ha dyskinesia.
Leha ho le joalo, Jenner o tsoela pele ho hlokomela tse latelang:
Tšebeliso ea pele ea L-dopa le eona e ile ea bontšoa e le phekolo e atlehang ka ho fetisisa bakeng sa matšoao a motlakase le hore e se ke ea ama kotsi ea nako e telele ea dyskinesia.
Ka sebele, bopaki bo joalo bo hanyetsanang bo totobatsa kamoo re sa tsebeng hakaalo ka ho kula le kalafo ea lefu la Parkinson.
Safinamide: E Sebetsa Joang?
Ho batho ba nang le lefu la Parkinson, boko ha bo hlahise mokhachane o lekaneng o bitsoang dopamine .
Lisele tse hlahisang dopamine li shoa kapa lia fokola. Dopamine e hlokahalang bakeng sa tsamaiso e nepahetseng ea motlakase le ho tsamaea.
Ha e le hantle, dopamine e fetisetsa lipontšo bokong tse amehang ka mekhoa e bonolo, e nang le morero joaloka ho ja, ho ngola le ho ngola. Joaloka selegeline le rasagaline, safinamide ke mofuta oa MAO-B inhibitor, e leng ho thibelang ho senyeha ha dopamine ka hona ho eketsa maemo a eona bokong.
Hape, safinamide e boetse e fetola ho lokolloa ha glutamate; leha ho le joalo, phello e tobileng ea ketso ena mererong ea phekolo ea meriana e sa tsejoe.
Ho fapana le tse ling tsa MAO-B inhibitors, tse ka etsoang li le bang ho ba nang le lefu la Parkinson la pele-pele , safinamide e reretsoe ho sebelisoa hammoho le mefuta e meng ea meriana ea antiparkinson bakeng sa mafu a morao-rao, haholo-holo levodopa hammoho le li-agonists tsa dopamine.
Ha batho ba qala ho qala kalafo ea matšoao a Parkinson, lithethefatsi li atisa ho sebetsa hantle 'me matšoao a laoloa ho pholletsa le letsatsi. Leha ho le joalo, pakeng tsa lilemo tse hlano le tse 10, ts'ebetsong ea lithethefatsi tse tloaelehileng tsa Parkinson e ea ho batho ba bangata, 'me ho laola matšoao ho ba thata ho fokotsa.
Haholo-holo, ho batho ba nang le lefu la Parkinson la nako e khutšoanyane, ho fetoha ha motlakase kapa mekhoa ea mesifa e sa ikhethang (dyskinesia le leqhoa ) e qala ho lema.
Dyskinesia e tsejoa ka ho fetisisa ho batho ba nkang levodopa mme ke phello e mpe ea phekolo ea lithethefatsi. Pontšo ea bodes ea dyskinesia hampe mabapi le ho phatlalatsoa ke mafu 'me ka ho loketseng e lokela ho lieha halelele kamoo ho ka khonehang. Ho feta moo, matšoao a se nang motlakase, a kang 'dementia' , ho tepella maikutlong, le ho hlophisa likokoana-hloko, tse sa ameheng haholo ke lithethefatsi tsa dopaminergic, hape li fetoha bothata.
Bakuli bao ba fanang ka ts'oaetso ka mor'a phekolo e lekaneng e ntseng e nka nako e itseng ho thata ho e tšoara ka feshene e bolokang ho tsamaea le boleng ba bophelo.
Ka mantsoe a mang, hang ha levodopa e khaotsa ho sebetsa, ka karolo e itseng hobane ha re utloisise bothata ba phoso ena, ho thata ho khutlisetsa batho sethaleng se tsitsitseng le boleng ba bophelo bo fetileng nakong ea lefu ha levodopa le li-agent tse ling tsa dopaminergic ba ne ba sebetsa.
Ho feta moo, esita le haeba mathata a likoloi a kenngoa, mathata a se nang motlakase joaloka mathata a mehopolo, mathata a ho robala le 'dementia' a ba khathatsang ho ba nang le lefu la Parkinson le leng le le leng.
Ka bomalimabe, re ke ke ra bolela esale pele hore na ke batho ba nang le lefuba la Parkinson la nakong e tlang ba tla hlahisa liphetoho le mathata a likoloi. Ka kakaretso, nako ea lefu, maloetse a bophelo, nako e telele ea phekolo le levodopa, levodopa dosage, tekano, le boima ba 'mele kaofela li lumela hore li phetha karolo ea ho qetella ho lefshoa.
KA Linako le Off Times
"KA nako" e bolela linako tseo meriana e sebetsang ka ho lekaneng 'me matšoao a lefu la Parkinson a laoloa.
"Nako ea nako" e bolela linako tseo meriana e khathetsoang ka eona 'me matšoao a Parkinson, a kang ho thothomela, ho tsitsisa, le ho thatafalloa ho tsamaea ho khutla hape.
Ho eketsoa ha safinamide ho mefuta ea lithethefatsi ea batho ba nang le lefu la Parkinson le tsoetseng pele ho nka levodopa ho eketsa nako ea ON le ho fokotsa nako ea nako.
Safinamide Clinic Trials
Liphello tse tsoang litsing tse peli tsa lits'ebeletso tsa bongaka li bontšitse melemo ea ho sebelisa safinamide har'a batho ba nang le lefu la Parkinson le tsoetseng pele. Barupeluoa bana ba ne ba fumanoe ba e-na le boloetse ba Parkinson lilemo tse tharo kapa tse hlano.
Teko ea pele ea bongaka e ile ea hlahloba barupeluoa ba 669 ba fokolang motlakase. Barupeluoa bana ba amohetse safinamide ho phaella ho meriana e meng ea antiparkinson kapa placebo (ha ho safinamide) le meriana e meng ea antiparkinson.
Karolelano KA nako ea barupeluoa e ne e le pakeng tsa lihora tsa 9.3 le 9.5. Ka mor'a likhoeli tse tšeletseng tsa teko, KA linako tse ling li eketsehile ka lihlopha tse peli tsa bakuli; leha ho le joalo, KA linako tse ling ho ne ho e-na le metsotso e ka bang 30 ho ba nkang safinamide.
Ka mor'a lilemo tse peli tsa phekolo, ka karolelano nako e ntse e lula e tšoana ho ba nkang safinamide empa ba fokotseha ho ba nkang sebaka sa bolulo. Kahoo ka mor'a lilemo tse peli ka karolelano, barupeluoa ba nkang safinamide hammoho le levodopa hammoho le meriana e meng ea antiparkinson ba na le nako e le 'ngoe ea phekolo ea phekolo ea lefu la Parkinson.
Ka hloko, safinamide e fokotsoe nako e ka bang metsotso e 35. Hopola hore linako tse fokolang li bua ka linako tseo lithethefatsi tsa antiparkinson li aparetseng, 'me matšoao a kang tšisinyeho a boetse a mpefala.
Ntle le ho lelefatsa ka linako le ho khutsisa linako, OFFSIDE e boetse e ntlafalitse ho tsamaea (motlakase) ho ba e nkang. Ho feta moo ka tekanyo e phahameng, safinamide e boetse e thusitse mesebetsing ea bophelo ba letsatsi le letsatsi le boleng ba bophelo.
Ka ho ts'oanang le liphello tsa teko ea bobeli, e kenyeletsang barupeluoa ba 549, ho fana ka maikutlo a keketseho ea nako ka nako e ka bang hora e le 'ngoe ho ba nkang safinamide ha bapisoa le ba ntseng ba nka placebo hammoho le ho fokotsa nako ea OFF. Ho phaella moo, ntlafatso ea ts'ebetsong le boleng ba liketsahalo tsa bophelo le tsona li ile tsa hlokomeloa.
Safinamide Negative Side Effects
Ka lebaka la litla-morao tse mpe, karolo ea 3.7 lekholong ea barupeluoa ba nkang safinamide ba tsoa litsing tsa lits'oaelo ha ba bapisoa le liphesente tse 2,4 tsa ba ntseng ba nka placebo.
Litholoana tse tloaelehileng tse mpe tse fumanoang nakong ea liteko tsena tsa meriana li kenyeletsa tse latelang:
- mekhoa e meholo kapa e arohaneng (ie, dyskinesia)
- oa oa
- ho nyekeloa ke pelo
- ho hlobaela
Bakeng sa matšoao ana, dyskinesia e ne e batla e tloaelehile ho batho ba nkang safinamide ha ba bapisoa le ba sa e sebeliseng (ke hore, ba ntseng ba nka placebo).
Liphello tse sa tloaelehang empa tse tebileng haholo li kenyeletsa tse latelang:
- ho mpefatsa khatello ea mali e phahameng
- ho bonts'a maikutlo le mokhoa oa kelello
- ho robala motšehare
- serotonin lefu (ha le sebelisoa le MAO inhibitors, li-anti-depressants le li-opioids)
- mathata a nang le tšusumetso kapa ho qobella (nahana ka OCD)
- feberu le pherekano
- mathata a retin
Mona ke lithethefatsi tse ling tseo u sa lokelang ho li nka ha u nka safinamide:
- li-anti-depressant (serotonin-norepinephrine reuptake inhibitors, tricyclics le tetracyclic)
- cyclobenzaprine
- dextromorphan (e fumanoang meriana e itseng ea ho khohlela)
- li-opioids
- Mokhoakho oa St. John's
Le hoja batho ba nang le ho holofala ha liphio ba ka nka safinamide, ba nang le mathata a matla a sebete ha baa lokela ho nka lithethefatsi.
Ntho e ka tlaase
Safinamide e thusa haholo ho ba nang le lefuba la Parkinson le leng le le leng la nako e khutšoanyane le ba fokotsang ho fetoha ha meriana (ie, dyskinesia) le ho fokotseha ha meriana ea bona (e leng, OFF linako). Safinamide e ka ba phekolo e ntlafetseng ea phekolo ea mantlha le levodopa ho feta mefuta e meng ea phekolo, ho akarelletsa le ma-inhibite a mang a MAO-B hammoho le li-inhibitors tsa COMT. Safinamide e ka boela ea sebelisoa hammoho le levodopa le lithethefatsi tse ling tsa antiparkinson. Safinamide ha e sebelisoe e le mong.
Sepheo se seholo ka ho fetisisa sa phello ea safinamide ke dyskenesia, kapa keketseho ea mekhatlo e ikemetseng. Batho ba nang le mathata a matla a sebete kapa ba nang le ts'oaetso e itseng ea meriana kapa meriana e meng ha baa lokela ho nka safinamide.
> Mehloli:
> Chaplin, S. Safinamide: Phekolo ea ho eketsa mafu a Parkinson. Prescriber. 2016.
> FDA e lumella lithethefatsi ho tšoara maloetse a Parkinson. La 21 March, 2017. www.fda.gov.
> Jenner, P. Tlhokomelo ea Mekhahlelo ea Mor'a Parkinson ea morao-rao - Tsela ea ho ea litlhaselong tsa meriana hona joale le nakong e tlang. Phetolelo ea Neurodegeneration. 2015; 4: 3.
> Jankovic, J, le Aguilar, LG. Mokhoa o teng hona joale oa Phekolo ea Mafu a Parkinson. Maloetse le Phekolo ea lefu la Neuropsychiatric. 2008; 4 (4): 743-757.
> Schapira, AH, le al. Tlhahlobo ea Tšireletseho le Ts'ebetso ea Safinamide e le Levodopa e Phethehileng ho bakuli ba nang le mafu a Parkinson le ho fokotseha ha motlakase. JAMA Neurology. 2017; 74 (2): 216-224.