Jakafi inomirira paradigm yekufambira mberi mune pharmacology.
Tiri kurarama munguva dzinoshamisa apo isu tisinganzwisisi zviri nani zvirongwa zvezvirwere asiwo maitiro ekutsvaga nzira idzi nemishonga inongobva kuwanikwa. Semuenzaniso, Jakafi (ruxolitinib) akava dhiyabhorosi yekutanga yeAIDS yaakagamuchirwa kurapa polycythemia vera , uye inoshanda kuburikidza nekudzivisa maitiro enyama Janus Associated Kinase 1 (JAK-1) naJanus Associated Kinase 2 (JAK-2).
Pamwe pamwe nedzimwe shanduko dzinoshanduka, ma enzyme anoenda haywire kune vanhu vane polycythemia vera.
Chii Chinonzi Polycythemia Vera?
Polycythemia vera chirwere chisingawanzovi ropa. Iyo chirwere chinonyangadza chinowanzopa zviitiko gare gare muupenyu (vanhu vari mumakore avo makumi matanhatu nemakumi matanhatu) uye pakupedzisira zvinokonzera thrombosis (funga kurwisa) mune chetatu chevanhu vose vanobatwa. Sezvo isu tose tinoziva, kurohwa kunogona kuurayisa saka kuongororwa kwePV kwakakosha zvikuru.
Nhau yekuti PV inotanga basa sei mumapfupa emapfupa. Nemafupa edu ane basa rekuita masero edu eropa. Mhando dzakasiyana dzemasero eropa mumuviri wedu dzine mabasa akasiyana. Masero matsvuku eropa anounza okisijeni kumatumbu edu uye nhengo, masero eropa ropa anobatsira kurwisana nehutachiona uye maplatelets anomira kubuda ropa. Mune vanhu vane PV, pane kuchinja mumasero ematokari akawanda anokonzera kubudiswa kwakanyanya kwemasero matsvuku eropa, masero eropa, uye maplatelets. Mune mamwe mazwi, muPV, masero emagetsi, anoshandura mumasero matsvuku eropa, masero machena eropa, uye maplatelet, anokandwa muhuwandu.
Kuwanda kwechinhu chero chipi zvacho hachisi chakanaka, uye munyaya yePV, masero akawanda eropa anogona kuvhara mishonga yedu yeropa inokonzera mhando dzose dzezvinetso zvekliniki kusanganisira zvinotevera:
- headache
- kushaya simba
- pruritis (itching iyo inowanzopa mushure mushure mekushisa mvura kana kugeza)
- chizoro
- sweating
- thrombosis kana kuwedzerwa ropa (clots clots) inogona kuvhara arteri uye inokonzera kushungurudzika, kurwadziwa kwemoyo, uye kuputika kwemapurmoni, kana mishonga yevhavha yakadai seyamapapiro anopa chiropa anokonzera kukuvadza kwechiropa.)
- kubuda ropa (Kwakawanda masero eropa-akawanda ayo ane mapurogiramu asina kukwana-anogona kukonzera kubuda ropa)
- splenomegaly (The spleen, iyo inosvina masero matsvuku eropa, kurira nekuda kwekuwedzera kwemajeri eropa muPV.)
- erythromelalgia (kurwadza uye kushambidzwa mumakadhi kunokonzerwa nemaplatelets akawanda asingadi ropa rinoputika muminwe uye zvigunwe zvinogona kuita kuti uwane kufa uye kutorwa.)
PV inogona kukonzerawo zvimwe zvirwere zvakadai sechironi chepfungwa uye kupemha kwepenemenhesi mbiri nekuda kwekuwedzera kwemajeri eropa kushambira kwekupararira uye kusakara kwemishu hyperplasia kana kukura kunowedzera kukonzera ropa. (Smooth muscle inogadzira masvingo emidziyo yedu yeropa, uye nhamba yakawedzerwa yemasero eropa zvichida inounza zvimwe zvinhu zvinokura zvinokonzera kusvibiswa kwemisvi kuti zvive.)
Vanhu vashomanana vane PV vanoenderera mberi kukudziridza myelofibrosis (apo fupa remafu rinoshandiswa kana kuti "rakapera" uye rakazadzwa kusina basa uye kuzadza-kufanana ne-fibroblasts inoita kuti chirwere chemahyamu chiwedzere) uye pakupedzisira kunyange yakaoma houkemia. Ramba uchifunga kuti PV inowanzotumidzwa semyeloproliferative neoplasm kana kenza nokuti seimwe marariya inokonzera kuwedzera kwechirwere mumatare esero. Zvinosuruvarisa, kune vamwe vanhu vane PV, chirwere chinokonzerwa neukemia chinomiririra kuguma kwemutsara pakuenderera mberi kwekenza.
Jakafi: Mishonga Inobatanidza Polycythemia Vera
Vanhu vari muchikwata chePV chechipiri kana chikamu chinoratidzwa nehuwandu hwemajeri eropa zvinorapwa nekupindira kwepamusoro kunoderedza zviratidzo uye kuvandudza hupenyu hwehupenyu. Nyaya inonyanya kuzivikanwa pakati pezvirapa izvi zvichida phlebotomy kana kubuda ropa kuderedza ropa masero.
Nyanzvi dzinobatawo PV ne myelosuppressive (funga chemotherapeutic) ma-agents-hydroxyurea, busulfan, 32p uye, munguva pfupi yapfuura, interferon-iyo inodzivisa kuwedzera kwekushandiswa kwemasero eropa. Myelosuppressive treatments inowedzera pfungwa yemurwere wehupenyu uye inofungidzirwa kubatsira vanhu vane PV kurarama kwenguva refu.
Zvinosuruvarisa, mamwe emishonga iyi seyakadai sechlorambucil inotakura njodzi yekukonzera chirwere cheukwepa.
Kune vanhu vane PV vane dambudziko rekushivirira kana kuti vasingateereri hydroxyurea, mutsara wokutanga myelosuppressive agent, Jakafi yakagamuchirwa neDFA munaDecember 2014. Jakafi inoshanda nekudzivisa JAK-1 neJAK-2 enzyme inotamirwa nevanhu vakawanda nePV. Izvi zvinokonzerwa neropa uye kushandiswa kwemunyanzvi, zvirongwa zvisingawanzoitiki kuvanhu vane PV.
Mune 21 kubva muzana yevanhu vasingafariri kana vasingateereri hydroxyurea, zvidzidzo zvinoratidza kuti Jakafi inoderedza ukuru hwepleen (inoderedza splenomegaly) uye inoderedza kudiwa kwephlebotomy. Kutsvakurudza kunoratidza kuti kunyange neine nzira dzakanakisisa dzokurapa dzinowanikwa, 1 muzana chete yevanhu vakadai vangadai vakawana rubatsiro rwakadaro. Nyaya iyi, Jakafi yakanga yambotenderwa neDDA yekurapa myelofibrosis muna 2011. Migumisiro yakaipa yakawanda yeJakafi (iyo FDA inonyatsoreva "migumisiro") inosanganisira anemia, pasi peplateti yezviverengero, chizuru, kuvimbiswa, uye shingles.
Izvo zvinofanira kuonekwa kuti sezvakaitika kune mamwe myelosuppressive treatments, hazvisi pachena kana Jakafi achabatsira vanhu kurarama kwenguva refu.
Kana iwe kana mumwe munhu waunoda ane PV iyo isingapinduri kune hydroxyurea, Jakafi inomirira mushonga mutsva unovimbisa. Kune isu tose, Jakafi inomiririra paradigm yemishonga yakawanda yemishonga ichagadziridzwa kuenda mberi. Vatsvakurudzi vari kuve nani pakutsvaga chaiwo nzira iyo inoshungurudzwa nezvirwere uye inotarisana nehutachiona ichi.
Sources:
"Utachiona hwemyeloproliferative neoplasms: rini, iyo inyanzvi, uye sei?" neHL Geyer uye RA Mesa rakabudiswa muRopa musi wa12/4/2014.
Prchal JT, Prchal JF. Chitsauko 86. Polycythemia Vera. Muna: Lichtman MA, Kipps TJ, Seligsohn U, Kaushansky K, Prchal JT. eds. Williams Hematology, 8e . New York, NY: McGraw-Hill; 2010.