Icatibant Acetate

Angiotensin-converting enzyme inhibitors (ACEIs) yog thawj zaug- cov tshuaj tiv thaiv kab mob ntshav siab tau siv dav hauv kev kho mob, thiab kuj tau qhia rau kev kho mob tom qab- myocardial infarction, plawv tsis ua hauj lwm, ntshav qab zib mellitus, kab mob raum thiab lwm yam kab mob. Kwv yees li 35 txog 40 lab tus neeg mob thoob ntiaj teb tam sim no tau txais kev kho ACEI. Txawm li cas los xij, muaj qhov tshwm sim tsis zoo tshwm sim hauv lawv qhov kev siv tshuaj kho mob -angioedema. Txawm hais tias nws qhov tshwm sim tsawg (kwv yees li 0.1% ~ 0.5%), nws muaj qhov pib mob hnyav thiab tuaj yeem cuam tshuam rau lub ntsej muag, daim di ncauj, lub ntsws thiab lwm qhov chaw. Laryngeal edema, tshwj xeeb tshaj yog, tuaj yeem cuam tshuam txoj hlab pa sai, ua rau lub cev tsis muaj zog thiab hem cov neeg mob lub neej.

Lub hauv paus pathogenesis ntawm ACEI-induced angioedema yog ze ze rau qhov txawv txav bradykinin metabolism: ACEIs inhibit qhov kev ua ntawm angiotensin- hloov enzyme, uas kuj ua hauj lwm rau degrade bradykinin. Qhov kev txwv no ua rau qhov nce siab ntawm bradykinin hauv lub cev. Ntau dhau ntawm bradykinin khi rau B₂ receptors nyob rau saum npoo ntawm vascular endothelial hlwb, ua rau muaj zog vascular permeability thiab plasma extravasation, thiab thaum kawg ua rau hauv zos edema. Txij li thaum hom edema no yog bradykinin - kho, cov tshuaj antihistamines thiab glucocorticoids muaj cov teebmeem kev kho mob tsis zoo, thiab muaj qhov xav tau kev kho mob sai rau cov tshuaj kho mob.

Raws li kev xaiv antagonist ntawm bradykinin B₂ receptor,Icatibant Acetatetuaj yeem thaiv qhov kev khi ntawm bradykinin rau B₂ receptors thiab inhibit qhov tshwm sim thiab kev loj hlob ntawm edema los ntawm cov kab mob hauv paus, yam tsis muaj kev cia siab rau kev tshem tawm cov metabolism ntawm ACEIs. Nws yog li ntawd muaj qhov sib txawv ntawm kev kho mob zoo thiab xav tias yuav dhau los ua thawj - kab mob tus neeg sawv cev rau ACEI-induced angioedema, tshwj xeeb tshaj yog tsim nyog rau kev cuam tshuam sai rau hauv qhov xwm txheej ceev, sau qhov sib txawv ntawm qhov kev kho mob ntawm qhov tsis zoo tshwm sim. Tsis tas li ntawd, nws txoj kev txhaj tshuaj subcutaneous yooj yim tuaj yeem pib ua haujlwm sai, ntxiv dag zog rau nws.

Kev mob hawb pob yog ib hom kab mob ua pa ntev ntev nrog cov kab mob sib txawv, cuam tshuam nrog ntau yam xws li kev ua pa ntawm lub ntsws, tso tawm cov kab mob inflammatory, thiab kev tiv thaiv kab mob. Nyob rau hauv xyoo tas los no, cov kev tshawb fawb tau pom tias bradykinin, uas yog ib qho tseem ceeb inflammatory mediator, plays lub luag hauj lwm tseem ceeb nyob rau hauv lub pathogenesis ntawm mob hawb pob: theem ntawm bradykinin nyob rau hauv bronchoalveolar lavage kua ntawm cov neeg mob hawb pob yog ho nce, thiab nws cov concentration yog zoo correlated nrog rau qhov mob hnyav ntawm txoj hlab pas.

Bradykinin khi rau B₂ receptors nyob rau saum npoo ntawm cov hlab ntsha ntawm cov leeg nqaij, cov qog nqaij hlav thiab cov hlwb inflammatory, ua rau cov leeg nqaij sib sib zog nqus, nce mucus secretion thiab inflammatory cell infiltration, uas ua rau txoj hlab ntsws nqaim, hawb pob, hnoos thiab lwm yam mob hawb pob. Nyob rau tib lub sijhawm, nws tuaj yeem txhim kho txoj hlab pa hyperresponsiveness thiab exacerbate kab mob rov tshwm sim.

Raws li cov txheej txheem saum toj no, cov khoom lag luam tuaj yeem thaiv bradykinin -kev kho mob hauv cov hlab ntsws inflammatory teb thiab cov hlab ntsws hyperresponsiveness los ntawm cov kev tawm tsam tshwj xeeb ntawm bradykinin B₂ receptor, thiab xav tias yuav dhau los ua cov tshuaj tshiab adjuvant rau kev kho mob hawb pob.In vitro kev sim thiab cov kev tshawb fawb tsiaj tau pib paub tseeb tias nws cov txiaj ntsig zoo: nyob rau hauv ib qho kev txhaj tshuaj ntawm npua guinea,Icatibant Acetatekoob tshuaj -nyob ntawm inhibited bradykinin-induced bronchoconstriction, txo pulmonary resistance thiab txhim kho lub ntsws ua raws.

Ib theem Ⅱ multicenter, ob npaug - dig muag, placebo- tswj kev soj ntsuam ntxiv tshawb nrhiav qhov ua tau zoo ntawm kev nqus cov khoom hauv cov neeg mob uas muaj mob hawb pob mus rau mob hawb pob. Txoj kev tshawb no tau tso npe rau 300 tus neeg mob hawb pob hnub nyoog 18 ~ 65 xyoo, uas tau muab faib ua peb pawg thiab tau txais 900 ug, 3000 ug nqus tau nws lossis cov placebo peb zaug hauv ib hnub rau 4 lub lis piam. Cov txiaj ntsig tau pom tias cov ntsuas kev ua haujlwm ntawm lub ntsws (piv txwv li, yuam lub ntim ntim hauv 1 thib ob [FEV1], qhov siab kawg ntws ntws [PEF]) hauv pawg khoom tau txhim kho nyob rau hauv ib koob tshuaj - nyob ntawm seb.

Hauv 3000 ug pab pawg, cov ntsuas kev ua haujlwm ntawm lub ntsws tau nce li ntawm 10% piv nrog cov placebo tom qab 4 lub lis piam ntawm kev kho mob (P<0.001). This improvement began to appear 1~2 weeks after the start of treatment, persisted until the end of treatment, and gradually declined after drug withdrawal, suggesting a definite anti-inflammatory effect of the drug.

Txawm hais tias txoj kev tshawb nrhiav pom tsis muaj txiaj ntsig zoo hauv kev txo cov qhab nia ntawm Asthma Control Test (ACT) lossis txo kev siv cov tshuaj cawm siav, kev txhim kho hauv lub ntsws ua haujlwm tseem ceeb rau nws daim ntawv thov hauv kev kho mob hawb pob.Tam sim no, kev tshawb fawb soj ntsuam ntawm kev mob hawb pob tseem tab tom ua, tsom mus rau kev tshawb nrhiav nws cov txiaj ntsig kho mob hauv refractory asthma thiab kev sib xyaw ua ke ntawm kev mob ntsws asthma. tshuaj.

Lub siab cirrhosis yog qhov kawg- kab mob siab nyob rau theem siab los ntawm ntau yam kab mob siab ntev, nrog cov kab mob tseem ceeb ntawm cov kab mob siab fibrosis thiab kev puas tsuaj ntawm cov kab mob hepatic lobule. Nws yog feem ntau nrog los ntawm cov teeb meem xws li portal hypertension, qhib kev sib koom ua ke thiab lub siab tsis txaus, uas cuam tshuam rau lub neej zoo thiab lub sijhawm muaj sia nyob ntawm cov neeg mob.

Nyob rau hauv xyoo tas los no, cov kev tshawb fawb tau pom tias cov metabolism tsis zoo ntawm cov tshuaj vasoactive xws li bradykinin ua lub luag haujlwm tseem ceeb hauv kev tshwm sim thiab kev loj hlob ntawm daim siab cirrhosis thiab nws cov teeb meem: nyob rau hauv cov neeg mob uas muaj daim siab cirrhosis, lub degradation muaj peev xwm ntawm bradykinin txo qis vim yog cov ntaub so ntswg puas. Nyob rau tib lub sijhawm, kev kub siab portal ua rau mob plab hnyuv thiab ua rau lub plab zom mov tsis zoo, thiab endotoxemia ua rau cov kab mob kallikrein -kinin system, uas ua rau muaj kev tso tawm loj ntawm bradykinin.

Bradykinin ntau dhau ua rau muaj kev kub ntxhov ntau ntxiv, ua rau splanchnic vasodilation thiab nce ntshav txaus, uas ua rau muaj kev pheej hmoo ntawm cov teeb meem xws li ascites thiab rupture ntawm esophagogastric varices. Lub caij no, bradykinin- kho cov lus teb inflammatory ua rau cov txheej txheem ntawm daim siab fibrosis thiab ua rau lub siab ua haujlwm puas tsuaj. Tsis tas li ntawd, bradykinin kuj tseem tuaj yeem cuam tshuam rau qhov tshwm sim ntawm lub raum kev ua haujlwm puas tsuaj rau cov neeg mob siab cirrhosis, ua rau muaj teeb meem loj xws li hepatorenal syndrome.

Los ntawm tshwj xeeb antagonizing lub bradykinin B₂ receptor, nws tuaj yeem tswj hwm qib bradykinin hauv lub cev thiab thaiv nws cov kev sib haum xeeb ntawm cov kab mob, yog li ua rau muaj txiaj ntsig zoo rau cov neeg mob uas muaj lub siab cirrhosis. Tam sim no, cov kev tshawb fawb tseem ceeb yog tsom rau kev sim tsiaj thiab kev tshawb fawb ua ntej: hauv cov tsiaj ua qauv ntawm daim siab cirrhosis, cov khoom kho tau txo qis portal siab, txo qis splanchnic ntshav txaus, txo cov ascites tsim, thiab ib txhij inhibited hepatic inflammatory teb thiab fibrogenesis, txhim kho hepatic thiab lub raum ua haujlwm.

Kev soj ntsuam ua ntej pom tau hais tias nyob rau hauv cov neeg mob uas muaj daim siab cirrhosis nyuaj nrog ascites, cov khoom kho mob sai sai ascites daws teeb meem, txo ascites ntim, thiab tsis pom muaj teeb meem tshwm sim.
Nyob rau hauv lub neej yav tom ntej, nrog rau kev sib sib zog nqus ntawm kev tshawb fawb, nws yuav tsum tau los ua ib tug adjuvant kho tus neeg saib xyuas rau cov teeb meem ntawm daim siab cirrhosis (xws li, ascites, portal hypertension), muab cov tswv yim tshiab thiab txoj kev kho mob siab cirrhosis, tshwj xeeb tshaj yog rau cov neeg mob uas tsis zoo teb rau cov pa kev kho mob. Nyob rau tib lub sijhawm, nws cov nyhuv inhibitory ntawm hepatic fibrosis kuj tseem tuaj yeem muab lub hom phiaj kho tshiab rau kev ncua kev loj hlob ntawm daim siab cirrhosis.