Ke eng eo U ka e khonang le eo u ke keng ua e nka ha u ntse u sebelisa Tamoxifen
Haeba o laetsoe tamoxifen bakeng sa kankere ea matsoele , mohlomong u utloile hore e ka sebelisana le meriana e meng. Kaha litšebelisano tsena li akarelletsa lithethefatsi tse sebelisoang hangata 'me li kenyelletsa li-suppress-over-the-counter le phepo e nepahetseng, sena ke sa bohlokoa haholo. Ho phaella moo, mohlomong u tla noa meriana bakeng sa bonyane lilemo tse 5 ho isa ho tse leshome, ho etsa hore u lemohe ka likamano tse khonehang eseng feela kameho ea nakoana.
Hape ho na le batho ba bang, ka lebaka la liphatsa tsa lefutso, ha ba ruele molemo ntle le hore tekano e phahameng e sebelisoe. U hloka ho tseba eng?
Matsoho a Tamoxifen
Tamoxifen e na le mesebetsi e meraro e ka sehloohong:
- E atisa ho sebelisoa e le phekolo ea meriana ea basali ba nang le kankere ea matsoele ea pele-pele e leng methapo ea estrogen e ntle le bao e leng li-premenopausal. Boemong bona, ho ka fokotsa kotsi ea ho khutla ka karolo ea 50 lekholong. E boetse e fokotsa menyetla ea ho hlahisa kankere ea bobeli ka lesea le ammeng (haeba u ne u e-na le lumpectomy) kapa ka letsoeleng la hao le leng.
- Tamoxifen e sebelisetsoa basali le banna ba nang le kankere ea matsoele ea metastatic e fumanoang ke estrogen receptor e ntle le e sa hanyetsanang le lithethefatsi.
- Tamoxifen e ka boela ea sebelisoa e le phekolo ea thibelo ho basali ba nang le kotsing e phahameng ea ho ba le kankere ea matsoele. Boemong bona, ho ka fokotsa kotsi ea basali ea ho tšoaroa ke kankere ea matsoele ka halofo.
Mokhoa o tloaelehileng ka ho fetisisa ke 20 mg ka letsatsi ka lilemo tse 5 ho isa ho tse 10.
(Batho bao e leng bo-postmenopausal kapa ba fumanoeng phekolo ea phekolo ea mahe a 'mele ba ka fetisetsoa ho aromatase inhibitor ho e-na le hoo).
Ithute haholoanyane karolo ea estrogen ka kankere ea matsoele le mekhoa ea phekolo ea hormone e fumanehang.
Kamoo Tamoxifen e Phelang Kateng Mmele oa Hao
Tamoxifen e hloka ho robeha 'meleng oa hao ka mokhoa o sebetsang.
"Metabolite" ena ke endoxifen mme ke motsoako o sebetsang ho thibela ho pheta-pheta.
Tamoxifen e robehile ho endoxifen ke enzyme ea Cytochrome P450 CYP2D6. (Ho boetse ho na le lik'hemik'hale tse ling tse kang CYP3A4 le tse ling, empa CYP2D6 e ka 'na ea e-ba ea bohlokoa ka ho fetisisa). Ntho efe kapa efe e fokotsang ts'ebetsong ea enzyme ena (CYP2D6) e ka fella ka palo e fokotsehileng ea metabolite e sebetsang, mme kahoo, ha e fane molemo. Mosebetsi o fokotsehileng oa enzyme o ka 'na oa etsahala haeba u noa meriana e meng kapa haeba u na le mefuta e itseng ea liphatsa tsa lefutso tse etsang hore enzyme e se ke ea sebetsa haholo.
Endoxifen, sehlahisoa se senyehileng, se sebetsa ka makhetlo a mararo ho isa ho a 100 ho thibela ho hōla ha cello ea estrogen ho feta tamoxifen, 'me ke molao-motheo o ikarabellang bakeng sa liphello tsa tamoxifen. U ka utloa tamoxifen e bitsoa "pro-drug" ka lebaka lena.
Lebaka Leo ho ka Khonehang ho Sebelisana le Lithethefatsi
Lebaka la hore ho utloisisa metabolism ea tamoxifen ke ea bohlokoa ke hore ho na le meriana e meng e mengata e amanang le enzyme ea CYP2D6. Lithethefatsi tse ling li thibela matla a enzyme e le hore ho se ke ha e-ba le endoxifen e nyenyane ha e etsoa ka tamoxifen. Ha e le hantle, ho tla tšoana le ha u sa ka ua nka lithethefatsi.
Meriana e amang enzyme ena e kenyelletsa e tloaelehileng ho basali ba tšoeroeng ke kankere ea matsoele, ba nang le bothata ba ho imeloa kelellong le esita le mefuta e tloaelehileng ea meriana le mefuta e meng ea phekolo.
Tlhahisoleseding e mabapi le likamano tsena e ncha (tamoxifen e ile ea amoheloa ka 1998, empa litšebelisano ha lia ka tsa tsejoa ho fihlela hamorao) 'me lithuto li ntse li tsoela pele ho sheba taba ena ka botebo bo tebileng. Hoa tsebahala hore liphuputso tsa morao-rao li fumane hore tekanyo ea vithamine ea hau e ka amahanngoa le katleho ea tamoxifen le hore maemo a endoxifen a atisa ho phahama haholo likhoeling tsa lehlabula. Kaha ho 'nile ha e-ba le liphuputso tse bontšang hore vithamine D e ka thusa ho loantša kankere ea matsoele , sena ke khopotso ea ho etsa hore oncologist ea hao a hlahlobe lebelo la hao la vithamine D haeba u e-s'o etse sena.
Litšebelisano tse ka 'nang tsa e-ba teng lithethefatsi ho Tamoxifen
Ka tlase re thathamisa meriana e mengata e ka sebelisanang le tamoxifen. Taba ke hore lithethefatsi tsena li ka fokotsa katleho ea tamoxifen empa e etsa joalo likarolong tse fapaneng. Lithethefatsi tse ling li na le methapo e matla haholo ea CYP2D6, ha tse ling li thibela enzyme hore e be likhato tse nyane. Lethathamo lena ha le feletse mme meriana e meng e sa sebelisoang haholo e ka sebelisana le tamoxifen hape. Ka kopo bua le oncologist le setsebi sa meriana ka meriana leha e le efe ea meriana, meriana e fetang e-counter, kapa phepo ea lijo e ntseng u nahana ha u ntse u le tamoxifen. Taba ea hore ho ka 'na ha e-ba le linako tseo melemo ea ho sebelisa e' ngoe ea lithethefatsi tsena e ka fetisisang kotsi ea ho fokotsa maemo a hau a endoxifen. Ho tseba, leha ho le joalo, ho ka u thusa hore u botse ngaka lipotso tse nepahetseng.
Meriana e lokelang ho qojoa ka tamoxifen e kenyelletsa:
- Selectional serotonin uptake inhibitors (SSRIs) : Prozac (fluoxetine) le Paxil (paroxetine) ke matla a inhibitors a CYP2D6. Luvox (fluvoxamine), Celexa (citalopram), Lexapro (escitalopram). 'me Zoloft (sertraline) e boetse e thibela enzyme e itseng. Ho ka etsahala hore likamano tsena li bakoa ke kotsi e eketsehileng ea lefu e fumanehang ho basali ba nkang Paxil.
- Selectional serotonin / norepinephrine reuptake inhibitors (SNRIs) : Effexor (venlafaxine), Pristiq (desvenlafaxine)
- Wellbutrin le Zyban (bupropion) : Ba sebelisetsoa ho tepella le ho khaotsa ho tsuba
- Tricyclic ho tepella maikutlo: Anafranil (clomipramine) le Norpramin (desipramine)
- Meriana ea endocrine : Sensipar (cinacalcet), Parlodel (bromocriptine), le Parnate (tranlcypromine)
- Mefuta e mengata ea antipsychotics e kang Mellaril (thioridazine), Trilafon (perphenazine), Orap (pimozide), le Thorazine (chlorpromazine) le li-antipychotic atypical tse kang Risperdal (risperidone), Clozaril (clozapine), Geodon (ziprasidone) le Seroquel (quetiapine)
- Meriana ea pelo : Cardioquin (quinidine), Ticlid (ticlopidine), Cardene (nicardipine)
- Antihistamines : Benadryl (diphenhydramine)
- Li-antibiotics : Rifampin e ka fokotsa boholo ba tamoxifen, isoniazid (e sebelisetsoang lefuba).
- Meriana ea Reflux : Tagamet (cimetidine)
- Li-antifungals : Hangata li sebelisoa bakeng sa maemo a maoto a moatlelete, ho tinea versicolor, ho hlahisa fungus, Lamisil ea lithethefatsi kapa Terbinex (terbinafine) ha ea lokela ho sebelisoa le tamoxifen, le hoja lithethefatsi tsena li sa kenyelletsoa lethathamong le lengata la lithethefatsi ho qoba.
- Meriana ea lefu la tsoekere: Actos (proglitazone)
- Meriana ea lefu la Parkinson : Requip (ropinirole)
- Meriana ea HIV / AIDS : Tse 'maloa
- Tse ling : Neurontin (gabapentin)
- Li-vithamine : Mafura a vithamine E a phahameng a ka sebelisana le tamoxifen
- Litlhoko tsa phepo e nepahetseng : Ha re na lithuto tse kholo tse shebang ho sebelisana ha litlama tse tlatsang le tamoxifen. Lisebelisoa tse nang le matla a matla a thibelo ea CYP2D6 ka laboraka li akarelletsa skullcap, lemon balm, echinacea le ginseng. Ka bongata bo bongata, ts'ebetso ea tee e tala e ka eketsa tekanyo ea tamoxifen maling, empa mohlomong ha hoa lekana ho baka matšoao a kliniki. Haeba u rerile ho sebelisa leha e le efe ea litlama e tlatsetsa ke habohlokoa ho bua le oncologist ea hau.
Mekhoa e meng: Meriana e ka 'Nang ea Sebetsoa ho E-na le Eona
U ka 'na ua ipotsa hore na u ka nka eng haeba u sebelisa tamoxifen:
- Ho tepella maikutlo ho fapana ho fapana le hore na ba ama tsela efe ea CYP2D6 ea enzyme. Cymbalta (duloxetine) e bonahala e thibela likarolo tsa CYP2D6 tlase ho tse ling tse ngata tsa ho imeloa kelellong. Meriana e boletsoeng ka holimo tlas'a "lithethefatsi tseo u lokelang ho e qoba" e fapane haholo ka tekanyo eo e thibelang matla a enzyme ka eona. Liphuputso tsa morao-rao li bontša hore tse ling tse fokolang ka matla li ka 'na tsa sireletseha ho sebelisoa le tamoxifen, empa lithuto tsa mehleng ena li sa tsejoe mabapi le hore na sena se ka' na sa e-ba le phello ea kliniki.
- Meriana ea mafu a phofo le a batang: Meriana e mengata ea batang e na le meriana e le 'ngoe feela, kahoo ke habohlokoa ho bala mangolo. Palo e kholo ea ho etsoa ka holim'a li-cold le feberu e na le Benadryl. Lithethefatsi tse kang tsa Zyrtec le Claritin li nahanoa hore li bolokehile ho sebelisoa le tamoxifen.
- Meriana ea reflux ea acid e ka 'nang ea e-ba e loketseng e akarelletsa Zantac (ranitidine) le tse ling.
Kamehla re ithuta ho eketsehileng ka litšebelisano tsa meriana 'me ke habohlokoa ho bua le oncologist le setsebi sa metsoako ka lithethefatsi leha e le life tseo u lakatsang ho li sebelisa hammoho le tamoxifen.
QT Prolongation
Haeba o shebile sephutheloana sa hao se o tsebang u ka 'na ua hlokomela hore tamoxifen ha ea lokela ho sebelisoa le meriana e meng e fokotsang nako ea QT. Nako ea QT e bua ka nako ea lipakeng tsa maqhubu a mabeli a bonngoeng ho electrocardiogram. Ho nahanoa hore haeba nako ea QT e nka nako e telele, e phahamisa kotsi ea pelo e sa tloaelehang, 'me mohlomong, lefu la tšohanyetso.
Boitsebiso ba liphutheloana bo lemosa hore tamoxifen e ka fella ka ho fokotsa ha QT ha e sebelisoa hammoho le lithethefatsi tse ling tse ka etsang hore nako ea QT e atolohe. Tlhahlobo ea 2017 ea liphuputso, leha ho le joalo, e bolela hore ho na le monyetla oa ho ba kotsi e tlaase ea kholiso ea QT ea bohlokoa khoeling ena, haholo-holo ka 20 mg feela ka letsatsi.
The Genetics of Tamoxifen le CYP2D6 Ho hlahloba
Ho na le liketsahalo tse ngata tsa enzyme ea CYP2D6, 'me sena se baka phapang pakeng tsa metabolism ea lithethefatsi. Phuputso ea lipatlisiso li fumane hore metsolizers e mengata e bonahala e e-na le liphello tse molemo ho feta li-poorabolizers tse futsanehileng. Ka kakaretso, hoo e ka bang karolo ea 20 lekholong ea batho ba fokolitse tšebetso ea enzyme ena.
Joale u tseba joang hore e ka 'na eaba u futsanehile? Ho na le liteko tsa lits'ebetso tsa liphatsa tsa lefutso tsa genotyping tse fumanehang bakeng sa genotyping ea CYP2D6, empa tlhahlobo ena ha e tloaelehe bakeng sa basali tleleniking ea tamoxifen bakeng sa kankere ea matsoele ea moriana oa poso ea estrogen. Ka mantsoe a mang, mohlomong u ke ke ua tseba. Hona ke sebaka sa khang hape, 'me bafuputsi ba bang ba lumela hore ho ba le enzyme e' ngoe, CYP3A4 * 22 e ka lefella ho fokotseha ha maikutlo a endoxifen a amanang le mosebetsi o tlaase oa CYP2D6.
Hape, re lokela ho hlokomela hore mosebetsi oa CYP2D6 o atisa ho ba o phahameng likhoeling tsa lehlabula (ho itšetlehile ka vithamine D ho isa tekanyo e itseng), le ho hlahlojoa ke vithamine D ke habohlokoa ho basali ba phelang le kankere ea matsoele.
Tlhaloso ea Tamoxifen Lithethefatsi tsa Meriana
Tamoxifen ke meriana eo basali ba e etsang letsatsi le leng le le leng ka nako e telele ka mor'a hore ba fumane lefu la kankere ea matsoele. Ha e nkoa e laoloa, e ka fokotsa kotsi ea ho khutlela morao (mme hamorao, lefu). Ka hona, ho utloisisa ho khoneha ho kopana ho bohlokoa haholo.
Litšebelisano tse ling tsa lithethefatsi li ka 'na tsa e-ba bonolo, athe lithethefatsi tse ling li ka' na tsa batla li hlokomoloha liphello tsa tamoxifen ha li nkoa ka nako e le 'ngoe. Sena se 'nile sa bontšoa eseng feela ka laborateng e shebileng metabolism ea lithethefatsi tsena, empa e bonoa setsing sa kliniki ka palo ea lefu la basali ba ileng ba nka Paxil hammoho le tamoxifen.
Boitsebiso bo bocha bo fihla holimo (joalo ka boitsebiso ba vithamine D bo boletsoeng ka holimo). Tsoelo-pele ena e potlakileng ea meriana ea kankere e etsa hore e be ea bohlokoa ho feta leha e le neng pele hore e be ' muelli oa hau ka tlhokomelo ea kankere , Phuputso e bontšang ntlha ena ke eona e shebileng basali ba nkang tamoxifen nakong ea nako ho tloha ka 2005 le 2010 (ka mor'a hore re tsebe tsa tse ling tsa litšebelisano tsena). Ka nako eo, Paxil e ne e le e 'ngoe ea li-anti-depressing tse tloaelehileng ka ho fetisisa bakeng sa basali ba tamoxifen. Leha ho le joalo, ho ameha ho hongata ke hore litokisetso tse ngata ho feta tse ling li ka sebelisana le tamoxifen, e siea batho ba le bang ho lemoha likamano tsa lithethefatsi.
> Mehloli:
> Antunes, M., Timm, T., de Oliveira, V. et al. Tšusumetso ea CYP2D6 le CYP3A4 Phenotypes, Meriana ea Lik'hamphani le Meriana ea Vithamine D le Tamoxifen Biotransformation. Tlhahlobo ea Litlhare Tsa Meriana . 2015. 37 (6): 733-44.
> Juurlink, D. Ho tsosolosa ho kopana ha lithethefatsi Pakeng tsa Tamoxifen le SSRI ho loantšana le mafu. BMJ . 2016. 354: i5309.