Yintoni onokuyenza kwaye ongenakukwazi ukuyisebenzisa ngexesha usebenzisa i-Tamoxifen
Ukuba unikwe i-tamoxifen yomhlaza wesifuba , mhlawumbi uye wakuva ukuba inokusebenzisana namanye amachiza. Ekubeni le ntsebenziswano ibandakanya iziyobisi eziqhelekileyo ezisetyenziswayo kwaye zibandakanya i-counter-counter-counter and nutrients supplements, oku kubaluleke kakhulu. Ukongeza, mhlawumbi uya kuthatha imithi ubuncinane ubuncinane kwiminyaka emi-5 ukuya kweyesi-10, ukunika ulwazi malunga nokusebenzisana okunokwenzeka kungekudala nje.
Kukho abantu abathile, ngenxa yokungafani kofuzo, abazuzekanga ngaphandle kokuba i-dose ephezulu yale mveliso isetyenziswa. Yintoni ofuna ukuyifumana?
Tamoxifen Uses
I-Tamoxifen inezinto ezintathu ezisisiseko:
- Kuqhelekileyo kusetyenziswa njengonyango oluxhasayo kubasetyhini abanomdlavuza webele we- esrogen owamkelekileyo kunye nabangama-foremenopausal. Kule ndlela, inokunciphisa umngcipheko wokuphindaphinda ngama-50 ekhulwini. Kwakhona kunciphisa amathuba okuphuhlisa umdlavuza wesibili kwibele echaphazelekayo (ukuba unayo i-lumpectomy) okanye kwenye yakho.
- I-Tamoxifen isetyenziselwa bobabini abasetyhini kunye nabesilisa abanomdlavuza webele we-metastatic receptor olungileyo kunye nabangenakuxhatshazwa kwisiza.
- I-Tamoxifen ingasetyenziselwa njengonyango lokukhusela kubasetyhini abanomngcipheko ophezulu wokuba nomhlaza wesibele. Kule ndlela, kunokunciphisa ingozi yabasetyhini yokuphucula umdlavuza webele.
Umlinganiselo oqhelekileyo ngowama-20 mg imihla ngemihla iminyaka emi-5 ukuya kwe-10.
(Abo ababa yi-postmenopausal okanye bafumene unyango lokunyanzelisa i-ovari banokuguqulwa kwi-aromatase inhibitor endaweni yoko).
Funda ngakumbi indima ye-estrogen kumdlavuza webele kunye neendlela zokwelapha ze-hormonal ezikhoyo.
Indlela i-Tamoxifen i-Metabolized Body yakho
I-Tamoxifen kufuneka iphulwe phantsi emzimbeni wakho kwifomu yayo esebenzayo.
Le "metabolite" iphela endoxifen kwaye yinkomfa esebenzayo ukukhusela ukuphindaphinda.
I-Tamoxifen idilizwe i-endoxifen yi-cytochrome P450 enzyme CYP2D6. (Kukho nezinye i-enzyme ezifana ne-CYP3A4 kunye nabanye, kodwa i-CYP2D6 ibonakala ibaluleke kakhulu). Nantoni na eyanciphisa umsebenzi we-enzyme (i-CYP2D6) inokubangela inani elincitshisiweyo le-metabolite esebenzayo, ngoko ke, inzuzo encinci. Umsebenzi ophungiweyo we-enzyme ungenzeka xa uthatha amanye amachiza okanye ukuba unesimo esithile sokwahluka kwemvelo eyenza i-enzyme ingasebenzi.
I-Endoxifen, umonakalo weemveliso, ngamaxesha angama-30 ukuya kuma-100 asebenzayo ngakumbi ekunciphiseni ukukhula kweeseligen ehambelanayo ne-tamoxifen, kwaye umgaqo-nkqubo uhambelana nemiphumo ye-tamoxifen. Unokuva i-tamoxifen ebizwa ngokuba yi "pro-drug" kwesi sizathu.
Kutheni ukudibenezelana kwezidakamizwa kungenzeka
Isizathu sokuba ukuqonda imetabolism ye-tamoxifen kubalulekile kukuba kukho ezinye ezininzi iimichiza ezichaphazela ngokufanayo i-CYP2D6 enzyme. Ezinye iziyobisi zivimbela kakhulu i-enzyme ukwenzela ukuba incinciifen iveliswe xa ithe yathathwa kunye ne-tamoxifen. Ngokwenene, kuya kuba ngathi awuzange uthathe le nkunkuma nhlobo.
Imithi echaphazela le nzyme iquka ezo ziqhelekileyo ezisetyenziselwa ngabafazi abanomhlaza wesifuba ezinjengezinto ezininzi zokuxhatshazwayo kunye neendlela eziqhelekileyo zokubanda kunye neendlela zokugula.
Ingcaciso malunga nale nxaxheba intsha (i-tamoxifen yavunywa ngo-1998, kodwa ukusebenzisana kwakungazange kuqaphelwe kude kube kamva) kunye nezifundo ngoku ziqhubeka zikhangele le ngxaki ngokubanzi. Ingqalelo, kukuba iziphumo zakutshanje zifumene ukuba izinga lakho le-vitamin D linokudibaniswa nokusebenza kwe-tamoxifen kwaye ukuba amanqanaba okuphela kokugcina afana nokuphakama kakhulu kwabesetyhini kwiinyanga zasehlobo. Ekubeni kubekho uphando olubonisa ukuba i- vitamin D inokukunceda ukulwa nomdlavuza webele , oku kukukhumbuza ukuba i-oncologist yakho iqaphele izinga lakho le- vitamin D ukuba ungakhange wenze oku.
Ukunxibelelana kweMithi yeTroxifen
Ngezantsi sibala inani lamachiza anokunxibelelana ne-tamoxifen. Ingqalelo kukuba ezi ziyobisi zinganciphisa ukusebenza kwe-tamoxifen kodwa yenza njalo kwii-degrees ezahlukeneyo. Ezinye iziyobisi zinamandla kakhulu kwi-CYP2D6, kanti ezinye zivimbela i-enzyme kwiidridi ezincinci. Olu luhlu aluphelelanga kwaye amanye amachiza angasetyenziswa kakhulu angasebenzisana ne-tamoxifen kunye. Nceda uthethe kwi-oncologist yakho kunye nekhemistiki malunga nayiphi na imishishini yeyeza, iyeza-counter-counter, okanye isongezelelo sesondlo ocingayo xa uhlala kwi-tamoxifen. Ingqalelo kukuba kunokubakho amaxesha apho iingenelo zokusebenzisa enye yezi zidakamizwa zinokuba ngaphezu komngcipheko wokunciphisa amanqanaba akho ekupheleni. Ukuba nolwazi, nangona kunjalo, lunokunceda ucele ugqirha wakho imibuzo efanelekileyo.
Amachiza okumele agwenywe nge-tamoxifen zibandakanya:
- I-serotonin i-inhibitors ekhethiweyo (SSRIs) : Iprozac (i-fluoxetine) ne-Paxil (i-paroxetine) inhibitors enamandla ye-CYP2D6. Luvox (i-fluvoxamine), iCelexa (citalopram), iLexapro (escitalopram). kwaye i-Zoloft (sertraline) inqanda i-enzyme kwinqanaba elithile. Kungenzeka ukuba lo msebenzi ujongene nobungozi obuninzi bokufa obufumaneka kubafazi abathatha uPaxil.
- I-serotonin / i-norepinephrine reuptake inhibitors (i-SNRIs) ekhethiweyo: Effexor (venlafaxine), i-Pristiq (desvenlafaxine)
- I-Wellbutrin kunye neZyban (bupropion) : Isetyenziselwa ukudandatheka kunye nokuyeka ukutshaya
- I-Tricyclic antidepressants: i-Anafranil (i-clomipramine) kunye ne-Norpramin (desipramine)
- Iyeza- endocrine: i-Sensipar (i-cinacalcet), i-Parlodel (i-bromocriptine), ne-Parnate (i-tranlcypromine)
- I-antipsychotics efana ne-Mellaril (thioridazine), i-Trilafon (perphenazine), i-Orap (i-pimozide), ne-Thorazine (i-chlorpromazine), kunye ne-antipyychotics e-atypical njenge-Risperdal (risperidone), i-Clozaril (clozapine), i-Geodon (ziprasidone) kunye ne-Seroquel (quetiapine)
- Iipilisi ze- cardiac : I-cardioquin (i-quinidine), iTiclid (ticlopidine), iKardene (nicardipine)
- I-Antihistamines : i-Benadryl (i-diphenhydramine)
- I-antibiotics : I-Rifampin inokunciphisa amanqanaba e-tamoxifen, i-isoniazid (isetyenziselwa i-TB).
- Imithi ye Reflux : iTagamet (cimetidine)
- Iimpawu zokufakelwa : Ngokuqhelekileyo zisetyenziselwa iimeko ezivela kwiinyawo zomdlali, ukuya kwi-tinea versicolor, ukuba zifake i-fungus, isilwanyana seLamisil okanye iTerbinex (terbinafine) ayifanele isetyenziswe ne-tamoxifen, nangona le nkunkuma ayifakiwe kwiintlobo ezininzi zamachiza ukuphepha.
- Isifo sikashukela: Actos (proglitazone)
- Iipilisi ze-Parkinson zesifo : Gweba (ropinirole)
- Imishanguzo yeHIV / AIDS : ezininzi
- Iziko : Neurontin (gabapentin)
- IiVithamini : I-vitamin E ephezulu isongezelelo isenokusebenzisana ne-tamoxifen
- Ukuncedisa okunomsoco : Asinayo nayiphi na iinjongo ezinkulu ezijongene nokusebenzisana kwezongezo zamanzi kunye ne-tamoxifen. Izongezelelo ezinomsebenzi onamandla we-CYP2D6 kwi-lab kubandakanya i-skullcap, i-lemon balm, i-echinacea kunye ne-ginseng. Kwimininzi enkulu, ukukhishwa kwetiyi eluhlaza kunokwandisa izinga le-tamoxifen egazini, kodwa oku akunakwanele ukuba kubangele iimpawu zeklinikhi. Ukuba uceba ukusebenzisa nayiphi na isongezelelo semfuyo kubalulekile ukuthetha ne-oncologist yakho.
Ezinye iindlela: Amachiza angasetyenziselwa endaweni
Usenokuzibuza ukuba ungayithatha ntoni xa usebenzisa tamoxifen:
- I-Antidepressants iyahluka kwinqanaba elichaphazela ngayo i-enzyme CYP2D6. I-Cymbalta (duloxetine) ibonakala igxotha amanqanaba e-CYP2D6 ngaphantsi kwamanye amaninzi okuxhatshazwayo. Amayeza adweliswe apha ngentla phantsi kwe "iziyobisi ukuphepha" ahluke kakhulu kwizinga apho aphelisa khona i-enzyme. Uphando olutshanje lubonisa ukuba abanye abaxhasi bancinci banokukhuseleka ukuba basebenzise kunye ne-tamoxifen, kodwa izifundo ngelo xesha azihambelani nokuba le nto ingaba nemiphumo yekliniki.
- I-allergies kunye neyeza ezibandayo: Uninzi lwamachiza anokubanda kunezithako ezingaphezulu kwesinye, ngoko kubalulekile ukufunda iilebula. Inani elikhulu lamalungiselelo okubanda kwamaqanda nomkhuhlane iqulethe uBenryryl. Izidakamizwa ezinjengezilwanyana ezifana neZyrtec kunye noClaritin zicingelwa ukuba zikhuselekile ukusebenzisa ne-tamoxifen.
- I-Acid i-reflux imithi efanelekileyo ifanele iquka iZantac (ranitidine) kunye nabanye.
Sisoloko sifunda ngokubanzi malunga nokusetyenziswa kwamachiza kwaye kubalulekile ukuthetha kunye ne-oncologist yakho kunye nekhemistiki malunga nayiphina imithi enqwenela ukuyisebenzisa kunye ne-tamoxifen.
QT Ukongezwa
Ukuba ukhangele i-package yakho yokubhaliweyo oye waqaphela ukuba i-tamoxifen ayifanele isetyenziswe ngamanye amayeza ancedisa ixesha le-QT. Ixesha le-QT libhekiselele kwinani lexesha phakathi kwamaza amabini abonwe kwi-electrocardiogram. Kucingelwa ukuba ukuba ixesha le-QT lide lide kakhulu, liphakamisa umngcipheko wesigqi senhliziyo esingavamile, kwaye mhlawumbi, ukufa ngokukhawuleza.
Ulwazi lokupakisha luxwayisa ukuba i-tamoxifen inokubangela ukuxiliswa kwe- QT xa kusetyenziswa kunye nezinye iziyobisi ezinokubangela ukunyusa kwe-QT. Ukuhlaziywa kweengxelo ze-2017, nangona kunjalo, kubangelwa ukuba kukho umngcipheko omncinci wokongezwa kwe-QT ekwimfuneko, ngokukodwa kwi-20 mg yemihla ngemihla.
I-Genetics yeTamoxifen ne-CYP2D6 Ukuvavanya
Kukho umsetyenzana wezenzo ze-CYP2D6 enzyme, kwaye oku kubangela ukungalingani kwi-metabolism yeziyobisi. Ukuphononongwa kweengxelo zifumene ukuba iimveliso ezininzi zibonakala zifumana iziphumo ezingcono kunezixhobo eziphathekayo. Ngokubanzi, malunga neepesenti ezingama-20 zabantu baye banciphisa umsebenzi wale enzyme.
Uyazi njani ukuba unokuba ngumgqugquzeli osweleyo? Kukho iimvavanyo zetekethi yokuthengisa i-genotyping ye-CYP2D6, kodwa olu vavanyo aluqhelekanga kubafazi kwi-tamoxifen unyango lwe-esrogen-receptor-positive cancer. Ngamanye amagama, mhlawumbi awuyi kukwazi. Le yindawo yokuphikisana nayo, kwaye abanye abaphandi bakholelwa ukuba ubukho bezinye i-enzyme, i-CYP3A4 * 22 inokuhlawulela ukunciphisa i-endoxifen ingqwalaselo ehambelana nomsebenzi ophantsi we-CYP2D6.
Kwakhona, kubalulekile ukuba uqaphele ukuba umsebenzi we-CYP2D6 uhlala ephakamileyo kwiinyanga zasehlotyeni (kuxhomekeka kwi-vitamin D kwinqanaba elithile), kunye nokuvavanya i-vitamin D kubalulekile kubasetyhini abahlala nomhlaza wesibele.
Ngaphantsi kwiTamoxifen Drug Interactions
I-Tamoxifen yile mithi abafazi bayithatha imihla ngemihla ixesha elide emva kokuxilongwa komhlaza webele. Xa kuthathwa njengalathiselweyo, inokunciphisa umngcipheko wokuphindaphinda (kwaye emva koko, ukufa). Ngaloo ndlela, ukuqonda ukusebenzisana okunokwenzeka kubaluleke kakhulu.
Ezinye iindlela zokusebenzisana kwezidakamizwa zingaba zincinci, kanti ezinye iziyobisi zingakhokelela ngokupheleleyo imiphumo ye-tamoxifen xa ithatyathwa ngokufanayo. Oku kuye kwaboniswa kungekhona kuphela kwibhanki ekhangelelanisa imetabolism yale michiza, kodwa ibonakala kwikliniki kwindleko yokufa kwabasetyhini abathatha uPaxil kunye ne-tamoxifen.
Ulwazi olutsha luza phezulu (njengolwazi lwe-vitamin D olukhankanywe ngasentla). Ukuqhubela phambili ngokukhawuleza kumachiza omhlaza kwenza ukuba kubaluleke ngakumbi kunokuba ube ngummeli wakho kwinkathalo yakho yomhlaza , isifundo esichaza le ngongoma ekhangele abafazi abathatha i-tamoxifen ngexesha lexesha ukususela ngo-2005 no-2010 (emva kokuba sazi ezinye zezi ntsebenzo). Ngeli xesha, uPaxil wayengomnye wezona zinto eziqhelekileyo ezichasene nezidlobongela kubafazi kwi-tamoxifen. Nangona ukhathazeka ngakumbi, nangona kunjalo, ukuba amaninzi amanqaku amalungiselelo angasebenzisana ne-tamoxifen, eshiya abantu ngokwabo ukuba baqonde ukusebenzisana kwezidakamizwa.
> Imithombo:
> Antunes, M., Timm, T., de Oliveira, V. et al. Impembelelo ye-CYP2D6 kunye ne-CYP3A4 i-Phenotypes, i-Drug Interactions kunye ne-Vitamin D Isimo kwi-Tamoxifen Biotransformation. Uhlolo loLwabiwo lweMithi . 2015. 37 (6): 733-44.
> Juurlink, D. Ukuhlaziya ukusebenzisana kwezidakamizwa phakathi kweTamoxifen kunye ne-SSRI Antidepressants. BMJ . 2016. 354: i5309.