Yini Ongayenza Futhi Ongenakukwazi Ukuyisebenzisa Ngesikhathi Usebenzisa i-Tamoxifen
Uma ngabe u-tamoxifen unqunyelwe umdlavuza webele , kungenzeka ukuthi wezwa ukuthi ungaxhumana neminye imithi. Njengoba lokhu kusebenzisana kuhilela izidakamizwa ezivame ukusetshenziswa futhi kubandakanya ngaphezulu-the-counter kanye nezondlo izithako, lokhu kubaluleke kakhulu. Ngaphezu kwalokho, cishe uzoyithatha imithi okungenani iminyaka emihlanu kuya kwengu-10, okwenza uqaphele ukuthi ukusebenzisana okungenzeka kungakukhathazeka okwesikhashana nje.
Kukhona nabanye abantu abathi, ngenxa yokungafani kwezakhi zofuzo, abazuzi ngaphandle uma umthamo ophakeme walesi sidakamizwa usetshenziswa. Yini okudingeka ukwazi?
Ukusetshenziswa kwe-Tamoxifen
I-Tamoxifen inezinhlobo ezintathu ezisemqoka:
- Kuvame ukusetshenziselwa ukwelashwa kwe-adjuvant kwabesifazane abanomdlavuza webele wesandulela-ngculaza okuyi- estrogen receptor positive futhi abangama-premenopausal. Kulesi silungiselelo, kunganciphisa ingozi yokuphindaphinda ngamaphesenti angu-50. Futhi kunciphisa amathuba okuthuthukisa umdlavuza wesibili esiswini sakho esithintekile (uma une-lumpectomy) noma kwesinye isifuba sakho.
- I-Tamoxifen isetshenziselwa kokubili abesifazane nabesilisa abanomdlavuza wesifuba we-metastatic is receptor positive futhi abangamelana nomuthi.
- I-Tamoxifen ingasetshenziselwa ukwelashwa okuvimbela abesifazane abanengozi enkulu yokuthuthukisa umdlavuza webele. Kulesi simo, kunganciphisa ingozi yabesifazane yokuthuthukisa umdlavuza webele ngesigamu.
Isilinganiso esivamile kakhulu singama-20 mg nsuku zonke iminyaka emihlanu kuya kwengu-10.
(Labo ababa yi-postmenopausal noma bathole ukwelashwa kokukhipha i-ovarian bangashintshwa ku-inhibitor ye-aromatase esikhundleni).
Funda kabanzi indima ye-estrogen emdlalweni webele webele kanye nezinketho zokwelapha ze-hormonal ezitholakala.
Indlela i-Tamoxifen isetshenziselwa ngayo umzimba wakho
I-Tamoxifen idinga ukuphulwa emzimbeni wakho ibe ifomu layo esebenzayo.
Le "metabolite" i-endoxifen futhi iyisakhi esisebenza ukuvimbela ukuphindaphindiwe.
I-Tamoxifen ihlehlisiwe ibe yi-endoxifen yi-cytochrome P450 enzyme CYP2D6. (Kunamanye ama-enzyme afana ne-CYP3A4 nabanye, kodwa i-CYP2D6 cishe ibaluleke kakhulu). Noma yini eyanciphisa umsebenzi wale enzyme (CYP2D6) ingabangela inani elinciphile le-metabolite esebenzayo, ngakho-ke, inzuzo encane. Umsebenzi wehlile we-enzyme ungase uvele uma uthatha ezinye izidakamizwa noma uma unezici ezithile zofuzo ezenza ukuthi i-enzyme ingasebenzi kancane.
I-Endoxifen, umkhiqizo odilizayo, usebenza ngokuphindaphindiwe izikhathi ezingu-30 kuya kwezingu-100 ekuvimbeleni ukukhula kweseli e-estrogen ehlobene ne-tamoxifen, futhi yiyona ndlela eyinhloko ephethe imiphumela ye-tamoxifen. Ungase uzwe i-tamoxifen ebizwa ngokuthi "i-pro-drug" ngalesi sizathu.
Kungani Ukusebenzisana Kwezidakamizwa Kungenzeka
Isizathu sokuthi ukuqonda umthamo we-tamoxifen kubalulekile ukuthi kunezinye imithi eminingi ephazamisa ngokufanayo i-CYP2D6 enzyme. Ezinye izidakamizwa zivimbela kakhulu i-enzyme ukuze kancane uma i-endoxifen ikhiqizwa uma ithathwa nge-tamoxifen. Empeleni, kuyoba sengathi awuzange uthathe isidakamizwa nhlobo.
Imithi ethinta le enzyme ifaka phakathi nalawo asetshenziselwa abesifazane abanomdlavuza wesifuba njengama-antidepressants amaningi kanye nemithi ejwayelekile yokushisa nokugula.
Ukwaziswa ngalezi zindlela zokuxhumana kubalulekile (i-tamoxifen ivunyelwe ngo-1998, kodwa ukuxhumana akuzange kuqaphelwe kuze kube kamuva) kanti izifundo okwamanje ziyaqhubeka zibheke ngalolu daba ngokujulile okukhulu. Okubalulekile, ukuthi lezo zinsuku zamuva zithole ukuthi izinga lakho le-vitamin D lingase lihlotshaniswe nokusebenza kwe-tamoxifen nokuthi amazinga endoxifen avame ukuphakama kakhulu kwabesifazane ezinyangeni zasehlobo. Njengoba sekuye kwaba nezifundo ezibonisa ukuthi i- vitamin D ingasiza ekulwa nomdlavuza webele , lokhu kuyisikhumbuzo sokuthi i-oncologist yakho ihlole izinga lakho le- vitamin D uma ungakenze lokhu.
Ukusebenzisana Okudakayo Kwezidakamizwa ku-Tamoxifen
Ngezansi sibhala imithi eminingi engase ixhumane ne-tamoxifen. Okuphawula ukuthi lezi zidakamizwa zinganciphisa ukusebenza kwe-tamoxifen kodwa zenze kanjalo ngezinga elihlukile. Ezinye izidakamizwa zinama-inhibitors enamandla kakhulu we-CYP2D6, kuyilapho ezinye zivimbela i-enzyme kuma-degree angaphansi. Lolu hlu aluphelele futhi amanye amayeza asetshenziswa kakhulu angase ahlanganyele ne-tamoxifen. Sicela ukhulume ne-oncologist yakho kanye ne-pharmist nganoma yimiphi imithi yokwelapha, imishanguzo engaphezu kwe-counter, noma ukwesekwa kokudla okucatshangelwayo ngenkathi usu-tamoxifen. Okuphawula ukuthi kungase kube nezikhathi lapho izinzuzo zokusebenzisa enye yalezi zidakamizwa zingase zenze ingozi yokunciphisa izinga lakho lokuphela kwe-endoxifen. Ukuqaphela, noma kunjalo, kungakusiza ukubuza udokotela wakho imibuzo efanele.
Imithi okufanele igwenywe nge-tamoxifen ihlanganisa:
- I-serotonin uptake inhibitors (SSRIs) ekhethiwe : Iprozac (i-fluoxetine) ne-Paxil (i-paroxetine) i-inhibitors enamandla ye-CYP2D6. Luvox (fluvoxamine), uCelexa (citalopram), Lexapro (escitalopram). futhi i-Zoloft (sertraline) ibuye ivimbele i-enzyme ngezinga elithile. Kungenzeka lokhu kusebenzisana kubangele ingozi yokufa etholakala kwabesifazane abaphatha i-Paxil.
- I-serotonin / i-norepinephrine reuptake inhibitors (i-SNRIs) ekhethiwe : Effexor (venlafaxine), i-Pristiq (desvenlafaxine)
- I-Wellbutrin ne-Zyban (bupropion) : Isetshenziselwa ukucindezeleka nokuyeka ukubhema
- Ama-anti-depressants e-Tricyclic: i-Anafranil (i-clomipramine) ne-Norpramin (desipramine)
- Imithi ye-endocrine : i-Sensipar (i-cinacalcet), i-Parlodel (i-bromocriptine), ne-Parnate (i-tranlcypromine)
- I-antipsychotics ejwayelekile njengeMellaril (thioridazine), i-Trilafon (perphenazine), i-Orap (i-pimozide), ne-Thorazine (i-chlorpromazine), ne-antipyytictics e-atypical efana ne-Risperdal (risperidone), i-Clozaril (clozapine), i-Geodon (i-ziprasidone) ne-Seroquel (quetiapine)
- Imithi ye-cardiac : I-Cardioquin (i-quinidine), i-Ticlid (ticlopidine), i-Cardene (i-nicardipine)
- Ama-antihistamine : i-Benadryl (i-diphenhydramine)
- Ama-antibiotics : I-Rifampin inganciphisa kakhulu amazinga e-tamoxifen, i-isoniazid (esetshenziselwa i-TB).
- Imithi ye-Reflux : i-Tagamet (cimetidine)
- Ama-antifungals : Ngokuvamile asetshenziselwa izimo ezinyaweni zomgijimi, ukuya ku-tinea versicolor, ukufaka imfucumfucu, i-Lamisil yezidakamizwa noma i-Terbinex (terbinafine) akufanele isetshenziswe nge-tamoxifen, nakuba lesi sidakamizwa asifakiwe kuzinhlu eziningi zezidakamizwa ukugwema.
- Imithi yesifo sikashukela: Actos (proglitazone)
- Imithi ye-Parkinson yesifo : Hlanganisa (ropinirole)
- Imithi ye-HIV / AIDS : Abaningana
- Ezihlukahlukene : Neurontin (gabapentin)
- Amavithamini : Izithako eziphakeme ze-vitamin E zingase zisebenze ne-tamoxifen
- Izithako zokudla okunempilo : Asinaso izifundo ezinkulu ezibheke ukusebenzisana kwe-herbal supplements ne-tamoxifen. Izithako ezinomsebenzi oqinile we-CYP2D6 ebhodini zihlanganisa i-skullcap, i-lemon balm, i-echinacea, ne-ginseng. Ngokwengeziwe, itiye elihlaza elikhishwe lingakhuphula izinga le-tamoxifen egazini, kodwa lokhu cishe akulanele ukwenza izibonakaliso zemitholampilo. Uma uhlela ekusebenziseni noma yikuphi ukondla kwemithi kubalulekile ukukhuluma ne-oncologist yakho.
Ezinye izindlela: Imithi Engasetshenziswa Ekuqaleni
Ungase uzibuze ukuthi ungathatha uma usebenzisa i-tamoxifen:
- Ama-antidepressants ahlukahluka ngezinga elithinta ngayo i-enzyme CYP2D6. I-Cymbalta (duloxetine) ibonakala icindezela amazinga we-CYP2D6 ngaphansi kwamanye ama-antidepressants amaningi. Imithi ebalulwe ngenhla ngaphansi kwe "izidakamizwa zokugwema" ihluke kakhulu ngokwezinga abavimbela ngayo i-enzyme. Ucwaningo lwamuva lubonisa ukuthi amanye amancane abacindezelayo angase abe ephephile ukusebenzisa ne-tamoxifen, kodwa izifundo ngalesi sikhathi azihambisani nalokho ukuthi lokhu kungase kube nomthelela emtholampilo.
- Imithi yokwelapha nokubandayo: Imishanguzo eminingi ebandayo inezithako ezingaphezu kweyodwa, ngakho-ke kubalulekile ukufunda amalebula. Inamba enkulu yokulungiselela imifula nomkhuhlane iqukethe i-Benadryl. Izidakamizwa ezibangelwa yizifo ezinjengeZyrtec noClaritin zicatshangwa ukuthi ziphephile ukusebenzisa ne-tamoxifen.
- Imithi ye-reflux ye-acid cishe elungile ifaka i-Zantac (ranitidine) nabanye.
Sifunda njalo mayelana nokusebenzisana kwezidakamizwa futhi kubalulekile ukukhuluma no-oncologist yakho kanye nekhemisi nganoma imiphi imithi ofuna ukuyisebenzisa kanye ne-tamoxifen.
QT Extended
Uma ubuke iphakethe lakho lokufaka uphawu okungenzeka ukuthi uqaphele ukuthi i-tamoxifen ayifanele isetshenziswe neminye imithi eyenza isikhathi eside se-QT. Isikhathi se-QT sibhekisela esilinganisweni sesikhathi phakathi kwamagagasi amabili abonwe ku-electrocardiogram. Kucatshangwa ukuthi uma isikhathi se-QT sikhula isikhathi eside kakhulu, sikhipha ingozi yesigqi senhliziyo engavamile, futhi kungenzeka, ukufa okungazelelwe.
Ulwazi lwephakheji luxwayisa ukuthi i-tamoxifen ingabangela ukuxilongwa kwe-QT uma isetshenziselwa kanye nezinye izidakamizwa ezingabangela ukuxilongwa kwe-QT. Ukubuyekezwa kwezifundo ezingu-2017, noma kunjalo, kuthiwa kungenzeka ukuthi ingozi ephansi yokwandiswa kwe-QT emtholampilo kulokhu kulungiselelwa, ikakhulukazi ku-20 mg kuphela nsuku zonke.
I-Genetics ye-Tamoxifen no-CYP2D6 Ukuhlola
Kunemisebenzi eminingi ye-CYP2D6 enzyme, futhi lokhu kubangela umehluko ekusetshenzisweni kwezidakamizwa. Ukubuyekezwa kokucwaninga kutholwe ukuthi ukuqubuzana okukhulu kwezinto ezibonakalayo kubonakala kunemiphumela engcono kunama-metabolizers abampofu. Ngokuvamile, cishe amaphesenti angu-20 abantu anciphise umsebenzi wale nzyme.
Ngakho wazi kanjani ukuthi ungaba umthamo we-metabolizer ompofu? Kukhona izivivinyo ze-genotyping kit ezithengiswayo ezitholakala ku-genotyping ye-CYP2D6, kodwa lokhu kuvamile akukwenziwe abesifazane besifo se-tamoxifen somdlavuza wesifuba we-estrogen we-receptor-positive. Ngamanye amazwi, cishe ngeke ukwazi. Lokhu kuyindawo yokuphikisana, futhi abanye abacwaningi bakholelwa ukuthi ukuba khona kwesinye isilwane, i-CYP3A4 * 22 ingase ikhokhele ukunciphisa ukubhekwa kwe-endoxifen ehlobene nomsebenzi ophansi we-CYP2D6.
Futhi, kufanele kuqaphele ukuthi umsebenzi we-CYP2D6 uvame ukuphakama ezinyangeni zasehlobo (kuxhomeke ku-vitamin D ngezinga elithile), nokuhlolwa kwe-vitamin D kubalulekile kwabesifazane abaphila nomdlavuza webele.
Ngezansi ku-Tamoxifen Ukusebenzisana Kwezidakamizwa
I-Tamoxifen imithi abesifazane abayithatha nsuku zonke isikhathi eside emva kokuxilongwa komdlavuza webele. Uma kuthathwe njengokuqondiswa, kunganciphisa ingozi yokuphindaphinda (futhi kamuva, ukufa). Njengalokhu, ukuqonda ukusebenzisana okungenzeka kubaluleke kakhulu.
Okunye ukusebenzisana kwezidakamizwa kungaba mnene, kanti ezinye izidakamizwa zingase zilahleke ngokuphelele imiphumela ye-tamoxifen uma kuthathwe ngesikhathi esifanayo. Lokhu kuye kwaboniswa hhayi kuphela ebhodini elibheke ekusetshenzisweni komzimba kwezidakamizwa, kepha kubonakala emtholampilo ekukhuphukeni kokufa kwabesifazane abathatha uPaxil kanye ne-tamoxifen.
Ulwazi olusha luza phezulu (njengolwazi lwe-vitamin D okukhulunywe ngenhla). Lokhu kuthuthuka okusheshayo emithi yomdlavuza kwenza kubaluleke kakhulu kunanini ngaphambili ukuba ube ngummeli wakho ekunakekelweni komdlavuza wakho , Ucwaningo olubonisa leli phuzu lunye olubheka abesifazane besithatha i-tamoxifen phakathi nesikhathi kusukela ngo-2005 no-2010 (ngemva kokuqaphela ezinye zalezi zokuxhumana). Ngaleso sikhathi, uPaxil wayengomunye wama-antidepressants ngokuvamile avunyelwe abesifazane ku-tamoxifen. Okukhathazeka nakakhulu, noma kunjalo, ukuthi ukulungiselela okuningi kuningi kungase kuhlangane ne-tamoxifen, kusale abantu bebodwa ukuthi babone ukusebenzisana kwezidakamizwa.
> Imithombo:
> Antunes, M., Timm, T., de Oliveira, V. et al. Ithonya le-CYP2D6 ne-CYP3A4 ama-Phenotypes, ukusebenzisana kwezidakamizwa, kanye nesimo se-Vitamin D esimweni se-Tamoxifen Biotransformation. Ukuqapha Imithi Yezokwelapha . 2015. 37 (6): 733-44.
> Juurlink, D. Ukubukeza ukusebenzisana kwezidakamizwa phakathi kwama-Anti-depressants we-Tamoxifen ne-SSRI. BMJ . 2016. 354: i5309.