Cishe iminyaka engama-50, odokotela bebelokhu besebenzisa izidakamizwa ze-sulfanilamide ukwelapha i-2 mellitus yesifo sikashukela, yize iqiniso ukuthi indlela yabo yokunciphisa ushukela iyinkimbinkimbi impela.
Ukulungiselela kweqembu le-sulfonamide kuthinta ikakhulukazi amaseli we-beta we-pancreas, ngaleyo ndlela kuthuthukisa ukukhiqizwa kwe-insulin okuphambili nokunamandla.
Ukulungiselela kweSulfanilamide kunomthelela omncane we-pancreatic. Kanye nalokhu, ukuqapha isikhathi eside kwe-glycemic ngesikhathi sokwelashwa nge-sulfonamides:
- kunciphisa ukukhiqizwa ushukela ngokweqile kwesibindi;
- kuthuthukisa ukuphendula kwe-insulin okuyimfihlo ekudleni kokudla;
- kuthuthukisa umphumela we-insulin kwizicubu nezicubu ze-adipose.
Ama-Sulfanilamides ahlukaniswe izidakamizwa zesizukulwane sokuqala (okwamanje asetshenziswa eRussia) nezidakamizwa zesizukulwane sesibili, uhlu lumi ngokulandelayo:
- glipizide
- gliclazide
- glycidone
- glibenclamide,
kokuba yiqembu eliphambili lokwelashwa kwesifo sikashukela.
Ukulungiswa kwe-sulfonamide group glimepiride, ngenxa yezimpawu zayo ezihlukile, kubhekiselwa ezintweni ezinciphisa ushukela esizukulwaneni sesithathu.
Indlela yokusebenza
Indlela yokusebenza yezidakamizwa zeqembu le-sulfanilamide group, esiza ukwehlisa amazinga kashukela, isuselwa ekuvuseleleni kokuvikelwa kwe-insulin, okulawulwa yiziteshi ze-potassium ezibucayi ze-potassium ezingxenyeni ze-plasma zeseli le-beta.
Iziteshi ze-potassium ezibucayi ze-ATP zinezi-2 subunits. Enye yalezi zinto ezifakiwe ziqukethe i-sulfonamide receptor, kanti enye iqukethe ngokuqondile isiteshi. Ezigulini ezinesifo sikashukela sohlobo lwe-2 mellitus, okuthi lapho ukusebenza kwamaseli we-beta kugcinwe kuye ngezinga elithile, i-receptor ibopha i-sulfonamide, okuholela ekutheni kuvalwe isiteshi se-potassium esibucayi se-ATP.
Ngenxa yalokho, i-potassium inqwabelana ngaphakathi kwamaseli we-beta, abese edonswa phansi, athola ukungena kwe-calcium esitokisini se-beta. Ukwanda kwesibalo se-calcium ngaphakathi kwamaseli we-beta kusebenze ukuthuthwa kwemigqumo ye-insulin ukuya kolwelwesi lwe-cytoplasmic lweseli abahlangana nalo, nendawo yokuhlangana igcwele nge-insulin.
Kumele kuqashelwe ukuthi ukugqugquzelwa kwe-insulin secretion ngama-secretogens akuxhomekile kuzinga le-glucose egazini, futhi ukwanda kwe-plulin ye-insulin okuhlinzekayo kuholela ekunciphiseni kwe-postprandial kanye ne-glycemia ye-postprandial.
Kulokhu, ama-secretogens-HbA1 ama-sulfanilamide anomphumela wokunciphisa ushukela, ukunciphisa ushukela kwenzeka ngo-1-2%. Uma welashwa ngemithi engeyona i-sulfanelamide, ushukela wehliswa kuphela ngu-0.5-1%. Lokhu kungenxa yesiphetho esisheshayo sokugcina.
Izidakamizwa zeSulfanilamide kungenzeka zibe nomphumela ongeziwe we-pancreatic kwezicubu ezikude ezincike kuma-insulin nesibindi. Kodwa-ke, izindlela eziqondile zokufaka isandla ekunciphiseni kwe-hyperglycemia azikasungulwa kuze kube namuhla.
Kungenzeka ukuthi i-sulfanilamide hyperstimulation ye-secretion ye-hormone-insulin ohlelweni lwesibindi se-portal ithuthukisa umphumela we-insulin esibindini futhi inciphise ukuzila kwe-hyperglycemia.
I-Normalization ye-glycemia inciphisa ubuthi be-glucose futhi ngaleyo ndlela ikhulisa ukuzwela kwe-insulin etholakala emngceleni wezicubu ezincike kwi-insulin (i-adipose, izicubu zomzimba).
I-Sulfanilamide gliclazide ngohlobo 2 sikashukela i-mellitus ibuyisa isigaba sokuqala (i-3-5 min) sesigaba se-insulin secretion, yona, ithuthukise ukuphazamiseka kwesigaba sesibili eside (amahora ama-1-2), isimilo sohlobo 2 sikashukela mellitus.
I-pharmacokinetics yezidakamizwa ze-sulfa ihlukile ngezinga le-adsorption, metabolism kanye ne-excretion rate. Izidakamizwa ezisohlwini lwesizukulwane sesibili nesesithathu aziboshelwa amaprotheni e-plasma, awahlukanisa nezidakamizwa ezisohlwini lwesizukulwane sokuqala.
Wonke amalungiselelo e-sulfanilamide acishe amunca ngokuphelele izicubu. Kodwa-ke, ukuqala kwesenzo sabo kanye nobude baso kuncike ezimweni zekhemisi eyodwa, ezinqunywa kwifomula yomuthi.
Izidakamizwa eziningi ze-sulfa zinempilo efushane eyi-half, ehlala amahora angama-4-10. Njengoba iningi lama-sulfonamides lisebenza lapho lithathwa kabili, naphezu kwengxenye emfushane yokuphila kusuka egazini, kungenzeka ukuthi kumaseli we-beta esezingeni lezicubu, ukuqedwa kwawo kuphansi kunegazi.
Isidakamizwa se-Glyclazide sulfanilamide manje sesiyatholakala ngesimo eside futhi sinikeza abantu abaningi kakhulu i-plasma amahora angama-24 (isifo sikashukela MB). Uhlu olukhulu lwezidakamizwa ze-sulfa luqhekeka esibindini, futhi ama-metabolites awo adalulwa ngokwengxenye yizinso futhi ngokwengxenye ipheshana lesisu.
Umthamo kanye nama-regimens okwelashwa
Imvamisa, ukwelashwa nge-sulfonamides kuqala ngethamo elincane futhi kuyanda ngokuphumula kwezinsuku ezingama-4-7 kuze kube nomphumela owufunayo. Iziguli ezinamathela ngokuqinile ekudleni, kanye nalabo abafuna ukunciphisa isisindo, zinganciphisa umthamo we-sulfonamides noma ubashiye ngokuphelele.
Noma kunjalo, kunobufakazi bokuthi ukusetshenziswa komthamo omncane we-sulfonamides kuvumela isikhathi eside ukuba kulondolozwe izinga elihle le-glucose.
Iningi leziguli lifinyelela amazinga azo afunekayo we-glycemic lapho usebenzisa i-1/3, 1/2 yethamo eliphakeme. Kodwa uma ngesikhathi sokwelashwa nge-sulfonamides ukuhlushwa kwe-glucose oyifunayo akuzange kwenzeke, khona-ke izidakamizwa zihlanganiswa nama-non-insulin hypoglycemic agents noma nge-insulin.
Lapho ukhetha ama-sulfonamides, izici eziningana kufanele zibhekwe:
- ukuqala kanye nesikhathi sokusebenza;
- amandla;
- isimo semetabolism;
- ukusabela okungekuhle.
Ukusebenza kwesinyathelo se-sulfonamide kuya ngesilinganiso sokuhlangana kwayo ne-sulfonamide receptor. Kulokhu, i-glyclazide, glimepiride, glibenclamide iqashelwa njengempumelelo futhi esebenzayo.
Kuyaphawuleka ukuthi izidakamizwa ze-sulfanilamide zithinta ukusebenza kweziteshi ze-calcium ezicutshini nasezitsheni ezahlukahlukene, ezithinta umshini we-vasodilation. Akukacaci noma le nqubo ibaluleke kangakanani ngokomtholampilo.
Uma kunokusebenza okwanele kwemishanguzo efakwe ohlwini lwama-sulfonamides, ungasebenzisa inhlanganisela yawo nanoma yiziphi izinto ezinciphisa ushukela. Okuhlukile yi-secretogens - meglitinides, nayo ebopha kuma-sulfonamide receptors.
Ukwelashwa okuhlanganisiwe nezidakamizwa ezifakiwe kuhlu lwama-sulfonamides wesenzo esilinganiselwayo kuhlanganiswa nezidakamizwa ezinomshini ohlukile kuma-sulfanilamides.
Ukuhlanganiswa kwezidakamizwa ze-sulfonamide nge-metformin kunesizathu esizwakalayo, ngoba lokhu kokugcina akukuthinti imfihlo ye-insulin ye-hormone, kepha kwandisa ukuzwela kwesibindi kuyo, ngenxa yalokho, umphumela wokwehla ushukela we-sulfonamide uyanda.
Inhlanganisela efanayo yezidakamizwa ibaluleke kakhulu ekwelashweni kwesifo sikashukela sohlobo 2. Ngokuhlanganiswa kwezidakamizwa ze-sulfa ezine-alpha glucosidase inhibitors, ushukela omncane uphuma emathunjini amancane ngemuva kokudla, ngakho-ke i-postprandial glycemia iyancipha.
Ama-glitazones akhulisa ukuzwela kwesibindi nezinye izicubu ezixhomekeka kuma-insulin kwi-hormone-insulin, eqinisa inqubo yokuvikelwa kwe-insfanilamide-ivuswe insulin. Uma sibheka inhlanganisela yezidakamizwa ezifakiwe kuhlu lwama-sulfonamides ane-insulin, khona-ke imibono yabodokotela kulolu daba ayinqikanga.
Ngakolunye uhlangothi, uma kunesidingo sokuyalela i-insulin, kucatshangwa ukuthi izinqolobane zayo emzimbeni ziphelile, yingakho isiphetho sokuthi ukwelashwa okuthe xaxa ngemithi ye-sulfonamide akunangqondo.
Ngaso leso sikhathi, uma isiguli esifaka ngisho ne-insulin secretion sigcinwa kancane sokwenqaba ukusebenzisa i-sulfanilamide, lokhu kuzodinga ukwanda okukhulu kakhulu kumthamo we-insulin.
Ngokunikezwa leli qiniso, ukuzilawula kokusebenza kwe-metabolism nge-insulin yendabuko kuphelele kakhulu kunolunye ukwelashwa kwe-insulin. Noma ngabe kunesilinganiso esilinganiselwe samaseli e-beta, ukungazinaki ukuzithiba akunangqondo.
Uhlu lwezidakamizwa ze-sulfonamide zesizukulwane sesibili esaziwa kakhulu eRussia:
- glycidone;
- i-gliclazide MV;
- glipizide;
- glimepiride;
- glibenclamide.
Izinkomba
Lapho uthatha ama-sulfonamides, izinga le-HbA1c kufanele lehle ngaphakathi kwe-1-2%. Izidakamizwa zeSulfanilamide, njengazo ezinye izidakamizwa ezisehlisa ushukela, zisebenza kakhulu ezigulini ezilawulwa kabi i-glycemic kunalezo ziguli ezinezinkomba zazo ezazisondele kwesejwayelekile (HbA1c 7%).
Amalungiselelo afanele kakhulu we-sulfanilamide ezigulini ezinesifo sikashukela sohlobo lwe-2, anokushodelwa okushiwo ekukhiqizeni kwe-insulin, kodwa, noma kunjalo, izitolo ze-insulin ezingamaseli we-beta azikaphelelwa isikhathi futhi zanele ukuvusa ama-sulfonamides.
Uhlu lweziguli ezinemiphumela emihle:
- Isifo sikashukela sikhule ngemuva kweminyaka engama-30.
- Isikhathi lesi sifo singaphansi kweminyaka emi-5.
- I-hyperglycemia esheshayo engaphansi kuka-17 mmol / L.
- Iziguli ezejwayelekile nezikhuluphele.
- Iziguli zinamathela ezinconyelweni zomondli, nangomzimba ophakeme.
- Iziguli ngaphandle kokuntuleka ngokuphelele kwe-insulin.
Okwesine kweziguli ezaqala ukutholwa zinesifo sikashukela sohlobo 2 azisabeli ekwelashweni nge-sulfonamides. Kubo, kuyadingeka ukukhetha ezinye izidakamizwa ezisebenza ngokunciphisa ushukela.
Phakathi kwezinye iziguli eziye zasabela kahle ekwelashweni, ama-3-4% alahlekelwa umuzwa we-sulfonamides kungakapheli unyaka (tachyphylaxis, okwesibili ukumelana)
Okokuqala, lokhu kwenzeka ngenxa yokwehla kokuqashelwa kwamaseli e-beta futhi ngenxa yokukhuluphala ngokweqile (ukwanda kokumelana ne-insulin).
Imiphumela yokwelashwa engeyinhle ibangelwa hhayi kuphela ngenxa yezizathu ezingenhla, kodwa futhi nezinye izici:
- umsebenzi ophansi womzimba;
- ukulandela ngendlela engeyiyo
- ukucindezela
- izifo ezithathanayo (isifo sohlangothi, ukushaya kwenhliziyo, ukutheleleka);
- ukuqokwa kwezidakamizwa ezinciphisa umphumela we-sulfonamides.
Kwezinye iziguli ezinesifo sikashukela sohlobo lwe-2 mellitus, ngesikhathi sokwelashwa nge-sulfonamides (glibenclamide), kwabonwa i- "looping syndrome", efana nese-Somogy's syndrome ngohlobo 1 sikashukela.
Ukushintsha i-glibenclamide nomuthi onomphumela ophansi we-hypoglycemic (glimepiride) kunxephezelwe isifo sikashukela i-mellitus.
Kungenzeka ukuthi i-nocturnal hypoglycemia nokusetshenziswa kwe-glibenclamide kuvusa i-hyperglycemia yasekuseni kulezi ziguli, okuphoqa udokotela ukuthi andise umthamo wezidakamizwa uphelele. Futhi i-hypoglycemia yasebusuku kuleli cala iyakhula futhi iholele ekunqobeni okukhulu kwesifo sikashukela ekuseni nantambama.
Lokhu yilokhu okushiwo yi-"looping syndrome" ekwelapheni uhlobo 2 lwesifo sikashukela esinezidakamizwa ze-sulfonamide. Namuhla, i-metformin (i-biguanide) isidakamizwa sokuqala sokukhetha sohlobo lokuqala lwesifo sikashukela esingu-2.
Ama-Sulfanilamides avame ukubekelwa ukwehluleka ukwelashwa nalesi sidakamizwa. Uma isiguli singakubekezeleli ukulungiswa kwe-metformin noma simenqaba ngezinye izizathu, ama-sulfonamides ngohlobo 2 lwesifo sikashukela angasetshenziswa njengokwelashwa kwe-basal.
Contraindication
Amalungiselelo weSulfanilamide afakwa emacaleni we-hypersensitivity kuwo, kanye naku-ketoacidosis yesifo sikashukela, ehambisana nokukhohlisa noma ngaphandle kwawo. Uma isimo sesikhule ngenxa yokwelashwa kohlobo lwe-2 yesifo sikashukela esinezidakamizwa ezifakiwe kuhlu lwama-sulfonamides, khona-ke kufanele sikhanseliwe futhi ne-DKA insulin kufanele inqunywe.
Kwezinye izivivinyo zemitholampilo ezingazange zihlangabezane ngokuphelele nezindinganiso eziphakeme zocwaningo lwesayensi, ingozi enkulu yokushona kwezifo zenhliziyo eqale nge-sulfonamide therapy yatholakala.
Kepha ocwaningweni oluningi ososayensi baseBrithani, leli qiniso alizange liqinisekiswe. Ngakho-ke, namuhla ingozi yezifo zenhliziyo ezibangelwa izidakamizwa ze-sulfa ayifakazeki.
Kubalulekile! I-complication ebaluleke kakhulu engakhula nge-sulfanilamide therapy yi-hypoglycemia nezindlela zayo ezinzima. Ngakho-ke, iziguli kufanele zaziswe kakhulu mayelana nokuthi kungenzeka kwalesi simo!
I-Hypoglycemia kunzima ukuyithola kweziguli esezikhulile neze-beta-blocker. Ukuthambekela kukho lapho uthatha ama-sulfonamides yile:
- Iziguli esezikhathele ezinezimpawu zokungondleki.
- Iziguli ezihlushwa i-pituitary, adrenal noma yesibindi ukwehluleka.
- Iziguli ezinomkhawulo oshiwo wokudla kwama-caloric.
- Iziguli ngemuva kokuphuza utshwala.
- Abantu abanesifo sikashukela ngemuva kokuzivocavoca okukhulu komzimba.
Iziguli ezingaphansi kwengcindezi, ngemuva kwenhlekelele, ukutheleleka, noma ukuhlinzwa, zingalahlekelwa ukulawula kwazo kwe-glycemic ngamalungiselelo weSulfanilamide. Kulokhu, kuzoba nesidingo semithamo eyengeziwe ye-insulin, okungenani njengesilinganiso sesikhashana. Kepha ubungozi bokuthola i-hypoglycemia, kanye nengozi yokuthi kuzoba ne-hypoglycemic coma, uyanda.
