Ukususa isifo sikashukela nezimpawu zayo, kusetshenziswa imishanguzo ekhethekile ehlose ukwehlisa izinga loshukela egazini lomuntu ogulayo. Ama-ejenti antidiabetesic (hypoglycemic) angasebenza ukusetshenziswa kwabazali, kanye nangomlomo.
Izidakamizwa ze-Oral hypoglycemic hypoglycemic zivame ukuhlukaniswa ngokulandelayo:
- derivatives sulfonylurea (lezi yiGlibenclamide, Glikvidon, Gliklazid, Glimepirid, Glipizid, Chlorpropamide);
- i-alpha glucosidase inhibitors ("Acarbose", "Miglitol");
- meglitinides ("Nateglinide", "Repaglinide");
- i-biguanides ("Metformin", "Buformin", "Fenformin");
- i-thiazolidinediones (iPioglitazone, iRosiglitazon, iTsiglitazon, i-Englitazon, iTroglitazon);
- incretinomimetics.
Izakhiwo nezenzo zokuphuma kwe-sulfonylurea
Izithako ze-sulfonylureas zatholakala ngengozi maphakathi nekhulu leminyaka edlule. Amandla ezinhlanganisela ezinjalo asungulwa ngesikhathi lapho kwavela ukuthi lezo ziguli ezaziphuza izidakamizwa ze-sulfa ukuqeda izifo ezithathelwanayo nazo zathola ukwehla kushukela wazo wegazi. Ngakho-ke, lezi zinto zibuye zibe nomphumela omenyezelwe we-hypoglycemic ezigulini.
Ngalesi sizathu, ngokushesha kwaqala ukufuna okuphuma ku-sulfonamides nekhono lokwehlisa izinga le-glucose emzimbeni. Lo msebenzi waba negalelo ekuhlanganiseni kokutholakala kokuqala kwe-sulfonylurea emhlabeni, okwakwazi ukuxazulula kufanelekile izinkinga zesifo sikashukela.
Ukuvezwa kokutholakala kwe-sulfonylurea kuhlotshaniswa nokwenza kusebenze kwamaseli we-pancreatic beta athile, ahlotshaniswa nokukhuthaza nokwanda kokukhiqizwa kwe-insulin. Isidingo esibalulekile somphumela omuhle ukuba khona kwamanyikwe kokuphila kwamaseli e-beta agcwele.
Kuyaphawuleka ukuthi ngokusetshenziswa isikhathi eside kokutholakala kwe-sulfonylurea, umphumela wabo omuhle wokuqala ulahlekile ngokuphelele. Umuthi uyeka ukuthinta ukuphepha kwe-insulin. Ososayensi bakholelwa ukuthi lokhu kungenxa yokwehla kwenani lama-receptors kumaseli e-beta. Kwabuye kwembulwa ukuthi ngemuva kwekhefu ekwelashweni okunjalo, ukusabela kwalawa maseli kulo muthi kungabuyiselwa ngokuphelele.
Amanye ama-sulfonylureas nawo anganikeza umphumela owengeziwe we-pancreatic. Isenzo esinjalo asinayo inani elibalulekile lomtholampilo. Imiphumela eyengeziwe ye-pancreatic ifaka:
- ukwanda kokucabanga kwezicubu ezixhomekeke kumsulin kuya ku-insulin yemvelo ye-endo native;
- kwehle ukukhiqizwa kwe-glucose esibindini.
Yonke inqubo yokuthuthukiswa kwale miphumela emzimbeni ingenxa yokuthi izinto ("Glimepiride" ikakhulukazi):
- khuphula inani lama-receptors azwela i-insulin esitokisini sokuqondiwe;
- kufaneleke ngcono ukusebenzisana kwe-insulin-receptor;
- shintsha ukuguqulwa kwesiginali ye-postreceptor.
Ngaphezu kwalokho kunobufakazi bokuthi i-sulfonylurea derivatives ingaba yisisulu sokukhishwa kwe-somatostatin, okuzokwenza ukuthi icindezele ukukhiqizwa kwe-glucagon.
Sulfonylureas
Kunezizukulwane eziningana zale nto:
- Isizukulwane sokuqala: "Tolazamide", "Tolbutamide", "Carbutamide", "Acetohexamide", "Chlorpropamide";
- Isizukulwane sesibili: Glibenclamide, Glikvidon, Glisoksid, Glibornuril, Gliklazid, Glipizid;
- Isizukulwane sesithathu: I-Glimepiride.
Kuze kube manje, ezweni lethu, izidakamizwa zesizukulwane soku-1 cishe azisetshenziswa ekusetshenzisweni.
Umehluko omkhulu phakathi kwezidakamizwa zesizukulwane sokuqala nesesi-2 ngamazinga ahlukahlukene womsebenzi wabo. Isizukulwane sesibili sulfonylurea singasetshenziswa kumithamo ephansi, esiza ukusiza ngokufanelekile ukunciphisa amathuba emiphumela emibi ehlukahlukene.
Ekhuluma ngamanani, umsebenzi wawo uzoba ngaphezu kwama-50 noma ngisho nokuphindwe kayikhulu. Ngakho-ke, uma isilinganiso esidingekayo somuthi wansuku zonke wezidakamizwa zesizukulwane sokuqala kufanele sisuke ku-0,75 siye ku-2 g, khona-ke izidakamizwa zesizukulwane sesibili zinikeza umthamo we-0,02-0.012 g.
Okunye okususelwa ku-hypoglycemic nakho kungahlukahluka ekubekezelelekeni.
Izidakamizwa ezaziwa kakhulu
I-Gliclazide - Lokhu kungenye yalezo zidakamizwa ezinqunywe kaningi. Umuthi awunagalelo lokulinganisa le-hypoglycemic kuphela, kepha futhi unengxenye ekuthuthukisweni:
- izinkomba ze-hematological;
- izakhiwo zegazi
- izinhlelo ze-heestatic, i-microcirculation yegazi;
- umsebenzi we-heparin ne-fibrinolytic;
- ukubekezelelwa kwe-heparin.
Ngaphezu kwalokho, i-Glyclazide iyakwazi ukuvimba ukuthuthukiswa kwe-microvasculitis (ukulimala kwe-retinal), icindezele noma yikuphi ukubonakaliswa okunolaka kwamapuleti, ikhulisa kakhulu inkomba yokuphambana futhi ibonise izakhiwo ze-antioxidant ezinhle kakhulu.
I-Glycvidon - umuthi ongabekelwa lawo maqembu eziguli onomthelela omncane wezinso. Ngamanye amagama, inqobo nje uma izinso zibiza amaphesenti ama-5 ama-metabolites, namanye asele angama-95 - amathumbu
I-Glipizide Inomphumela omenyezelwe futhi ungamelela izingozi ezimbalwa ezenzakalelayo ekuphendukeni kwe-hypoglycemic. Lokhu kwenza ukuthi kungenzeki ukuhlanganisa futhi kungabi nama-metabolites asebenzayo.
Izici zokusetshenziswa kwama-ejenti omlomo
Amaphilisi we-antidiabetesic kungaba ukwelashwa okuyinhloko kohlobo lwesifo sikashukela 2, esizimele sokudla i-insulin. Leyo mishanguzo iyanconywa ezigulini ezineminyaka engaphezu kwengu-35 futhi ngaphandle kwezinkinga ezinjalo.
- ketoacidosis;
- ukusilela kokudla okunempilo;
- izifo ezifuna usizo oluphuthumayo lwe-insulin.
Ukulungiswa kwe-Sulfonylurea akuboniswanga kulezi ziguli, noma ngokudla okwanele, imfuneko yansuku zonke ye-insulin ye-hormone idlula uphawu lwamayunithi angama-40. Ngaphezu kwalokho, udokotela ngeke abanikeze incwadi uma kukhona uhlobo olunamandla lwesifo sikashukela, umlando wokukhathazeka kwesifo sikashukela kanye ne-glucosuria ephezulu emelene nemvelaphi yokwelashwa okufanele.
Ukudluliselwa ekwelapheni nge-sulfonylurea kungenzeka ngaphansi kwesimo se-carbohydrate metabolism ephazamisekile, kunxephezelwe ngemijovo eyengeziwe ye-insulin ngemithamo yamayunithi angaphansi kwama-40. Uma kudingekile, kuze kufinyelele kumayunithi angama-10, ukuguqulwa kuzokwenziwa kokutholwa kwalesi sidakamizwa.
Ukusetshenziswa isikhathi eside kwe-sulfonylurea derivatives kungadala ukukhula komzimba, okunganqotshwa kuphela ngokuhlanganiswa kwenhlanganisela nokulungiselela kwe-insulin. Ngohlobo 1 sikashukela, iqhinga elinjalo lizonikeza umphumela omuhle ngokushesha ngokwanele futhi lizosiza ukunciphisa isidingo sansuku zonke se-insulin, futhi sithuthukise inkambo yesifo.
Ukuncipha kokuqhubeka kwe-retinopathy ngenxa ye-sulfonylurea kwaphawulwa, futhi i-retinopathy yesifo sikashukela iyinkinga enkulu. Lokhu kungahle kube ngenxa yomsebenzi we-angioprotective we-derivatives wawo, ikakhulukazi lawo wesizukulwane sesi-2. Noma kunjalo, kukhona amathuba athile womphumela wabo we-atherogenic.
Kumele kuqashelwe ukuthi okususelwa kulo muthi kungahlanganiswa ne-insulin, kanye nama-biguanides kanye ne- "Acarbose". Lokhu kungenzeka ezimweni lapho impilo yesiguli ingathuthuki ngisho nangamayunithi ayi-100 e-insulin ngosuku.
Usebenzisa izidakamizwa ezinciphisa ushukela, kufanele kukhunjulwe ukuthi umsebenzi wabo unganciphisa:
- ama-anticoagulants angaqondile;
- ama-salicylates;
- "I-Butadion";
- Ethionamide;
- ICyclophosphamide;
- ama-tetracyclines;
- I-Chloramphenicol.
Lapho usebenzisa lezi zimali ngaphezu kwezidakamizwa ze-sulfa, i-metabolism ingathikamezeka, okuzoholela ekwakhiweni kwe-hyperglycemia.
Uma uhlanganisa okususelwa ku-sulfonylurea ne-thiazide diuretics (ngokwesibonelo, "Hydrochlorothiazod") ne-BKK ("Nifedipine", "Diltiazem") kumthamo omkhulu, khona-ke ukuphikisana kungaqala ukukhula. Ama-Thiazides avimba ukusebenza kokuphuma kwe-sulfonylurea ngokuvula iziteshi ze-potassium. Ama-LBCs aholela ekuphazamisweni ekunikezelweni kwama-calcium ion kumaseli we-beta wamanyikwe.
Okususelwa ku-sulfonylureas kukhulisa kakhulu umphumela nokubekezelela utshwala. Lokhu kungenxa yokulibaziseka kwenqubo yoku-oxidation ye-acetaldehyde. Ukubonakaliswa kokuphendula okufana ne-antabuse nakho kungenzeka.
Ngaphezu kwe-hypoglycemia, imiphumela engathandeki ingaba:
- ukuphazamiseka kwe-dyspeptic;
- i-cholestatic jaundice;
- isisindo somzimba;
- i-aplastic noma i-hemolytic anemia;
- ukuthuthukiswa kokungafani komzimba;
- leukopenia eguqukayo;
- i-thrombocytopenia;
- i-agranulocytosis.
Meglitinides
Ngaphansi kwama-meglitinides kufanele aqondwe ngabalawuli be-prandial.
I- "Repaglinide" ithathwe kwe-benzoic acid. Umuthi uhlukile ngesakhiwo samakhemikhali kusuka kokutholakala kwe-sulfonylurea, kepha banomphumela ofanayo emzimbeni. I-Repaglinide ivimba iziteshi ze-potassium ezincike ku-ATP kumaseli e-beta asebenzayo futhi ikhuthaza ukwenziwa kwe-insulin.
Ukuphendula komzimba kuza isigamu sehora ngemuva kokudla futhi kuboniswa ngokuncipha koshukela wegazi. Phakathi kokudla, ukugcwala kwe-insulin akushintshi.
Njengezidakamizwa ezisuselwa kokususweni kwe-sulfonylurea, ukusabela okuyinhloko okuyiphutha yi-hypoglycemia. Kakhulu ngokucophelela, umuthi unganconywa kulezo ziguli ezinokwehluleka kwe-renal noma kwesibindi.
INateglinide ithathwe ku-D-phenylalanine. Umuthi wehluka kwezinye ezifanayo ekusebenzeni kahle ngokushesha, kepha ungazinzi. Kuyadingeka ukusebenzisa umuthi ngohlobo lwe-2 yesifo sikashukela ukunciphisa izinga lokuqina kwe-postprandial hyperglycemia.
AmaBiguanides abaziwa kusukela ngeminyaka yama-70s yekhulu leminyaka edlule futhi ayebekelwe ukugcinwa kwe-insulin ngamaseli e-beta pancreas. Umphumela wazo unqunywa ukuvinjelwa kwe-gluconeogenesis esibindini kanye namandla akhulayo okubamba ushukela. Ngaphezu kwalokho, ithuluzi linganciphisa ukungasebenzi kwe-insulin futhi lenyuse ukubopha kwalo kuma-insulin receptors. Kule nqubo, i-metabolism kanye nokumuncwa kwe-glucose kuyanda.
AmaBiguanides awawehlisi ushukela wegazi lomuntu ophilile nalabo abahlushwa uhlobo lwe-2 sikashukela mellitus (okunikezwe ukuzila ebusuku).
I-Hypoglycemic biguanides ingasetshenziswa ekwakhiweni kwesifo sikashukela sohlobo 2. Ngaphezu kokunciphisa ushukela, lesi sigaba sezidakamizwa ngokusetshenziswa kwazo isikhathi eside sithinta kahle i-fat metabolism.
Njengomphumela wokusetshenziswa kwezidakamizwa zaleli qembu:
- i-lipolysis iyasebenza (inqubo yokuhlukanisa amafutha);
- ukwehla kwesifiso sokudla;
- isisindo kancane kancane sibuyela kokujwayelekile.
Kwezinye izimo, ukusetshenziswa kwazo kuhambisana nokuncipha kokuqukethwe kwama-triglycerides ne-cholesterol egazini, kungashiwo ukuthi ama-biguanides amaphilisi okwehlisa ushukela wegazi.
Kuhlobo 2 sikashukela i-mellitus, i-carbohydrate metabolism engenampilo ingahle ihlotshaniswe nezinkinga ku-fat metabolism. Cishe amaphesenti angama-90 amacala, iziguli zikhuluphele. Ngenxa yalesi sizathu, ngokuthuthukiswa kwesifo sikashukela, kanye nokukhuluphala okusebenzayo, kuyadingeka ukusebenzisa izidakamizwa ezenza ukuthi umzimba ube ne-lipid metabolism.
Isibonakaliso esiyinhloko sokusetshenziswa kwe-biguanides uhlobo lweshukela sikashukela. Umuthi ubaluleke kakhulu ngokubhekisele emuva ngemuva kwesisindo ngokweqile kanye nokwelashwa kokudla okungasebenzi noma ukusebenza okunganele kokulungiselela kwe-sulfonylurea. Isenzo se-Biguanides asibonakaliswa uma kungekho i-insulin egazini.
I-Alpha glucose inhibitors ivimbela ukuqhekeka kwama-polysaccharides nama-oligosaccharides. Ukufakwa nokukhiqizwa kweglucose kuyancishiswa futhi ngaleyo ndlela kunesixwayiso sokuthuthuka kwe-postprandial hyperglycemia. Wonke ama-carbohydrate aphuthwe nokudla, esimweni sawo esingashintshiwe, angena ezingxenyeni eziphansi zamathumbu amancane nakakhulu. Ukufakwa kwe-monosaccharides kuthatha amahora ama-4.
Ngokungafani nezidakamizwa ze-sulfa, i-alpha glucose inhibitors ayikhulisi ukukhishwa kwe-insulin futhi ayinakubangela i-hypoglycemia.
Njengomphumela wezifundo, kwafakazelwa ukuthi ukwelashwa ngosizo lwe- "Acarbose" kungahle kuhambisane nokuncipha kwamathuba okuthola imithwalo emibi ye-atherossteosis.
Ukusetshenziswa kwama-inhibitors anjalo kungaba ngesimo se-monotherapy, futhi futhi ukuwahlanganisa nezinye izidakamizwa zomlomo ezinciphisa ushukela wegazi. Umthamo wokuqala uvame ukuba ngama-25 kuye kwangama-50 mg ngokushesha ngaphambi noma ngesikhathi sokudla. Ngokulashwa okwalandela, umthamo ungakhushulwa ufike ku-maximum (kepha ungabi ngaphezu kwama-600 mg).
Izinkomba eziphambili zokuqokwa kwe-alpha-glucosidase inhibitors yilezi: uhlobo lwe-2 sikashukela i-mellitus nge-tiba elibi lokudla, uhlobo 1 lwesifo sikashukela, kepha kuncike ekwelashweni okuhlanganisa.
