Kwa zaka pafupifupi 50, madokotala akhala akugwiritsa ntchito mankhwala a sodiumfanfanuside 2 ngakhale atakhala kuti njira yawo yotsitsira shuga ndiyovuta.
Kukonzekera kwa gulu la sulfonamide kumakhudza makamaka ma cell a beta, motero kumapangitsanso insulin.
Kukonzekera kwa Sulfanilamide kuli ndi zochepa zowonjezera pancreatic. Pamodzi ndi izi, kuwunika kwa nthawi yayitali glycemic nthawi ya mankhwala ndi sulfonamides:
- amachepetsa kuphatikiza kwa shuga m'magazi;
- Amachita bwino poyambira insulin pakudya;
- bwino mphamvu ya insulin pa minofu ndi adipose minofu.
Ma Sulfanilamides amagawidwa mu mankhwala a m'badwo woyamba (sagwiritsidwa ntchito pano ku Russia) ndi mankhwala a m'badwo wachiwiri, mndandanda uli motere:
- glipizide
- gliclazide
- glycidone
- glibenclamide,
kukhala gulu lalikulu lothandizira matenda ashuga.
Kapangidwe ka sulfonamide group glimepiride, chifukwa cha mawonekedwe ake apadera, amatanthauza zinthu zomwe zimachepetsa shuga za m'badwo wachitatu.
Njira yamachitidwe
Kupanga kwa zochita za mankhwala a gulu la sulfanilamide, omwe amathandizira kuchepetsa shuga, kumachitika chifukwa cha kukondoweza kwa insulin, komwe kumayendetsedwa ndi njira zamtundu wa potaziyamu wa ATP zomwe zimagwira mu cell ya plasma ya cell ya beta.
Njira zopangira potaziyamu za ATP zimakhala ndi 2 subunits. Chimodzi mwazigawozi zili ndi sulfonamide receptor, ndipo ina imakhala mwachindunji. Odwala omwe ali ndi matenda a shuga 2 a mtundu wa mellitus, omwe ntchito ya maselo a beta amasungidwa mpaka penapake, receptor imamanga sulfonamide, yomwe imatsogolera kutsekedwa kwa njira ya potaziyamu ya ATP.
Zotsatira zake, potaziyamu imadziunjikira mkati mwa maselo a beta, omwe amatsitsidwa, omwe amachititsa kuchuluka kwa calcium kulowa mu cell ya beta. Kuchuluka kwa calcium mkati mwa ma cell a beta kumapangitsa kuti ma cell a insulin atengeke kupita ku cytoplasmic membrane ya cell yomwe amaphatikiza, ndipo malo a interellular amadzaza ndi insulin.
Tiyenera kudziwa kuti kukondoweza kwa insulin katulutsidwe ndi secretogens sikudalira kuchuluka kwa glucose m'magazi, komanso kuchuluka kwa plasma insulin concentration kumapangitsa kuchepa kwa postprandial komanso kudya glycemia.
Pankhaniyi, sulfanilamide secretogens-HbA1 ali ndi kutchulidwa kotsitsa shuga, kuchepetsa shuga kumachitika ndi 1-2%. Mukamathandizidwa ndi mankhwala omwe si a sulfanelamide, shuga amachepetsedwa ndi 0.5-1% yokha. Izi ndichifukwa chomaliza mwachangu.
Mankhwala a Sulfanilamide mwina ali ndi chiwopsezo chowonjezereka cha zimakhala ndi chiwindi. Komabe, njira zomwe zikuthandizira kuchepetsa hyperglycemia sizinakhazikitsidwebe mpaka pano.
N`zotheka kuti sulfanilamide hyperstimulation ya secretion ya mahomoni-insulin mu portal chiwindi timapitiriza mphamvu ya insulin pa chiwindi ndi amachepetsa kudya hyperglycemia.
Matenda amtundu wa glycemia amachepetsa kuwopsa kwa glucose ndipo potero amawonjezera mphamvu ya insulin yomwe ili pachiwopsezo cha insulin yotengera insulin (adipose, minofu).
Sulfanilamide gliclazide mu mtundu 2 wa matenda a shuga amabwezeretsa gawo loyambitsidwa (3-5 min) gawo la insulin katulutsidwe, kamene, kamapangitsa kusokonezeka kwa gawo lachiwiri lalitali (maora 1-2), wokhala ndi mtundu wa 2 shuga.
Mankhwala a pharmacokinetics a mankhwala a sulfa amasiyana pamlingo wina wa adsorption, kagayidwe kake komanso kuchuluka kwa zotulutsa. Mankhwala osokoneza bongo omwe ali pamndandanda wam'badwo wachiwiri ndi wachitatu samangidwa ndi mapuloteni a plasma, omwe amawasiyanitsa ndi mankhwala omwe ali pamndandanda wam'badwo woyamba.
Kukonzekera konse kwa sulufanilamide kumakhala kofikira kwathunthu ndi minofu. Komabe, kuyambika kwa zochita zawo ndi kutalika kwake zimatengera mikhalidwe ya pharmacokinetic, yomwe imatsimikiziridwa ndi kapangidwe ka mankhwala.
Mankhwala ambiri a sulfa amakhala ndi theka lalitali, amakhala nthawi yayitali 4-10. Popeza ambiri a sulfonamides amagwira ntchito bwino ngati amwedwa kawiri, ngakhale atakhala hafu ya moyo kuchokera m'magazi, mwina m'maselo a beta pamsempha wa minofu, kuchotsedwa kwawo kumakhala kotsika kuposa magazi.
Mankhwala a Glyclazide sulfanilamide tsopano akupezeka kwa nthawi yayitali ndipo amapereka kuchuluka kwa plasma kwa maola 24 (diabeteson MB). Mndandanda waukulu wa mankhwala a sulfa umagwera m'chiwindi, ndipo ma metabolites awo amachotsedwamo pang'ono ndi impso ndipo pang'ono ndi thirakiti la m'mimba.
Mlingo ndi mitundu yothandizira
Nthawi zambiri, mankhwalawa sulfonamides amayamba ndi mlingo wochepa ndipo umachulukitsa pakadutsa masiku 4-7 kufikira pomwe zotsatira zake zingachitike. Odwala omwe amatsatira zakudya, komanso omwe amachepetsa kuchepa thupi, amatha kuchepetsa kuchuluka kwa sulfonamides kapena kuwasiya kwathunthu.
Komabe, pali umboni wosonyeza kuti kugwiritsa ntchito mankhwala ochepa a sulfonamides kumapereka mpata kwa nthawi yayitali kuti mukhale shuga.
Odwala ambiri amakwaniritsa kuchuluka kwawo komwe akufuna glycemic akagwiritsa ntchito 1/3, 1/2 ya mlingo waukulu. Koma ngati munthawi ya chithandizo ndi sulfonamides kufunika kwa glucose komwe sikunachitike, ndiye kuti mankhwalawo amaphatikizidwa ndi osagwiritsa ntchito insulin hypoglycemic kapena ndi insulin.
Mukamasankha sulfonamides, pali zinthu zingapo zofunika kuziganizira:
- nthawi ndi nthawi yochitapo kanthu;
- kukakamiza;
- chikhalidwe cha kagayidwe;
- zochitika zoyipa.
Limagwirira a zochita za sulfonamide zimatengera muyeso wa mgwirizano wake ndi sulfonamide receptor. Pankhaniyi, glyclazide, glimepiride, glibenclamide amadziwika kuti ndi othandiza komanso othandizira.
Ndizofunikira kudziwa kuti mankhwala a sulfanilamide amakhudza magwiridwe antchito a calcium m'misempha ndi ziwiya zosiyanasiyana, zomwe zimakhudza makina a vasodilation. Sizikudziwikabe kuti njirayi ndi yofunika kwambiri mwachipatala.
Ngati mankhwala osakwanira alipo osakwanira, mutha kugwiritsa ntchito kuphatikiza ndi zinthu zilizonse zomwe zimachepetsa shuga. Chosiyana ndi secretogens - meglitinides, amenenso amamangira ku sulfonamide receptors.
Mankhwalawa ophatikizidwa ndi mankhwala omwe amaphatikizidwa ndi mndandanda wa sulfonamides a zochita zowonjezera amathandizidwa ndimankhwala omwe ali ndi limakanidwe mosiyana ndi sulfanilamides.
Kuphatikiza kwa mankhwala a sulfonamide ndi metformin ndikolondola, chifukwa chomaliza sichikhudza kutulutsidwa kwa insulin ya mahomoni, koma kumawonjezera kukhudzika kwa chiwindi kwa izo, chifukwa chake, kutsitsa kwa shuga kwa sulfonamides kumawonjezeka.
Kuphatikiza komweku kwa mankhwalawa ndikofunikira kwambiri pochiza matenda amtundu wa 2 shuga. Ndi kuphatikiza kwa mankhwala a sulfa okhala ndi alpha glucosidase inhibitors, shuga wochepa amachokera m'matumbo ang'ono atatha kudya, motero glycemia ya postprandial imachepa.
Glitazones imawonjezera kukhudzika kwa chiwindi ndi minofu ina yodalira insulini ku insulin-insulin, yomwe imalimbitsa magwiritsidwe a sulfanilamide-analimbikitsa insulin secretion. Ngati tilingalira za kuphatikiza kwa mankhwala omwe amaphatikizidwa ndi mndandanda wa sulfonamides omwe ali ndi insulin, ndiye kuti malingaliro a madokotala pankhaniyi ndiwosangalatsa.
Kumbali ina, ngati pakufunika mankhwala a insulin, ndiye kuti matupi ake atha, ndiye kuti lingaliro lina la mankhwala a sulfonamide ndilopanda tanthauzo.
Nthawi yomweyo, ngati wodwala yemwe amadziwikanso insulin atasungidwa pang'ono akukana kugwiritsa ntchito sulfanilamide, izi zidzafunika kuchuluka kwa insulini kwambiri.
Poganizira izi, kudziwunikira kwa kagayidwe kake ka mankhwala amkati mwa insulin ndi njira yabwino kwambiri kuposa mankhwala ena a insulin. Ngakhale ndikakhala ndi maselo ochepa a beta, kunyalanyaza kudziletsa sikulakwa.
Mndandanda wa mankhwala a sulfonamide a m'badwo wachiwiri wotchuka kwambiri ku Russia:
- glycidone;
- gliclazide MV;
- glipizide;
- glimepiride;
- glibenclamide.
Zizindikiro
Mukamamwa sulfonamides, mulingo wa HbA1c uyenera kuchepa mkati mwa 1-2%. Mankhwala a Sulfanilamide, monga mankhwala ena ochepetsa shuga, ndi othandiza kwambiri kwa odwala omwe ali ndi vuto lotsika la glycemic kuposa omwe ali ndi odwala omwe zizindikiro zawo zinali pafupi ndi zachilendo (HbA1c 7%).
Kukonzekera koyenera kwambiri kwa sodfanilamide kwa odwala omwe ali ndi mtundu wa matenda a shuga 2, omwe ali ndi vuto la kupanga insulini, komabe, malo ogulitsira a cell a beta sanathebe ndipo ali okwanira kulimbikitsa sulfonamides.
Mndandanda wamgulu la odwala omwe ali ndi zotsatira zabwino:
- Matenda a shuga adayamba pambuyo pa zaka 30.
- Kutalika kwa matendawa ndi ochepera zaka 5.
- Kuthamanga kwa hyperglycemia kosakwana 17 mmol / L.
- Odwala achilendo komanso onenepa kwambiri.
- Odwala kutsatira malangizo a wathanzi, komanso masewera olimbitsa thupi.
- Odwala opanda insulin kwathunthu.
Wachinayi mwa odwala omwe adapezeka ndi mtundu wachiwiri wa matenda osokoneza bongo samvera pa mankhwala a sulfonamides. Kwa iwo, ndikofunikira kusankha mankhwala ena othandiza kuchepetsa shuga.
Pakati pa odwala ena omwe adalandira bwino chithandizo, 3-4% amasiya kutaya mtima pakapita chaka chimodzi (tachyphylaxis, kachiwiri kugonjetsedwa).
Choyamba, izi zimachitika chifukwa chakuchepa kwa kubisalira kwa maselo a beta komanso chifukwa cholemera kwambiri (kuchuluka kwa insulin).
Zotsatira zoyipa zakumwa sizingachitike chifukwa chazomwe tafotokozazi, komanso zifukwa zina:
- zolimbitsa thupi zochepa;
- kusatsatira bwino
- kupsinjika
- matenda oyamba (kugunda, kugunda kwa mtima, matenda);
- Kukhazikitsidwa kwa mankhwala amene amachepetsa mphamvu ya sulfonamides.
Odwala ena omwe ali ndi matenda a shuga a mtundu wachi 2, akamamwa mankhwala a sulfonamides (glibenclamide), akuti "looping syndrome" amawoneka, ofanana ndi a Somogy syndrome amtundu wa 1 ashuga.
Kusintha kwa glibenclamide ndi mankhwala osakhudzika pang'ono (hypimepiride) kulipiritsa shuga.
Ndizotheka kuti nocturnal hypoglycemia yogwiritsa ntchito glibenclamide imakhumudwitsa m'mawa hyperglycemia mwa odwalawa, omwe amakakamiza dokotala kuti awonjezere kuchuluka kwa mankhwalawa. Ndipo usiku hypoglycemia pamenepa imakulitsidwa ndipo zimatsogolera kuwonongeka kwakukulu kwa matenda ashuga m'mawa ndi masana.
Izi ndizomwe "looping syndrome" imatanthawuza pochiza matenda a shuga 2 a mellitus omwe ali ndi mankhwala a sulfonamide. Masiku ano, metformin (biguanide) ndi mankhwala oyamba a mtundu woyamba wa matenda ashuga 2.
Sulfanilamides nthawi zambiri amapatsidwa mankhwala oletsa ntchito ndi mankhwalawa. Ngati wodwala samvera kukonzekera kwaformform kapena kumukana pazifukwa zina, sulfonamides a 2 mtundu wa mellitus angagwiritsidwe ntchito ngati chithandizo cha basal.
Contraindication
Kukonzekera kwa Sulfanilamide kumapikisidwa chifukwa cha hypersensitivity kwa iwo, komanso matenda ashuga a ketoacidosis, omwe amakhala ndi chikomokere kapena popanda iwo. Ngati vutoli layamba chifukwa cha mankhwalawa a mtundu wachiwiri wa shuga omwe ali ndi mndandanda wa sulfonamides, ndiye kuti ayenera kuthetsedwa ndipo insulini ya DKA iyenera kukhazikitsidwa.
M'mayeso ena azachipatala omwe sanakwaniritse bwino miyezo yapamwamba ya kafukufuku wa sayansi, chiopsezo chachikulu cha kufa chifukwa cha matenda amtima omwe adayamba ndi sulfonamide mankhwala adapezeka.
Koma pakufufuza kwakukulu kwa asayansi aku Britain, izi sizinatsimikizidwe. Chifukwa chake, lero, chiwopsezo cha matenda amtima oyamba chifukwa cha mankhwala a sulufa sichitsimikiziridwa.
Zofunika! Vuto lalikulu kwambiri lomwe limatha kukhala ndi mankhwala a sulfanilamide ndi hypoglycemia ndi mitundu yake yoopsa. Chifukwa chake, odwala ayenera kudziwitsidwa kwakukulu za kuthekera kwa vutoli!
Hypoglycemia ndizovuta kudziwa odwala okalamba ndi beta-blocker. Chizolowezi chake mukamamwa sulfonamides ndi:
- Odwala otopa omwe ali ndi vuto la kuperewera kwa zakudya.
- Odwala omwe ali ndi vuto la pituitary, adrenal kapena chiwindi.
- Odwala ndi kutchulidwa choletsa caloric kudya.
- Odwala atamwa mowa.
- Anthu omwe ali ndi matenda ashuga pambuyo polimbitsa thupi kwambiri.
Odwala omwe apsinjika, atavulala, atachira, kapena akuchitidwa opaleshoni, amatha kutaya ululu wa glycemic ndi kukonzekera kwa svetfanilamide. Poterepa, pakufunika kuwonjezera kwa insulin, osachepera monga gawo lakanthawi. Koma chiwopsezo cha kukhala ndi hypoglycemia, komanso chiwopsezo chakuti pakhale chikomokere cha hypoglycemic, chikuwonjezeka.
