GCS - ukuthi lo muthi? Isenzo nemiphumela izidakamizwa glucocorticosteroids

Ngokuqinisekile uke wezwa hormone steroid. umzimba wethu njalo ukhiqiza ukuba alawule izinqubo zokuphila. Kulesi sihloko, sizoxoxa glucocorticoids - hormone steroid, okuyinto akhiqizwa cortex adrenal. Nakuba iningi lethu unesithakazelo zokwenziwa analogue zabo - GCS. Kuyini imithi? Ngoba yikuphi bajwayele nokuthi uluhlobo luni umonakalo babangela? Ake sibone.

ulwazi olujwayelekile mayelana GCS. Kuyini imithi?

umzimba wethu lwati hormone steroid ezifana glucocorticoids. Basuke ezivezwa cortex adrenal, kanye nokusetshenziswa yabo ikakhulu ezihlobene ekwelapheni esingamahlalakhona adrenal. Namuhla, usebenzisa hhayi kuphela glucocorticoids yemvelo, kodwa futhi zokwenziwa analogue zabo - GCS. Kuyini imithi? Ukuze isintu, lezi analogs kusho okuningi, njengoba babe emzimbeni eqeda ukuvuvukala, immunosuppressive, antishock, umphumela anti-iguliswa.

Glucocorticoids sezikujwayele njengoba izidakamizwa (okukhulunywa ngayo esihlokweni - PM) ku-yalolucwaningo 40 XX leminyaka. Ngu ekupheleni 30s kwekhulu lamashumi amabili, ososayensi bathole steroid i-hormone compounds e cortex womuntu adrenal, kwathi ngo-1937 khona eyedwa deoxycorticosterone mineralocorticoid. Ngasekuqaleni kwawo-40-yalolucwaningo zathathwa glucocorticoid hydrocortisone futhi cortisone. imiphumela kwemithi ye cortisone futhi hydrocortisone babe ahlukahlukene ngakho, ukuthi kwanqunywa ukuzisebenzisa njengoba izidakamizwa. Ngemva kwesikhathi esithile, ososayensi wayifeza zamagama abo.

I glucocorticoid kakhulu asebenzayo umzimba womuntu - cortisol (Analogue - hydrocortisone, ogama intengo - ruble 100-150), futhi kubhekwa ezinkulu. Kungenzeka futhi ukwaba kancane esebenzayo: corticosterone, cortisone, 11-deoxycortisol, 11-dehydrocorticosterone.

Kuzo zonke glucocorticoids zemvelo njengoba ukusetshenziswa kwezidakamizwa atholakala kuphela hydrocortisone futhi cortisone. Nokho, lona wamuva izimbangela side effects kaningi kunanoma iyiphi enye i-hormone, yingakho ngesikhathi samanje ukusetshenziswa kwaso kwezokwelapha lilinganiselwe. Kuze kube manje, kuphela esetshenziswa glucocorticoid hydrocortisone noma esters yayo (hydrocortisone hemisuccinate futhi hydrocortisone acetate).

Ngokuphathelene glucocorticosteroids (zokwenziwa glucocorticoids), okwamanje thina kwemiqondo eziningi ejenti ezinjalo, phakathi lapho fluorinated (flumethasone, triamcinolone, betamethasone, dexamethasone, njll) Futhi-non-fluorinated (methylprednisolone, prednisolone, prednisone) glucocorticoids.

ejenti okunjalo asebenzayo kuka nozakwabo zemvelo, futhi kudingeka for ekwelapheni ngemithamo ezincane.

Lo mshini wezenzo ka corticosteroids

Isenzo glucocorticoids ezingeni yamangqamuzana bengayiqondi ngokugcwele. Ososayensi bakholelwa ukuthi lezi izidakamizwa isinyathelo amaseli ezingeni ukulawulwa isakhi sofuzo umbhalo.

Corticosteroids uxhumana intracellular glucocorticoid receptor abakhona cishe kuzo zonke cell zomzimba womuntu. Uma engekho ama-hormone receptor (okuyizinto amaprotheni cytosolic) zimane ingasebenzi. In the state ngasebenzi, bayingxenye le heterocomplexes, okuhlanganisa futhi immunophilin, ukushisa ukushaqeka amaprotheni nokunye.

Lapho ama zingene amaseli (ngokusebenzisa ulwelwesi), babopha ukuba receptor futhi kusebenze eziyinkimbinkimbi "glucocorticoid + yokwamukela", ngemva kwalokho-ke engena kuyi-nucleus yengqamuzana futhi baxhumana izifunda DNA okuyinto zitholakala isakhi sofuzo umgqugquzeli isinqamu steroid ohambelana (bebizwa futhi glucocorticoid 'kuphendula izakhi). Inxanxathela "+ glucocorticoid yokwamukela" uyakwazi lokulawula (zivimbela noma, Ngakolunye uhlangothi, kusebenze) inqubo umbhalo zezakhi zofuzo ezithile. Yilokhu kuholela ukucindezelwa noma ukukhuthazwa mRNA, kanye ushintsho synthesis enzyme ahlukahlukene namaprotheni wekulawula sokulamula imiphumela yeselula.

izifundo ezihlukahlukene ukukhombisa ukuthi eziyinkimbinkimbi "glucocorticoid + yokwamukela" is wasithukuthelela umbhalo ezicini eziningana, isib, ezifana isici yenuzi kappa B (NF-kB), noma Activator of umbhalo amaprotheni (AP-1) elawula izakhi zofuzo ehilelekile ukuzivikela komzimba, futhi ukuvuvukala (adhesion amangqamuzana, izakhi zofuzo cytokine, protease nokunye.).

Imiphumela eyinhloko GCS

glucocorticoids imiphumela emzimbeni womuntu baningi. La ma-hormone babe antitoxic, antishock, imunnodepressivnoe, antiallergic, isenzo antiinflammatory futhi antiinflammatory. Ake sihlolisise ukuthi izenzo corticosteroids.

• imiphumela anti-inflammatory ka corticosteroids. Ibangelwa nokucindezela umsebenzi phospholipase A liberatiou _2. Lapho okusithiyayo lokhu enzyme umzimba womuntu ukuyiveza (ukukhululwa) lo okusithiyayo of arachidonic acid ukwakheka ezinye balamuli ukuvuvukala (ezifana prostaglandins, leukotrienes, futhi troboksan t. D.). Ngaphezu kwalokho, glucocorticosteroids reception kunciphisa uketshezi exudation, vasoconstriction (ukuvaleka) capillary, ngcono microcirculation ku ukuvuvukala.
• umphumela Anti-iguliswa ka GCS. Kwenzeka ngenxa ukwehlisa uketshezi kanye synthesis mediators njengemithi yokungezwani komzimba nokuthile, ukunciphisa afundwa basophils, okusithiyayo of histamine ukukhululwa basophils futhi insika amaseli batiswe, wanciphisa inani B ne-T lymphocyte, ekunciphiseni ukuzwela lamaseli kuya mediators njengemithi yokungezwani komzimba nokuthile, impendulo izinguquko mzimba, kanye nokucindezela ukukhiqizwa omzimba.
• umsebenzi Immunosuppressive ka GCS. Kuyini imithi? Lokhu kusho ukuthi imithi zivimbela immunogenez, ukucindezela ukukhiqizwa kwamasosha omzimba. Corticosteroids zivimbela yokufuduka umnkantsha stem cells, zivimbela umsebenzi B ne-T lymphocyte zivimbela ukukhululwa kwe cytokines kusukela macrophage kanye leukocyte.
• Anti-esinobuthi antishock umphumela corticosteroids. Umthelela hormone kubangelwa-high blood pressure kubantu, kanye ukusebenza enzyme isibindi ehilelekile umzimba Xenon futhi endobiotikov.
• umsebenzi Mineralocorticoid. Glucocorticosteroids unekhono kuthiye sodium ne amanzi emzimbeni, sikhuthaze excretion potassium. Lokhu zokwenziwa esikhundleni akuzona kwafana hormone yemvelo, kodwa umphumela emzimbeni banayo.

Pharmacokinetics

Kuze kuphele isikhathi isinyathelo kwezidakamizwa letindzala zingahlukaniswa zibe:

1. Glucocorticosteroids isinyathelo emifushane (isib, hydrocortisone, intengo zazo kuhluka ruble 100 kuya ku-150).
2. Glucocorticosteroids nge ubude isilinganiso isenzo (prednisolone (impendulo okuyinto kahle), methylprednisolone).
3. Glucocorticosteroids nesenzo isikhathi eside (triamcinolone acetonide, dexamethasone, betamethasone).

Kodwa hhayi kuphela kungenzeka kuze kuphele isikhathi glucocorticosteroids kunqunywa. Ukwahlukanisa kubo kungase futhi kube imodi yokuphathwa:

• ngomlomo;
• intranasal;
• glucocorticosteroids imuncwe.

Nokho, Lokhu kuhlukaniswa, usebenza kuphela uhlelo glucocorticosteroids.

Kukhona ezinye izidakamizwa ngesimo yokugcoba kanye okhilimu (corticosteroids sendawo). Ngokwesibonelo, "Afloderm". Uphenyo ukwakhiwa okunjalo zinhle.

Ake sibheke izinhlobo corticosteroids letindzala wedwa.

steroid Oral ugxile ngokuphelele emathunjini ngaphandle kokudala izinkinga. Ngezenzo abophezele namaprotheni-plasma (transcortin, albumin). Ubuningi esiphezulu corticosteroids temlomo egazini kufinyelelwe emva 1.5 amahora ngemva kokuphathwa. Ebhekene biotransformation esibindini, izinso (kancane) kanye nezinye izicubu ngu conjugation ukuba glucuronide noma sulfate.

Cishe u-70% GCS conjugated excreted ku umchamo, omunye u-20% ngo-indle izobonisa kamuva, kanti bonke abanye - ne olunye uketshezi begazi (isib kamuva). Ingxenye - kusuka amahora 2 kuya ku-4.

Ungakha itafula elincane nge nemingcele pharmacokinetic ka corticosteroids ngomlomo.

Glucocorticosteroids. Izidakamizwa (amagama)	Ingxenye-ukuphila kwezicubu	Plasma isigamu-nokuphila
hydrocortisone	amahora 8-12	amahora 0.5-1.5
cortisone	amahora 8-12	amahora 0.7-2
Prednisolone (izibuyekezo kahle)	amahora 18-36	amahora 2-4
methylprednisolone	amahora 18-36	amahora 2-4
fludrocortisone	amahora 18-36	3.5 amahora
dexamethasone	amahora 36-54	5:00

steroid imuncwe e umkhuba emtholampilo yesimanje ethulwa triamcinolone acetonide, fluticasone propionate, mometasone furoate, budesonide futhi beclomethasone dipropionate.

Amapharamitha Pharmacokinetic kungabuye okwethulwa itafula:

Glucocorticosteroids. Izidakamizwa (amagama)	Wendawo umsebenzi eqeda ukuvuvukala	ivolumu yokusabalalisa	Plasma isigamu-nokuphila	Nekusebenta nokuwela kwawo isibindi
beclomethasone dipropionate	amayunithi 0,64.	-	0.5 amahora	70%
budesonide	1 iyunithi.	4.3 l / kg	1,7-3,4 ihora	90%
triamcinolone acetonide	amayunithi 0,27.	1.2 l / kg	amahora 1.4-2	80-90%
fluticasone propionate	1 iyunithi.	3.7 l / kg	amahora 3.1	99%
flunisolide	amayunithi 0,34.	1.8 l / kg	amahora 1.6	-

steroid acinene kwezokwelapha namuhla ethulwa fluticasone propionate, flunisolide, triamcinolone acetonide, mometasone furoate, budesonide futhi beclomethasone dipropionate. Abanye kwazo babizwa ngokuthi ngendlela efanayo njengoba corticosteroids imuncwe.

Ngemuva kwesicelo umthamo intranasal corticosteroids ugxile emathunjini nenye yalotshwa livela mucosa umgudu ngokuqondile egazini.

Glucocorticosteroids, ivaleleke ipheshana wokugaya ukudla, esikuthola cishe 1-8 amaphesenti, futhi pass lokuqala ngokusebenzisa isibindi biotransformed cishe ngokuphelele metabolites esingasebenzi.

Glucocorticosteroids okuyinto baye baba igazi, hydrolyze ukuba izinto esingasebenzi. Nasi etafuleni ngezimiso zawo pharmacokinetic:

Glucocorticosteroids. amalungiselelo	Bioavailability lapho bengena igazi, njengoba amaphesenti	Bioavailability lapho matasa kusukela ipheshana emathunjini, e amaphesenti
budesonide	34	11
beclomethasone dipropionate	44	20-25
mometasone furoate	<0.1	<1
triamcinolone acetonide	Ayikho Imininingwane	10,6-23
fluticasone propionate	0.5-2
flunisolide	40-50	21

Kushaqwe izidakamizwa ezifana ne "Afloderm" (impendulo egcina ziyavela on inetha), ukuchaza eceleni kwenza akukho mqondo. Ngamunye wabo ayisithako esiyinhloko esebenzayo, okuyinto kungenzeka kakade eshiwo ngenhla. Le mithi - corticosteroids zendawo, futhi achazwa avame ngesimo yokugcoba noma okhilimu.

Beka yokwelapha glucocorticosteroid (izinkomba ukusetshenziswa)

Ukuze uhlobo glucocorticosteroids izinkomba zayo ukusetshenziswa ngamunye. Ngakho, corticosteroids ngomlomo zisetshenziselwa ukwelapha:

• isifo Crohn;
• izilonda emathunjini;
• interstitial wamaphaphu iziyaluyalu;
• acute ukucindezeleka zokuphefumula syndrome;
• inyumoniya ezinzima;
• ezingamahlalakhona obstructive isifo yamaphaphu isigaba acute;
• isifuba somoya bronchial;
• thyroiditis subacute;
• azalwa naso Hyperplasia adrenal (kuleli cala, umuntu angenakho ukukhiqiza corticoids yena kanye iyaphoqeleka ukuba zokwenziwa analogue zabo);
• acute esingamahlalakhona adrenal.

Futhi ama asetshenziswa replacement therapy ye zamabanga aphansi naphezulu ukwehluleka napochechnikovoy.

corticosteroids Intranasal asetshenziselwa:

• rhinitis idiopathic (vasomotor);
• rhinitis non-iguliswa nge eosinophilia;
• pilipoze ekhaleni;
• zisetshenziswa rhinitis nomzimba (eziphikelelayo);
• ezithile zonyaka rhinitis nomzimba (ngezikhathi).

corticosteroids imuncwe zisetshenziselwa ukwelapha ezingamahlalakhona obstructive isifo samaphaphu, isifuba somoya bronchial.

Izimo

Okumele kuqashelwe kufanele aphathe GCS kulezi zimo emitholampilo:

• lactation;
• ukufiphala;
• Ezinye izifo cornea, elihlanganiswa kwezinso we epithelium;
• ukukhunta izifo ezibangelwa amagciwane esweni;
• ubovu ukutheleleka;
• isikhathi lokugoma;
• ugcunsula;
• ifomu abakhuthele of sofuba;
• herpes ukutheleleka;
• izifo letindzala fungal;
• abanye ukugula ngengqondo kanye nezimpawu elikhiqizayo;
• degree okunzima ukwehluleka kwezinso;
• nomfutho wegazi ophezulu;
• thromboembolism;
• isilonda duodenal noma esiswini;
• sikashukela;
• isifo Cushing sika.

Strictly contraindicated corticosteroids intranasal ezimweni ezinjalo:

• umongozima njalo emlandweni;
• oluhambisana diathesis;
• hypersensitivity.

Glucocorticosteroids: side effects

imiphumela emibi corticosteroids zingahlukaniswa zibe zendawo letindzala.

Endaweni side effects

Ihlukaniswe yaba imithelela corticosteroids imuncwe futhi intranasal.

1. imiphumela Local esibuhlungu esivela glucocorticosteroids imuncwe:

• ukukhwehlela;
• dysphonia;
• candidiasis we ngalo ingaphakathi ngomlomo kanye pharynx.

2. Endaweni imiphumela engemihle corticosteroids intranasal:

• perforation we septum acinene;
• umongozima;
• ukushiswa nokuphangwa ezomile nolwelwesi lwamafinyila kwekhala kanye pharynx;
• sneezing;
• ekhaleni silume.

Lefundo side effects

Umkhaya Ohlukene ngokusho izingxenye zomzimba, letisebenta.

1. Ingxenye isimiso sezinzwa esiyinhloko:

• kwengqondo;
• nokucindezeleka;
• Isasasa;
• ukuqwasha;
• ukucasuka.

2. Njengoba yisimiso senhliziyo nemithambo yegazi:

• thromboembolism;
• deep vein thrombosis;
• umfutho wegazi ophakeme;
• myocardiodystrophy.

3. Kusukela uhlelo zokuzala:

• hirsutism;
• imisiwe ukuthuthukiswa ngokobulili;
• nenkinga ocansini;
• engazinzile umjikelezo wokuya esikhathini.

4. Kusukela isimiso sokugaya ukudla bungene:

• okunamafutha isibindi;
• pancreatitis;
• opha pheshana emathunjini;
• izilonda steroid isisu namathumbu.

5. Kusukela ohlelweni endocrine:

• sikashukela;
• Cushing Syndrome;
• ukukhuluphala;
• yoma we- cortex adrenal ngenxa okusithiyayo umsebenzi wayo.

6. Kusukela eceleni umbono:

• ukufiphala;
• posterior ngwengwezi subcapsular.

7. Kusukela uhlelo zemisipha:

• imisipha esincunzayo;
• myopathy;
• efanele ukukhula izingane;
• avascular necrosis bone waphuka;
• kwamathambo.

8. Ukuze isikhumba:

• Alopecia;
• striae;
• ehlambulula kwesikhumba.

9. Eminye imiphumela emibi:

• amafomu acute ezithathelwanayo futhi ezingalapheki izinqubo ukuvuvukala;
• ukuvuvukala;
• sodium ne amanzi nokugcinwa emzimbeni.

izinyathelo zokuqapha

Kwezinye izimo, corticosteroids kufanele siyisebenzise ngokuqapha.

Ngokwesibonelo, iziguli isifo sokusha, i-hypothyroidism, hypoalbuminemia, kanye neziguli senile noma asebekhulile kungaba isinyathelo of corticosteroids ukugqanyiswa.

Ngo ukusetshenziswa corticosteroids ngesikhathi sokukhulelwa kufanele bacabangele umphumela olulindelekile yokuphathwa umama futhi ingozi nomphumela omubi zomuthi embungwini, njengoba corticosteroids zingaphazamisa ukuthuthukiswa ukukhula fetus ngisho ukukhubazeka ezifana ulwanga emfantwini nokunye.

Uma ngesikhathi ukusetshenziswa GCS nesineke ehlupheka ukutheleleka (inkukhu Pox, isimungumungwana, nokunye. D.), Kungase kwenzeke njengento ebaluleke kakhulu.

Esikhathini nokwelashwa kweziguli corticosteroids noma Izifo ukuvuvukala sokuhlasela kwamasosha omzimba (rheumatoid arthritis, izifo wamathumbu, omzimba izicubu erythematosus nokunye okunjalo. D.) Sightings ukumelana steroid kungabonakala nasemkhakheni.

Iziguli ethola ama temlomo isikhathi eside, kubalulekile ngezikhathi ukuthatha fecal igazi yokulumba futhi sidlule fibroezofagogastroduodenoskopiyu njengoba isilonda steroid ngesikhatsi ukwelashwa nge kungenzeka corticosteroids uze uphazanyiswe.

Ngo 30-50% eziguli ziphathwe corticosteroids isikhathi eside, ukuthuthukisa kwamathambo. Njengomthetho, kuthinta ngezinyawo, isandla, ukhalo, izimbambo, emgogodleni.

Ukuxhumana nezinye izidakamizwa

Zonke glucocorticosteroids (ngezigaba akunandaba lapha) uma nabo nezinye izidakamizwa ukunikeza umphumela othile, futhi lo mphumela akuyona omuhle umzimba wethu njalo. Nakhu okudingeka ukuthi ukwazi ngaphambi kokufaka corticosteroids ngokuhlanganyela nezinye izidakamizwa:

1. GCS futhi antacids - glucocorticosteroids ukumuncwa incipha.
2. GCS futhi barbiturates, phenytoin, hexamidine, diphenhydramine, carbamazepine, rifampicin - glucocorticosteroids biotransformation esibindini luyanda.
3. GCS futhi isoniazid, erythromycin - glucocorticosteroids biotransformation esibindini incipha.
4. SCS futhi salicylates, Phenylbutazone, barbiturates, digitoxin, penicillin akuzange kusize, chloramphenicol - ukuqedwa zonke lezi izidakamizwa buyathuthuka.
5. GCS futhi isoniazid - kokunikezwa kwe-psyche womuntu.
6. Corticosteroids futhi reserpine - ukuvela isimo sokucindezeleka.
7. GCS futhi tricyclic antidepressant - anda ingcindezi intraocular.
8. GCS futhi agonists - isenzo le mithi liyakhuphuka.
9. Corticosteroids futhi theophylline - isinyathelo eqeda ukuvuvukala we glucocorticoids inyuka, ukuthuthukisa imiphumela cardiotoxic.
10. SCS futhi isisu, amphotericin B, mineralocorticoid - kwandisa ingozi hypokalemia.
11. GCS futhi engaqondile anticoagulants, fibrinolytics, butadiene, ibuprofen, ethacrynic acid - kungase kulandelwe yezinkinga oluhambisana.
12. SCS futhi indomethacin, salicylates - le nhlanganisela kungabangela izilonda emathunjini yokusetshenziswa pheshana emathunjini.
13. Corticosteroids futhi paracetamol - the ubuthi zomuthi luyanda.
14. Corticosteroids futhi azathioprine - kwandisa ingozi ale nkinga, myopathy.
15. GCS futhi mercaptopurine - inhlanganisela kungaholela lokuhlushwa anda uric acid egazini.
16. GCS futhi hingamin - iyakhula imiphumela engadingeki lokhu izidakamizwa (corneal opacity, myopathy, dermatitis).
17. GCS futhi methandrostenolone - agqamise imiphumela emibi glucocorticoids.
18. Corticosteroids nensimbi amalungiselelo, androgens - anda zamagama ye-erythropoietin, futhi nalemvelaphi, anda erythropoiesis.
19. GCS futhi hypoglycemic izidakamizwa - ukunciphisa pheze ephelele ukusebenza kwabo.

isiphetho

Ama-steroid - izidakamizwa, ngaphandle okuyinto imithi yesimanje akunakwenzeka ukuba abiza. Zisetshenziswa ekwelapheni izigaba kakhulu lesi sifo, noma umane ukuthuthukisa isenzo izidakamizwa. Nokho, njengoba nazo zonke imithi, glucocorticosteroids side effects kanye babe Izimo kakhulu. Ungakhohlwa ngakho. Ngenhla siye ohlwini zonke izimo lapho akudingekile ukusebenzisa ama futhi wanikeza uhlu nokuxhumana corticosteroids nezinye izidakamizwa. lo mshini wezenzo ka corticosteroids futhi yonke imiphumela yabo tiphindze wachaza ngokuningiliziwe lapha. Manje konke okudingayo ukuze ukwazi mayelana GCS, is endaweni eyodwa - lesi sihloko. Nokho, noma kunjalo, musa ukuqala ukwelashwa kuphela ngemva kokufunda ulwazi olujwayelekile mayelana GCS. Le mithi, yebo, angathengwa ngaphandle kadokotela, kodwa kungani uludinga? Ngaphambi kokusebenzisa imithi kufanele ubheke onguchwepheshe. Yiba enempilo futhi akazibekanga medicate!