Dərman metabolizmi.Biotransformasiya prosesi

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          Dərmanların böyük əksəriyyəti kimyəvi maddələrdən təşkil olunduğuna görə digər kimyəvi birləşmələr kimi orqanizmə daxil olduqdan sonra biotransformasiya prosesinə məruz qalırlar.Bəzi dərmanlar isə : quruluşundan asılıolaraq biotransformasiya proseslərinə girmədən xaric olunur, bir qismi isə enzimatik olmayan yollarla parçalanırlar.Kimyəvi maddələrin çevrilmə reaksiyaları sonunda intoksikasiyaya və ya detoksifikasiyaya məruz qalırlar. Biotransformasiya reaksiyalarının əsas vəzifəsi hidrofobik və neytral olan birləşmələrin hidrofil tərkibə gətirilməsidir. Dərman metabolizmi – dərmanın orqanizmə daxil olduqdan sonra fərqli bir kimyəvi quruluşa çevrilməsi kimi başa düşülür. Dərmanların biotransformasiya prosesinin sonunda bir və ya daha çox metabolit əmələ gələ bilər. Əmələ gələn bu yeni maddələr təsir baxımından əsas maddədən fərqlənə bilər. Belə ki , yeni maddə əsas maddədən daha güclü toksikiliyə, zəif toksikiliyə və toksiki olmayan təsirə görə fərqlənir. Dərman metabolizmi başlıca olaraq qaraciyər hüceyrələrinin düz endoplazmatik retikulumlarında baş verməklə birliktə digər bütün bioloji toxumalarda az da olsa metabolizmə uğrayır. Dərman metabolizmində müxtəlif sayıda və fərqli təsir mexanizminə sahib olan enzimlər rol almaqla bərabər, fermentativ təsirə malik olmayan yollarda mövcuddur. Enzimlərin iştirakı ilə gedən reaksiyalarda iki əsas faza ayırd edilir. Faz I və Faza II reaksiyaları olaraq bilinən bu reaksiyalar dərmanların eliminasiyasında son dərəcə önəmlidir.

          Qan plazmasında böyük miqdarda həm endogen, həm ekzogen (sulfanilamidlər, antibiotiklər, salisilatlar) albuminlə birləşərək nəql olunurlar. Hüceyrələrdə, xüsusilə qara ciyərdə poliaromatik karbohidrogenlər, kanserogenlər, nitrotörəmələr, antibiotiklər qlutationtransferazalarla birləşirlər. Metallar SH- qrupları ilə G-SH-la və sistein qalıqları ilə zəngin olan metallotionein zülalı ilə birləşirlər. Birləşmiş ksenobiotiklər aktiv deyillər, tədricən azad olurlar, metabolizmə məruz qalırlar və xaric olunurlar. Ksenobiotiklərin orqanizmdən xaric olunmasının ən vacib mexanizmi P-qlikoproteinin funksiyasıdır. Bir çox ksenobiotiklərin metabolizm nəticəsində hidrofilliyi azalır, qanın plazmasına daxil olur, oradan da böyrəklər vasitəsilə xaric olunur. Qaraciyər və böyrəyin birgə funksiyası orqanizmdən xaric olunan ksenobiotiklərin böyük miqdarının zərərsizləşdirilməsində və xaric olunmasında  böyük rol oynayır. Çox hidrofil və ya böyük molekul kütləsinə malik olan (300-dən çox) maddələr ən çox ödlə birlikdə bağırsağa keçir və xaric olunur.Biotransformasiya prosesləri böyük çoxluqla qaraciyərdə gerçəkləşməklə bərabər digər orqanlarda da baş verə bilir. Oksiprenalin, noradrenalin, salbutamol və asetil salisilik asit kimi dərmanların başlıca metabolizmə yerləri bağırsaqlardır. Qaraciyər və bağırsaqların xaricində, ağciyərlərdə, böyrəklərdə və beyində də dərmanların biotransformasiyası baş verə bilməkdədir. Dərmanlar biotransformasiya müddətindən sonra orqanizmdən atılaraq eliminasiya mərhələsini tamamlamış olurlar.  Xaric olunma:ağciyərlər, öd kisəsi, dəri və ya böyrəklər vasitəsi ilə baş verir. Dərmanlar üçün başlıca olaraq xaric olunma yolu böyrəklərdir.

Mənbə:”Ekotoksikoloji” H.Parlak,Ö.Ç.Arslan,M.Boyacıoğlu, M.A.Karaaslan.İzmir.2011

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