Thunell Stig
Porphyria Centre - Laboratory Medicine, Centre for metabolic diseases. Stockholm, Sweden Porphyria Centre - Laboratory Medicine, Centre for metabolic diseases. Stockholm, Sweden.
Lakartidningen. 2016 Sep 9;113:DXML.
The attack of acute porphyria Based on in silico evidence of pharmacokinetic, pharmacodynamic, and physiologic properties, have approximately 1 300 medicinal drugs been assessed with regard to the specific risk to carriers of acute porphyria. The classifications have been published in booklet form, together with prophylactic advice to the carriers and suggestions for doctors in charge of their care. The risk-classifications rest on the behavior of the drug in an extended molecular model of the attack of acute porphyria. In this, symptoms are effects of 5-aminolevulinate (ALA) produced in surplus after acceleration of enzyme-deficient heme biosynthesis, taking place during induction of drug-metabolizing cytochromes P450 and triggered by hepatocellular nuclear receptors, activated by the drug. The process is enhanced by glucagon- and sirtuin-dependent molecular processes activated in stress and cellular energy deficit, and enhanced and prolonged by auto-generating ALA.
基于药代动力学、药效学和生理学特性的计算机模拟证据，已对约1300种药物进行了急性卟啉病携带者特定风险的评估。这些分类已以小册子形式出版，并向携带者提供了预防性建议，同时也为负责其护理的医生提供了建议。风险分类基于药物在急性卟啉病发作的扩展分子模型中的行为。在此模型中，症状是在药物代谢细胞色素P450诱导过程中，酶缺陷型血红素生物合成加速后产生的过量5-氨基乙酰丙酸（ALA）的作用，该过程由药物激活的肝细胞核受体触发。该过程通过在应激和细胞能量不足时激活的胰高血糖素和沉默调节蛋白依赖性分子过程而增强，并通过自身生成ALA而增强和延长。
