1.
Pharmacogenomics of Cytochrome P450 of Nimodipine Metabolism After Aneurysmal Subarachnoid Hemorrhage.
Peacock, SH, James, C, Turnbull, MT, Cowart, JB, Reid, JM, Freeman, WD
The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses. 2019;(5):238-242
Abstract
INTRODUCTION Aneurysmal subarachnoid hemorrhage (aSAH) is a type of stroke that is life threatening with high rates of mortality, and many survivors are left with permanent neurologic deficits. Nimodipine is the treatment of choice for aSAH with the goal of reduction of delayed cerebral ischemia. It is the only evidence-based medication that has been shown to have improved outcomes for delayed cerebral ischemia; therefore, it is important for neuroscience nurses to be knowledgeable of the pharmacology and pharmacogenomics properties of this medication, including cytochrome P450 (CYP450) enzymes. METHODS AND RESULTS This article reviews the CYP450 enzyme system including a review of the pharmacotherapy and pharmacogenomics of nimodipine for patients with aSAH illustrated with case study of a patient with abnormal drug metabolism. CONCLUSION CYP450 enzymes can be inhibited or induced by multiple medications resulting in clinically significant differences in drug metabolism. Food and Drug Administration-approved medication nimodipine is the only medication shown to improve outcomes in patients with aSAH. Hence, it is important to have awareness of potential drug-to-drug interactions and pharmacogenomics of nimodipine when caring for critically ill patients with aSAH.
2.
Cytochrome P450 oxidoreductase deficiency caused by R457H mutation in POR gene in Chinese: case report and literature review.
Bai, Y, Li, J, Wang, X
Journal of ovarian research. 2017;(1):16
Abstract
BACKGROUND Cytochrome P450 oxidoreductase deficiency (PORD) is a rare disease exhibiting a variety of clinical manifestations. It can be difficult to differentiate with other diseases such as 21-hydroxylase deficiency (21-OHD), polycystic ovary syndrome (PCOS) and Antley-Bixler syndrome (ABS). Nearly 100 cases of PORD have been reported worldwide. However, the genetic characters and clinical management are still unclear, especially in China. CASE PRESENTATION In this study, we report a 27-year-old female Chinese patient who first presented with amenorrhea and recurrence of large ovary cyst. She was misdiagnosed with PCOS and non-classical 21-OHD due to ovary cysts and elevated 17-hydroxy-progesterone. The patient's complaining of a mild difficulty of bending the metacarpophalangeal joints reminded us to consider PORD, which usually presents with skeletal deformities and sexual dysfunction. The diagnosis of PORD was confirmed by genetic analyses, which showed the patient harboring a homozygous missense mutation in the POR gene (R457H) and her parents carrying the heterozygous mutation. The patient was treated with low-dose corticosteroids and estrogen/progesterone sequential therapy, and her ovarian cyst gradually reduced with regular menstruation in the follow-up. Moreover, the clinical and genetic characteristics of 104 previously reported PORD cases were also summarized and analyzed. CONCLUSIONS PORD is a very rare disease which can be easily misdiagnosed in mild cases. Clinicians should keep in mind of this disease in patients with sexual dysfunction, especially combined with special skeletal deformities. Our data could provide a consciously understanding of this disease for clinic practicers. Low-dose corticosteroids combined with estrogen/progesterone sequential therapy will be effective in PORD patients with recurrence of large ovary cyst. The fact that the reported PORD patients in China carrying an identical variant R457H in POR gene also give us a viewpoint that R457H mutation in POR gene maybe important in causing PORD in Chinese as same as in Japanese.