Once attempting to conceive, most women with LOCAH will become pregnant within a year with or without treatment, but women with LOCAH have an increased risk of miscarriage.The diagnostic procedure varies according to the specific enzyme deficiency causing LOCAH and the precise serum androgen levels required for diagnosis are the subject to variance from different measurement methods, refinement in specific cases and are under active research. Some protocols are based on measuring 17α-hydroxyprogesterone levels, with or without ACTH stimulation test. 21-Hydroxylase deficiency
Screening
The condition of 21-hydroxylase deficiency is screened by measuring serum levels of 17α-hydroxyprogesterone (17-OHP) in the morning and between day 3 and 5 of the menstrual cycle (for females) to reduce the possibility of false positive results. 17-OHP is used as a marker of the 21-hydroxylase enzyme activity since the 1980s. The cutoff basal 17-OHP value is matter of debate. Most commonly, the value of 2.0 ng/mL is used, but a value of 1.7 ng/mL provides better selectivity. Most research on the biochemical diagnosis of LOCAH relied on direct immunoassays, such as radioimmunoassays or time-resolved fluorescence assay to measure 17-OHP, therefore, cross-reactivity and reliability problems of these methods might have caused differences in the 17-OHP cutoff values recommended, so the use of liquid chromatography–mass spectrometry aims to improve the accuracy of 17-OHP measurement and increase diagnostic quality of LOCAH. Randomly timed measurements of 17-OHP have not been shown to be useful for screening since they are often normal and are known to be very high in the luteal phase of the female menstrual cycle.
Mechanism of action
The medication works by binding to and inhibiting the ATP-sensitive potassium channels (KATP) inhibitory regulatory subunit sulfonylurea receptor 1 (SUR1) in pancreatic beta cells. This inhibition causes cell membrane depolarization, opening voltage-dependent calcium channels. This results in an increase in intracellular calcium in the pancreatic beta cell and subsequent stimulation of insulin release.After a cerebral ischemic insult, the blood–brain barrier is broken and glibenclamide can reach the central nervous system. Glibenclamide has been shown to bind more efficiently to the ischemic hemisphere. Moreover, under ischemic conditions SUR1, the regulatory subunit of the KATP- and the NCCa-ATP-channels, is expressed in neurons, astrocytes, oligodendrocytes, endothelial cells and by reactive microglia.As per the research papers, this sulphonylurea drugs also has extra hepatic effects. It works by inhibiting the enzyme Carnityl Acyl Transferase I (CAT-I) indirectly which is present in the mitochondria. This prevents the transport of long chain fatty acids into the mitochondria for beta-oxidation. This prevents hyperglycemia for which it is prescribed. History
It was developed in 1966 in a cooperative study between Boehringer Mannheim (now part of Roche) and Hoechst (now part of Sanofi-Aventis). Society and culture
Names
Glibenclamide is available as a generic medication, is manufactured by many pharmaceutical companies and is sold under many brand names including Gliben-J, Daonil, Diabeta, Euglucon, Gilemal, Glidanil, Glybovin, Glynase, Maninil, Micronase and Semi-Daonil. It is also available in a fixed-dose combination drug with metformin that is sold under various trade names, e.g. Bagomet Plus, Benimet, Glibomet, Gluconorm, Glucored, Glucovance, Metglib and many others. References
External links
"Glyburide". Drug Information Portal.