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Drugs and Therapeutics
Published in James Sherifi, General Practice Under the NHS, 2023
Metformin reduces insulin resistance by facilitating the cellular uptake of glucose. Unlike the other commonly used glycaemic drugs of the time, the sulfonylureas, it did not cause hypoglycaemia or weight gain. In fact, it had few adverse effects, the most common being diarrhoea. Metformin has since found other medical indications, its anti-androgenic properties leading to its unlicensed use in treating hirsutism and polycystic ovarian syndrome. Chlorpropamide—1958Diabetes Chlorpropamide26, a first-generation sulphonylurea, acts by stimulating pancreatic beta-cells to produce insulin. Therefore, by definition, it is ineffective when these cells are totally depleted, as in Type 1 Diabetes Mellitus (T1DM). It was an excellent drug at reducing blood glucose but had one major drawback, a long half-life that could, albeit infrequently, lead to profound hypoglycaemia and coma. It was a not uncommon cause, often overlooked by clinicians, of comatose patients being admitted to hospital. Chlorpropamide was the mainstay of treatment for Type 2 Diabetes Mellitus (T2DM) until the 1980s when second-generation sulphonylureas replaced it. Glibenclamide and gliclazide were no more potent but had a shorter half-life and, thus, were less likely to cause hypoglycaemia.
Endocrine Disorders, Contraception, and Hormone Therapy during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
This drug has been withdrawn from the market and is no longer available in the US. Acetohexamide administration throughout pregnancy was significantly associated with neonatal hypoglycemia (Kemball et al., 1970). Pregnant rats given acetohexamide at many times the usual human dose on days 9 and 10 had approximately 50 percent embryonic death but no abnormalities (Bariljak, 1965). The frequency of congenital anomalies was increased, other than those expected in diabetes mellitus. Chlorpropamide is a closely related drug.
DRCOG MCQs for Circuit C Questions
Published in Una F. Coales, DRCOG: Practice MCQs and OSCEs: How to Pass First Time three Complete MCQ Practice Exams (180 MCQs) Three Complete OSCE Practice Papers (60 Questions) Detailed Answers and Tips, 2020
In pregnancy complicated by diabetes mellitus:Insulin requirement rises during pregnancy.Insulin requirement increases immediately after delivery.Delivery should be arranged at 36 weeks to prevent late intrauterine death.Chlorpropamide may cause neonatal hypoglycaemia.Diabetes is confirmed by the 75 g oral glucose tolerance test.
Home management of pediatric sulfonylurea ingestions
Published in Clinical Toxicology, 2022
Courtney Temple, Ruby Hoang, Shana Kusin
Accidental pediatric sulfonylurea ingestions have raised concerns regarding both delayed and prolonged hypoglycemia. This class of medications frequently appears on “one pill can kill” lists, leading many health care providers to adopt a one-size-fits-all approach to even small, exploratory pediatric ingestions, a practice shored up by some cautionary tales in the medical literature. An early retrospective study that included pediatric and adult patients found that patients with sulfonylurea overdose and known time of ingestion had variable onset of hypoglycemia (up to 21 h with glyburide and 48 h with chlorpropamide) [11]. A prospective poison center study of pediatric sulfonylurea exposures later found that one third of patients developed hypoglycemia, on average 5.3 h after ingestion, but with some cases delayed by as much as 21 h [12]. Both of these series focused on all overdoses, and not specifically on single pill exposures.
Evaluation system for cell-permeable CYP3A4 inhibitory activity using 1α,25-dihydroxy-vitamin D3-induced intestinal cell lines
Published in Xenobiotica, 2021
Toshiya Ueno, Saori Takahashi, Tomoya Nakamura, Yasuhiro Tanaka, Hisako Hori, Kenta Mizoi, Takuo Ogihara
Metabolic activity of CYP3A4 was measured with reference to previous reports (Mizoi et al.2020b) as follows. The metabolic activity was quantitated in terms of the amounts of remaining MDZ and generated 1′-OH MDZ, which were determined using an LCMS-8040 triple quadrupole liquid chromatography mass spectrometer (LC-MS/MS) (Shimadzu, Kyoto, Japan) coupled with an LC-20A system (Shimadzu, Kyoto, Japan). Separation was performed on a CAPCEL PAK Type MG III-H (C18, 3 µm 2.0 mmID × 100 mm, Osaka Soda, Osaka, Japan). The mobile phases consisted of 0.1% formic acid in water: 0.1% formic acid in acetonitrile in a ratio of 50:50. The electrospray mass spectrometer was operated in the positive ion mode for MDZ and 1′-OH MDZ, and in the negative ion mode for chlorpropamide. Multiple reaction monitoring (MRM) was conducted at m/z 326.05 > 291.10 for MDZ, at m/z 342.00 > 323.95 for 1′-OH MDZ and at m/z 274.90 > 190.05 for chlorpropamide. Collision energy was −23 V for MDZ, −24 V for 1′-OH MDZ, and 24 V for chlorpropamide. Chlorpropamide was used as an internal standard for analytical LC-MS/MS. The operating parameters of LC-MS/MS were as follows: block heater temperature 400 °C, nebuliser gas flow rate 3 L/min, drying gas flow rate 15 L/min.
Metabolic profiling of coumarins by the combination of UPLC-MS-based metabolomics and multiple mass defect filter
Published in Xenobiotica, 2020
Yao Xiao, Yi-Kun Wang, Xue-Rong Xiao, Qi Zhao, Jian-Feng Huang, Wei-Feng Zhu, Fei Li
Chromatographic analysis of coumarins metabolites was performed on an Agilent 1290 infinity UPLC system (Agilent Technologies, Santa Clara, CA, USA) equipped with a XDB-C18 column (2.1 × 100 mm, 1.8 µM, Agilent). Column temperature was maintained at 45 °C throughout the run. The flow rate was 0.3 mL/min with a gradient ranging from 2% to 98% acetonitrile containing 0.01% formic acid in 16 min run. The mass signals of ions were collected in both positive and negative mode by the electrospray ionization QTOFMS (Agilent 6500, Santa Clara, CA, USA). Nitrogen was applied as both drying gas (9 L/min) and collision gas. The drying gas temperature was set at 350 °C and nebulizer pressure was kept at 35 psi. Capillary voltage was set at 3.5 kV. The MS/MS of three coumarins metabolites was performed in the targeted mode by collision energy of 15 eV. Relative quantitation of metabolites was determined based on the abundance of peak area normalized by the internal standard (chlorpropamide).