China
Africa
Explore chapters and articles related to this topic
Gastrointestinal disorders
Published in Anne Lee, Sally Inch, David Finnigan, Therapeutics in Pregnancy and Lactation, 2019
Treatment aims to relieve the major symptoms. Avoidance of ‘trigger’ foods and simple dietary change may help. Bulking agents, with an adequate fluid intake, relieve constipation and are better tolerated than bran. Anticholinergic agents (dicyclomine and hyoscine) and smooth muscle relaxants (mebeverine and alverine) are not recommended in pregnancy because there is inadequate safety data.7,20 Peppermint is widely used in confectionery and peppermint oil is probably safe, though pharmacological safety data is lacking.
Information on level of drugs into breastmilk
Published in Wendy Jones, Breastfeeding and Medication, 2018
Alverine is widely used in the UK to treat symptoms of IBS, but one study shows that it was no better than placebo in providing relief of symptoms (Mitchell et al.2002). It is licenced for use in patients over the age of 12 years. There is no information on its passage into breastmilk.
Information on level of drugs into breastmilk
Published in Wendy Jones, Breastfeeding and Medication, 2013
Alverine is widely used to treat symptoms of IBS, but one study shows that it was no better than placebo in providing relief of symptoms (Mitchell 2002). It is licensed for use in patients over the age of 12 years. There is no information on its passage into breastmilk. The BNF states that limited information is available and that the manufacturer advises it is avoided during breastfeeding. Avoid if possible as no information on passage into breastmilk. Peppermint Oil or mebeverine are preferable, based on limited research on other drugs.
A transcriptional regulatory network of HNF4α and HNF1α involved in human diseases and drug metabolism
Published in Drug Metabolism Reviews, 2022
Jianxin Yang, Xue Bai, Guiqin Liu, Xiangyang Li
HNF4A mutations cause pancreatic β-cell dysfunction, induce MODY1 (Yamagata et al. 1996), and may promote the development of type 2 diabetes (Gupta and Kaestner 2004). The mechanism might be due to the mutated HNF4α protein losing its ability to bind the HNF4α binding site, consequently leading to the abnormal expression of genes during glucose transport and glycolysis, and affecting the enterohepatic circulation of glucose and uptake into liver cells and insulin secretion by pancreatic β-cell (Stoffel and Duncan 1997; Gupta et al. 2005). To date, the Human Gene Mutation Database (HGMD) has reported more than 100 HNF4A mutations, of which single amino acid mutations are directly associated with MODY1 phenotypes. Several rare phenotypes, including hyperinsulinemia, hypoglycemia, and renal Fanconi syndrome, are also associated with HNF4A mutations (Cubuk and Yalcin 2021). Moreover, alverine and benfluorex are agonists of HNF4α, and these are well-known drugs that have been used to treat irritable bowel syndrome and type 2 diabetes, respectively (Lee et al. 2013). Benfluorex has been studied in clinical trials for type 2 diabetes and was proven to be effective in reducing hemoglobin A1c (Del et al. 2003; Moulin et al. 2006). Therefore, HNF4α agonists might be potential drugs to treat some metabolic diseases, such as diabetes, dyslipidemia, and cholestasis (Chiang 2009).
How can we develop better antispasmodics for irritable bowel syndrome?
Published in Expert Opinion on Drug Discovery, 2019
Sheyda Ranjbar, Seyed Afshin Seyednejad, Shekoufeh Nikfar, Roja Rahimi, Mohammad Abdollahi
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder (FGID) without organic abnormality characterized by recurrent abdominal pain and altered bowel habits [1]. Based on the predominant bowel symptom, IBS can be categorized into diarrhea predominant IBS (IBS‐D), constipation‐predominant IBS (IBS‐C) or mixed diarrhea and constipation IBS (IBS-M) [1]. IBS affects nearly 11% of the global population [2] and can seriously impair patients’ quality of life (QOL) by imposing absenteeism from work and school and increased health-care use and costs [3]. IBS usually tends to become chronic with 55% of patients still meeting the diagnostic criteria after 7 years of treatment [4]. The exact pathophysiology of IBS is still not understood but evidence suggests it is most likely multifactorial with the involvement of complex neuro-immune brain-gut interactions, including disturbed GI motility, low-grade mucosal inflammation, dysregulation of the enteric nervous system (ENS), bile acid malabsorption, altered gut flora and genetic susceptibility. Current medications are diverse and each address specific underlying mechanisms involved in the pathophysiology of the disease. One of the mechanisms underlying IBS is altered GI motility that is addressed by a group of drugs known as antispasmodics. Antispasmodics or spasmolytics are a heterogeneous pharmacological category with different mechanisms of action, some known like direct relaxation of smooth muscles (papaverine, mebeverine, peppermint oil), blocking cholinergic receptors (hyoscine butyl bromide, hyoscyamine, pirenzepine), blocking calcium (Ca2+) channels (Alverine citrate, pinaverium bromide, otilonium bromide) and some unknown or mixed action mechanisms. These widely used drugs mainly help bowel symptoms of IBS-D patients by decreasing colonic motility, improving stool form and frequency and relieving abdominal pain. These drugs are generally well tolerated, however, associated with mild atropine-like adverse effects including dry mouth, nausea, dizziness and etc. Nonetheless, the situation is not as favorable as it seems, in a report; half of the patients with IBS-D stated that the available medications failed to control their symptoms [3]. In addition, evaluation of the present antispasmodics revealed that some of them failed to exhibit superiority over placebo and only imposed an economic burden on patients [5]. Therefore, considering GI motility as a key mechanism involved in the etiology of IBS, there is a tremendous need for the discovery of novel, more effective and safe long-term antispasmodics that help improve patients’ QOL. Here, we discuss the current discovery approaches as well as presenting thoughts on how to develop better antispasmodics.