Introduction to Toxicology
David Woolley, Adam Woolley in Practical Toxicology, 2017
There are many instances of interactions between herbal remedies and prescribed drugs, either through increased or decreased effect. Even simple dietary components can have unexpected effects; grapefruit juice consumption is known to be associated with inhibition of cytochrome P450 (CYP3A4), which is responsible for the metabolism of a wide range of drugs. This has been associated with increased plasma concentrations of cisapride, a drug given for irritable bowel syndrome. Inhibition of cisapride metabolism, which probably takes place in the small intestine, can increase the likelihood of life-threatening cardiac arrhythmias in some patients. A similar effect has been reported with carbamazepine, a drug given in epilepsy. Equally, administration of metabolism inhibitors can have useful effects, for instance, in reducing the doses of some drugs needed to achieve therapeutic effect.
Acne Antibiotics
Sarah H. Wakelin, Howard I. Maibach, Clive B. Archer in Handbook of Systemic Drug Treatment in Dermatology, 2015
Erythromycin has numerous drug interactions due to its inhibitory effects on the cytochrome p450 (CYP450) 3A isoenzyme, and the cardiotoxicity of certain drugs may also be increased. It should not be prescribed with the following: Antipsychotic drugs including droperidol, pimozide, sertindole.Cisapride (discontinued in the UK and USA), due to the risk of ventricular arrhythmias.Ergot alkaloids (unlicensed use for headache), due to increased risk of ergotism.Mizolastine, due to QT prolongation.Simvastatin, lovastatin, due to increased risk of myopathy.
Dyspepsia
Andrew Stevens, James Raftery, Jonathan Mant, Sue Simpson in Health Care Needs Assessment, 2018
Prokinetics were more effective than placebo in a meta-analysis (RRR = 50%; 95% CI: 30–70%), but there was significant heterogeneity between trials.84 This heterogeneity could be partly explained by year of publication, larger more recent trials being less likely to show an effect. A funnel plot revealed that the results of the prokinetic meta-analysis could be due to publication bias or related quality issues. Most of these trials evaluated cisapride, which has now been withdrawn from the UK market. The relative tolerability and cost-effectiveness of metoclopramide and domperidone in NUD remain to be established.
Current and emerging therapeutic options for the management of functional dyspepsia
Published in Expert Opinion on Pharmacotherapy, 2020
A. Vandenberghe, J. Schol, K. Van den Houte, I. Masuy, F. Carbone, J. Tack
Cisapride is a 5-HT4-receptor agonist and 5- HT3-receptor antagonist developed at the end of last century, indicated for nocturnal heartburn and regurgitations in adults, and reflux or regurgitations in neonates [37]. It was the leading prokinetic, mainly prescribed for dyspeptic symptoms and other upper gastrointestinal motility disorders, up to its withdrawal in the year 2000 due to its affinity for the human ether-a-gogo (HERG) channel, responsible for cardiac arrhythmias [37]. In absence of alternative drugs, a post-marketing surveillance program took place and a few gastroenterologists and endocrinologists in some European countries continued to prescribe cisapride in gastroparesis patients. However, the program was discontinued in 2006. In neonates, PPIs, which can decrease the volume of gastric secretion, replaced the banned prokinetic with mitigated results. The therapeutic gap left by cisapride remains to be filled up to now, and based on current evidence, only acotiamide may have some potential to replace it.
Use of prucalopride in adults with chronic idiopathic constipation
Published in Expert Review of Clinical Pharmacology, 2019
Priya Vijayvargiya, Michael Camilleri
There are seven isoforms of the 5-HT receptor. 5-HT4 isoform is found in the human body within the alimentary tract, substantia nigra, and cardiac system. Because 5-HT4 receptors are also found within the heart, there is a concern for receptor cross-reactivity, similar to previous 5-HT4 receptor agonists such as cisapride and tegaserod. However, there are differences between these three prokinetic agents. An important distinction is that cisapride interacts with the human ether-a-go-go [hERG] potassium channel, resulting in cardiac arrhythmias such as ventricular tachycardia, ventricular fibrillations, torsade de pointes, and QTc interval prolongation. Because of the risk of cardiac arrhythmias, cisapride was withdrawn from the market in July 2000, though it has subsequently become available in some countries, but not in the United States. Tegaserod was associated with ischemic or vascular events secondary to the concomitant activation of 5-HT1D and 5-HT2A receptors [21].
An update on the latest chemical therapies for reflux esophagitis in children
Published in Expert Opinion on Pharmacotherapy, 2019
Marc Bardou, Kyle J. Fortinsky, Nicolas Chapelle, Maxime Luu, Alan Barkun
Currently, several meta-analyses have found that prokinetic agents have minimal benefit, if any, for the empiric treatment for GER [24,43–46]. Furthermore, there is substantial evidence of potential harm. As such, current guidelines from NASPGHAN and ESPGHAN do not recommend routine use of domperidone, metoclopramide or any other prokinetics (i.e., erythromycin, bethanechol) for the management of GER (week recommendation) [1]. Metoclopramide is currently contraindicated in infants less than 1 year of age due to an increased risk of extrapyramidal symptoms. Cisapride has a black box warning for cardiac arrhythmias and has been removed from the American and European markets [47,48]. There are certain circumstances when prokinetics such as metoclopramide or erythromycin may be useful including situations where patients have gastric motility disorders such as gastroparesis. Further research may uncover the benefit of these agents in specific pediatric populations.
Related Knowledge Centers
- Enteric Nervous System
- Gastrointestinal Tract
- Parasympathomimetic Drug
- Prokinetic Agent
- Serotonin
- Medication
- Motility
- 5-Ht4 Receptor
- Agonist
- Acetylcholine