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Drugs in pregnancy and lactation
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
As mentioned earlier, the CYP3A isozyme is essential in the metabolism of endogenous steroids. In view of its importance for the fetal development, it is not surprising that it is expressed early in gestation. The N-demethylating activity of ethylmorphine is inhibited by various steroids (progesterone, dehydroepiandrosterone, etc.), which yields indirect evidence that the drug and the steroid substrates utilise the same catalyst [9].
Theoretical Biochemical Mechanisms for Drug Dependence
Published in S.J. Mulé, Henry Brill, Chemical and Biological Aspects of Drug Dependence, 2019
The mechanisms of the induction of microsomal drug-metabolizing enzymes (DMEs) in liver are not clearly understood. A proliferation of the liver endoplasmic reticulum is accompanied by an increase in protein synthesis6 and an increase in RNA synthesis,7 and by a decrease in RNA breakdown due to the progressive inhibition of RNAase activity during induction.8,9 The specificity in induction of the synthesis of the protein enzyme involved in the microsomal respiratory system is quite distinct from the general increase in protein synthesis induced by hepatec-tomy or by anabolic steriod hormones such as nortestosterone.10 In addition to the effect of the induction of the DMEs by inducer drugs, there is a direct competition between drugs for the DMEs in liver. In in vitro systems, many drugs can be shown to be competitive inhibitors for other drugs.11 In the intact animal, however, there are requirements of similarity of Km and Vmax values before one drug can have an important effect on the metabolism of another drug.12 Thus, ethylmorphine and codeine which have similar kinetic properties to hexobarbital inhibit hexobarbital metabolism in vivo while morphine and norcodeine do not.13
The Effects of Experimental Diabetes on the Cytochrome P450 System and Other Metabolic Pathways
Published in John H. McNeill, Experimental Models of Diabetes, 2018
Costas Ioannides, Peter R. Flatt, Christopher R. Barnett
After 3 weeks of treatment of rats with streptozotocin, an increase was evident in the hepatic N-demethylations of erythromycin and ethylmorphine, two activities associated with the CYP3A subfamily; these effects were antagonized by insulin and were not manifested when nicotinamide was administered concurrently with the diabetogen.85 The activities of these enzymes correlated with the apoprotein levels in Western blot analysis. The increase in CYP3A1 activity was transient and was not detectable by 4 weeks after injection of the diabetogen.59 A similar increase has been reported in hepatic CYP3A2 apoprotein levels and in the associated activities of testosterone 2β- and 6β-hydroxylase 2 weeks after the administration of the diabetogen.67 Other workers reported,68 in contrast, lower apoprotein levels in diabetic rats. Withdrawal of insulin from BB rats for 5 days prior to sacrifice resulted in an increase in the N-demethylation of ethylmorphine in 4-week-old animals; the increase became less pronounced as the disease progressed and was only just detectable in 24-week-old animals.61
“Purple Drank” (Codeine and Promethazine Cough Syrup): A Systematic Review of a Social Phenomenon with Medical Implications
Published in Journal of Psychoactive Drugs, 2020
A. Miuli, G. Stigliano, A. Lalli, M. Coladonato, L. D’Angelo, F. Esposito, C. Cappello, M. Pettorruso, G. Martinotti, F Schifano, M. Di Giannantonio
In addition to Garcin et al. (2016), four articles investigated the Purple Drank phenomenon from epidemiological points of view. Jouanjus and Falcou (2018) administered questionnaires to 19 pharmacists in France in order to detect unusual requests of nonprescription drugs of customers, focusing on the population under 26 years of age. These questionnaires revealed 29 requests for drugs containing codeine, 17 requests for drugs containing promethazine (both components of Purple Drank) while only 3 reports concerned the prescription for dextromethorphan and one the prescription for ketamine. Those requesting these drugs were mainly males (85%) aged between 15 to 25, most of which between 18 and 20 years old (Statista 2019). Codeine, dextromethorphan, ethylmorphine and noscapine were listed as prescription drugs in July 2017. By contrast, in Australia, drugs containing codeine and promethazine are still bought without prescription, since pharmacists strongly state that listing these substances as prescription drugs would negatively impact people’s management of pain.
Detection of opioids in umbilical cord lysates: an antibody-based rapid screening approach
Published in Toxicology Mechanisms and Methods, 2019
Stuart J. Knight, Alexander D. Smith, Tricia E. Wright, Abby C. Collier
For opioids taken for pain management on a standard oral dosing schedule, PK analysis indicated codeine, its metabolite dihydrocodeine, the morphine metabolite ethylmorphine, and oxycodone could be detected even after 5 half-lives – well beyond therapeutic levels and more sensitive than clinical laboratories calibrated to therapeutic ranges (Tables S1 and S2). For the remainder of the analytes in the oral schedule, and for all IV opioids ingested on a standard medical dosing schedule, only drugs ingested within 5 half-lives (effective elimination) are predicted to be detected (Tables S3 and S4). Predictive PK for some of the water soluble and longer resident metabolites (e.g. morphine-3-glucuronide and morphine-6-glucuronide) could not be performed as data for these compounds do not exist in the literature, but we expect the metabolites to persist beyond 5 half-lives of the parent drug.
Effect of piperine on the bioavailability and pharmacokinetics of rosmarinic acid in rat plasma using UPLC-MS/MS
Published in Xenobiotica, 2018
Jun-Hui Yang, Kun-Jun Mao, Ping Huang, Yin-Jun Ye, Hua-Shan Guo, Bao-Chang Cai
Piperine (PP), a main active component in both black pepper (Piper nigrum Linn.) and long pepper (Piper longum Linn.), was validated as the world’s first bioenhancer in 1979 (Atal, 1979). Black pepper and long pepper are important traditional medicinal plants (Singh, 1992). PP has been shown to possess some health-promoting effects such as antioxidant, antimutagenic, and antitumor activities (Do et al., 2013; Srinivasan, 2007). In recent years, PP has excited increasing interest among researchers owing to its excellent bio-enhance effect and low toxicity (Ajazuddin et al., 2014). It was reported that co-administration of PP and linarin to rats could enhance the bioavailability of linarin by 381% (Feng et al., 2014). In several studies, PP has been shown to be an effective bioavailability enhancer of several drugs and other pharmacological active substances, such as curcumin, resveratrol, epigallocatechin-3-gallate, and puerarin, in animals and human volunteers (Johnson et al., 2011; Lambert et al., 2004; Liang et al., 2014; Shoba et al., 1997). Several mechanisms of PP’s bioavailability-enhancing effect have been postulated, including the formation of polar complexes with other compounds, and inhibition of efflux transport as well as inhibition of gut and hepatic metabolism enzymes. Notably, PP has revealed strong inhibition on hepatic UDP-glucuronyltransferase activities, arylhydrocarbon hydroxylase, and ethylmorphine-N-demethylation in vitro (Atal et al., 1985; Han et al., 2008).