Forensic and Clinical Usage of X-rays in Body Packing
Michael J. Thali M.D., Mark D. Viner, B. G. Brogdon in Brogdon's Forensic Radiology, 2010
Opium is the dried chyle of still-verdant fruit capsules of the opium poppy, Papaver somniferum, which is rough opium. Opium contains morphine, codeine, noscapine, papaverine, and thebaine. All but thebaine, which lacks an analgesic effect, are used clinically as analgesics to reduce pain without loss of consciousness. Heroin is a synthetic morphine (appearing as white to brownish powder), which can be man-ufactured either directly from opium or from semi-purified morphine.13 Heroin was initially used to suppress the urge to cough, especially due to the raging tuberculosis at the turn of the century. Tragically, heroin was also used to fight morphine addiction, just as morphine was used to overcome opium addiction. It was quickly clear that heroin exceeded the narcotic and addictive potential of morphine or opium, because of its quick metabolism and faster penetration of the blood-brain barrier.
An Introduction to the Ethnopharmacology of Wild Plants
Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa in Ethnopharmacology of Wild Plants, 2021
Terrestrial plants, Licorice (Glycyrrhiza glabra), Myrrh (Commiphora species), and Poppy capsule latex (Papaver somniferum), were recorded from Mesopotamia in 2600 BC, and are still in use today (Newman et al. 2000). A semisynthetic derivative of glycyrrhizic acid found in licorice (i.e., Hemisuccinate carbenoxolone sodium) is recommended for gastric and duodenal ulcers (Dewick 2002). Furthermore, morphine, codeine, noscapine (narcotine), and papaverine isolated from P. somniferum were developed as single chemical drugs and are still used clinically (Dewick 2002). Codeine is an alkaloid prepared from Opium or morphine by methylation. Opium is an isoquinolone alkaloid obtained from poppy plant [Papaver somniferum]. Codeine is used as a pain reliever, and for cough suppression (Online Medical Dictionary 2007, Bhandari et al. 2011).
Nutraceutical’s Role in Proliferation and Prevention of Gynecological Cancers
Sheeba Varghese Gupta, Yashwant V. Pathak in Advances in Nutraceutical Applications in Cancer, 2019
Majority of nutraceuticals with antioxidant activity inhibit NF-κB-regulated anti-apoptotic proteins target by inhibiting NF-κB activation. Garcinol causes apoptosis in human breast carcinoma, MDA-MB-231 and MCF-7, cells through the activation of caspase and NF-κB-regulated genes down regulation [63]. γ-Tocotrienol, acetoxychavicol acetate, evodiamine, thymoquinone, noscapine have shown inhibiting plumbagin-induced apoptosis with related inactivation of DNA binding activity of NF-κB and Bcl-2 in breast tumor cells [64]. Isodeoxyelephantopin, anacardic acid, indirubin, coronarin D, β-escin, and withanolides, are some of the most popular among nutraceuticals reported to have antioxidant activities for cancer treatment [4].
“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.
Inhibition of CYP2C9 by natural products: insight into the potential risk of herb-drug interactions
Published in Drug Metabolism Reviews, 2020
Kai Wang, Qing Gao, Tingting Zhang, Jinqiu Rao, Liqin Ding, Feng Qiu
Noscapine, a naturally occurring phthalide isoquinoline alkaloid obtained from Papaver somniferum L., has been broadly accepted as a safe and promising oral antitussive for a long time (Chen et al. 2015). Nevertheless, several clinical DDI reports related to noscapine showed that serious adverse drug response (bleeding or increased INR (international normalized ratio)) occurred when warfarin was coadministered (Ohlsson et al. 2008; Scordo et al. 2008). Noscapine also markedly increased the losartan phenotypic index after multiple dosing of twelve healthy subjects, which was indicative of CYP2C9 enzyme inhibition (Rosenborg et al. 2010). The human liver microsome (HLM) incubation study showed that noscapine exhibited time-dependent inhibition (TDI) of CYP2C9, and kinetic analysis demonstrated that the inhibition mode showed the best fit for noncompetitive type with a Ki value of 8.9 μM (Fang et al. 2010). Interestingly, further research demonstrated that noscapine inhibited (S)-warfarin metabolism in both an NADPH- and time-dependent manner, and CYP2C9 activity was not recovered by ultrafiltration analysis, suggesting that noscapine was a mechanism-based inactivator of CYP2C9. The mechanism related to the MBI of CYP2C9 by noscapine was likely to be correlated with the metabolic activation of the methylenedioxyphenyl group that was incorporated into the noscapine structure (Zhang et al. 2013). Specifically, its bioactivation is possibly initiated by O-dealkylation, by which the methylenedioxyphenyl group is metabolized to the corresponding catechol, and sequential oxidation of the catechol produces an ortho-quinone. The resulting quinone may be responsible for enzyme inhibition (Mao et al. 2015).
Bioactivation of herbal constituents: mechanisms and toxicological relevance
Published in Drug Metabolism Reviews, 2019
Another clinically relevant herb-drug interactions involve the opioid alkaloid noscapine and warfarin (Rosenborg et al. 2010). Noscapine (Figure 9(b)), a close structural analog of hydrastine containing the MDP moiety, is a nonaddictive phthalideisoquinoline alkaloid obtained from opium poppy latex and has been widely used as an antitussive drug (Empey et al. 1979). In recent years, noscapine has drawn much attention for its excellent anticancer activity and low toxicity (Tomar et al. 2017). Despite the therapeutic benefits, studies suggested that noscapine is potentially carcinogenic (Porter et al. 1992). Oral administration of noscapine in rats led to decreased GSH levels and enhanced lipid peroxidation (Aneja et al. 2004). Of significant concern was the clinical drug interactions between noscapine and warfarin (Scordo et al. 2008). Noscapine was found to be both a competitive and a mechanism-based inhibitor of CYP2C9 with estimated kinact/KI = 6.0 ml/min/μmol, indicating high inactivation efficiency (Zhang et al. 2013). Noscapine is a 2- to 3-fold more efficient inactivator of CYP2C9.2 and CYP2C9.3 variants than the wild type. In vitro GSH trapping suggested that noscapine formed a reactive o-quinone via initial CYP2C9-mediated O-demethylenation of the MDP moiety to a catechol followed by two-electron oxidation (Fang et al. 2012) (Figure 9(b)). Spectral scanning of the reaction between CYP2C9 and noscapine revealed the formation of an absorption spectrum at 458 nm, indicating formation of the MDP carbene complexes with ferrous heme iron of CYP2C9 (Zhang et al. 2013). It’s estimated that co-administration of noscapine and warfarin could lead to up to 7-fold increases in AUC of (S)-warfarin mainly due to mechanism-based inactivation of CYP2C9 by noscapine, which would warrant reduction of warfarin dose (Fang et al. 2010; Zhang et al. 2013).
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