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Biotransformation of Xenobiotics in Living Systems—Metabolism of Drugs: Partnership of Liver and Gut Microflora
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
The primary site of alcohol metabolism is the liver. The main pathway of ethanol metabolism involves its conversion to acetaldehyde, an oxidative reaction that is catalyzed by enzymes known as alcohol dehydrogenases. In a second reaction mediated by aldehyde dehydrogenase, acetaldehyde is oxidized to acetate (Fig. 6.7). Other enzymes, such as cytochrome P450 (e.g., CYP2E1), metabolize a small fraction of the ingested ethanol (Edenberg, 2007). Some drugs may inhibit the activity of aldehyde dehydrogenase leading to the accumulation of acetaldehyde during ethanol ingestion, which is associated with flushing, nausea and vomiting, palpitations and dyspnea. The well-known interaction is between disulfiram and ethanol. Because of its ability to cause these extremely unpleasant symptoms, disulfiram may be used to effectively treat alcohol dependence (Kitson, 1977). Other drugs that can cause disulfiram-like effects when administered concurrently with ethanol include chloramphenicol, furazolidone (Karamanakos et al., 2007) and some of cephalosporin antibiotics (Ren et al., 2014).
In Silico Approach to Cancer Therapy
Published in Anjana Pandey, Saumya Srivastava, Recent Advances in Cancer Diagnostics and Therapy, 2022
Anjana Pandey, Saumya Srivastava
In anticancer pharmaceutics, repurposing the obsolete FDA-approved drugs for novel therapeutic use became a fascinating approach (Hsieh et al., 2019; Lo and Torres, 2019; Melge et al., 2019; Costa et al., 2020; Dinić et al., 2020; GNS et al., 2020; Irham et al., 2020; De et al., 2021; Mahdian et al., 2021). This process is also called drug repurposing. The primary benefit of this process is associated with the cost of drug and time issues. Drug repurposing significantly reduces drug development’s associated risk and expense and curtails the time gap from drug finding to its availability for patients because of having suitable and appropriate pharmacokinetics and clinical data (Shaughnessy, 2011; Papapetropoulos and Szabo, 2018; Fayed et al., 2021; Issa et al., 2021; Karaman Mayack and Sippl, 2021; Li et al., 2021; Mottini et al., 2021; Sankhe et al., 2021; Sohraby and Aryapour, 2021; Zhang et al., 2021). Generally, experimental-driven drug repurposing is just a matter of uncertainty; it can’t be driven hypothetically. Instead, it can be obtained from screening drug experiments or by the target similarities identification in different diseases (Wilkinson and Pritchard, 2015). In the case of cancer, examples of current drug repurposing include (i) Disulfiram, which was initially used for the treatment of alcoholism and discovered as therapeutics for cancer treatment (Iljin et al., 2009; Huang et al., 2016; Skrott et al., 2017); (ii) Valproic Acid, an antiepileptic repurposed to the anticancer drug in many clinical trials (Chateauvieux et al., 2010); (iii) Nelfinavir, originally used to treat HIV infection and now it is under clinical trials for the treatment of breast, lung, and melanoma cancers (Shim and Liu, 2014).
Pesticides and Chronic Diseases
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
William J. Rea, Kalpana D. Patel
Thiram is the methyl analog of disulfiram (Antabuse), an agent used to condition alcoholics against ingested alcohol. Much more is known of the toxic effects of disulfiram than of thiram, although the acute toxicity of thiram in laboratory animals is substantially greater. Given to animals in extreme doses, disulfiram has caused GI irritation, demyelinization of CNS tissues, and necrosis of liver, splenic, and kidney tissues. Peripheral neuropathy and psychotic reactions have occurred in humans taking large doses of disulfiram regularly.
The Neurostructure of Morality and the Hubris of Memory Manipulation
Published in The New Bioethics, 2018
Historically, drug aversion therapies have included electroconvulsive techniques,21 satiation,22 and chemical aversant pairings with the undesired behavior.23 Ethical concerns, as well as a lack of controlled scientific studies in these areas, have led to the demise of traditional aversion techniques. Despite the demise, it is important to note that some drug programs still include aversion therapy into their methodologies (Clifasefi et al. 2013, p. 14). Current (acceptable) pharmacological treatments for substance addiction include the administration of inhibitory agents (e.g. Disulfiram) that act by blocking the breakdown of acetaldehyde, the chemical believed to contribute to withdrawal symptoms. The interaction of Disulfiram with any amount of the addictive substance enhances unpleasant physical symptoms,24 deterring the individual from subsequent use. Today, an alternate approach to curbing substance addiction can be found in the false memory literature.25 Results from a handful of studies have indicated that adopting a false memory as part of one’s personal autobiography can affect an individual’s current and future preferences related to that memory (Clifasefi et al. 2013, p. 15).