Current drug metabolism
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Current drug metabolism · Jan 2018
ReviewReplacing GHB with GBL in Recreational Settings: A New Trend in Chemsex.
Recently, Gamma-hydroxybutyrate (GHB) consumption in the recreational setting has been replaced by that of its prodrug Gamma-butyrolactone (GBL), cheaper and easier to obtain due to several legal industrial applications. ⋯ GBL currently represents a growing public health issue since the substance is relatively cheaper and easier to obtain than GHB. Improvement and implementation of laws and policies to place GBL under control are needed to limit its diffusion, the eventual health threat for users and its non -negligible abuse liability and dependence risk.
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Current drug metabolism · Jan 2016
ReviewSmad7 and its Potential as Therapeutic Target in Inflammatory Bowel Diseases.
The etiology of Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD) in humans, is still unknown, but evidence suggests that genetic and environmental factors interact to promote an excessive immune response that leads to tissue damage. Defects in the counter-regulatory mechanisms are also supposed to make a major contribution to the amplification and maintenance of the IBD-related inflammatory response. One such a mechanism involves TGF-β1, a cytokine synthesized by both immune and non-immune cells in the gut, which is essential in the maintenance of immune homeostasis. In both CD and UC, active inflammation occurs in areas characterized by enhanced production of TGF-β1 and reduced ability of this cytokine to activate Smad-associated signaling and suppress inflammatory pathways. The defective TGF-β1 activity is due to elevated levels of Smad7, an intracellular protein that inhibits TGF-β1-associated Smad signaling. ⋯ Data indicate that, in IBD, high Smad7 contributes to sustain detrimental immune responses and knockdown of this molecule can help attenuate the ongoing mucosal inflammation in patients with such disorders.
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Current drug metabolism · Jan 2016
Molecular Targets for Small-Molecule Modulators of Circadian Clocks.
Circadian clocks are endogenous timing systems that regulate various aspects of mammalian metabolism, physiology and behavior. Traditional chronotherapy refers to the administration of drugs in a defined circadian time window to achieve optimal pharmacokinetic and therapeutic efficacies. In recent years, substantial efforts have been dedicated to developing novel small-molecule modulators of circadian clocks. ⋯ Small-molecule clock modulators target clock components or diverse cellular pathways that functionally impinge upon the clock. Target identification of new small-molecule modulators will deepen our understanding of key regulatory nodes in the circadian network. Studies of clock modulators will facilitate their therapeutic applications, alone or in combination, for clock-related diseases.
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Current drug metabolism · Jan 2014
ReviewPharmacokinetic interactions between herbal medicines and prescribed drugs: focus on drug metabolic enzymes and transporters.
Herbal medicines have been widely used for thousands of years, and now are gaining continued popularity worldwide as a complementary or alternative treatment for a variety of diseases, rehabilitation and health care. Since herbal medicines contain more than one pharmacologically active ingredient and are commonly used with many prescribed drugs, there are potential herb-drug interactions. A variety of reported herb-drug interactions are of pharmacokinetic origin, arising from the effects of herbal medicines on metabolic enzymes and/or transporters. ⋯ This review summarizes the mechanism underlying herb-drug interactions and the approaches to identify the interactions, and discusses pharmacokinetic interactions of eight widely used herbal medicines (Ginkgo biloba, ginseng, garlic, black cohosh, Echinacea, milk thistle, kava, and St. John's wort) with conventional drugs, using various in vitro, animal in vivo, and clinical studies. The increasing understanding of pharmacokinetic herb-drug interactions will make health care professionals and patients pay more attention to the potential interactions.
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Current drug metabolism · Feb 2013
ReviewVasopressin and terlipressin in neonates and children with refractory septic shock.
Vasopressin and its analogue terlipressin are potent vasopressors which have been recently proposed in the treatment of catecholamine-resistant septic shock. We review the physiology, metabolism and pharmacology of vasopressin and terlipressin, as well as the available data on their efficacy and safety in neonates and children with septic shock. In adults, vasopressin deficiency can contribute to refractory shock states associated with sepsis. ⋯ In particular, terlipressin has a higher selectivity for V1-receptors and a longer half-life when compared to vasopressin, allowing for intermittent bolus doses. However, the pharmacology of vasopressin/terlipressin in newborns and children has not been sufficiently investigated and data on potential short and long-term adverse effects are still lacking. Further clinical, pharmacokinetic and pharmacodynamic studies are needed to better define the role of vasopressin and terlipressin in septic shock, as well as to prove their effectiveness and safety in infants and children.