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Topic Review
Biography
Topic Review
Peimine, an Anti-Inflammatory Compound from Chinese Herbal Extracts
Fritillaria bulbs are used in Traditional Chinese Medicine to treat several illnesses. Peimine (Pm), an anti-inflammatory compound from Fritillaria, is known to inhibit some voltage-dependent ion channels and muscarinic receptors, but its interaction with ligand-gated ion channels remains unexplored.
404
29 Mar 2022
Topic Review
Drug Interaction of Sorafenib and Morphine
A combination of the tyrosine kinase inhibitor—sorafenib—and the opioid analgesic—morphine—can be found in the treatment of cancer patients. Since both are substrates of P-glycoprotein (P-gp), and sorafenib is also an inhibitor of P-gp, their co-administration may affect their pharmacokinetics, and thus the safety and efficacy of cancer therapy.
404
23 Dec 2021
Topic Review
Two Non-Tablet Oral Formulations of L-Thyroxine
Increased knowledge of the pharmacokinetic characteristics of orally administered levothyroxine (L-T4) has improved individualization of dosing regimens. However, up to 40–45% of patients, depending on the leading cause of hypothyroidism, are still over- or, more often, undertreated. Unintentional non-adherence to L-T4 replacement therapy includes all situations of unintended drug–drug and drug–food interactions as well as fasting conditions that are not necessarily respected by patients. The non-tablet L-T4 soft-gel capsules and solution have proven bioequivalence with the usual L-T4 tablet Princeps and generic formulations. Clinical studies have suggested higher performance of non-tablet formulations than tablet in those patients with suboptimal adherence.
404
22 Jul 2022
Topic Review
Advice of Medicine Shortages in Europe
The following recommendations should be considered to handle the issue of drug shortages more effectively in Europe. Since drug shortages do not respect borders and cross-country collaboration would be beneficial for more effective shortage management, a unified European definition and reporting criteria of shortages would be necessary to assure internationally consistent monitoring, reporting, comparisons, responses, and solutions. National authorities across Europe should be aware of shortages through coordinated systems, increasing cross-country transparency, and facilitating solutions in every country. It was a significant step forward in the European Union that in July 2019, the EMA published the “Guidance on detection and notification of shortages of medicinal products for Marketing Authorisation Holders in the Union”. The document contains the effort to facilitate the more uniform reporting and communication of drug shortages and create a harmonization “drug shortage” definition. The document “Good practice guidance for communication to the public on medicines availability issues”contains communication guidelines for the national authorities and the EMA for patients and healthcare professionals.
403
06 Apr 2022
Topic Review
Neurodegenerative Disorders Characterized by Mitochondrial Involvement
Neurodegenerative diseases comprise a wide spectrum of pathologies characterized by progressive loss of neuronal functions and structures. Despite having different genetic backgrounds and etiology, many studies have highlighted a point of convergence in the mechanisms leading to neurodegeneration: mitochondrial dysfunction and oxidative stress have been observed in different pathologies, and their detrimental effects on neurons contribute to the exacerbation of the pathological phenotype at various degrees.
403
08 Mar 2023
Topic Review
BMVs for Drug Delivery Applications
Numerous factors need to be considered to develop a nanodrug delivery system that is biocompatible, non-toxic, easy to synthesize, cost-effective, and feasible for scale up over and above their therapeutic efficacy. With regards to this, worldwide, exosomes, which are nano-sized vesicles obtained from mammalian cells, are being explored as a biomimetic drug delivery system that has superior biocompatibility and high translational capability. However, the economics of undertaking large-scale mammalian culture to derive exosomal vesicles for translation seems to be challenging and unfeasible. Recently, Bacterial Membrane Vesicles (BMVs) derived from bacteria are being explored as a viable alternative as biomimetic drug delivery systems that can be manufactured relatively easily at much lower costs at a large scale. Until now, BMVs have been investigated extensively as successful immunomodulating agents, but their capability as drug delivery systems remains to be explored in detail.
402
24 Sep 2021
Topic Review
Ligand-Free Signaling of G-Protein-Coupled Receptors
Numerous G-protein-coupled receptors (GPCRs) display ligand-free basal signaling with potential physiological functions, a target in drug development. As an example, the μ opioid receptor (MOR) signals in ligand-free form (MOR-μ*), influencing opioid responses. In addition, agonists bind to MOR but can dissociate upon MOR activation, with ligand-free MOR-μ* carrying out signaling. Opioid pain therapy is effective but incurs adverse effects (ADRs) and risk of opioid use disorder (OUD). Sustained opioid agonist exposure increases persistent basal MOR-μ* activity, which could be a driving force for OUD and ADRs. Antagonists competitively prevent resting MOR (MOR-μ) activation to MOR-μ*, while common antagonists, such as naloxone and naltrexone, also bind to and block ligand-free MOR-μ*, acting as potent inverse agonists. A neutral antagonist, 6β-naltrexol (6BN), binds to but does not block MOR-μ*, preventing MOR-μ activation only competitively with reduced potency.
402
17 Oct 2022
Topic Review
Gender-Specific Pharmacokinetics and Pharmacodynamics
Women and men respond differently to treatments; this mainly depends on physiological, anatomical, and hormonal characteristics. The existence of the differences in therapeutic agent pharmacokinetics and pharmacodynamics influences the response to treatments.
403
30 May 2023
Topic Review
Developments on 14-Oxygenated-N-methylmorphinan-6-ones
Adequate pain management, particularly chronic pain, remains a major challenge associated with modern-day medicine. Current pharmacotherapy offers unsatisfactory long-term solutions due to serious side effects related to the chronic administration of analgesic drugs. Morphine and structurally related derivatives (e.g., oxycodone, oxymorphone, buprenorphine) are highly effective opioid analgesics, mediating their effects via the activation of opioid receptors, with the mu-opioid receptor subtype as the primary molecular target. However, they also cause addiction and overdose deaths, which has led to a global opioid crisis in the last decades. Therefore, research efforts are needed to overcome the limitations of present pain therapies with the aim to improve treatment efficacy and to reduce complications.
400
30 Sep 2021
Topic Review
Enhancing Brain Drug Bioavailability in Depression and Anxiety
Depression and anxiety are high incidence and debilitating psychiatric disorders, usually treated by antidepressant or anxiolytic drug administration, respectively. Three main strategies have been used to improve brain drug targeting: the intranasal route of administration, which allows the drug to be directly transported to the brain by neuronal pathways, bypassing the blood–brain barrier and avoiding the hepatic and gastrointestinal metabolism; the use of nanosystems for drug encapsulation, including polymeric and lipidic nanoparticles, nanometric emulsions, and nanogels; and drug molecule functionalization by ligand attachment, such as peptides and polymers. Pharmacokinetic and pharmacodynamic in vivo studies’ results have shown that intranasal administration can be more efficient in brain targeting than other administration routes, and that the use of nanoformulations and drug functionalization can be quite advantageous in increasing brain–drug bioavailability. These strategies could be the key to future improved therapies for depressive and anxiety disorders.
399
31 Mar 2023
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