Insights into Newly Approved Drugs from a Medicinal Chemistry Perspective.

The development of new drugs is becoming notably harder each decade. To overcome the present pitfalls in the drug development pipeline, such as those related to potency, selectivity, or absorption, distribution, metabolism, excretion and toxicity properties, medicinal chemistry strategies need to be in continuous evolution and need to become even more multidisciplinary. In this review, we present how structure-based, ligand-based, and fragment-based drug design (SBDD, LBDD, and FBDD, respectively) and their respective techniques were used for the design and optimization of successful cases of New Molecular Entities (NMEs) approved by the Food and Drug Administration (FDA).

Compounded non-FDA-approved menopausal hormone therapy prescriptions have increased: results of a pharmacy survey.

OBJECTIVE: From a survey of compounding pharmacists, specific questions regarding compounded menopausal hormone therapy were used to estimate compounded hormone therapy (CHT) prescribing in the United States. METHODS: A national online survey was conducted by Rose Research--a market research company consisting of 12,250 US pharmacists from independent community pharmacies (ICPs) and compounding pharmacies (CPs). Pharmacists who completed the survey and met the prespecified criteria were eligible. Data from the survey were extrapolated to estimate overall CHT prescription volume and annual costs of CHT prescriptions for the United States based upon industry data from the National Community Pharmacists Association and IBISWorld. RESULTS: Surveys were completed by 483 pharmacies, including 365 ICPs and 118 CPs. On the basis of the survey responses and extrapolated industry data, an estimated 26 to 33 million CHT prescriptions were filled annually, with total sales estimated at $1.3 to $1.6 billion. CPs (vs ICPs) accounted for a higher proportion of CHT prescriptions. More than half of the ICPs (52%) and CPs (75%) expected continued compounding business growth, with most predicting 5% to 25% growth within 2 years, despite the potential effect of restrictive legislation regarding compounding. CONCLUSIONS: On the basis of extrapolated data from numbers of prescriptions reported by pharmacists participating in the survey, the volume of CHT seems to approach that of Food and Drug Administration (FDA)-approved menopausal hormone therapy, and growth in the CHT market is expected. Thus, physicians should educate themselves and the women consulting them about the differences between the FDA-approved and the less-tested CHT formulations. More research on the efficacy, safety, and consistency of non-FDA-approved CHT is needed.

Dietary supplements: International legal framework and adulteration profiles, and characteristics of products on the Brazilian clandestine market.

The objectives of this work were to evaluate current legislation on dietary supplements in the United States, the European Union and Brazil, and the profile of adulterated and/or irregular products on these markets. Due to a less restrictive legal framework, a supplement product that is freely available in the US may be considered a drug or even be proscribed in the EU and Brazil, thus giving rise to a clandestine market based on smuggling. From 2007 to 2014, the United States Food and Drug Administration reported 572 cases of supplement adulterations in the country, mainly products for sexual enhancement (41.6%). Data from the European Union Rapid Alert System for Food and Feed showed 929 adulterations during the same period, over 40% due to unauthorized ingredients or undeclared medicines. From 2007 to 2013, the Brazilian Federal Police Department seized 5470 supplement products, 92.2% with an American-declared origin. Qualitative chemical analyses performed on 2898 products found 180 adulterations, 41.1% due to undeclared drugs, mainly anabolic steroids, anorectics and products for erectile dysfunction, all considered medicines in Brazil. Educating the public regarding the potential risks they are taking when consuming adulterated or irregular products is necessary to protect the health of consumers.

The tragedy of the commodity and the farce of AquAdvantage Salmon.

The US Food and Drug Administration is expected to approve AquAdvantage Salmon as the first genetically modified animal for human consumption. The genetic modifications allow the proprietary fish to grow at a rate twice as fast as a wild salmon, leading to greater 'efficiency' in terms of reduced costs and reduced time to market. This article provides an analysis of the ways in which AquAdvantage Salmon exemplifies capitalist market forces controlling and guiding the terms of salmon recovery and conservation. The authors trace historical developments within the salmon industry to demonstrate how capitalist commodity production has impacted fishing communities. They reject the oft-cited 'tragedy of the commons' hypothesis offered to explain fisheries crises. In its place, they offer the conceptual framework of the 'tragedy of the commodity' to explore how capitalist market forces and complicit state regulations amplify rather than resolve global environmental problems.

[Do antidepressants really increase suicide rates in childhood and adolescence?]. / ¿Es efectivo que los antidepresivos aumentan el riesgo de suicidio?

The use of antidepressant in depressive illness results in a reduction of suicidal attempts and deaths due to suicide, conditions that are generally present in this disorder. Recently, the Federal Drug Administration (FDA) prohibited the use of antidepressants during childhood and adolescence. This decision was based on a supposed increase in suicidal thinking in these age groups. However, the evidence came from flawed clinical studies, some of them not even published, in which no significant differences were observed when compared to placebo. It is not possible to ascribe a direct responsibility to antidepressants, because depression, by definition, has suicidal ideation. On the contrary, the reduction of suicidal rates supports the effectiveness of these medications.

¿Es efectivo que los antidepresivos aumentan el riesgo de suicidio? / Do antidepressants really Increase suicide rates In childhood and adolescence?

The use of antidepressant in depressive illness results in a reduction of suicidal attempts and deaths due to suicide, conditions that are generally present in this disorder. Recently, the Federal Drug Administration (FDA) prohibited the use of antidepressants during childhood and adolescence. This decision was based on a supposed increase in suicidal thinking in these age groups. However, the evidence came from flawed clinical studies, some of them not even published, in which no significant differences were observed when compared to placebo. It is not possible to ascribe a direct responsibility to antidepressants, because depression, by definition, has suicidal ideation. On the contrary, the reduction of suicidal rates supports the effectiveness of these medications.

Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges.

Ayahuasca is a hallucinogenic beverage that is prominent in the ethnomedicine and shamanism of indigenous Amazonian tribes. Its unique pharmacology depends on the oral activity of the hallucinogen, N,N-dimethyltryptamine (DMT), which results from inhibition of monoamine oxidase (MAO) by beta-carboline alkaloids. MAO is the enzyme that normally degrades DMT in the liver and gut. Ayahuasca has long been integrated into mestizo folk medicine in the northwest Amazon. In Brazil, it is used as a sacrament by several syncretic churches. Some of these organizations have incorporated in the United States. The recreational and religious use of ayahuasca in the United States, as well as "ayahuasca tourism" in the Amazon, is increasing. The current legal status of ayahuasca or its source plants in the United States is unclear, although DMT is a Schedule I controlled substance. One ayahuasca church has received favorable rulings in 2 federal courts in response to its petition to the Department of Justice for the right to use ayahuasca under the Religious Freedom Restoration Act. A biomedical study of one of the churches, the Uñiao do Vegetal (UDV), indicated that ayahuasca may have therapeutic applications for the treatment of alcoholism, substance abuse, and possibly other disorders. Clinical studies conducted in Spain have demonstrated that ayahuasca can be used safely in normal healthy adults, but have done little to clarify its potential therapeutic uses. Because of ayahuasca's ill-defined legal status and variable botanical and chemical composition, clinical investigations in the United States, ideally under an approved Investigational New Drug (IND) protocol, are complicated by both regulatory and methodological issues. This article provides an overview of ayahuasca and discusses some of the challenges that must be overcome before it can be clinically investigated in the United States.