The Causes of Heroin Addiction—A Review of the Literature. Part I

The causes of heroin addiction have been studied and debated, and many theories have evolved. This article reviews the extensive literature on the subject and groups the material under the categories of Psychological, Pharmocological, Genetic, Sociological, Social Protest, The Family, and Stepping Stone theories.     

The Causes of Heroin Addiction—A Review of the Literature. Part II

Theories on the causes of heroin addiction are reviewed in this two part article. Part II reviews the literature that considers the family of the addict and the stepping stone theory.     

The Unitary Patent and UPC – Implications for the pharmaceutical sector

Intellectual property, and particularly patents, are an essential commercial tool for companies involved in drug discovery. The European patent system is about to undergo one of its largest changes for a generation, involving the establishment of a European unitary patent and Unified Patent Court (UPC). The new system will usher in a new European patent right (the unitary patent) which will have unitary effect across participating member states. A new court system (the UPC) will be established to handle litigation of not only the new unitary patents, but also European patents that are validated nationally in participating member states. The new system brings many potential advantages to patent holders and third parties. However, there is significant uncertainty, drawbacks and potential risks that patent owners will need to consider when deciding whether to use the unitary patent system. This article will explore some of the factors that organisations in the pharmaceutical sector should consider in advance of the new system coming into effect.     

Targeting Parkinson's Disease – The Case for Early Referral

Summary

Parkinson's disease (PD) is a chronic and disabling condition, for which guidelines for best practice have recently been implemented in the UK. One of the key issues discussed is the provision of a continuum of care by a multidisciplinary team, which must comprise professionals with specialist expertise, including a PD specialist nurse and patient carer(s). Emphasis is placed on the importance of referral of de novo patients to specialist centres for confirmation of diagnosis and management. A synopsis of the classes of drugs available, differential diagnosis and the role of drug treatment in PD are also presented. The guidelines highlight that revision of national guidelines to form local protocols and working practices will improve and integrate care for PD patients. The significance of teamwork and good communication between primary care specialists in the management of PD is emphasised throughout.     

Tip-enhanced Raman scattering—Targeting structure-specific surface characterization for biomedical samples

Tip-enhanced Raman scattering (TERS) has become a powerful tool for nanoscale structural analysis for several branches of organic, inorganic, and biological chemistry. This highly sensitive technique enables molecular characterization with a lateral resolution far beyond Abbe's diffraction limit and correlates structural and topographic information on a nanometer scale. In this review, the current experimental concepts with respect to their strengths and obstacles are introduced and discussed. A further focus was set to biochemistry comprising applications like nucleic acids, proteins, and microorganisms, thus demonstrating the potential use towards the pharmaceutically relevant challenges where nanometer resolution is required.     

Expanding Bedside Filtration—A Powerful Tool to Protect Patients From Protein Aggregates

Protein immunogenicity is intensively researched by academics, biopharmaceutical companies, and authorities as it can compromise the safety and efficacy of a biopharmaceutical drug. So far, the exact protein aggregate properties inducing immune responses are not known. Possible protein-related factors could be size, chemical modifications, or higher order structures. It is impossible to achieve an absolute absence of protein aggregates even for very stable formulations. The application of “bedside filtration,” meaning filtration during the preparation or administration of the drug product immediately before injection, has the potential to increase the safety of every drug container and could prevent the undesired injection of particulate matter into the patient. In this study, the high efficiency of filtration for reducing the amount of protein particles was demonstrated with more than 19 stressed and nonstressed biopharmaceutical products which covered a broad concentration and molecular weight range. Furthermore, critical aspects regarding the usage of filters such as particle shedding from filters, protein loss as a result of protein adsorption, or the hold-up volume of the filters were assessed. Although differences between the filters were observed, no negative impact by the investigated filters could be found. A broader application of bedside filtration is therefore proposed.     

Next Generation Ligand Binding Assays—Review of Emerging Real-Time Measurement Technologies

Over the last few years, numerous ligand binding assay technologies that utilize real-time measurement have been introduced; however, an assemblage and evaluation of these technologies has not previously been published. Herein, we describe six emerging real-time measurement technologies: Maverick™, MX96 SPR™, NanoDLSay™, AMMP®/ViBE®, SoPrano™, and two Lab-on-a-Chip (LoC) microfluidic devices. The development stage gate of these technologies ranges from pre-commercial to commercially available. Due to the novelty, the application and utility of some of the technologies regarding bioanalysis are likely to evolve but it is our hope that this review will provide insight into the direction the development of real-time measurement technologies is moving and the vision of those that are taking us there. Following the technology discussions, a comprehensive summary table is presented.KEY WORDS: acoustic wave mass dampening, dynamic light scattering, integrated microfluidic systems, localized surface plasmon resonance, microring array     

Novel Therapies Targeting Inner Mitochondrial Membrane—From Discovery to Clinical Development

Mitochondrial oxidative stress and dysfunction have been implicated in the aging process and in numerous chronic diseases. The need for therapies that can protect and/or improve mitochondrial function is obvious. However, the development of mitoprotective drugs has been hampered by a number of challenges, and there are at present no approved therapies for mitochondrial dysfunction. This article describes the original discovery, preclinical development, and clinical development of a novel class of small peptide molecules that selectively target the inner mitochondrial membrane and protect mitochondrial function. These compounds have the potential to be a paradigm-shifting approach to the treatment of mitochondrial dysfunction, which underlies many common diseases, including cardiorenal, neurologic, and metabolic disorders.     

Introduction — The coxib controversies

Much concern has arisen in the past year concerning the occurrence of serious cardiovascular adverse reactions from rofecoxib, celecoxib and some other members of the coxib group of NSAIDs. Factors underlying the sudden appearance of these events have been proposed to include the use of high doses of the drugs, undue reliance on their safety profile from controlled clinical trails and potent marketing leading to exposure of a large population who would inevitably present risks of cardiovascular adverse events. Suggestions are presented for future uses of the coxibs and approaches for their more cautious use and marketing. The use of the term "COX-2 inhibitor" to describe the coxibs is unhelpful and should be avoided since all NSAIDs have some degree of COX-2 inhibitory effect, though they may vary in their selectivity. Coxibs should be set aside in a group of their own within the broader category of the NSAIDs in view of both their cardiovascular risk and unique pharmacology.     

DPS—The PMA Perspective

The continuing education paper by Parker et al. published in the September 1991 issue of American Pharmacy (p. 47) is a comprehensive and useful review of the Orange Book. The Pharmaceutical Manufacturers Association (PMA) wishes to offer comments on the paper and on policies of the Food and Drug Administration (FDA) relative to multisource drug products.     

The Toxicology Investigators Consortium Case Registry—The 2012 Experience

In 2010, the American College of Medical Toxicology (ACMT) established its Case Registry, the Toxicology Investigators Consortium (ToxIC). All cases are entered prospectively and include only suspected and confirmed toxic exposures cared for at the bedside by board-certified or board-eligible medical toxicologists at its participating sites. The primary aims of establishing this Registry include the development of a realtime toxico-surveillance system in order to identify and describe current or evolving trends in poisoning and to develop a research tool in toxicology. ToxIC allows for extraction of data from medical records from multiple sites across a national and international network. All cases seen by medical toxicologists at participating institutions were entered into the database. Information characterizing patients entered in 2012 was tabulated and data from the previous years including 2010 and 2011 were included so that cumulative numbers and trends could be described as well. The current report includes data through December 31st, 2012. During 2012, 38 sites with 68 specific institutions contributed a total of 7,269 cases to the Registry. The total number of cases entered into the Registry at the end of 2012 was 17,681. Emergency departments remained the most common source of consultation in 2012, accounting for 61 % of cases. The most common reason for consultation was for pharmaceutical overdose, which occurred in 52 % of patients including intentional (41 %) and unintentional (11 %) exposures. The most common classes of agents were sedative-hypnotics (1,422 entries in 13 % of cases) non-opioid analgesics (1,295 entries in 12 % of cases), opioids (1,086 entries in 10 % of cases) and antidepressants (1,039 entries in 10 % of cases). N-acetylcysteine (NAC) was the most common antidote administered in 2012, as it was in previous years, followed by the opioid antagonist naloxone, sodium bicarbonate, physostigmine and flumazenil. Anti-crotalid Fab fragments were administered in 109 cases or 82 % of cases in which a snake envenomation occurred. There were 57 deaths reported in the Registry in 2012. The most common associated agent alone or in combination was the non-opioid analgesic acetaminophen, being reported in 10 different cases. Other common agents and agent classes involved in death cases included ethanol, opioids, the anti-diabetic agent metformin, sedatives-hypnotics and cardiovascular agents, in particular amlodipine. There were significant trends identified during 2012. Abuse of over-the-counter medications such as dextromethorphan remains prevalent. Cases involving dextromethorphan continued to be reported at frequencies higher than other commonly abused drugs including many stimulants, phencyclidine, synthetic cannabinoids and designer amphetamines such as bath salts. And, while cases involving synthetic cannabinoids and psychoactive bath salts remained relatively constant from 2011 to 2012 several designer amphetamines and novel psychoactive substances were first reported in the Registry in 2012 including the NBOME compounds or “N-bomb” agents. LSD cases also spiked dramatically in 2012 with an 18-fold increase from 2011 although many of these cases are thought to be ultra-potent designer amphetamines misrepresented as “synthetic” LSD. The 2012 Registry included over 400 Adverse Drug Reactions (ADRs) involving 4 % of all Registry cases with 106 agents causing at least 2 ADRs. Additional data including supportive cares, decontamination, and chelating agent use are also included in the 2012 annual report. The Registry remains a valuable toxico-surveillance and research tool. The ToxIC Registry is a unique tool for identifying and characterizing confirmed cases of significant or potential toxicity or complexity to require bedside care by a medical toxicologist.     

The Toxicology Investigators Consortium Case Registry—The 2010 Experience

Introduction

The American College of Medical Toxicology Case Registry was established in 2010 as a method of identifying cases cared for by medical toxicologists at participating institutions. The Registry allows for the extraction of information from medical records making it the most robust multicenter database on chemical toxicities in existence. The current report is a summary of the data collected in 2010.

Methods

All cases seen by medical toxicologists at participating institutions were entered on a database. Information characterizing patients entered in 2010 was tabulated.

Results

Over the course of 2010, the number of institutions contributing cases grew from 4 to 50. Three thousand nine hundred forty-eight cases were entered. Emergency departments were the most common source of consultations, accounting for approximately 50% of the cases. The most common reason for consultations was for pharmaceutical overdoses, which occurred in 42% of the patients. The most common classes of agents were non-opioid analgesics (14%), sedative/hypnotics/muscle relaxants (10%), ethanol (8%), and opioids (8%). N-acetylcysteine was the most common antidote used, followed by opioid antagonists, sodium bicarbonate, and physostigmine. Anti-crotalidae Fab fragments were administered in 72% of the cases in which an antivenin was used. Signals were detected suggesting the possibility that amlodipine and metoprolol were associated with greater toxicity than had been previously recognized.

Conclusions

The Registry can identify and characterize patients who have sufficient toxicity to require a consultation by a medical toxicologist. Hypotheses for further investigation emerged from the data. The Registry appears to be a potentially powerful tool for toxicovigilance and research.