A History of Drug Discovery for Treatment of Nausea and Vomiting and the Implications for Future Research.

The origins of the major classes of current anti-emetics are examined. Serendipity is a recurrent theme in discovery of their anti-emetic properties and repurposing from one indication to another is a continuing trend. Notably, the discoveries have occurred against a background of company mergers and changing anti-emetic requirements. Major drug classes include: (i) Muscarinic receptor antagonists-originated from historical accounts of plant extracts containing atropine and hyoscine with development stimulated by the need to prevent sea-sickness among soldiers during beach landings; (ii) Histamine receptor antagonists-searching for replacements for the anti-malaria drug quinine, in short supply because of wartime shipping blockade, facilitated the discovery of histamine (H1) antagonists (e.g., dimenhydrinate), followed by serendipitous discovery of anti-emetic activity against motion sickness in a patient undergoing treatment for urticaria; (iii) Phenothiazines and dopamine receptor antagonists-investigations of their pharmacology as "sedatives" (e.g., chlorpromazine) implicated dopamine receptors in emesis, leading to development of selective dopamine (D2) receptor antagonists (e.g., domperidone with poor ability to penetrate the blood-brain barrier) as anti-emetics in chemotherapy and surgery; (iv) Metoclopramide and selective 5-hydroxytryptamine3(5-HT3) receptor antagonists-metoclopramide was initially assumed to act only via D2 receptor antagonism but subsequently its gastric motility stimulant effect (proposed to contribute to the anti-emetic action) was shown to be due to 5-hydroxytryptamine4 receptor agonism. Pre-clinical studies showed that anti-emetic efficacy against the newly-introduced, highly emetic, chemotherapeutic agent cisplatin was due to antagonism at 5-HT3 receptors. The latter led to identification of selective 5-HT3 receptor antagonists (e.g., granisetron), a major breakthrough in treatment of chemotherapy-induced emesis; (v) Neurokinin1receptor antagonists-antagonists of the actions of substance P were developed as analgesics but pre-clinical studies identified broad-spectrum anti-emetic effects; clinical studies showed particular efficacy in the delayed phase of chemotherapy-induced emesis. Finally, the repurposing of different drugs for treatment of nausea and vomiting is examined, particularly during palliative care, and also the challenges in identifying novel anti-emetic drugs, particularly for treatment of nausea as compared to vomiting. We consider the lessons from the past for the future and ask why there has not been a major breakthrough in the last 20 years

The bridge between classical and ‘synthetic’/chemical psychoses: towards a clinical, psychopathological and therapeutic perspective

© 2019 Orsolini, Chiappini, Papanti, De Berardis, Corkery and Schifano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.The critical spread and dissemination of novel psychoactive substances (NPS), particularly among the most vulnerable youngsters, may pose a further concern about the psychotic trajectories related to the intake of new synthetic drugs. The psychopathological pattern of the “new psychoses” appears to be extremely different from the classical presentation. Therefore, clinicians need more data on these new synthetic psychoses and recommendations on how to manage them. The present mini-review aims at deepening both the clinical, psychopathological features of synthetic/chemical NPS-induced psychoses and their therapeutic strategies, according to the different NPS classes implicated, by underlining the main differences with the “classical” psychoses. A comprehensive review was conducted using the PubMed/Medline database by combining the search strategy of free-text terms and exploding a range of MESH headings relating to the topics of novel psychoactive substances and synthetic/chemical psychoses as follows: {(Novel Psychoactive Substances[Title/Abstract]) AND Psychosis[Title/Abstract])} and for each NPS categories as well, focusing on synthetic cannabinoids and cathinones, without time and/or language restrictions. Finally, an overview of the main clinical and psychopathological features between classical versus NPS-induced chemical/synthetic psychoses is provided for clinicians working with dual disorders and addiction psychiatry. Further insight is given here on therapeutic strategies and practical guidelines for managing patients affected with synthetic/chemical NPS-induced psychoses.Peer reviewedFinal Published versio

The Benefits of Olanzapine in Palliating Symptoms

Olanzapine has become a major drug in the management of chemotherapy-induced nausea and vomiting as a prophylactic agent. In addition, a recent randomized trial has demonstrated its benefits in treating nausea and vomiting associated with advanced cancer. The added benefit to olanzapine is that it also stimulates appetite. As a result, since it treats multiple symptoms associated with advanced cancer, it is likely to become the antiemetic of choice in palliative care at least in the United States. The added benefit of treating insomnia and the avoidance of benzodiazepines should place olanzapine in at the top of the list of drugs to use for patients who do complain of insomnia. There is no good evidence that it potentiates the respiratory depression of opioids unlike benzodiazepines. The evidence is weak that olanzapine in as an adjuvant analgesic. Hopefully, future trials will explore this in greater depth. The benefits of adding olanzapine to potent opioids is that it may reduce craving, drug cues and opioid misuse. Other symptoms like anxiety and depression may be addressed by the addition of olanzapine to standard antidepressants

Misconceptions of Opioids in Palliative and End of Life Care

Opioids are the most used medication in palliative or end-of-life care to manage patients’ pain levels in different settings where these services are offered. Opioids are considered versatile pain medication because they are used for varying degrees of pain levels and are administered through different routes. Over the years, observations have been made regarding the many misconceptions held by patients and nurses about the use of opioids. These misconceptions led to poor pain management of patients since opioids were not administered as frequently or in the right doses as they should have been to alleviate patients’ pain levels. For nurses especially, this element was detrimental as these misconceptions regarding opioid use allowed these views to be spread to patients which allowed most to oversee administering opioids as they saw fit. The research aimed to describe the different misconceptions that patients and nurses had about opioid use in palliative or end-of-life care. The purpose of the research was to provide valid guidelines that dissipated misconceptions held by nurses and patients about opioid use in palliative or end-of-life care, so that poor pain management would be decreased. The method used was a literature review which used eight guidelines that came from PubMed, CINHAL, and Medline. Chosen data underwent content analysis and provided information from guidelines that could dispel any misconceptions about opioid use. The main misconceptions held by nurses about opioid use in palliative or end-of-life care were addiction, side effects, legal ramifications, and euthanasia. When it came to the misconceptions about opioid use in palliative care or end-of-life care held by patients included side effects, fear that the opioids would mask their symptoms, and religious barriers. The findings provided vital information about how different side effects can be easily managed through non-pharmacological and pharmacological methods and how giving different opioids through different routes decreased side effects in many patients. This provided necessary information about how opioids do not cause euthanasia if they are given in correct doses and at the right times. The difference between sedation as a side effect and intentional palliative sedation was clearly emphasized, which showed that opioids do not play as great a role in palliative sedation as many individuals thought. The research recognized the limitations of this study and purposed that future research should focus more on opioid use specifically for patients in palliative or end-of-life care

Reference Notes for Palliative Care Consultation

The interprofessional health care specialty of palliative care employs holistic evaluation and person-centered communication in the care of people with life-threatening illness. Palliative care clinicians are consulted for one or more of the following reasons: Symptom assessment and management Assistance with making difficult decisions about continued use or withdrawal of life-sustaining interventions Communication for planning the most appropriate care setting to meet person/family goals for end-of-life care Assessment of suitability and eligibility for hospice care This resource is a compilation of previously published documents and tools useful to palliative care clinicians in preparing for and conduction these consultations. In addition, it can be a reference for students and clinical trainees doing course work, analyzing case studies, or simulating clinical communication scenarios. The materials are indexed for easy retrieval, referenced to acknowledge sources and allow further exploration, and organized into the following categories: Palliative Care Definitions/Domains/Dimensions Communication Symptom Assessment Functional Status Evaluation Prognostication End-of-Life Assessment and Management Symptom Management Hospice Eligibility Criteria Withholding and Withdrawing Life-Sustaining Interventions Pediatric End-of-Life Issueshttps://scholarworks.gvsu.edu/books/1017/thumbnail.jp

Alcohol and other drug withdrawal: practice guidelines.

Clinical guidelines seek to direct clinical practice by outlining recognised, evidence-based treatment interventions. They draw on current literature and clinical practice expertise. These Guidelines provide guidance for clinical decision-making in the context of individual client requirements, withdrawal setting, treatment availability and individual service protocols. These Guidelines are consistent with the World Health Organisation’s (WHO) United Nations Principles of Drug Dependence Treatment (United Nations Office on Drugs and Crime and World Health Organization, 2008). They outline current best practice for the management of AOD-dependent clients accessing withdrawal care. 1 Introduction - page 1 2 Definitions of dependence and withdrawal - page 5 3 Principles of AOD withdrawal care - page 9 4 Continuity of Care - page 11 5 Features of AOD withdrawal - page 13 6 Special needs groups - page 19 7 Presentation to AOD withdrawal - page 29 8 AOD withdrawal settings - page 31 9 Assessment - page 37 10 Alcohol withdrawal - page 45 11 Opioid withdrawal - page 65 12 Benzodiazepines - page 87 13 Amphetamine-type substances (ATS) - page 99 14 Cannabis - page 111 15 Nicotine - page 121 16 AOD withdrawal for clients with a dual diagnosis - page 133 17 References - page 16

2021 KSCCM clinical practice guidelines for pain, agitation, delirium, immobility, and sleep disturbance in the intensive care unit

We revised and expanded the “2010 Guideline for the Use of Sedatives and Analgesics in the Adult Intensive Care Unit (ICU).” We revised the 2010 Guideline based mainly on the 2018 “Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption (PADIS) in Adult Patients in the ICU,” which was an updated 2013 pain, agitation, and delirium guideline with the inclusion of two additional topics (rehabilitation/mobility and sleep). Since it was not possible to hold face-to-face meetings of panels due to the coronavirus disease 2019 (COVID-19) pandemic, all discussions took place via virtual conference platforms and e-mail with the participation of all panelists. All authors drafted the recommendations, and all panelists discussed and revised the recommendations several times. The quality of evidence for each recommendation was classified as high (level A), moderate (level B), or low/very low (level C), and all panelists voted on the quality level of each recommendation. The participating panelists had no conflicts of interest on related topics. The development of this guideline was independent of any industry funding. The Pain, Agitation/Sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep Disturbance panels issued 42 recommendations (level A, 6; level B, 18; and level C, 18). The 2021 clinical practice guideline provides up-to-date information on how to prevent and manage pain, agitation/sedation, delirium, immobility, and sleep disturbance in adult ICU patients. We believe that these guidelines can provide an integrated method for clinicians to manage PADIS in adult ICU patients

A multidisciplinary expert opinion on CINV and RINV, unmet needs and practical real-life approaches

Introduction: A range of combination chemotherapy regimens are currently used in clinical practice. However, international antiemetic guidelines often only categorize the emetogenic potential of single agents rather than the emetogenicity of combination chemotherapy regimens. To manage the nausea and vomiting induced by antineoplastic combinations, guidelines suggest antiemetics that are appropriate for the component drug with the highest emetogenic potential. Furthermore, antiemetic guidelines generally do not consider the influence of other factors, including individual patient characteristics, on the emetic effects of cancer treatments. Similarly, the emetogenic potential of radiotherapy is stratified only according to the site of radiation, while other factors contributing to emetic risk are overlooked. Areas covered: An Expert Panel was convened to examine unresolved issues and summarize the current clinical research on managing nausea and vomiting associated with combination chemotherapy and radiotherapy. Expert opinion: The panel identified the incidence of nausea and vomiting induced by multi-drug combination therapies currently used to treat cancer at different anatomic sites and by radiotherapy in the presence of other risk factors. Based on these data and the clinical experience of panel members, several suggestions are made for a practical approach to prevent or manage nausea and vomiting due to chemotherapy regimens and radiation therapy