Modulation of transient receptor potential (TRP) channels by plant derived substances used in over-the-counter cough and cold remedies.

BACKGROUND: Upper respiratory tract infections (URTIs) impact all age groups and have a significant economic and social burden on society, worldwide. Most URTIs are mild and self-limiting, but due to the wide range of possible causative agents, including Rhinovirus (hRV), Adenovirus, Respiratory Syncytial Virus (RSV), Coronavirus and Influenza, there is no single and effective treatment. Over-the-counter (OTC) remedies, including traditional medicines and those containing plant derived substances, help to alleviate symptoms including inflammation, pain, fever and cough. PURPOSE: This systematic review focuses on the role of the major plant derived substances in several OTC remedies used to treat cold symptoms, with a particular focus on the transient receptor potential (TRP) channels involved in pain and cough. METHODS: Literature searches were done using Pubmed and Web of Science, with no date limitations, using the principles of the PRISMA statement. The search terms used were 'TRP channel AND plant compound', 'cough AND plant compound', 'cough AND TRP channels AND plant compound', 'cough AND P2X3 AND plant compound' and 'P2X3 AND plant compound' where plant compound represents menthol or camphor or eucalyptus or turpentine or thymol. RESULTS: The literature reviewed showed that menthol activates TRPM8 and may inhibit respiratory reflexes reducing irritation and cough. Menthol has a bimodal action on TRPA1, but inhibition may have an analgesic effect. Eucalyptus also activates TRPM8 and inhibits TRPA1 whilst down regulating P2X3, aiding in the reduction of cough, pain and airway irritation. Camphor inhibits TRPA1 and the activation of TRPM8 may add to the effects of menthol. Activation of TRPV1 by camphor, may also have an analgesic effect. CONCLUSIONS: The literature suggests that these plant derived substances have multifaceted actions and can interact with the TRP 'cough' receptors. The plant derived substances used in cough and cold medicines have the potential to target multiple symptoms experienced during a cold.

GABAA receptors as targets for anaesthetics and analgesics and promising candidates to help treat coronavirus infections: A mini-review.

GABA is a major inhibitory neurotransmitter that regulates the balance between excitatory and inhibitory circuits in the human nervous system. The GABA receptors are divided into three main subtypes, GABAA , GABAB , and GABAC (also termed GABAA rho) receptors. GABAA receptors are pentameric ligand-gated ion channels widely expressed throughout the central and peripheral nervous system. The activation of GABAA receptors results in opening of an anion-selective channel that mainly gates chloride ions and allows them to flow into the neuron, causing hyperpolarization of the cell membrane that dampens neural excitability. This makes GABAA receptors critical anaesthetic and analgesic targets for existing as well as for the development of novel drugs. In this review, we first summarize the biochemical properties of GABAA receptors and the clinical anaesthetics and analgesics targeting the receptors. In a forward-looking section, we summarize the emerging role of GABAergic signalling in treatment of COVID-19 related infections. Finally, we discuss the opportunities arising from targeting specific and unique subunit interfaces for the development of novel anaesthetics and analgesics leading to more efficient therapies.

In the Swim of Cannabis: Developmental Toxicity and Metabolomic Pathway Alterations of Zebrafish Larvae Exposed to THC for the Assessment of Its Potential Environmental and Human Health Impact.

As the pharmacological properties and therapeutic applications of Cannabis sativa L. pace with the upsurge of interest of the scientific community in harnessing its constituent phytocannabinoids, illicit use may raise serious health issues. Tetrahydrocannabinol (THC) is one of the most well-known phytoactive constituents of cannabis and continues to garner scientific and public attention not only because of its pharmacological value but also because over-the-counter products of THC and prescription medications are becoming increasingly available from pharmacies, dispensaries, Internet, local retail stores, or by illicit means. Hence, a multidimensional approach was employed to examine the impact of THC on zebrafish larvae. The acute toxicity, expressed as LC50, was 1.54 mg/L. Adverse effects were observed on the phenotype, such as tail bending, pericardial edema, etc., even at concentrations lower than LC50, and fundamental functions of larvae (e.g., heart rate and cardiac contractility, and rhythm) were significantly affected. Behavioral changes were noticed, which were reflected in locomotor activity and sensitivity to light/dark changes. Finally, an untargeted metabolomic study was carried out to shed light on the metabolic alterations that occurred, providing substantiating evidence of the observed phenotype alterations. Overall, the potentially detrimental effects of THC on a vertebrate model are depicted.

Effect of Stellate Ganglion Block Combined with Lidocaine at Different Concentrations for Preemptive Analgesia on Postoperative Pain Relief and Adverse Reactions of Patients Undergoing Laparoscopic Cholecystectomy.

Objective: To explore the effect of stellate ganglion block (SGB) combined with lidocaine at different concentrations for preemptive analgesia on postoperative pain relief and adverse reactions of patients undergoing laparoscopic cholecystectomy (LC). Methods: Ninety patients undergoing LC in our hospital from June 2019 to June 2020 were selected as the subjects and were randomly divided into group A (30 cases), group B (30 cases), and group C (30 cases), all patients received SGB, and 10 mL of lidocaine at concentrations of 0.25%, 0.5%, and 0.75% was, respectively, administered to patients in groups A, B, and C, so as to compare the analgesic effect, adverse reactions, and clinical indicators among the three groups. Results: At T 1 and T 2, group C obtained obviously lower NRS scores than groups A and B (P < 0.001); compared with groups A and B, group A had obviously higher onset time (P < 0.001) and significantly lower duration (P < 0.001); no obvious differences in the hemodynamic indexes among the groups were observed (P > 0.05); group C obtained obviously higher BCS score than groups A and B; and the total incidence rate of adverse reactions was obviously higher in group C than in groups A and B (P < 0.05). Conclusion: Performing SGB combined with 0.5% lidocaine to patients undergoing LC achieves the optimal analgesic effect; such anesthesia plan can effectively stabilize patients' hemodynamics, present higher safety, and promote the regulation of the body internal environment. Further research will be conducive to establishing a better anesthesia plan for such patients.

Reviewing the physiology, pharmacology and therapeutic uses of ketamine.

Ketamine is a synthetic drug with unique properties which started to be used therapeutically in humans in the 1970s and is now widely used in all fields of nursing. Ketamine acts on the central nervous system, primarily through inhibiting N-methyl-D-aspartate receptors. However, the precise understanding of its mechanisms of action remains elusive in many respects. Ketamine is frequently used as an anaesthetic in medical and surgical procedures and as an analgesic in children and adults. It is increasingly used in mental health settings to treat depression. It has potential to be used more often in areas such as palliative care and mental health care. This article reviews the physiological and pharmacological properties of ketamine, explores its main therapeutic uses, and considers the associated implications for nursing practice.

Opportunities, Challenges and Pitfalls of Using Cannabidiol as an Adjuvant Drug in COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to coronavirus disease 2019 (COVID-19) which, in turn, may be associated with multiple organ dysfunction. In this review, we present advantages and disadvantages of cannabidiol (CBD), a non-intoxicating phytocannabinoid from the cannabis plant, as a potential agent for the treatment of COVID-19. CBD has been shown to downregulate proteins responsible for viral entry and to inhibit SARS-CoV-2 replication. Preclinical studies have demonstrated its effectiveness against diseases of the respiratory system as well as its cardioprotective, nephroprotective, hepatoprotective, neuroprotective and anti-convulsant properties, that is, effects that may be beneficial for COVID-19. Only the latter two properties have been demonstrated in clinical studies, which also revealed anxiolytic and antinociceptive effects of CBD (given alone or together with Δ9-tetrahydrocannabinol), which may be important for an adjuvant treatment to improve the quality of life in patients with COVID-19 and to limit post-traumatic stress symptoms. However, one should be aware of side effects of CBD (which are rarely serious), drug interactions (also extending to drugs acting against COVID-19) and the proper route of its administration (vaping may be dangerous). Clearly, further clinical studies are necessary to prove the suitability of CBD for the treatment of COVID-19.

A comprehensive review on the biological interest of quinoline and its derivatives.

Amongst heterocyclic compounds, quinoline is an advantaged scaffold that appears as a significant assembly motif for the development of new drug entities. Quinoline and its derivatives tested with diverse biological activity constitute an important class of compounds for new drug development. Therefore, many scientific communities have developed these compounds as intent structure and evaluated their biological activities. The present, review provides brief natural sources of quinoline and including a new extent of quinoline-based marketed drugs. This review also confers information about the biological activities of quinoline derivatives such as antibacterial, antifungal, antimycobacterial, antiviral, anti-protozoal, antimalarial, anticancer, cardiovascular, CNS effects, antioxidant, anticonvulsant, analgesic, anti-inflammatory, anthelmintic and miscellaneous activities.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Where will the drugs come from?

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating disease characterized by severe and disabling fatigue that fails to improve with rest; it is commonly accompanied by multifocal pain, as well as sleep disruption, and cognitive dysfunction. Even mild exertion can exacerbate symptoms. The prevalence of ME/CFS in the U.S. is estimated to be 0.5-1.5 % and is higher among females. Viral infection is an established trigger for the onset of ME/CFS symptoms, raising the possibility of an increase in ME/CFS prevalence resulting from the ongoing COVID-19 pandemic. Current treatments are largely palliative and limited to alleviating symptoms and addressing the psychological sequelae associated with long-term disability. While ME/CFS is characterized by broad heterogeneity, common features include immune dysregulation and mitochondrial dysfunction. However, the underlying mechanistic basis of the disease remains poorly understood. Herein, we review the current understanding, diagnosis and treatment of ME/CFS and summarize past clinical studies aimed at identifying effective therapies. We describe the current status of mechanistic studies, including the identification of multiple targets for potential pharmacological intervention, and ongoing efforts towards the discovery of new medicines for ME/CFS treatment.

Standard headache and neuralgia treatments and SARS-CoV-2: opinion of the Spanish Society of Neurology's Headache Study Group. / Tratamientos habituales utilizados en cefaleas, neuralgias y SARS-CoV-2. Posicionamiento del grupo de estudio de cefaleas de la Sociedad Española de Neurología.

INTRODUCTION: In recent months, doubts have arisen among patients, general practitioners, and neurologists as to whether some drugs commonly used in patients with headaches and neuralgia may favour or complicate the disease caused by SARS-CoV-2. MATERIAL AND METHODS: We collected information on the opinions of scientific societies and medicines agencies (American, European, and Spanish) to clarify doubts regarding the use of drugs such as lisinopril, candesartan, ibuprofen, corticosteroids, carbamazepine, and monoclonal antibodies targeting the calcitonin gene-related peptide in the context of the COVID-19 pandemic. RESULTS: We make recommendations about the use of standard headache treatments in the context of the COVID-19 pandemic, based on the current scientific evidence. CONCLUSIONS: At present, there is no robust scientific argument to formally contraindicate any of the standard treatments employed for headaches and neuralgias.

Pharmacokinetics/Pharmacodynamics of Antiviral Agents Used to Treat SARS-CoV-2 and Their Potential Interaction with Drugs and Other Supportive Measures: A Comprehensive Review by the PK/PD of Anti-Infectives Study Group of the European Society of Antimicrobial Agents.

There is an urgent need to identify optimal antiviral therapies for COVID-19 caused by SARS-CoV-2. We have conducted a rapid and comprehensive review of relevant pharmacological evidence, focusing on (1) the pharmacokinetics (PK) of potential antiviral therapies; (2) coronavirus-specific pharmacodynamics (PD); (3) PK and PD interactions between proposed combination therapies; (4) pharmacology of major supportive therapies; and (5) anticipated drug-drug interactions (DDIs). We found promising in vitro evidence for remdesivir, (hydroxy)chloroquine and favipiravir against SARS-CoV-2; potential clinical benefit in SARS-CoV-2 with remdesivir, the combination of lopinavir/ritonavir (LPV/r) plus ribavirin; and strong evidence for LPV/r plus ribavirin against Middle East Respiratory Syndrome (MERS) for post-exposure prophylaxis in healthcare workers. Despite these emerging data, robust controlled clinical trials assessing patient-centred outcomes remain imperative and clinical data have already reduced expectations with regard to some drugs. Any therapy should be used with caution in the light of potential drug interactions and the uncertainty of optimal doses for treating mild versus serious infections.

Potential drug-drug interactions associated with drugs currently proposed for COVID-19 treatment in patients receiving other treatments.

Patients with COVID-19 are sometimes already being treated for one or more other chronic conditions, especially if they are elderly. Introducing a treatment against COVID-19, either on an outpatient basis or during hospitalization for more severe cases, raises the question of potential drug-drug interactions. Here, we analyzed the potential or proven risk of the co-administration of drugs used for the most common chronic diseases and those currently offered as treatment or undergoing therapeutic trials for COVID-19. Practical recommendations are offered, where possible.