Central Nervous System Agents Research Articles

Ocular side effects of systemic drugs 3 - Central nervous system agents

Dr Doina Gherghel continues our series looking at the potential ocular adverse impact of a range of commonly prescribed systemic drugs with a look at those used in treating diseases, both mental and physical, affecting the central nervous system.

Synthesis, molecular modelling and biological activity of some pyridazinone derivatives as selective human monoamine oxidase-B inhibitors.

Since brain neurotransmitter levels are associated with the pathology of various neurodegenerative diseases like Parkinson and Alzheimer, monoamineoxidase (MAO) plays a critical role in balancing these neurotransmitters in the brain. MAO isoforms appear as promising drug targets for the development of central nervous system agents. Pyridazinones have a broad array of biological activities. Here, six pyridazinone derivatives were synthesized and their human monoamine oxidase inhibitory activities were evaluated by molecular docking studies, in silico ADME prediction and in vitro biological screening tests. The compounds were synthesized by the reaction of different piperazine derivatives with 3 (2H)-pyridazinone ring and MAO-inhibitory effects were investigated. Docking studies were conducted with Maestro11.8 software. Most of the synthesized compounds inhibited hMAO-B selectively except compound 4f. Compounds 4a-4e inhibited hMAO-B selectively and reversibly in a competitive mode. Compound 4b was found as the most potent (ki = 0.022 ± 0.001µM) and selective (SI (Ki hMAO-A/hMAO-B) = 206.82) hMAO-B inhibitor in this series. The results of docking studies were found to be consistent with the results of the in vivo activity studies. Compounds 4a-4e were found to be non-toxic to HepG2 cells at 25μM concentration. In silico calculations of ADME properties indicated that the compounds have good pharmacokinetic profiles. It was concluded that 4b is possibly recommended as a promising nominee for the design and development of new pyridazinones which can be used in the treatment of neurological diseases.

Discovery and Optimization of Chromone Derivatives as Novel Selective Phosphodiesterase 10 Inhibitors.

Phosphodiesterase 10 (PDE10) inhibitors have received much attention as promising therapeutic agents for central nervous system (CNS) disorders such as schizophrenia and Huntington's disease. Recently, a hit compound 1 with a novel chromone scaffold has shown moderate inhibitory activity against PDE10A (IC50 = 500 nM). Hit-to-lead optimization has resulted in compound 3e with an improved inhibitory activity (IC50 = 6.5 nM), remarkable selectivity (>95-fold over other PDEs), and good metabolic stability (RLM t1/2 = 105 min) by using an integrated strategy (molecular modeling, chemical synthesis, bioassay, and cocrystal structure). The cocrystal structural information provides insights into the binding pattern of 3e in the PDE10A catalytic domain to highlight the key role of the halogen and hydrogen bonds toward Tyr524 and Tyr693, respectively, thereby resulting in high selectivity against other PDEs. These new observations are of benefit for the rational design of the next generation PDE10 inhibitors for CNS disorders.

Is drug consumption correlated with benign paroxysmal positional vertigo (BPPV) recurrence?

Benign paroxysmal positional vertigo (BPPV) is the most common cause of peripheral vertigo and its recurrence is fairly common. Several studies correlated the pathophysiological role of different comorbidities-such as diabetes, osteoporosis, vascular, psychiatric and autoimmune diseases-in the development and recurrence of BPPV. The aim of this study is to analyse the pharmacological history of patients with idiopathic BPPV in relation to the risk of developing recurrence. Data regarding 715 patients aged 12 to 87years (62.7 ± 14) with non-traumatic BPPV were retrospectively evaluated. These refer to the Vestibular Service, day clinic, and were collected over a 4-year period, between 2014 and 2018. Recurrence of BPPV was observed in 220/715 patients (30.76%). A statistically significant correlation (p < 0.006) between recurrence and drug consumption was observed for SNC agents (p = 0.0001), vitamin D (p = 0.0005), PPI (p = 0.0007), thyroid hormones (p = 0.0011), and antihypertensives in single use (p = 0.0031). On the contrary, cholesterol-lowering statin drugs, hypoglycaemic agents, antiplatelet medication, estroprogestins and combination of two or more antihypertensives did not show significant correlation. Specific classes of drugs are significantly associated with recurrence: antihypertensive therapy with a singular agent, central nervous system agents, PPIs, vitamin D and thyroid hormones. On the other hand, the lack of correlation between some drugs and recurrence could be linked to the effectiveness of therapy in controlling hypertension, dyslipidaemia and diabetes. Pharmacological history is an essential tool to identify patients at risk of BPPV recurrence.

Central Nervous System Agent Classes and Fragility Fracture Risk among Elderly Japanese Individuals in a Nationwide Case-Crossover Design Study.

Central nervous system (CNS) agents cause fractures among the elderly, but fracture risks of a wide range of CNS agent classes have not been analyzed in a study with the same population and definitions of variables. This study aimed to estimate the degree of fragility fracture risk of a wide range of CNS agent classes in elderly Japanese people. A case-crossover design study, with a case window and three control windows of 3 d each, as well as longer windows up to 15 d, was conducted among opioid non-users who lived without hospitalization for ≥13 months and incurred fragility fractures at ≥65 years of age, using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Conditional logistic regression estimated adjusted odds ratios (ORs) of CNS agent classes for fragility fractures for groups including and excluding users of pro re nata CNS agents (PRN-CNS agents) and for windows of 3-15 d. Antiepileptic agents had the highest adjusted ORs, 2.4 (95% confidence interval 2.3-2.5) for the group including PRN-CNS agent users (n = 446101). The next-highest classes were anti-dementia agents 1.5 (1.5-1.6), antipsychotics 1.5 (1.4-1.6), anti-Parkinson agents 1.3 (1.2-1.5), and antidepressants 1.1 (1.1-1.2). Similar ORs were found when PRN-CNS agent users were excluded (n = 352828), and slightly higher ORs were found for longer windows, with almost the same order of classes. Elderly individuals who use antiepileptic agents or a combination of antiepileptic agents and CNS agent classes with the next-highest ORs should be carefully monitored.

Compatibility of acetaminophen with central nervous system medications during simulated Y-site injection.

The critical care patient commonly receives alot of medications including acetaminophen and central nervous system (CNS) agents. However, research on compatibility between acetaminophen and CNS medication is still limited. Physical compatibility was evaluated using Y-site simulation by mixing one CNS medication with 10 mg mL-1 of acetaminophen solution under aseptic conditions with a1 : 1 ratio. The Y-site simulation mixture was subsequently kept in aclean glass tube for incompatibility investigation during 24 hours. The aliquot solutions were visually inspected with bare eyes then additionally with aTyndall light beam, microscope, and pH at 0, 1, 4, and 24 hours. Medications were considered compatible if there was no visual change (color/gas or turbidity), and no significant particles or precipitates, which referred to United States Pharmacopeia 788 (USP 788), and pH changes less than 0.5 units. During 24 hours, intravenous acetaminophen was physically compatible with haloperidol, ketamine, midazolam, pethidine, rocuronium and tramadol. Meanwhile, phenytoin, and propofol showed incompatibility with acetaminophen right away. Within four hours, five medications (dexketoprofen, fentanyl, ketorolac, diazepam and phenobarbital) showed incompatibility. Two medications (atropine sulfate and metamizole) were also found to be incompatible with acetaminophen under observation for 24 hours. Nine of 15 common CNS medications in critical care tested with acetaminophen were physically incompatible for 24 hours.

Fever as an Adverse Drug Reaction of Different Therapeutic Groups

Fever (t>38°C) developed in association with drug usage is rare but sometimes severe side effect (SE). It could manifest as single symptom or as a part of such life-threatening syndromes like malignant hyperthermia (MH), serotonin syndrome (SS), neuroleptic malignant syndrome (NMS). Fever could be caused by different therapeutic groups of drugs but the leading positions are occupied by antibiotics (mainly beta-lactams), substances acting on central nervous system (CNS) and chemotherapeutic agents. Main mechanisms are allergic and receptive. Curative measures include discontinuation of the suspected drug, introduction of agents blocking the action of the trigger factor - dantrolene (МН), bromocriptine (NMS), cyproheptadine (SS). Purpose of this review: to present the global and Russian data concerning fever as a drug-induced side effect. To distinguish the groups of patients and drugs of the highest risk. To evaluate aid measures. Results: fever as monosymptom of drug allergy is a difficult condition to be diagnosed and there are only few things that could help to recognize it such as temporal association with the suspected drug use and manifestation of fever along with the following resolution after suspected drug discontinuation and recurrence fever after suspected drug re-challenge. Among four syndromes described in this review such as serum sickness-like reaction (SSLR), NMS, SS and MH just fever at MH is not only a sign like in case of three others but it is significant and life-threatening manifestation and therefore requires additional curative methods (in addition to pharmacological support with dantrolene) – rapid cooling measures: ice-water nasogastric and rectal lavage, infusion of crystalloid solutions cooled up to 4°C, ice packs placing on main blood vessels and liver area, ventilatory measurements.

A Scoping Review of Medications Studied in Pediatric Polypharmacy Research.

The purpose of this study is to describe medications most commonly studied in pediatric polypharmacy research by pharmacologic classes and disease using a scoping review methodology. A search of electronic databases was conducted in July 2019 that included Ovid Medline, PubMed, Elsevier Embase, and EBSCO CINAHL. Primary observational studies were selected if they evaluated polypharmacy as an aim, outcome, predictor, or covariate in children 0-21years of age. Studies not differentiating between adults and children or those not written in English were excluded. Study characteristics, pharmacologic categories, medication classes, and medications were extracted from the included studies. The search identified 8790 titles and after de-duplicating and full-text screening, 414 studies were extracted for the primary data. Regarding global pharmacologic categories, central nervous system (CNS) agents were most studied (n = 185, 44.9%). The most reported pharmacologic category was the anticonvulsants (n = 250, 60.4%), with valproic acid (n = 129), carbamazepine (n = 123), phenobarbital (n = 87), and phenytoin (n = 83) being the medications most commonly studied. In studies that reported medication classes (n = 105), serotonin reuptake inhibitors (n = 32, 30.5%), CNS stimulants (n = 30, 28.6%), and mood stabilizers (n = 27, 25.7%) were the most studied medication classes. While characterizing the literature on pediatric polypharmacy in terms of the types of medication studied, we further identified substantive gaps within this literature outside of epilepsy and psychiatric disorders. Medications frequently identified in use of polypharmacy for treatment of epilepsy and psychiatric disorders reveal opportunities for enhanced medication management in pediatric patients.

Prescribing patterns of polypharmacy in Korean pediatric patients.

BackgroundSeveral studies have examined the risk and health outcomes related to polypharmacy among the elderly. However, information regarding polypharmacy among pediatric patients is lacking.ObjectiveThe aim of this study was to investigate the prevalence of polypharmacy and its related factors among the pediatric population of South Korea.MethodsWe used national claim data from the Health Insurance Review and Assessment Service—Pediatric Patients Sample (HIRA-PPS) in Korea originating from 2012 through 2016. Polypharmacy was defined as a daily average of two or more drugs used yearly. Complex chronic conditions (CCCs) were examined to evaluate concomitant chronic diseases in pediatric patients. Age-specific contraindications and potential drug-drug interactions were assessed according to criteria established by the Korea Institute of Drug Safety & Risk Management (KIDS). Descriptive statistics and logistic regression were conducted to analyze the status of polypharmacy and its associated risk factors in pediatric patients.ResultsThe 5-year prevalence of pediatric polypharmacy in pediatric patients was 3.7%. The prevalence of polypharmacy was much higher in younger pediatric patients: 9.5% for patients between the ages of 1–7 years, 0.9% for ages 6–11 years, and 1.1% for ages 12–19 years. Pediatric patients with CCCs, Medical Aid benefits, or a hospital admission history had a significantly higher prevalence of polypharmacy when compared to their counterparts without those conditions. The most commonly prescribed drugs were respiratory agents (29%) followed by anti-allergic drugs (18.7%), central nervous system agents (15.9%), antibiotics (10.1%), and gastrointestinal drugs (7.7%). There was a positive correlation between the daily average number of inappropriate prescriptions and the degree of polypharmacy, especially in pediatric patients between the ages of 1–7 years. Contraindications and potential drug-drug interactions occurred in 11.0% and 10.1% of patients exposed to polypharmacy, respectively.ConclusionsOne in ten pediatric patients under the age of 7 years was prescribed two or more concurrent drugs on average per day. Furthermore, pediatric patients exposed to polypharmacy showed an increased risk of inappropriate drug use. The implementation of a medication review system that considers pediatric patient polypharmacy exposure would reduce inappropriate drug use and prevent unwanted adverse outcomes.

A population-based study of prescribing trends in a potentially vulnerable paediatric population from 1999 to 2012.

There is a limited understanding of paediatric medication prescribing trends and patterns, thus poorly positioning decision-makers to identify quality and safety concerns related to medication use. The objective of this study was to determine overall medication prescribing trends and patterns among children receiving Ontario Drug Benefits over a thirteen-year period in the province of Ontario, Canada. Administrative health databases housed within the Institute for Clinical Evaluative Sciences (ICES), Ontario, Canada, were used to identify outpatient prescriptions dispensed from 1999 to 2012 through a publicly funded programme to children ≤18 years of age. Medications were classified according to the American Hospital Formulary Service Pharmacologic-Therapeutic Classification system. Descriptive statistics were used to summarize prescribing patterns. This study identified 457 037 children who were dispensed a new prescription between 1999 and 2012. About 56% received their first prescription before 6.5 years of age, and 85% of the children in this study were from families who received social assistance. The most commonly prescribed drugs were antiinfectives (56.1%). Prescriptions for several central nervous system agents, including antipsychotics and agents for attention-deficit/hyperactivity disorder, increased across the study period. Changes in prescribing patterns within opioids, hormones and autonomic agents were noted. The results suggest that historically, prescribing trends have shifted with public policy, pharmaceutical marketing and diagnostic patterns, thus identifying them as a possible tool to measure the impact of policydriven practice changes. Anti-infective prescribing increased markedly with the global H1N1 pandemic. Pharmaceutical marketing, formulary decisions and diagnostic trends may affect the prescribing of ADHD medications globally. The prescribing of codeine-containing products and medroxyprogesterone appeared to fluctuate in response to important publications in the medical literature, and the use of epinephrine syringes increased after public policy changes in the province of Ontario. The steady rise in the use of medications whose long-term effects in children are unknown, such as antipsychotics and proton pump inhibitors, identifies areas in need of future research. This study presents the first overview of Canadian prescribing trends for children, the majority of which are of low socioeconomic status and represent a potentially vulnerable population. Our analysis suggests that future research is required to determine whether prescribing trends could be used as indicators of policy effectiveness, pharmacovigilance and diagnostic trends.

A Study of Acute Poisoning Cases Admitted to the National Poisoning Center

Objectives: There is a necessity to study the pattern of poisoning of patients who visited national poisoning centers to take up appropriate management and prevention techniques. Methods: This study includes all cases of human poisoning exposures (11181 poisoning cases) presenting to the national poisoning center, Cairo, from 1 January 2016 to 31 December 2016. The data were statistically analyzed to assess a correlation for a gender, age, agents and poisoning type. Results: It was found that 24% of patients were younger than 4 years. The female-to-male ratio was 1.6:1. Therapeutic drugs (68%) were the most common cause of poisoning followed by a household product (13%), pesticides (9%), and abuse agents (5%), bites of snakes and scorpions (3%) and food poisoning (1%). Detailed information on groups of pharmaceuticals and the most frequent agents causing poisonings was presented. Analgesics (24%) and central nervous system agents (21%) were the most common therapeutic pharmaceutical poisons. Synthetic opioid; tramadol (45%) was the most common abuse agent. Accidental poisoning of abuse agents in children younger than 4 years represented 20.4 % of the abuse agents poisoning cases. The mortality rate for the patients was 0.3% (32 patients). Conclusion: The prevention of medicinal poisoning should merit high priority in the education interventions and preventive efforts. An important concern toward drugs and abuse agents’ availability at homes within the reach of children should be raised. The most risk factors of poisoning are female gender and young age patients.

Drug-Nutrition Interactions and the Brain: It's Not All in Your Head.

The interactions between nutrition and medication can be numerous with potential impact on health outcomes. Several subtypes of drug-nutrition interactions exist. Each of these interaction subtypes may influence patients receiving medication for neurologic disorders. After defining drug-nutrition interactions, this review will describe the various types using a handful of widely used central nervous system agents as examples. Medication may be the object of interactions perpetrated by a specific meal, a food component, a nutrient, or nutrition status thereby altering drug disposition and clinical effect. On the other hand, drugs can influence nutrition status generally or the status of specific nutrients by any number of mechanisms. Individuals using medication for neurologic disorders are at risk for drug-nutrition interactions of all types.

RETRACTED: Human Suicide, Modern Diagnosis Assistance and Magic Bullet Discovery

The article entitled “Human Suicide, Modern Diagnosis Assistance and Magic Bullet Discovery”, by Da-Yong Lu, Peng- Peng Zhu, Hong-Ying Wu, Nagendra Sastry Yarla, Bin Xu, Jian Ding, Ajit Varki and Ting-Ren Lu, has been retracted on the request of one co-authors, Dr. Ajit Varki and Dr. Nagendra Sastry Yarla available at: Cent Nerv Syst Agents Med Chem 2019; 19(1): 15-23. http://www.eurekaselect.com/169003/article. The Corresponding Author Dr. Da-Yong Lu has included the names of the co-authors, Dr. Ajit Varki and Dr. Nagendra Sastry Yarla without their consent and the manuscript has been published in the journal, Central Nervous System Agents in Medicinal Chemistry (CNSAMC). Kindly see Bentham Science Policy on Article retraction at the link given below: (https://benthamscience.com/journals/central-nervous-system-agents-in-medicinal-chemistry/author-guidelines/) Submission of a manuscript to the respective journals implies that all authors have read and agreed to the content of the Copyright Letter or the Terms and Conditions. As such, this article represents a severe abuse of the scientific publishing sys- tem. Bentham Science Publishers takes a very strong view on this matter and apologizes to the readers of the journal for any inconvenience this may cause.

English

The incidence of meningoencephalitis in developing countries is high and its diagnosis being inadequate as it is mainly based on conventional methods with a limited diagnostic capacity for bacterial, fungal and viral detection. This results in prescription of a cocktail of antibiotics, antifungal, or anti-viral drugs, since the causative agent is often unknown. There is therefore need for timely and appropriate diagnosis to guide treatment. This study aims at evaluating the utility of molecular diagnostic over conventional methods in detection of etiologic agents of central nervous system infections in Rwanda. Using a cross sectional design, 845 hospitalized patients suspected to have meningoencephalitis were enrolled from 8 study sites across the country. Four sterile tubes of Cerebral Spinal Fluid (CSF) specimens were collected from each patient. Two tubes were analyzed on site for bacteriology, fungal, biochemistry and cytology while the other two were transported to the National Reference Laboratory (NRL) for culture and Real-Time Multiplex Polymerase Chain Reaction (PCR) assays. Data entry and analysis was done using Epi Info7, Excel; SPSS and STATA16. In the study, no viruses were detected using the conventional methods while a range of viruses, 152/845 (18%) were detected using real time multiplex PCR. In addition, 185/845 (22%) samples were detected as positive for different types of bacteria using the PCR compared with the 59/845(7%) that were positive using conventional methods. There was however no difference in the detection capacity of fungal agents between the two methods with a detection level of 6% (49). This study has shown increased capacity for detection of bacterial and viral causative agents of Central Nervous System (CNS) infections using RT multiplex PCR compared with conventional methods. This result facilitated the development of a novel algorithm for both conventional and molecular diagnostic methods for CNS infections. Key words: Meningoencephalitis, RT- Multiplex PCR, conventional methods, causative agents, diagnostic capacity, cerebral spinal fluid.

Patient-Level Medication Regimen Complexity in an Adolescent and Adult Population with Autism Spectrum Disorders.

Adults with autism spectrum disorder (ASD) frequently experience polypharmacy. However, there is limited understanding of how to quantify medication complexity in this vulnerable population. This study examined medication administration difficulty using the Medication Regimen Complexity Index (MRCI) tool in adolescents and adults with ASD. The outcomes compared the mean total MRCI score with the medication count, described MRCI contributions for over-the-counter medication (OTC), and compared MRCI scores by patient characteristics. This was a retrospective chart review of patients aged 7-45years (mean=20.1) enrolled in a primary care ASD transitions program. Each patient's listed medications were counted and then scored using the validated MRCI tool. For the 142 patients studied, mean total MRCI was 14.6±14.6 (range 0-89) and mean medication count was 6.3±5.4 (range 0-38). For patients on 0-4 medications (66 of 142; 46.5%), the mean MRCI was 5.5±4.2, 5-9 medications (50 of 142; 35.2%) the mean MRCI was 15.2±6.8, and 10-38 medications (26 of 142; 18.3%) the mean MRCI was 36.5±18.9 (p<0.001). Sixty percent (85 of 142) reported OTC use, which contributed 26.6% to the mean total MRCI. Reported benzodiazepine (mean MRCI 25.8±17.2), antiepileptic (mean MRCI 23.7±16.9), antipsychotic (mean MRCI 19.7±15.9), or antidepressant (mean MRCI 17.0±14.8) use received higher MRCI scores compared to nonuse (p<0.001 for all except antidepressants [p=0.004]). Total MRCI did not differ significantly by age group, sex, or attention-deficit-hyperactivity disorder (ADHD) medication use (stimulant or nonstimulant). Medication regimen complexity in adolescents and adults with ASD was increased significantly for individuals taking ≥ 5 medications. Central nervous system agent use, other than ADHD therapy, identified patients with higher regimen complexity. The related clinical effects of these findings warrant further investigation.

Longitudinal prevalence of potentially serious alcohol-medication interactions in community-dwelling older adults: a prospective cohort study.

This study aims to estimate (i) the prevalence of potentially serious alcohol-medication interactions in a nationally representative sample of older adults using the Potentially Serious Alcohol-Medication Interactions in Older adults (POSAMINO) criteria, and (ii) whether POSAMINO prevalence changes over time. A prospective cohort study of adults aged ≥ 65years, using data from the first three waves of The Irish Longitudinal Study on Ageing (TILDA). All 38 POSAMINO criteria were applied at each wave using respondents' information on regular medications and alcohol consumption. Multilevel logistic regression and negative binomial models were used to investigate whether the prevalence of POSAMINO varied over time. The overall prevalence of POSAMINO was 18% at baseline, with 8% at risk of one potentially serious alcohol-medication interaction, and 10% at risk of two or more. The most common POSAMINO involved cardiovascular (CVS) agents (15% baseline; 11% wave 2; 14% wave 3), followed by central nervous system (CNS) agents (4% baseline; 4% wave 2; 5% wave 3). Prevalence of any POSAMINO (AOR 0.94, 95% CI 0.81, 1.08) or number of POSAMINO criteria (AIRR 0.97, 95% CI 0.91, 1.04) did not change over time. Any POSAMINO and number of POSAMINO were associated with younger age, male sex and number of medications and chronic conditions. Potentially serious alcohol-medication interactions occurred in 18% of older adults in this study. Alcohol screening and brief interventions should be considered for high-risk groups at the point of prescribing, particularly among younger older adults, men and as patients receive more medications or develop additional illnesses.

Tools in the Design of Therapeutic Drugs for CNS Disorders: An up-to-date Review.

The brain is a vital part of the central nervous system (CNS), characterized by the presence of soft tissue in its internal structure which protects itself. Research on design of drugs for CNS disorders is in progress and up to date information is required for further investigation. The present paper is written with the objective to compile all the available data and information on CNS disorders and CNS acting drugs. CNS acting drugs are important to consider because some drugs get ineffective owing to incapability to efficiently deliver and sustain them within the brain for effective treatment. The current trend to design therapeutic drugs for CNS disorders focuses on neurotransmitters release and their reuptake, including Parkinson's, Alzheimer's, and other CNS disorders. The disorders associated with CNS are characterized by the progressive loss of gray matter and/or white matter structures. CNS stimulants are the class of drugs, producing response to alleviate a particular medical condition. CNS stimulants improve the brain function in patients with schizophrenia and related diseases. CNS stimulants are a class of therapeutic drugs used to treat CNS disorder including the conditions like lack of adrenergic stimulation, symptoms of narcolepsy and neonatal apnea, etc. Apart from drugs, a number of smart tools including Multi-Target Designed Ligands (MTDL) and "predictor" models are contemporarily used to design therapeutic agents for CNS disorders. The majority of CNS stimulants causes stimulation of the traditional "fight or flight" syndrome which is concerned with activation of sympathetic nervous system. These neurotransmitters associated receptors are concerned in drug abuse and addiction withdrawal related phenomenon. The present review embarks on detail up-to-date information on CNS stimulant drugs, their mechanism of action, in vivo models for biological evaluations with major emphasis on tools in design of therapeutic drugs for CNS disorders.

2163 Polypharmacy and patterns of prescription medication use among cancer survivors

OBJECTIVES/SPECIFIC AIMS: The population of cancer survivors is rapidly growing in the United States. Long term and late effects of cancer, combined with ongoing management of other chronic conditions, make cancer survivors particularly vulnerable to polypharmacy and its adverse effects. We examined patterns of prescription medication use and polypharmacy in a population-based sample of cancer survivors. METHODS/STUDY POPULATION: Using data from the Medical Expenditure Panel Survey (MEPS), we matched cancer survivors (n=5216) to noncancer controls (n=19,588) by age, sex, and survey year. We defined polypharmacy as using 5 or more unique medications. We also estimated proportion of respondents prescribed specific medications within therapeutic classes and total prescription expenditures. RESULTS/ANTICIPATED RESULTS: A higher proportion of cancer survivors were prescribed 5 or more unique medications (64.0%, 95% CI 62.3%–65.8%) compared with noncancer controls (51.5%, 95% CI 50.4%–52.6%), including drugs with abuse potential. Across all therapeutic classes, a higher proportion of newly (≤1 year since diagnosis) and previously (&gt;1 years since diagnosis) diagnosed survivors were prescribed medications compared to controls, with large differences in central nervous system agents (65.8% vs. 57.4% vs. 46.2%), psychotherapeutic agents (25.4% vs. 26.8% vs. 18.3%), and gastrointestinal agents (31.9% vs. 29.6% vs. 22.0%). Specifically, nearly 10% of cancer survivors were prescribed benzodiazepines and/or opioids compared to about 5% of controls. Survivors had more than double prescription expenditures (median $1633 vs. $784 among noncancer controls). Findings persisted similarly across categories of age and comorbidity. DISCUSSION/SIGNIFICANCE OF IMPACT: Cancer survivors were frequently prescribed a higher number of unique medications and inappropriate medications or drugs with abuse potential, increasing risk of adverse drug events, financial toxicity, poor adherence, and drug-drug interactions. Adolescent and young adult survivors appear at increased risk of polypharmacy.

Polypharmacy and patterns of prescription medication use among cancer survivors.

The population of cancer survivors is rapidly growing in the United States. Long-term and late effects of cancer, combined with the ongoing management of other chronic conditions, make survivors particularly vulnerable to polypharmacy and its adverse effects. In the current study, the authors examined patterns of prescription medication use and polypharmacy in a population-based sample of cancer survivors. Using data from the Medical Expenditure Panel Survey (MEPS), the authors matched cancer survivors (5216 survivors) with noncancer controls (19,588 controls) by age, sex, and survey year. Polypharmacy was defined as ≥5 unique medications. The authors estimated the percentage of respondents prescribed medications within therapeutic classes and total prescription expenditures. A higher percentage of cancer survivors were prescribed ≥5 unique medications (64.0%; 95% confidence interval [95% CI], 62.3%-65.8%) compared with noncancer controls (51.5%; 95% CI, 50.4%-52.6%), including drugs with abuse potential. Across all therapeutic classes, a higher percentage of newly (≤1 year since diagnosis) and previously (>1 years since diagnosis) diagnosed survivors were prescribed medications compared with controls, with large differences observed with regard to central nervous system agents (65.8% [95% CI, 62.3%-69.3%] vs 57.4% [95% CI, 55.3%-59.5%] vs 46.0% [95% CI, 45.0%-46.9%]). Specifically, nearly 10% of survivors were prescribed benzodiazepines and/or opioids compared with approximately 5% of controls. Survivors had more than double the prescription expenditures (median of $1633 vs $784 among controls). Findings persisted across age and comorbidity categories. Cancer survivors were prescribed a higher number of unique medications, including drugs with abuse potential, thereby increasing their risk of adverse drug events, financial toxicity, poor adherence, and drug-drug interactions. Cancer 2018;124:2850-2857. © 2018 American Cancer Society.

Dopamine synergizes with caffeine to increase the heart rate of Daphnia

Dopamine is a key neurotransmitter, and is widely used as a central nervous system (CNS) agent. Dopamine plays an important role in humans, including a major role in reward and motivation behaviour. Several addictive drugs are well known to increase neuronal dopamine activity. We selected Daphnia, an important model organism, to investigate the effect(s) of selected CNS agents on heart rate. Dopamine’s effects on Daphnia’s heart has not been previously reported. Caffeine is a well-known and widely consumed stimulant. Ethanol is well known for its effects on both neurological and physiological processes in mammals. We tested the effect of dopamine on the heart rate of Daphnia, and compared its effect with caffeine and ethanol alone and in combination. Both caffeine and dopamine were found to instantly increase the heart rate of Daphnia in a dose-dependent manner. Interestingly, caffeine synergized with dopamine to increase Daphnia’s heart rate. As ethanol decreased the heart rate of Daphnia and dopamine increased the heart rate of Daphnia, we wanted to test the effect of these molecules in combination . Indeed, Dopamine was able to restore the ethanol-induced decrease in the heart rate of Daphnia. Effects of these CNS agents on Daphnia can possibly be correlated with similar effects in the case of mammals.