scholarly journals DRUGPATH: A New Database for Mapping Polypharmacology

2019 ◽  
Vol 2 (3) ◽  
pp. 4
Author(s):  
Rajeev Jaundoo ◽  
Travis J.A. Craddock
Keyword(s):  
Side Effects ◽  
Drug Repurposing ◽  
Post Traumatic Stress ◽  
Gene Target ◽  
Gene Pathway ◽  
Pathway Data ◽  
National Drug ◽  
Extraneous Information ◽  
Multiple Drugs ◽  
Sqlite Database

While there are existing databases that curate only drug, target, or pathway data for instance, none of these alone are exhaustive. The Drug Gene Pathway (DRUGPATH) meta database was created as a response to the complex treatment required for various diseases including Gulf War Illness (GWI) and post-traumatic stress disorder (PTSD), where therapy involves using multiple drugs in combination. Here, drug-drug interactions can occur due to the promiscuous nature of pharmaceuticals, which can then lead to various side effects or can alternatively be utilized towards drug repurposing. The objective was to develop a database that maps the interactions between drugs, genes, pathways, and targets for use in the treatment of complex diseases, including the prediction of off-target interactions, otherwise known as side effects. Using MATLAB and Python scripts, interactions between known drugs, genes, targets, and pathways amalgamated from numerous expert-curated sources such as PharmGKB, DrugBank, DGIdb, ConsesusPathDB, Guide to PHARMACOLOGY, HUGO Gene Nomenclature Committee, Toxin and Toxin-Target Database, repoDB, the FDA’s National Drug Code database, etc. were mapped together. The raw data was first downloaded from its source and subsequently cleaned, where extraneous information such as data from non-humans, internal identifiers, timestamps, etc. were removed. The remaining information was then integrated into an SQLite database. DRUGPATH currently contains a total of 2,632,516 unique entries, and of these, there are 54,757 unique genes, 2,632,242 unique pathways, and 31,042 unique drugs. DRUGPATH allows researchers and clinicians to discern which pathways are affected by each drug, reducing the likelihood of an adverse drug reaction occurring. The incorporation of drug, gene, target, and pathway information makes DRUGPATH a powerful resource for predicting potential side effects when designing or refining a given drug combination therapy. Not only that, but we have additionally added the FDA status, half-life, and indication for each drug whenever possible for clinical applications of this database.

Evaluating the effectiveness of post-traumatic stress disorder (PTSD) treatment using acupuncture combined with cognitive behavioral therapy in Thua Thien Hue province

2019 ◽  
pp. 74-80
Author(s):  
Thi Tan Nguyen ◽  
Van Minh Doan ◽  
Nhat Minh Tran ◽  
Van Hung Nguyen
Keyword(s):  
Side Effects ◽  
Cognitive Behavioral Therapy ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Behavioral Therapy ◽  
Post Traumatic Stress ◽  
Dsm 5 ◽  
Effectiveness Rate ◽  
Post Traumatic

Post-traumatic Stress Disorder (PTSD) is a mental disorder that develops in people who have experienced or witnessed a serious traumatic event, such as natural catastrophes, sexual assaults, war… Some studies showed that acupuncture was effective for PTSD. However, there is no published research on the treatment of PTSD using acupuncture and cognitive behavioral therapy (CBT) in Vietnam. The aim of this study was to evaluate the effectiveness of treating PTSD using acupuncture combined with CBT in Thua Thien Hue province. Method and subject: This study was an interventional study conducted in two districts of Thua Thien Hue province. Thirty patients were diagnosed with PTSD using Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Participants were assessed on PTSD symptoms using PTSD Checklist for DSM-5 (PCL–5); depression, anxiety and stress status using DASS-21; and other health states before and after treatment. Result: The effectiveness rate of treatment was 83.3% by PCL–5 and 86.7% by DASS-21. The improvement of symptoms after 5 weeks of treatment was statistically significant (p <0.05). Side effects were itch (5.0%), pain (4.3%); bleeding (1.3%); and others (0%). Conclusion: Treatment of PTSD using acupuncture and CBT has a high effectiveness rate on PCL - 5 scale and DASS21 scale. Improvement was similar when evaluated by the two scales. Acupuncture was safe and did not cause any significant side effects. Key words: Post-traumatic Stress Disorder, PTSD, acupuncture, cognitive behavior therapy, CBT, Thua Thien Hue

scholarly journals Study on Highly Active Anti- Retroviral Therapy: prescription pattern and side effects

2012 ◽  
Vol 26 (1) ◽  
pp. 12-18
Author(s):  
Sujata Sapkota ◽  
Rajani Shakya ◽  
Basudev Pandey
Keyword(s):  
Side Effects ◽  
Drug Regimen ◽  
World Health ◽  
Management Tools ◽  
Prescription Pattern ◽  
Highly Active ◽  
Regimen Change ◽  
Initial Regimen ◽  
Health Organization ◽  
Multiple Drugs

Since the introduction of Highly Active Anti Retroviral therapy (HAART) by World Health Organization in 1996, it has been the employed method of drug use in HIV management. Involvement of multiple drugs in the regimen, has also invited multiple complications and side effects is one of them. High chances of occurrence of side effects has called for the need of proper identification and therapy management tools for each HAART user and has highlighted the importance of individualized drug therapy. The aim of the study the prescription pattern of the HAART regimen; frequency of regimen change and its major causes; and the side- effects from HAART. The study was conducted in the ART Clinic of SukraRaj Tropical & Infectious Disease Hospital, Teku. 109 patients, who came to the clinic to refill their prescription, were interviewed by the researcher. After interview, medication file of each patient was reviewed to study the prescribed drug regimen, drug changes and identified reasons for the drug change (as identified by the physicians and recorded in patient medication file); reported side effect experience and laboratory reports were analyzed to study the effect of the HAART regimen on hemoglobin and Alanine Aminotransferase enzyme. The study revealed that the most prescribed HAART regimen constituted a combination of Zidovudine, Lamivudine and Nevirapine. 52% of the patients reported having experienced side effects from HAART. 23.85% patients had to have their initial regimen changed because of drug toxicity. Nausea (15.6%), vertigo (14.7%), decreased hemoglobin (11.9%), skin rash/ allergy (9.2%) were the major side effects experience reported by the patients. In addition to some side effects like nausea, vertigo etc; decrease in the level of hemoglobin after the initiation of HAART was evident. Decrease in Zidovudine containing regimen, during the regimen change was apparent and was mostly related to its hemoglobin lowering activity. DOI: http://dx.doi.org/10.3126/jnpa.v26i1.6630 JNPA. XXVI(1) 2012 12-18

scholarly journals Novel T7-modified pH-responsive targeted nanosystem for co-delivery of docetaxel and curcumin in the treatment of esophageal cancer

2020 ◽  
Author(s):  
Lian Deng ◽  
Xiongjie Zhu ◽  
Zhongjian Yu ◽  
Ying Li ◽  
Lingyu Qin ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Side Effects ◽  
High Efficiency ◽  
In Vivo Studies ◽  
Ph Responsive ◽  
Therapeutic Platform ◽  
Multiple Drugs ◽  
Esophageal Cancer Cells

Abstract Although single-drug chemotherapy is still an effective treatment for esophageal cancer, its long-term application is limited by severe side effects. Nanomedicines have increasingly attracted attention because of their good biological safety, targeting and high-efficiency loading of multiple drugs. Herein, we have developed a pH-responsive nanocarrier that has high affinity for the transferrin receptor, which is overexpressed by tumor cells. The system is capable of simultaneous delivery of the chemotherapy drug, docetaxel, and the Chinese Medicine, curcumin, for treatment of esophageal cancer. This novel T7-modified targeting nanosystem releases loaded drugs when exposed to the acidic microenvironment of the tumor, and exerts a synergistic anti-tumor effect, and T7-NP-DC with docetaxel and curcumin loading of 10% and 6.1%, respectively. In vitro and in vivo studies showed that improved anti-tumor efficacy could be obtained by loading docetaxel and curcumin into the T7-modified nanocarrierwithout obvious toxicity or side effects, compared to drug without nanocarrier. Furthermore, the nanocarriers conjugated with T7 short peptides were more readily taken up by esophageal cancer cells compared with normal cells.Together, our findings indicate that the materials can safely exert synergistic anti-tumor effects and provide an excellent therapeutic platform for combination therapy of esophageal cancer.

Development and Advances of Drugs for Cancer Theranostics – PART-IV

2021 ◽  
Vol 21 (18) ◽  
pp. 1644-1644
Author(s):  
Lian-Shun Feng
Keyword(s):  
Drug Discovery ◽  
Side Effects ◽  
Anticancer Activity ◽  
Anticancer Drug ◽  
Anticancer Agents ◽  
Drug Repurposing ◽  
Biological Properties ◽  
Drug Candidates ◽  
Pharmacokinetic Profiles ◽  
Hybrid Molecules

Cancer, a highly heterogeneous disease at intra/inter patient levels, is one of the most serious threats to human health across the world [1, 2]. Notwithstanding the noteworthy advances in its treat-ment, the morbidity and mortality of cancer are projected to grow for a long period, and the global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020 [3]. Accordingly, there is a constant need to explore novel anticancer agents. <p> There are several strategies to discover novel anticancer candidates: (1) new lead hits or candidates from natural resources [4] whichexhibit various biological properties and are a rich source of com-pounds in drug discovery due to the structural and mechanistic diversity, and more than 60% anti-cancer agents can be traced to a natural product; (2) Molecular hybridization is one of the most prom-ising strategies for the discovery of novel anticancer drug candidates since hybrid molecules have the potential to bind multiple targets or to enhance the effect through acting with another bio-target or to counterbalance the side effects caused by the other part of the hybrid [5]; (3) Dimerization is a useful tool to develop novel anticancer drug candidates with enhanced biological activity, reduced side effects and improved pharmacokinetic profiles [6]; (4) Drug repurposing strategy is is an attractive strategy and has been approved, along with non-anticancer macrolide drugs for the treatment of cancer, for anticancer drug discovery since toxicity and pharmacokinetic profiles have already been estab-lished [7]. <p> Heterocycles coumarin, β-lactone, macrolide and triazole are useful anticancer pharmacophores since their derivatives could exert the anticancer activity through diverse mechanisms, inclusive of inhibition of aromatase, carbonic anhydrase, ki-nase, P-glycoprotein, sulfatase, telomerase, vascular endothelial growth factor receptor 2 and tubulin [8-11]. In particular, nat-ural-derived coumarin, β-lactone and macrolide derivatives are important sources of new anticancer lead hits/candidates; mac-rolide repurposed drugs can circumvent high cost and long-time associated with traditional drug discovery strategies; couma-rin, β-lactone and macrolide hybrids as well as bis-triazole compounds have the potential to enhance the anticancer activity, overcome drug resistance, reduce the side effects and improve pharmacokinetic profiles.

Repurposing Drugs to Combat Drug Resistance in Leprosy: A Review of Opportunities

2021 ◽  
Vol 25 ◽  
Author(s):  
Mukul Sharma ◽  
Pushpendra Singh
Keyword(s):  
Synergistic Effects ◽  
Drug Repurposing ◽  
New Drugs ◽  
Resistance Testing ◽  
Promising Alternative ◽  
Drug Molecules ◽  
Conventional Drug ◽  
Repurposed Drugs ◽  
Multiple Drugs

: Leprosy is caused by extremely slow-growing and uncultivated mycobacterial pathogens, namely Mycobacterium leprae and M. lepromatosis. Nearly 95% of the new cases of leprosy recorded globally are found in India, Brazil, and 20 other priority countries [WHO, 2019], of which nearly two-thirds of the cases are reported in India alone. Currently, leprosy is treated with dapsone, rifampicin, and clofazimine, also known as multi-drug therapy [MDT], as per the recommendations of WHO since 1981. Still, the number of new leprosy cases recorded globally has remained constant in the last one-decade ,and resistance to multiple drugs has been documented in various parts of the world, even though relapses are rare in patients treated with MDT. Antimicrobial resistance testing against M. leprae or the evaluation of the anti-leprosy activity of new drugs remains a challenge as leprosy bacilli do not grow in vitro. Besides, developing a new drug against leprosy through the conventional drug development process is not economically attractive or viable for pharma companies. Therefore, a promising alternative is the repurposing of existing drugs/approved medications or their derivatives for assessing their anti-leprosy potential. It is an efficient method to identify novel medicinal and therapeutic properties of approved drug molecules. Any combinatorial chemotherapy that combines these repurposed drugs with the existing first-line [MDT] and second-line drugs could improve the bactericidal and synergistic effects against these notorious bacteria and can help in achieving the much-cherished goal of “leprosy-free world”. This review highlights novel opportunities for drug repurposing to combat resistance to current therapeutic approaches.

Arzneimittelinteraktionen, die man kennen muss!

2019 ◽  
Vol 144 (04) ◽  
pp. 264-275
Author(s):  
Niels Voigt ◽  
Katharina Ort ◽  
Samuel Sossalla
Keyword(s):  
Cytochrome P450 ◽  
Plasma Concentration ◽  
Side Effects ◽  
Daily Practice ◽  
Modern Medicine ◽  
Ageing Society ◽  
Mortality And Morbidity ◽  
Exponential Increase ◽  
Number Of Patients ◽  
Multiple Drugs

AbstractDrug-drug interactions (DDI) represent a significant problem in modern medicine. The number of patients with multi-morbidity, who take multiple drugs, is constantly increasing (polypharmacy). The related exponential increase in potential DDI is almost incomprehensible. In this article, we review pharmacodynamic DDI and provide clinically relevant examples. In addition, we extensively review pharmakokinetic DDI (e. g. through the cytochrome P450-system or p-glycoproteins) that can modify the plasma concentration of many compounds, thereby also increasing the likelihood of unwanted side effects. Finally we provide tools, which may help clinicians in their daily practice to identify and avoid potential DDI. In the context of an ageing society receiving polypharmacy, a better awareness of DDI and of strategies to prevent them is expected to reduce mortality and morbidity.

scholarly journals Monotherapy or Polytherapy for Epilepsy?

1998 ◽  
Vol 25 (S4) ◽  
pp. S3-S8 ◽  
Author(s):  
Alan Guberman
Keyword(s):  
Side Effects ◽  
Seizure Control ◽  
Lower Cost ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
First Line ◽  
New Antiepileptic Drugs ◽  
Epilepsy Treatment ◽  
Multiple Drugs ◽  
The Ideal

ABSTRACT:Monotherapy has been promoted as the ideal in epilepsy treatment because of reduced side effects, absence of drug interactions, better compliance, lower cost and, in many cases, improved seizure control compared to polytherapy. The question of monotherapy vs. polytherapy has assumed increasing importance with the availability of multiple new antiepileptic drugs (AEDs), initially tested as add-on agents. The new drugs clobazam, lamotrigine, vigabatrin, gabapentin and topiramate, have also been shown to be effective as monotherapy. These data bring up the possibility of using them as first-line agents. However, a high percentage of patients with resistant epilepsy are treated with polytherapy, which probably benefits only a minority of them. The availability of multiple drugs with different mechanisms of action favours the possibility of "rational polytherapy", taking advantage of possible synergism, a yet unproven concept. This article reviews the theoretical advantages of monotherapy and monotherapy with traditional and newer AEDs.

scholarly journals Audit of the use of psychotropic medication for challenging behaviour in a community learning disability service

2004 ◽  
Vol 28 (12) ◽  
pp. 447-450 ◽  
Author(s):  
Tom Marshall
Keyword(s):  
Side Effects ◽  
Learning Disability ◽  
Psychotropic Medication ◽  
Evidence Base ◽  
Challenging Behaviour ◽  
Duration Of Treatment ◽  
Community Learning ◽  
Disability Service ◽  
People With Dementia ◽  
Multiple Drugs

Aims and MethodThe aims of the study were to identify patients in a community learning disability service receiving psychotropic medication for challenging behaviour, to examine prescribing practice and to compare this against local consensus standards. Local consensus standards were agreed by the consultants and the notes were reviewed by the author.ResultsA total of 102 patients were identified as receiving psychotropic medication for challenging behaviour (26.7% of notes examined). The most common additional diagnoses were autism (29%) and epilepsy (28%). The average duration of treatment was 5.3 years, and multiple drugs were used in 34% of these patients. Antipsychotics were the most commonly used drugs (96% of patients). There was rarely a detailed description of the challenging behaviour. There was little regular monitoring of side-effects or warning about potential side-effects when the medication was started.Clinical ImplicationsChallenging behaviour is a common cause of multiple prescribing in learning disability patients, and is often long-term in the absence of a strong evidence base. Other specialties use medication to control disturbed behaviour, particularly in people with dementia or personality disorder, so this audit may also be of interest to old age, adult and forensic psychiatrists.

scholarly journals Polypharmacological study of Ceritinib using a structure based in silico approach

Bionatura ◽  
2019 ◽  
Vol 4 (2) ◽  
pp. 836-840
Author(s):  
Tammanna R. Sahrawat ◽  
Prabhjeet Kaur Kaur
Keyword(s):  
Side Effects ◽  
Binding Sites ◽  
In Silico ◽  
Protein Tyrosine Kinase ◽  
Drug Repurposing ◽  
Aurora Kinase ◽  
Specific Protein ◽  
Binding Energies ◽  
Aurora Kinase B ◽  
Anaplastic Lymphoma

Drug repurposing has gained mass recognition over the past few years as it has paved new therapeutic applications for already approved FDA drugs. It focuses on finding new molecular targets of drugs for medical uses different than the one originally proposed. Ceritinib, an Anaplastic Lymphoma Kinase (ALK) inhibitor is given orally in the treatment of non-small cell lung cancer (NSCLC). This treatment has been reported to be associated with a number of side effects such as hyperglycemia, convulsion, pneumonitis etc. The side effects are usually due to the unintended interaction of the drug with other protein targets. In silico polypharmacological studies of Ceritinib suggests that it binds to multiple targets other than the intended one which may largely be due to different proteins possessing similar binding sites. ProBis server was used to retrieve probable off-targets of Ceritinib based on presence of structurally similar protein binding sites as that of ALK. Ceritinib was found to bind effectively to three proteins namely Lymphocyte Cell-Specific Protein-Tyrosine Kinase, Tropomyosin receptor kinase B and Aurora kinase B having favorable binding energies and inhibition constants, with no reported side-effects as compared to their marketed drugs. Therefore, it is concluded from the present study that Ceritinib may act as an effective therapeutic target against its polypharmacological targets.

scholarly journals Unify Markov model for Rational Design and Synthesis of More Safe Drugs. Predicting Multiple Drugs Side Effects

2005 ◽  
Author(s):  
Humberto González-Díaz ◽  
Maykel Cruz-Monteagudo ◽  
Miguel Cabrera-Pérez ◽  
Reinaldo Molina-Ruiz ◽  
Yunierkis Pérez-Castillo
Keyword(s):  
Side Effects ◽  
Markov Model ◽  
Rational Design ◽  
Design And Synthesis ◽  
Multiple Drugs
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