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("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/12/13

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/12/12

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Paradoxical psoriasiform reactions of anti-tumour necrosis factor therapy in inflammatory bowel disease patients.

Intern Med J. 2017 Dec;47(12):1445-1448

Authors: Peer FC, Miller A, Pavli P, Subramaniam K

Abstract
Anti-tumour necrosis factor (TNF) agents have demonstrated efficacy in inflammatory bowel disease (IBD). Cutaneous reactions such as new onset psoriasis or psoriasiform-like reactions are among the most common adverse reactions. We retrospectively identified cases of anti-TNF-induced psoriasis or psoriasiform manifestations in IBD patients at a tertiary centre in Australia. A total of 10 (six females) of 270 (3.7%) IBD patients treated with anti-TNF therapy developed drug-induced psoriatic or psoriasiform-like reactions: five patients were treated with infliximab and five with adalimumab; nine had Crohn disease. The time from initiation of anti-TNF agent to onset of rash was 7.5 months on average. The most frequent distributions were the scalp (7/10) and extremities (6/10). Three patients discontinued anti-TNF treatment with resolution of the rash. Topical treatment of the lesions allowed continued use of biological agent in the majority. Paradoxical psoriatic lesions are recognised adverse events associated with anti-TNF therapy, but discontinuation of therapy due to dermatological complications is required only rarely, even in patients with psoriasiform lesions.

PMID: 29224199 [PubMed - in process]

Negative Impact of Testosterone Deficiency and 5α-Reductase Inhibitors Therapy on Metabolic and Sexual Function in Men.

Adv Exp Med Biol. 2017;1043:473-526

Authors: Traish AM

Abstract
Androgens are steroid hormones with pleotropic and diverse biochemical and physiological functions, and androgen deficiency exerts a negative impact on human health. Testosterone (T) either directly or via its transformation into the more potent metabolite 5α-dihydrotestosterone (5α-DHT) or via aromatization into estradiol (E2) modulates important biochemical signaling pathways of human physiology and plays a critical role in the growth and/or maintenance of functions in a host of tissues and organs. T and 5α-DHT play an important role in regulating physiology of the muscle, adipose tissue, liver, bone, and central nervous system, as well as reproductive and sexual functions. Thus, androgen deficiency (also referred to as hypogonadism) is a well-recognized medical condition and if remained untreated will have a negative impact on human health and quality of life.In this chapter, we have summarized the negative impact of T deficiency (TD) on a host of physiological functions including reduced lean body mass (LBM), increased fat mass (FM), increased insulin resistance (IR), metabolic syndrome (MetS) and adiposity, reduced bone mineral density (BMD), anemia, sexual dysfunction, and reduced quality of life and increased mortality. In addition, we discuss another critical aspect of unrecognized form of androgen deficiency resulting from inhibition of 5α-reductases with drugs, such as finasteride and dutasteride, to block transformation of T into 5α-DHT in the course of treatment of benign prostatic hyperplasia (BPH) and male pattern hair loss, also known as androgenetic alopecia (AGA). The negative impact of drugs that inhibit transformation of T to 5α-DHT by 5α-reductases on metabolic function is manifested in fat accumulation in the liver, which may predispose to nonalcoholic fatty liver disease (NAFLD). Also, inhibition of 5α-DHT formation increases glucose synthesis and reduces glucose disposal potentially contributing to hyperglycemia, IR, and elevated activities of liver function enzymes concomitant with reduction in circulating T levels, worsening erectile dysfunction (ED), and reduced quality of life.Although we have attempted to summarize the current literature pertaining to this critical topic "androgen deficiency" and its impact on men's health and quality of life, there remain many gaps in the knowledge regarding the biochemical pathways that are involved in the pathophysiology of androgen deficiency. We wish to clearly state that there are areas of controversies, including whether age-related androgen deficiency (functional hypogonadism) merits treatment and whether T therapy provided real proven benefits. Finally, considerable debate exists with respect to the potential and purported cardiovascular (CV) risks of treating TD with exogenous T. For brevity sake, we will not discuss in detail the benefits of T therapy in men with TD since this topic is comprehensively covered by Dr. F. Saad's chapter in this book, entitled "Testosterone Therapy and Glucose Homeostasis in Men with Testosterone Deficiency (Hypogonadism)."We have made a concerted effort to address the controversy of T therapy in men with TD in the discussion. However, we wish to acknowledge that these issues will remain a matter of debate for some time to come. Only with advances in fundamental basic science and clinical research, some of these controversial issues may be laid to rest. Nevertheless, we believe that there is considerable body of credible evidence to suggest that T therapy of men with TD is safe and effective and provides a host of health benefits and therefore merits considerations in men with TD, irrespective of the underlying cause or etiology. An additional aspect of androgen deficiency is the drug-induced reduction in 5α-DHT levels by the use of 5α-reductase inhibitors. We also believe that physicians prescribing 5α-reductase inhibitors (i.e., finasteride or dutasteride) for relief of BPH symptoms or treatment of hair loss should engage their patients in a productive discussion regarding the potential adverse side effects of these medications on their overall health and quality of life.

PMID: 29224108 [PubMed - in process]

Evaluating Safety Reporting in Paediatric Antibiotic Trials, 2000-2016: A Systematic Review and Meta-Analysis.

Drugs. 2017 Dec 07;:

Authors: Pansa P, Hsia Y, Bielicki J, Lutsar I, Walker AS, Sharland M, Folgori L

Abstract
BACKGROUND: There are very few options to treat multidrug-resistant bacterial infections in children. A major barrier is the duration and complexity of regulatory trials of new antibiotics. Extrapolation of safety data from adult trials could facilitate drug development for children.
OBJECTIVE: We performed a systematic review on the safety of antibiotic clinical trials (CTs) in children (0-18 years) to evaluate the overall quality of safety trials conducted in children and to determine if age-specific adverse events (AEs) could be identified for specific antibiotic classes.
DATA SOURCES: We searched the MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov electronic databases for trials conducted between 2000 and 2016.
STUDY SELECTION: All trials in which safety was declared a primary or secondary endpoint were included. Exclusion criteria were (1) topical or inhalational route of administration; (2) non-infectious conditions; (3) administration for prophylaxis rather than treatment; (4) selected population (i.e. cystic fibrosis, malignancies, HIV and tuberculosis); and (5) design other than randomized controlled trials. Trials reporting data on both adults and children were included only if paediatric results were reported separately.
DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted the data. To assess the quality of published trials, the Extension for harms for Consolidated Standards of Reporting Trials (CONSORT) Statement 2004 was used.
MAIN OUTCOME AND MEASURE: In order to quantitatively assess the rate of developing AEs by drug class, the numbers of overall and body-system-specific AEs were collected for each study arm, and then calculated per single drug class as median and interquartile range (IQR) of the proportions across CTs. The AEs most frequently reported were compared in the meta-analysis by selecting the CTs on the most represented drug classes.
RESULTS: Eighty-three CTs were included, accounting for 27,693 children. Overall, 69.7% of CONSORT items were fully reported. The median proportion of children with any AE was 22.5%, but did not exceed 8% in any single body system. Serious drug-related AEs and drug-related discontinuations were very rare (median 0.3 and 0.9%, respectively). Limitations included the inability to stratify by age group, particularly neonates.
CONCLUSIONS AND RELEVANCE: Overall, AEs in paediatric antibiotic CTs were predictable and class-specific, and no unexpected (age-specific) side effects were identified. Smaller, open-label, dose-finding, high-quality, single-arm pharmacokinetic trials seem potentially sufficient for certain common antibiotic classes, extrapolating well-established safety profiles determined from large adult efficacy trials. This approach could reduce duration and enhance subsequent registration of urgently needed new antibiotics. This will need to be combined with enhanced methods of pharmacovigilance for monitoring of emerging AEs in routine clinical practice.

PMID: 29218501 [PubMed - as supplied by publisher]

Efficacy of transdermal buprenorphine patch on post-operative pain relief after elective spinal instrumentation surgery.

Indian J Anaesth. 2017 Nov;61(11):923-929

Authors: Niyogi S, Bhunia P, Nayak J, Santra S, Acharjee A, Chakraborty I

Abstract
Background and Aims: Transdermal buprenorphine patch (TDB) is increasingly used for chronic pain management because of non-invasive dosing, longer duration of action and minimal side effects. However its role in acute post-operative pain management for spinal instrumentation surgery is not well established. The aim of this study was to evaluate the analgesic efficacy of buprenorphine patch for postoperative pain relief in patients undergoing spinal instrumentation surgery.
Methods: In this randomised, placebo-controlled, double-blinded, prospective study, 70 adult patients undergoing elective spinal instrumentation surgery were randomly allocated into two groups-TDB Group (buprenorphinepatch) and TDP Group (placebo patch). Time to first rescue analgesic requirement was the primary outcome. All patients also were monitored for total rescue analgesic requirement, drug-related adverse effect and haemodynamic status till 48 h after surgery. Statistical analysis was carried out using student independent t-test if normally distributed or with Mann-Whitney U-test if otherwise.
Results: Time to first post-operative rescue analgesic (tramadol) requirement was much delayed in TDB Group than TDP Group (708.0 ± 6.98 min vs 54 ± 0.68 min, P < 0.001) and the total tramadol requirement was higher in TDB Group (490.60 ± 63.09 averagevs. 162.93 ± 63.91 mg, P < 0.001). Intra-and post-operative haemodynamic status was also stable in TDB Group without any adverse event.
Conclusion: A TDB patch (10 μg/hour) applied 24 hours before surgery can be used as a postoperative analgesic for lumber fixation surgery without any drug-related adverse effect.

PMID: 29217859 [PubMed]

Genetic Determinants of Clozapine-Induced Metabolic Side Effects.

Can J Psychiatry. 2017 Feb;62(2):138-149

Authors: Vasudev K, Choi YH, Norman R, Kim RB, Schwarz UI

Abstract
OBJECTIVE: Atypical antipychotics are linked to a higher incidence of metabolic side effects, including weight gain, dyslipidemia, and diabetes. In this study, we examined the prevalence and potential genetic predictors of metabolic side effects in 60 adult patients on clozapine.
METHOD: Genetic variants of relevance to clozapine metabolism, clearance, and response were assessed through targeted genotyping of cytochrome P450 enzymes CYP1A2 and CYP2C19, the efflux transporter ABCB1, the serotonin receptor (HTR2C), leptin (LEP), and leptin receptor (LEPR). Clozapine levels and other potential confounders, including concurrent medications, were also included in the analysis.
RESULTS: More than half of the patients were obese (51%), had metabolic syndrome (52.5%), and 30.5% were overweight. There was a high prevalence of antipsychotic polypharmacy (61.9%). With multivariable linear regression analysis, LEP -2548G>A, LEPR c.668A>G, and HTR2C c.551-3008 C>G were identified as genetic predictors of body mass index (BMI) after considering effects of clozapine dose, blood level, and concurrent medications (adjusted R2 = 0.305). Metabolic syndrome was found to be significantly associated with clozapine level and CYP2C19*2 and LEPR c.668 G alleles. Clozapine levels in patients with metabolic syndrome were significantly higher compared to those without metabolic syndrome (1886 ± 895 vs. 1283 ± 985 ng/mL, P < 0.01) and were associated with the CYP2C19*2 genotype. No association was found between the genetic variants studied and lipid or glucose levels.
CONCLUSION: This study confirms a high prevalence of metabolic side effects with clozapine and suggests higher clozapine level and pharmacogenetic markers in CYP2C19, LEP, LEPR, and HTR2C receptors as important predictors of BMI and metabolic syndrome.

PMID: 27681143 [PubMed - indexed for MEDLINE]

Omalizumab and allergen immunotherapy in a patient with asthma and inhaled corticosteroid-induced adrenal suppression.

Ann Allergy Asthma Immunol. 2016 Sep;117(3):335-7

Authors: Forbush JT, Banks TA

PMID: 27613470 [PubMed - indexed for MEDLINE]

Severe adverse drug reactions induced by hydrochlorothiazide: A persistent old problem.

Ann Allergy Asthma Immunol. 2016 Sep;117(3):334-5

Authors: Corominas M, Andrés-López B, Lleonart R

PMID: 27613469 [PubMed - indexed for MEDLINE]

Polypharmacy and potentially inappropriate medication use in geriatric oncology.

J Geriatr Oncol. 2016 Sep;7(5):346-53

Authors: Sharma M, Loh KP, Nightingale G, Mohile SG, Holmes HM

Abstract
Polypharmacy is a highly prevalent problem in older persons, and is challenging to assess and improve due to variations in definitions of the problem and the heterogeneous methods of medication review and reduction. The purpose of this review is to summarize evidence regarding the prevalence and impact of polypharmacy in geriatric oncology patients and to provide recommendations for assessment and management. Polypharmacy has somewhat variably been incorporated into geriatric assessment studies in geriatric oncology, and polypharmacy has not been consistently evaluated as a predictor of negative outcomes in patients with cancer. Once screened, interventions for polypharmacy are even more uncertain. There is a great need to create standardized interventions to improve polypharmacy in geriatrics, and particularly in geriatric oncology. The process of deprescribing is aimed at reducing medications for which real or potential harm outweighs benefit, and there are numerous methods to determine which medications are candidates for deprescribing. However, deprescribing approaches have not been evaluated in older patients with cancer. Ultimately, methods to identify polypharmacy will need to be clearly defined and validated, and interventions to improve medication use will need to be based on clearly defined and standardized methods.

PMID: 27498305 [PubMed - indexed for MEDLINE]

The role of drug profiles as similarity metrics: applications to repurposing, adverse effects detection and drug-drug interactions.

Brief Bioinform. 2017 Jul 01;18(4):670-681

Authors: Vilar S, Hripcsak G

Abstract
Explosion of the availability of big data sources along with the development in computational methods provides a useful framework to study drugs' actions, such as interactions with pharmacological targets and off-targets. Databases related to protein interactions, adverse effects and genomic profiles are available to be used for the construction of computational models. In this article, we focus on the description of biological profiles for drugs that can be used as a system to compare similarity and create methods to predict and analyze drugs' actions. We highlight profiles constructed with different biological data, such as target-protein interactions, gene expression measurements, adverse effects and disease profiles. We focus on the discovery of new targets or pathways for drugs already in the pharmaceutical market, also called drug repurposing, in the interaction with off-targets responsible for adverse reactions and in drug-drug interaction analysis. The current and future applications, strengths and challenges facing all these methods are also discussed. Biological profiles or signatures are an important source of data generation to deeply analyze biological actions with important implications in drug-related studies.

PMID: 27273288 [PubMed - indexed for MEDLINE]

Attempted replication of SNPs in RANKL and OPG with musculoskeletal adverse events during aromatase inhibitor treatment for breast cancer.

Physiol Genomics. 2017 Dec 06;:physiolgenomics.00085.2017

Authors: Dempsey JM, Xi J, Henry NL, Rae JM, Hertz DL

Abstract
Aromatase inhibitor (AI) therapy is highly efficacious in the treatment of estrogen receptor-positive breast cancer, however in a subset of patients AI use is discontinued due to drug-induced musculoskeletal adverse events (MS-AE). Several studies have investigated the role of germline single nucleotide polymorphisms on patients' risk of MS-AE's, however no associations have yet to be validated for translation into clinical practice. This study attempted to replicate SNPs in RANKL (rs7984870) and OPG (rs2073618) on the risk of AI-induced MS-AEs, and screen for secondary associations with MS-AE related treatment discontinuation and serum and urine markers of bone health. Previously reported associations were not replicated with our primary hypothesis, change in MS-AE from baseline to three months, however, patients homozygous for the G allele of rs7984870 in RANKL had lower risk of MS-AE-associated treatment discontinuation in analyses of secondary phenotypes without statistical correction.

PMID: 29212847 [PubMed - as supplied by publisher]

Leukocytoclastic vasculitis complicating cisplatin + radiation treatment for laryngeal cancer: a case report.

BMC Cancer. 2017 Dec 06;17(1):831

Authors: Quintanilha JCF, Visacri MB, Amaral LS, Lima CSP, Cintra ML, Moriel P

Abstract
BACKGROUND: Leukocytoclastic vasculitis is typically mediated by deposition of immune complexes and is related to many causes, including medication. To the best of our knowledge, leukocytoclastic vasculitis related to cisplatin has not yet been described in the scientific literature.
CASE PRESENTATION: We report a rare case of leukocytoclastic vasculitis after the first cycle of high-dose cisplatin chemotherapy in a patient with larynx carcinoma. A 48-year-old Caucasian man with larynx carcinoma received a high-dose of cisplatin monochemotherapy (100 mg/m2 every 21 days), along with 70 Gy of radiotherapy divided into 35 sessions, as a therapeutic schedule. Twelve days after the first chemotherapy administration and after 8 sessions of radiotherapy (total of 16 Gy), the patient presented with acute onset of palpable purpura in the lower limbs. The patient was hospitalized for 10 days, and during this period, he underwent several examinations to rule out infectious, autoimmune, and neoplastic disorders. A skin biopsy showed leukocytoclastic vasculitis with a positive pattern for IgM and C3, as detected through direct immunofluorescence. Twenty-five days after cisplatin administration, the chemotherapy regimen was changed to carboplatin AUC 5, and the episodes of purpura ceased, reinforcing the hypothesis of an adverse reaction to cisplatin.
CONCLUSIONS: Cisplatin can induce leukocytoclastic vasculitis and clinicians should be aware of this potential effect for better case management and diagnosis.

PMID: 29212535 [PubMed - in process]

[NEPHROTOXIC DRUGS].

Acta Med Croatica. 2016 12;70(4-5):309-14

Authors: Popović B, Šutić I, Marković NB

Abstract
Renal tissue is sensitive to the effect of potentially nephrotoxic drugs and other substances that are available over-the-counter or can be purchased at healthy food stores or elsewhere, and harmful substances from the environment. The harmful effects of these substances lead to the development of recognizable clinical syndromes, including acute or chronic renal failure, tubulopathy, and proteinuria. Risk factors that influence the development of kidney disease induced by drugs are divided into those related to patient characteristics, drug characteristics, and renal function. Drugs that commonly exhibit nephrotoxic effects are analgesics, antimicrobials, chemotherapeutics, contrast agents, immunosuppressants, herbal preparations and substances containing heavy metals. Family physician must carefully observe their patients, nurturing individual approach to drug selection and determining the dose. Renal function can quickly return to normal if the damage is recognized on time. Recent research yields insights into the identification of new biomarkers that will contribute to early detection of drug induced kidney damage.

PMID: 29087164 [PubMed - indexed for MEDLINE]

Legacy data sharing to improve drug safety assessment: the eTOX project.

Nat Rev Drug Discov. 2017 Dec;16(12):811-812

Authors: Sanz F, Pognan F, Steger-Hartmann T, Díaz C, eTOX, Cases M, Pastor M, Marc P, Wichard J, Briggs K, Watson DK, Kleinöder T, Yang C, Amberg A, Beaumont M, Brookes AJ, Brunak S, Cronin MTD, Ecker GF, Escher S, Greene N, Guzmán A, Hersey A, Jacques P, Lammens L, Mestres J, Muster W, Northeved H, Pinches M, Saiz J, Sajot N, Valencia A, van der Lei J, Vermeulen NPE, Vock E, Wolber G, Zamora I

Abstract
The sharing of legacy preclinical safety data among pharmaceutical companies and its integration with other information sources offers unprecedented opportunities to improve the early assessment of drug safety. Here, we discuss the experience of the eTOX project, which was established through the Innovative Medicines Initiative to explore this possibility.

PMID: 29026211 [PubMed - indexed for MEDLINE]

Mitochondrial disease patients' perception of dietary supplements' use.

Mol Genet Metab. 2016 Sep;119(1-2):100-8

Authors: Karaa A, Kriger J, Grier J, Holbert A, Thompson JL, Parikh S, Hirano M

Abstract
Surveys of mitochondrial disease physicians conducted through the Mitochondrial Medicine Society have shown that virtually all providers recommend a variety of dietary supplements as treatments to their patients in an effort to enhance energy production and reduce oxidative stress. In this survey, we asked patients and their parents about their experiences taking these dietary supplements for mitochondrial disease. The survey was disseminated through the North American Mitochondrial Disease Consortium (NAMDC) and the Rare Disease Clinical Research Network (RDCRN) registries and gathered 162 responses. The study ascertained each patient's mitochondrial disease diagnosis, dietary supplements used, adjunct therapy, and effects of the supplements on symptoms and health. Regardless of the specific underlying mitochondrial disease, the majority of the survey respondents stated they are or have been on dietary supplements. Most patients take more than four supplements primarily coenzyme Q10, l-carnitine, and riboflavin. The majority of patients taking supplements reported health benefits from the supplements. The onset of perceived benefits was between 2weeks to 3months of initiating intake. Supplements seem to be safe, with only 28% of patients experiencing mild side-effects and only 5.6% discontinuing their intake due to intolerance. Only 9% of patients had insurance coverage for their supplements and when paying out of pocket, 95% of them spend up to $500/month. Despite the use of concomitant therapies (prescribed medications, physical therapy, diet changes and other), 45.5% of patients think that dietary supplements are the only intervention improving their symptoms. Some limitations of this study include the retrospective collection of data probably associated with substantial recall bias, lack of longitudinal follow up to document pre- and post-supplement clinical status and second hand reports by parents for children which may reflect parents' subjective interpretation of symptoms severity and supplements effect rather than real patients' experience. More extensive prospective studies will help further elucidate this topic.

PMID: 27444792 [PubMed - indexed for MEDLINE]

Small cell lung cancer: Time to revisit DNA-damaging chemotherapy.

Sci Transl Med. 2016 Jul 06;8(346):346fs12

Authors: Thomas A, Pommier Y

Abstract
Rational use of DNA-damaging chemotherapy, with new combinations to heighten DNA replication stress, could improve outcomes in small cell lung cancer.

PMID: 27384345 [PubMed - indexed for MEDLINE]

Content, Consistency, and Quality of Black Box Warnings.

Ann Intern Med. 2016 07 05;165(1):74-5

Authors: Elraiyah T, Murad MH

PMID: 27380161 [PubMed - indexed for MEDLINE]

Incidence of adverse events in paediatric procedural sedation in the emergency department: a systematic review and meta-analysis.

BMJ Open. 2016 Jun 15;6(6):e011384

Authors: Bellolio MF, Puls HA, Anderson JL, Gilani WI, Murad MH, Barrionuevo P, Erwin PJ, Wang Z, Hess EP

Abstract
OBJECTIVE AND DESIGN: We conducted a systematic review and meta-analysis to evaluate the incidence of adverse events in the emergency department (ED) during procedural sedation in the paediatric population. Randomised controlled trials and observational studies from the past 10 years were included. We adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
SETTING: ED.
PARTICIPANTS: Children.
INTERVENTIONS: Procedural sedation.
OUTCOMES: Adverse events like vomiting, agitation, hypoxia and apnoea. Meta-analysis was performed with random-effects model and reported as incidence rates with 95% CIs.
RESULTS: A total of 1177 studies were retrieved for screening and 258 were selected for full-text review. 41 studies reporting on 13 883 procedural sedations in 13 876 children (≤18 years) were included. The most common adverse events (all reported per 1000 sedations) were: vomiting 55.5 (CI 45.2 to 65.8), agitation 17.9 (CI 12.2 to 23.7), hypoxia 14.8 (CI 10.2 to 19.3) and apnoea 7.1 (CI 3.2 to 11.0). The need to intervene with either bag valve mask, oral airway or positive pressure ventilation occurred in 5.0 per 1000 sedations (CI 2.3 to 7.6). The incidences of severe respiratory events were: 34 cases of laryngospasm among 8687 sedations (2.9 per 1000 sedations, CI 1.1 to 4.7; absolute rate 3.9 per 1000 sedations), 4 intubations among 9136 sedations and 0 cases of aspiration among 3326 sedations. 33 of the 34 cases of laryngospasm occurred in patients who received ketamine.
CONCLUSIONS: Serious adverse respiratory events are very rare in paediatric procedural sedation in the ED. Emesis and agitation are the most frequent adverse events. Hypoxia, a late indicator of respiratory depression, occurs in 1.5% of sedations. Laryngospasm, though rare, happens most frequently with ketamine. The results of this study provide quantitative risk estimates to facilitate shared decision-making, risk communication, informed consent and resource allocation in children undergoing procedural sedation in the ED.

PMID: 27311910 [PubMed - indexed for MEDLINE]

Updates on drug-target network; facilitating polypharmacology and data integration by growth of DrugBank database.

Brief Bioinform. 2016 Nov;17(6):1070-1080

Authors: Barneh F, Jafari M, Mirzaie M

Abstract
Network pharmacology elucidates the relationship between drugs and targets. As the identified targets for each drug increases, the corresponding drug-target network (DTN) evolves from solely reflection of the pharmaceutical industry trend to a portrait of polypharmacology. The aim of this study was to evaluate the potentials of DrugBank database in advancing systems pharmacology. We constructed and analyzed DTN from drugs and targets associations in the DrugBank 4.0 database. Our results showed that in bipartite DTN, increased ratio of identified targets for drugs augmented density and connectivity of drugs and targets and decreased modular structure. To clear up the details in the network structure, the DTNs were projected into two networks namely, drug similarity network (DSN) and target similarity network (TSN). In DSN, various classes of Food and Drug Administration-approved drugs with distinct therapeutic categories were linked together based on shared targets. Projected TSN also showed complexity because of promiscuity of the drugs. By including investigational drugs that are currently being tested in clinical trials, the networks manifested more connectivity and pictured the upcoming pharmacological space in the future years. Diverse biological processes and protein-protein interactions were manipulated by new drugs, which can extend possible target combinations. We conclude that network-based organization of DrugBank 4.0 data not only reveals the potential for repurposing of existing drugs, also allows generating novel predictions about drugs off-targets, drug-drug interactions and their side effects. Our results also encourage further effort for high-throughput identification of targets to build networks that can be integrated into disease networks.

PMID: 26490381 [PubMed - indexed for MEDLINE]