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Epilepsy & Behavior : E&B Feb 2020Among people with epilepsy, levetiracetam (LEV) can cause neuropsychiatric adverse events (NPAEs) that impact negatively on quality of life. It has been suggested that...
OBJECTIVE
Among people with epilepsy, levetiracetam (LEV) can cause neuropsychiatric adverse events (NPAEs) that impact negatively on quality of life. It has been suggested that pyridoxine can ameliorate LEV-related NPAEs. We conducted a systematic review of studies on the use of pyridoxine supplementation to relieve NPAEs associated with LEV therapy.
METHODS
The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medline, EMBASE, Scholar, Cochrane-CENTRAL (2000-2019), and EThOS platform were searched for studies on the use of pyridoxine in patients with LEV-related NPAEs. Proportions of patients reported to benefit from pyridoxine supplementation were tabulated, and a random-effect model meta-analysis was conducted.
RESULTS
Eleven retrospective studies/case reports and one randomized prospective study, mostly including pediatric populations, were identified. Retrospective studies, which were rated as low quality due to failure to control for bias, reported an overall improvement of NPAEs after pyridoxine supplementation in 72.5% (108/149) of patients. The proportion of patients showing improvement in a pooled analysis of the four largest retrospective studies (n = 134) was 72.1% (95% confidence interval (CI) 47.1-88.3), although there was high heterogeneity across studies (I = 82%, p < 0.01). In the only prospective trial, patients randomized to pyridoxine supplementation were more likely to show relief from NPAEs than patients not receiving supplementation (p < 0.01), but outcomes might have been affected by assessment bias.
CONCLUSION
This systematic review suggests that pyridoxine might be of benefit in relieving LEV-related NPAEs. However, the quality of the evidence is poor, and better-designed prospective studies that include quantitative as well as qualitative data are needed to define the role of pyridoxine in the management of LEV-related NPAEs.
Topics: Anticonvulsants; Diagnostic Tests, Routine; Dietary Supplements; Drug Therapy, Combination; Epilepsy; Humans; Levetiracetam; Mental Disorders; Prospective Studies; Pyridoxine; Quality of Life; Retrospective Studies; Vitamin B Complex
PubMed: 31917143
DOI: 10.1016/j.yebeh.2019.106861 -
Lipids in Health and Disease Oct 2019Chronic illnesses like obesity, type 2 diabetes (T2D) and cardiovascular diseases, are worldwide major causes of morbidity and mortality. These pathological conditions...
BACKGROUND
Chronic illnesses like obesity, type 2 diabetes (T2D) and cardiovascular diseases, are worldwide major causes of morbidity and mortality. These pathological conditions involve interactions between environmental, genetic, and epigenetic factors. Recent advances in nutriepigenomics are contributing to clarify the role of some nutritional factors, including dietary fatty acids in gene expression regulation. This systematic review assesses currently available information concerning the role of the different fatty acids on epigenetic mechanisms that affect the development of chronic diseases or induce protective effects on metabolic alterations.
METHODS
A targeted search was conducted in the PubMed/Medline databases using the keywords "fatty acids and epigenetic". The data were analyzed according to the PRISMA-P guidelines.
RESULTS
Consumption fatty acids like n-3 PUFA: EPA and DHA, and MUFA: oleic and palmitoleic acid was associated with an improvement of metabolic alterations. On the other hand, fatty acids that have been associated with the presence or development of obesity, T2D, pro-inflammatory profile, atherosclerosis and IR were n-6 PUFA, saturated fatty acids (stearic and palmitic), and trans fatty acids (elaidic), have been also linked with epigenetic changes.
CONCLUSIONS
Fatty acids can regulate gene expression by modifying epigenetic mechanisms and consequently result in positive or negative impacts on metabolic outcomes.
Topics: Animals; Cardiovascular Diseases; Chronic Disease; DNA Methylation; Diabetes Mellitus, Type 2; Dietary Fats; Disease Models, Animal; Epigenesis, Genetic; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Gene-Environment Interaction; Humans; Insulin Resistance; Lipid Metabolism; Obesity; Trans Fatty Acids
PubMed: 31615571
DOI: 10.1186/s12944-019-1120-6 -
Proteomics Mar 2023Peptide-mediated interactions (PMIs) play a crucial role in cell signaling network, which are responsible for about half of cellular protein-protein associations in the... (Review)
Review
Peptide-mediated interactions (PMIs) play a crucial role in cell signaling network, which are responsible for about half of cellular protein-protein associations in the human interactome and have recently been recognized as a new kind of promising druggable target for drug development and disease therapy. In this article, we give a systematic review regarding the proteome-wide discovery of PMIs and targeting druggable PMIs (dPMIs) with chemical drugs, self-inhibitory peptides (SIPs) and protein agents, particularly focusing on their implications and applications for therapeutic purpose in omics. We also introduce computational peptidology strategies used to model, analyze, and design PMI-targeted molecular entities and further extend the concepts of protein context, direct/indirect readout, and enthalpy/entropy effect involved in PMIs. Current issues and future perspective on this topic are discussed. There is still a long way to go before establishment of efficient therapeutic strategies to target PMIs on the omics scale.
Topics: Humans; Peptides; Proteins; Entropy
PubMed: 36461811
DOI: 10.1002/pmic.202200175 -
Pharmacotherapy Dec 2023This systematic review evaluates the extent to which the effect of anticoagulants may be altered in the presence of cannabinoids. The following databases were searched:... (Review)
Review
This systematic review evaluates the extent to which the effect of anticoagulants may be altered in the presence of cannabinoids. The following databases were searched: EMBASE, PubMed, Web of Science, Scopus, PscycINFO, and CINAHL from database inception through May 2023. Search terms included cannabis AND anticoagulant AND drug interactions and related keywords. The major outcome was hemorrhage or thrombosis and if available the relative change in quantitative intensity of anticoagulation after cannabinoid exposure. The search generated 959 citations. After the removal of 440 duplicates, 519 citations were screened. Overall, with the exception of warfarin, evidence supporting an interaction between cannabinoids and anticoagulants is non-existent. Seven case reports evaluating an interaction with warfarin were reported. Cannabis doses involved were either extremely high (e.g., >260 mg/day of delta-9-tetrahydrocannabidiol [THC] or >600 mg/day of cannabidiol [CBD]) or were not known. Hemorrhage was identified in 14.2% (1/7) of reports and thrombosis in 0%. Quantitative anticoagulation levels were increased in patients on warfarin (elevated International Normalized Ratio [INR]) in six of seven cases. A maximum INR change was available in five of seven reports, ranging from +0.4 to +9.61. One report found no change in INR after 4 days of medical cannabis exposure. Another report outlined two separate episodes of INR elevation associated with bleeding requiring hospitalization and reversal after marijuana smoking. Four cases involved reduction in weekly warfarin dose ranging from 22% to 31%. The Drug Information Probability Score was calculated in six cases, with a score of probable for five cases and possible for one. Very low-quality data support a potential drug-drug interaction with warfarin and both THC and CBD. Clinician recognition of this potential interaction is important. Available evidence supports the need to conduct a drug interaction study between cannabinoids and warfarin to clarify the existence of an interaction.
Topics: Humans; Anticoagulants; Warfarin; Cannabinoids; Hemorrhage; Drug Interactions; Cannabis; Thrombosis; Cannabidiol; International Normalized Ratio
PubMed: 37740600
DOI: 10.1002/phar.2881 -
Therapeutic Drug Monitoring Feb 2020Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistant Enterococcus faecium, multi-drug...
Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistant Enterococcus faecium, multi-drug resistant Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus. The adverse effects of linezolid can include thrombocytopenia and neuropathy, which are more prevalent with higher exposures and longer treatment durations. Although linezolid is traditionally administered at a standard 600 mg dose every 12 hours, the resulting exposure can vary greatly between patients and can lead to treatment failure or toxicity. The efficacy and toxicity of linezolid are determined by the exposure achieved in the patient; numerous clinical and population pharmacokinetics (popPK) studies have identified threshold measurements for both parameters. Several special populations with an increased need for linezolid dose adjustments have also been identified. Therapeutic Drug Monitoring (TDM) is a clinical strategy that assesses the response of an individual patient and helps adjust the dosing regimen to maximize efficacy while minimizing toxicity. Adaptive feedback control and model-informed precision dosing are additional strategies that use Bayesian algorithms and PK models to predict patient-specific drug exposure. TDM is a very useful tool for patient populations with sparse clinical data or known alterations in pharmacokinetics, including children, patients with renal insufficiency or those receiving renal replacement therapy, and patients taking co-medications known to interact with linezolid. As part of the clinical workflow, clinicians can use TDM with the thresholds summarized from the current literature to improve linezolid dosing for patients and maximize the probability of treatment success.
Topics: Anti-Bacterial Agents; Bayes Theorem; Drug Dosage Calculations; Drug Interactions; Drug Monitoring; Half-Life; Humans; Linezolid; Liver Failure; Metabolic Clearance Rate; Microbial Sensitivity Tests; Models, Biological; Pediatrics; Renal Insufficiency; Renal Replacement Therapy; Tuberculosis
PubMed: 31652190
DOI: 10.1097/FTD.0000000000000710 -
Drugs Jul 2021We conducted a narrative review of the literature to compare the pharmacological, efficacy and safety profiles of tapentadol and tramadol, and to assess the clinical...
We conducted a narrative review of the literature to compare the pharmacological, efficacy and safety profiles of tapentadol and tramadol, and to assess the clinical interest of tapentadol in adult patients. Tapentadol and tramadol share a mixed mechanism of action, including both mu-agonist and monoaminergic properties. Tapentadol is approximately two to three times more potent than tramadol and two to three times less potent than morphine. It has no identified analgesically active metabolite and is not significantly metabolised by cytochrome P450 enzymes, thus overcoming some limitations of tramadol, including the potential for pharmacokinetic drug-drug interactions and interindividual variability due to genetic polymorphisms of cytochrome P450 enzymes. The toxicity profiles of tramadol and tapentadol are similar; however tapentadol is likely to result in less exposure to serotoninergic adverse effects (nausea, vomiting, hypoglycaemia) but cause more opioid adverse effects (constipation, respiratory depression, abuse) than tramadol. The safety of tapentadol in real-world conditions remains poorly documented, particularly in at-risk patient subgroups and also in the ability to assess the risk associated with its residual serotonergic activity (serotonin syndrome, seizures). Because of an earlier market introduction, more real-world safety data are available for tramadol, including data from at-risk patient subgroups. The level of evidence on the efficacy of both tramadol and tapentadol for the treatment of chronic pain is globally low. The trials published to date show overall that tapentadol does not provide a clinically significant analgesic improvement compared to existing treatments, for which the safety profile is much better known. In conclusion, tapentadol is not a first-line opioid but represents an additional analgesic in the therapeutic choices, which some patients may benefit from after careful examination of their clinical situation, co-morbidities and co-medications.
Topics: Analgesics, Opioid; Cytochrome P-450 CYP2D6; Dose-Response Relationship, Drug; Humans; Liver Failure; Pain; Renal Insufficiency; Tapentadol; Tramadol
PubMed: 34196947
DOI: 10.1007/s40265-021-01515-z -
Journal of Cystic Fibrosis : Official... May 2023The combination of CFTR modulators ivacaftor, tezacaftor and elexacaftor (Trikafta®, Kaftrio®) significantly improve outcomes, including survival in a broad range of... (Review)
Review
The combination of CFTR modulators ivacaftor, tezacaftor and elexacaftor (Trikafta®, Kaftrio®) significantly improve outcomes, including survival in a broad range of cystic fibrosis patients. These drugs have complicated metabolic profiles that make the potential for drug interactions an important consideration for prescribers, care providers and patients. Prolonged survival also increases risk of age-related disease and their associated pharmacotherapy, further increasing the risk of drug interactions and the need for increased vigilance amongst care providers. We systematically searched the literature for studies identifying and evaluating pharmacokinetic and pharmacodynamic drug interactions involving the components of Trikafta®/Kaftrio®. We also searched electronic databases of drugs for possible drug interactions based on metabolic profiles. We identified 86 potential drug interactions of which 13 were supported by 14 studies. There is a significant need for research to describe the likelihood, magnitude and clinical impact of the drug interactions proposed here.
Topics: Humans; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Mutation; Aminophenols; Benzodioxoles; Drug Combinations; Drug Interactions
PubMed: 36653239
DOI: 10.1016/j.jcf.2023.01.005 -
Drug and Chemical Toxicology Mar 2022In India, traditional herbal medicines have been an essential part of therapy for the last centuries. However, a large portion of the general populace is using these...
In India, traditional herbal medicines have been an essential part of therapy for the last centuries. However, a large portion of the general populace is using these therapies in combination with allopathy lacking a proper understanding of possible interactions (synergistic or antagonistic) between the herbal product and the allopathic drug. This is based on the assumption that herbal drugs are relatively safe, i.e. without side effects. We have established a comprehensive understanding of the possible herb-drug interactions and identified interaction patterns between the most common herbs and drugs currently in use in the Indian market. For this purpose, we listed common interactors (herbs and allopathic drugs) using available scientific literature. Drugs were then categorized into therapeutic classes and aligned to produce a recognizable pattern present only if interactions were observed between a drug class and herb in the scientific literature. Interestingly, the top three categories (with highest interactors), antibiotics, oral hypoglycemics, and anticonvulsants, displayed synergistic interactions only. Another major interactor category was CYP450 enzymes, a natural component of our metabolism. Both activation and inhibition of CYP450 enzymes were observed. As many allopathic drugs are known CYP substrates, inhibitors or inducers, ingestion of an interacting herb could result in interaction with the co-administered drug. This information is largely unavailable for the Indian population and should be studied in greater detail to avoid such interactions. Although this information is not absolute, the systematic literature review proves the existence of herb-drug interactions in the literature and studies where no interaction was detected are equally important.
Topics: Cytochrome P-450 Enzyme System; Herb-Drug Interactions; India; Pharmaceutical Preparations; Plants, Medicinal
PubMed: 32160796
DOI: 10.1080/01480545.2020.1738454 -
Drug Metabolism Reviews Nov 2023Nebivolol is a beta-1 receptor blocker used to treat hypertension, heart failure, erectile dysfunction, vascular disease, and diabetes mellitus. This review investigated... (Review)
Review
Nebivolol is a beta-1 receptor blocker used to treat hypertension, heart failure, erectile dysfunction, vascular disease, and diabetes mellitus. This review investigated the data regarding pharmacokinetic (PK) parameters, drug-drug interactions, dextrorotatory (D), and levorotatory (L) stereoisomers of nebivolol. The articles related to the PK of nebivolol were retrieved by searching the five databases; Google Scholar, PubMed, Cochrane Library, ScienceDirect, and EBSCO. A total of 20 studies comprising plasma concentration-time profile data following the nebivolol's oral and intravenous (IV) administration were included. The area under the concentration-time curve from zero to infinity (AUC) was 15 times greater in poor metabolizers (PMs) than in extensive metabolizers (EMs). In hypertensive patients, L-nebivolol expressed a higher maximum plasma concentration (C) than D-nebivolol, i.e. 2.5 ng/ml vs 1.2 ng/ml. The AUC of nebivolol was 3-fold greater in chronic kidney disease (CKD). The clearance (CL) was increased in obese than in controls from 51.6 ± 11.6 L/h to 71.6 ± 17.4 L/h when 0.5 mg/ml IV solution was infused. Nebivolol showed higher C, AUC and half-life (t) when co-administered with bupropion, duloxetine, fluvoxamine, paroxetine, lansoprazole, and fluoxetine. This concise review of nebivolol would be advantageous in assessing all PK parameters, which may be crucial for clinicians to avoid drug-drug interactions, prevent adverse drug events and optimize the dosage regimen in diseased patients diagnosed with hypertension and cardiovascular disorders.
Topics: Male; Humans; Nebivolol; Hypertension; Fluvoxamine; Lansoprazole; Drug Interactions
PubMed: 37849071
DOI: 10.1080/03602532.2023.2271195 -
Journal of Pharmaceutical Policy and... Apr 2021Drug-related problems (DRPs) can occur at any stages of medication use processes, and a single drug could be associated with multiple DRPs. Once happened, it adversely... (Review)
Review
BACKGROUND
Drug-related problems (DRPs) can occur at any stages of medication use processes, and a single drug could be associated with multiple DRPs. Once happened, it adversely affects health outcomes. In Ethiopia, evaluation of the magnitude and factors associated with DRPs had not been attempted at the national level.
METHOD
The literature search was conducted in the following databases; PubMed, Embase, Medline, and Google Scholar. The quality of the included studies was checked using Joanna Brigg's Institute (JBI's) checklist, and data were analyzed using Stata software (version 14.0). The pooled estimate of DRPs was computed by a Random effect model (DerSimonian-Laird method). Cochran's Q test (I) statistic)), and Begg's correlation and Egger's regression test were assessed for heterogeneity and publication bias, respectively.
RESULT
Overall, 32 studies with a total sample size of 7,129 were included in the review. The estimated pooled prevalence of DRPs was 70% [0.70 (95% CI 0.64-0.76; I = 97.6% p = 0.000)]. Polypharmacy (taking ≥ 5 drugs) [RR = 1.3], medical comorbidity [RR = 1.3], poor medication adherence [RR = 1.7], uncontrolled blood pressure [RR = 1.4], substance use [RR = 1.2], type 2 diabetes [RR = 1.8], significant drug interaction [RR = 1.33], and a negative medication belief [RR = 3.72] significantly influenced the occurrence of DRPs.
CONCLUSION
The estimated national prevalence of DRPs in Ethiopia was high. Presence of medical comorbidity, using multiple drugs, significant drug interaction, poor medication adherence, uncontrolled blood pressure, type 2 diabetes, substance use and a negative belief about medication significantly influenced the occurrence of DRPs. Initiating and/or strengthening pharmaceutical care services at the health care facilities could lower the occurrence of DRPs. PROSPERO registration number CRD42020162329.
PubMed: 33902729
DOI: 10.1186/s40545-021-00312-z