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Expert Opinion on Pharmacotherapy Aug 2018Hyponatremia is the most common electrolyte disorder with a prevalence of up to 30% in hospitalized patients. Furthermore, it is associated with increased morbidity and... (Review)
Review
INTRODUCTION
Hyponatremia is the most common electrolyte disorder with a prevalence of up to 30% in hospitalized patients. Furthermore, it is associated with increased morbidity and mortality.
AREAS COVERED
This review discusses the efficacy and side effects of the currently available treatment options for hyponatremia and the differences in the pharmacological approach between the European and USA guidelines. Additionally, the authors provide their expert perspectives on current treatment strategies and what they expect from this field in the future.
EXPERT OPINION
Several pharmacological options are available for the treatment of hyponatremia, but data from trials examining and comparing these treatments are missing. Regarding chronic hyponatremia, the role of vaptans should be further analyzed, focusing on comparisons with other active treatments on patient-relevant outcomes and not only on serum sodium concentration. Clinicians should be cautious to an overly rapid increase in serum sodium levels with all available treatment strategies. Finally, it is important to ascertain whether correction of serum sodium levels improves mortality in hyponatremic patients.
Topics: Chronic Disease; Humans; Hyponatremia
PubMed: 30071178
DOI: 10.1080/14656566.2018.1504920 -
Cureus May 2018We present the case of a 55-year-old Caucasian male with a history of schizophrenia presenting with severe hyponatremia attributed to long-acting injectable risperidone...
We present the case of a 55-year-old Caucasian male with a history of schizophrenia presenting with severe hyponatremia attributed to long-acting injectable risperidone treatment. Antipsychotic-induced hyponatremia is an uncommon but serious side effect that should be considered when assessing individuals on chronic psychiatric regimens. In this report, we will discuss our treatment plan for the patient when water deprivation and hypertonic saline failed to correct his serum sodium levels. The goal of this case report is to raise awareness of severe hyponatremia as a side effect of long-acting risperidone, and to encourage further studies to create guidelines for its management when current protocols fail to correct sodium levels.
PubMed: 30042908
DOI: 10.7759/cureus.2657 -
European Endodontic Journal 2018Tetracyclines are a unique class of antibiotics which also have additional effects including anti-inflammatory, anti-resorptive and substantive within the root canal.... (Review)
Review
Tetracyclines are a unique class of antibiotics which also have additional effects including anti-inflammatory, anti-resorptive and substantive within the root canal. There has been a long-held view that tetracycline medicaments discolour teeth and should be avoided. The evidence base around this topic was explored, including a review of the methodology used in laboratory studies. A search of PubMed, Medline and Scopus databases was conducted to identify studies of demeclocycline and doxycycline medicaments used in root canal therapy. An analysis of the methodology used in these studies was performed to determine if these replicate current clinical practice. The related literature on mechanisms of tetracycline stability and the effects of light, oxidation, moisture and chemical interactions was examined. Studies investigating the effects of Ledermix paste on segments of bovine dentine and avulsed or reimplanted teeth as well as combinations with other antibiotics were excluded from this review. Even though demeclocycline medicament pastes were introduced in 1962, the first laboratory studies of discolouration were not done until 2000. All later studies followed a similar approach, which included exposure to sodium hypochlorite for up to 30 minutes and storage in moist conditions with 100% humidity. Staining during dark storage and enhanced staining on exposure to light were reported, indicating multiple pathways of degradation of demeclocycline and its reaction products. Light, moisture and oxidation are the key factors which drive discolouration from demeclocycline. Clinical issues from tooth staining can be prevented by removal of medicament pastes from the access cavity, and placement of a sound interim restoration. Use of a doxycycline paste obviates concerns of staining. Laboratory assessments of the potential for staining should replicate in vivo conditions.
PubMed: 32161858
DOI: 10.14744/eej.2018.47966 -
The Cochrane Database of Systematic... Jun 2018Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs frequently, can be caused by various conditions, and is associated with shorter survival and longer... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs frequently, can be caused by various conditions, and is associated with shorter survival and longer hospital stays. Many treatments, such as fluid restriction or vasopressin receptor antagonists can be used to improve the hyponatraemia, but whether that translates into improved patient-important outcomes is less certain.
OBJECTIVES
This review aimed to 1) look at the benefits and harms of interventions for chronic non-hypovolaemic hypotonic hyponatraemia when compared with placebo, no treatment or head-to-head; and 2) determine if benefits and harms vary in absolute or relative terms dependent on the specific compound within a drug class, on the dosage used, or the underlying disorder causing the hyponatraemia.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 1 December 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We also screened the reference lists of potentially relevant studies, contacted authors, and screened the websites of regulatory agencies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of any intervention with placebo, no treatment, standard care, or any other intervention in patients with chronic non-hypovolaemic hypotonic hyponatraemia. We also included subgroups with hyponatraemia from studies with broader inclusion criteria (e.g. people with chronic heart failure or people with cirrhosis with or without hyponatraemia), provided we could obtain outcomes for participants with hyponatraemia from the report or the study authors.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed risk of bias. We expressed treatment effects as mean difference (MD) for continuous outcomes (health-related quality of life, length of hospital stay, change from baseline in serum sodium concentration, cognitive function), and risk ratio (RR) for dichotomous outcomes (death, response and rapid increase in serum sodium concentration, hypernatraemia, polyuria, hypotension, acute kidney injury, liver function abnormalities) together with 95% confidence intervals (CI).
MAIN RESULTS
We identified 35 studies, enrolling 3429 participants. Twenty-eight studies (3189 participants) compared a vasopressin receptor antagonist versus placebo, usual care, no treatment, or fluid restriction. In adults with chronic, non-hypovolaemic hypotonic hyponatraemia, vasopressin receptor antagonists have uncertain effects on death at six months (15 studies, 2330 participants: RR 1.11, 95% CI 0.92 to 1.33) due to risk of selective reporting and serious imprecision; and on health-related quality of life because results are at serious risk of performance, selective reporting and attrition bias, and suffer from indirectness related to the validity of the Short Form Health Survey (SF-12) in the setting of hyponatraemia. Vasopressin receptor antagonists may reduce hospital stay (low certainty evidence due to risk of performance bias and imprecision) (3 studies, 610 participants: MD -1.63 days, 95% CI -2.96 to -0.30), and may make little or no difference to cognitive function (low certainty evidence due to indirectness and imprecision). Vasopressin receptor antagonists probably increase the intermediate outcome of serum sodium concentration (21 studies, 2641 participants: MD 4.17 mmol/L, 95% CI 3.18 to 5.16), corresponding to two and a half as many people having a 5 to 6 mmol/L increase in sodium concentration compared with placebo at 4 to 180 days (moderate certainty evidence due to risk of attrition bias) (18 studies, 2014 participants: RR 2.49, 95% CI 1.95 to 3.18). But they probably also increase the risk of rapid serum sodium correction - most commonly defined as > 12 mmol/L/d (moderate certainty evidence due to indirectness) (14 studies, 2058 participants: RR 1.67, 95% CI 1.16 to 2.40) and commonly cause side-effects such as thirst (13 studies, 1666 participants: OR 2.77, 95% CI 1.80 to 4.27) and polyuria (6 studies, 1272 participants): RR 4.69, 95% CI 1.59 to 13.85) (high certainty evidence). The potential for liver toxicity remains uncertain due to large imprecision. Effects were generally consistent across the different agents, suggesting class effect.Data for other interventions such as fluid restriction, urea, mannitol, loop diuretics, corticosteroids, demeclocycline, lithium and phenytoin were largely absent.
AUTHORS' CONCLUSIONS
In people with chronic hyponatraemia, vasopressin receptor antagonists modestly raise serum sodium concentration at the cost of a 3% increased risk of it being rapid. To date there is very low certainty evidence for patient-important outcomes; the effects on mortality and health-related quality of life are unclear and do not rule out appreciable benefit or harm; there does not appear to be an important effect on cognitive function, but hospital stay may be slightly shorter, although available data are limited. Treatment decisions must weigh the value of an increase in serum sodium concentration against its short-term risks and unknown effects on patient-important outcomes. Evidence for other treatments is largely absent.Further studies assessing standard treatments such as fluid restriction or urea against placebo and one-another would inform practice and are warranted. Given the limited available evidence for patient-important outcomes, any study should include these outcomes in a standardised manner.
Topics: Antidiuretic Hormone Receptor Antagonists; Chronic Disease; Humans; Hyponatremia; Length of Stay; Quality of Life; Randomized Controlled Trials as Topic; Sodium
PubMed: 29953167
DOI: 10.1002/14651858.CD010965.pub2 -
PloS One 2018Antimicrobial photodynamic inactivation (aPDI) employs photosensitizing dyes activated by visible light to produce reactive oxygen species. aPDI is independent of the...
Antimicrobial photodynamic inactivation (aPDI) employs photosensitizing dyes activated by visible light to produce reactive oxygen species. aPDI is independent of the antibiotic resistance status of the target cells, and is thought unlikely to produce resistance itself. Among many PS that have been investigated, tetracyclines occupy a unique niche. They are potentially dual-action compounds that can both kill bacteria under illumination, and prevent bacterial regrowth by inhibiting ribosomes. Tetracycline antibiotics are regarded as bacteriostatic rather than bactericidal. Doxycycline (DOTC) is excited best by UVA light (365 nm) while demeclocycline (DMCT) can be efficiently activated by blue light (415 nm) as well as UVA. Both compounds were able to eradicate Gram-positive (methicillin-resistant Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria (>6 log(10) steps of killing) at concentrations (10-50μM) and fluences (10-20J/cm2). In contrast to methylene blue, MB plus red light, tetracyclines photoinactivated bacteria in rich growth medium. When ~3 logs of bacteria were killed with DMCT/DOTC+light and the surviving cells were added to growth medium, further bacterial killing was observed, while the same experiment with MB allowed complete regrowth. MIC studies were carried out either in the dark or exposed to 0.5mW/cm2 blue light. Up to three extra steps (8-fold) increased antibiotic activity was found with light compared to dark, with MRSA and tetracycline-resistant strains of E. coli. Tetracyclines can accumulate in bacterial ribosomes, where they could be photoactivated with blue/UVA light producing microbial killing via ROS generation.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Escherichia coli; Light; Methicillin-Resistant Staphylococcus aureus; Methylene Blue; Microbial Sensitivity Tests; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Ribosomes; Tetracyclines
PubMed: 29742128
DOI: 10.1371/journal.pone.0196485 -
Acta Clinica Croatica Jun 2017When taking different drugs, their possible side effects on the skin should be considered, including skin reactions connected to photosensitivity. This photosensitivity... (Review)
Review
When taking different drugs, their possible side effects on the skin should be considered, including skin reactions connected to photosensitivity. This photosensitivity caused by drugs can appear as phototoxic reactions (which occur more often) or photoallergic reactions (which occur less often and include allergic mechanisms). The following drugs stand out as medications with a high photosensitivity potential: nonsteroidal anti-inflammatory drugs (NSAIDs), cardiovascular drugs (such as amiodarone), phenothiazines (especially chlorpromazine), retinoids, antibiotics (sulfonamides, tetracyclines, especially demeclocycline and quinolones), etc. In recent years, photosensitive reactions to newer drugs have appeared, e.g., targeted anticancer therapies such as BRAF kinase inhibitors (vemurafenib, dabrafenib), EGFR inhibitors, VEGFR inhibitors, MEK inhibitors, Bcr-Abl tyrosine kinase inhibitors, etc. In patients taking drugs over a longer period of time (e.g., NSAIDs, cardiovascular drugs, etc.), a particular problem arises when an unrecognized drug-induced photosensitivity on the skin manifests in summer months. When taking patient histories, the physician/dermatovenereologist should bear in mind that any drug the patient is currently taking may be the cause of skin reactions. Therefore, patients who use potentially photosensitive drugs and treatments on a long term basis should be warned of the possibility of these side effects on their skin and advised to avoid direct exposure to sunlight and to use adequate photoprotection. If patients carefully protect themselves from the sun, it is often not necessary to stop treatments that include photosensitive drugs. If such reactions appear, anti-inflammatory and antiallergic therapies should be introduced.
Topics: Dermatitis, Photoallergic; Dermatitis, Phototoxic; Diagnosis, Differential; Drug-Related Side Effects and Adverse Reactions; Humans; Photosensitivity Disorders; Sunlight
PubMed: 29485795
DOI: 10.20471/acc.2017.56.02.11 -
Journal of the Science of Food and... Sep 2018Antibiotic drugs are excreted to a large proportion by livestock. Thus, antibiotics are distributed on fields with slurry and can be taken up by plants. In the present...
BACKGROUND
Antibiotic drugs are excreted to a large proportion by livestock. Thus, antibiotics are distributed on fields with slurry and can be taken up by plants. In the present study, hydroponic experiments were performed to reveal whether the widely administered chlortetracycline is taken up into wheat grain in a concentration-dependent manner. A further goal was to determine (chlor)tetracyclines in wheat and rye grain from agricultural practice.
RESULTS
Increasing chlortetracycline deposition in wheat grain was observed with a rising chlortetracycline spiking level in the hydroponic solution. In 371 selected wheat and rye samples from three growing years of agricultural practice, the overall detection frequency was 21% for tetracyclines. In the most highly contaminated sample, tetracyclines occurred at 18.2 μg kg . Tetracycline residues were also found in rye grain. Conversion and degradation products of (chlor)tetracycline such as tetracycline, doxycycline and demeclocycline were detected in grains from hydroponic experiments and from agricultural practice.
CONCLUSION
Concentrations of tetracyclines found in wheat and rye grains were of no concern with respect to toxicity regarding human consumption. However, antibiotic concentrations below the minimum inhibitory concentration can select for antibiotic resistance in bacteria. Thus, low levels of different tetracycline residues contained in food should be taken into account regarding risk assessment. © 2018 Society of Chemical Industry.
Topics: Anti-Bacterial Agents; Chlortetracycline; Consumer Product Safety; Drug Residues; Food Contamination; Humans; Secale; Seeds; Tetracyclines; Triticum
PubMed: 29484666
DOI: 10.1002/jsfa.8982 -
Australian Dental Journal Jun 2018Many studies have investigated the effectiveness of root canal irrigants and medicaments against Enterococcus faecalis. The aim of this study was to compare the efficacy... (Comparative Study)
Comparative Study
BACKGROUND
Many studies have investigated the effectiveness of root canal irrigants and medicaments against Enterococcus faecalis. The aim of this study was to compare the efficacy of commonly used medicaments against E. faecalis cultured as a biofilm on dentine substrate.
METHODS
An E. faecalis biofilm was established on human dentine slices using a continuous flow cell. Each test medicament (Ledermix, Ca(OH) , Odontopaste, 0.2% chlorhexidine and 50:50 combinations of Ledermix/Ca(OH) and Odontopaste/Ca(OH) ) was introduced into the flow cell and biofilms were harvested and quantitated by determining cellular protein. Cellular viability was determined using serial plating and the number of colony-forming units was normalized against cellular protein to allow treatment protocols to be compared. Qualitative scanning electron microscopy analyses of the biofilm were performed after a 48-h exposure to each test agent.
RESULTS
Sodium hypochlorite achieved total bacterial elimination. Ledermix and Odontopaste had no significant effect on the E. faecalis biofilm. Ca(OH) and 50:50 combinations of Ca(OH) /Ledermix or Ca(OH) /Odontopaste reduced the viability by more than 99% while 0.2% chlorhexidine reduced bacterial numbers by 97%.
CONCLUSIONS
Sodium hypochlorite remains the gold standard for bacterial elimination in root canal therapy. However, Ca(OH) in isolation and combined with Ledermix, and Odontopaste was highly effective in reducing bacterial viability.
Topics: Biofilms; Calcium Hydroxide; Chlorhexidine; Demeclocycline; Dental Pulp Cavity; Dentin; Drug Combinations; Enterococcus faecalis; Humans; Microbial Viability; Microscopy, Electron, Scanning; Root Canal Irrigants; Sodium Hypochlorite; Triamcinolone Acetonide
PubMed: 29181844
DOI: 10.1111/adj.12580 -
Acta Biochimica Et Biophysica Sinica Dec 20176-Demethylchlortetracycline (6-DCT), a tetracycline antibiotic produced by Streptomyces aureofaciens, is a crucial precursor employed for the semi-synthesis of...
6-Demethylchlortetracycline (6-DCT), a tetracycline antibiotic produced by Streptomyces aureofaciens, is a crucial precursor employed for the semi-synthesis of tigecycline, minocycline, and amadacyclin (PTK 0796). In this study, the 6-DCT biosynthetic gene cluster (BGC) was cloned from genomic DNA of a high 6-DCT-producing strain, S. aureofaciens DM-1, using the transformation-associated recombination method. An extra copy of the 6-DCT BGC was introduced and integrated into the chromosome of S. aureofaciens DM-1. Duplication of the 6-DCT BGC resulted in a maximum increase of the 6-DCT titer by 34%.
Topics: Anti-Bacterial Agents; Demeclocycline; Multigene Family; Recombination, Genetic; Streptomyces aureofaciens
PubMed: 29087452
DOI: 10.1093/abbs/gmx110 -
Journal of Clinical Research in... Sep 2017Hyponatremia is the most common electrolyte disorder among hospitalized patients and it is sometimes considered as a poor outcome predictor. Its correction is thus... (Review)
Review
Hyponatremia is the most common electrolyte disorder among hospitalized patients and it is sometimes considered as a poor outcome predictor. Its correction is thus indicated, even in asymptomatic patients. The conventional treatment consists of fluid restriction in presence of euvolemia or hypervolemia; loop diuretics are used in some hypervolemic conditions such as cardiac heart failure, liver cirrhosis and nephrotic syndrome, while intravenous isotonic or hypertonic solutions are administered in hypovolemic conditions. The utilization of demeclocycline and urea is not indicated in pediatric ages due to lack of data on their toxicity and poor tolerance. Recently, a new therapeutic option has been developed, a class of non-peptide arginine vasopressin receptor antagonists called vaptans. Tolvaptan is the only such agent approved in Europe for the treatment of hyponatremia caused by syndrome of inappropriate antidiuretic hormone secretion (SIADH) in adults. In USA, tolvaptan and conivaptan have been approved for treatment of euvolemic and hypervolemic hyponatremia. Few data are so far available in paediatric patients, since only one trial has been registered in Europe which includes children and adolescents, but this trial is still ongoing. Here, we report three children with chronic hyponatremia due to SIADH in which tolvaptan has been used successfully.
Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Child; Child, Preschool; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Tolvaptan
PubMed: 28515029
DOI: 10.4274/jcrpe.4531