SummaryThis narrative review summarizes current available information about cardiac arrhythmias (QT prolongation, Torsade de pointes Tachycardia [TdP], sudden cardiac death) associated with psychiatric medication. Among the most commonly used antipsychotics, amisulpride and ziprasidone are most frequently associated with TdP. Treatment with some antidepressants (SSRIs, tricyclic antidepressants) is associated with a 5- to 6-fold increase in the incidence of out-of-hospital cardiac arrest. Lithium is associated with bradycardia, T-wave changes and AV-block; anxiolytics of the benzodiazepine group do usually not have cardiac side effects. The combination of multiple drugs (including medications from general medicine) that prolong the QT interval has a particularly high cardiac risk.
Paediatric Acquired ImmunoDeficiency Syndrome (AIDS) is a life-threatening and infectious
disease in which the Human Immunodeficiency Virus (HIV) is mainly transmitted through Mother-To-
Child Transmission (MTCT) during pregnancy, labour and delivery, or breastfeeding. This review provides
an overview of the distinct therapeutic alternatives to abolish the systemic viral replication in paediatric
HIV-1 infection. Numerous classes of antiretroviral agents have emerged as therapeutic tools for
downregulation of different steps in the HIV replication process. These classes encompass Non-
Nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs), Nucleoside/Nucleotide Analogue Reverse
Transcriptase Inhibitors (NRTIs/NtRTIs), INtegrase Inhibitors (INIs), Protease Inhibitors (PIs),
and Entry Inhibitors (EIs). Co-administration of certain antiretroviral drugs with Pharmacokinetic Enhancers
(PEs) may boost the effectiveness of the primary therapeutic agent. The combination of multiple
antiretroviral drug regimens (Highly Active AntiRetroviral Therapy - HAART) is currently the standard
therapeutic approach for HIV infection. So far, the use of HAART offers the best opportunity for prolonged
and maximal viral suppression, and preservation of the immune system upon HIV infection. Still,
the frequent administration of high doses of multiple drugs, their inefficient ability to reach the viral reservoirs
in adequate doses, the development of drug resistance, and the lack of patient compliance compromise
the complete HIV elimination. The development of nanotechnology-based drug delivery systems
may enable targeted delivery of antiretroviral agents to inaccessible viral reservoir sites at therapeutic
concentrations. In addition, the application of Computer-Aided Drug Design (CADD) approaches
has provided valuable tools for the development of anti-HIV drug candidates with favourable pharmacodynamics
and pharmacokinetic properties.
Aims and Objective:
The infectious disease treatment remains a challenging concern
owing to the increasing number of pathogenic microorganisms associated with resistance to
multiple drugs. A promising approach for combating microbial infection is to combine two or more
known bioactive heterocyclic pharmacophores in one molecular platform. Herein, the synthesis
and biological evaluation of novel thiazole-thiazolidinone hybrids as potential antimicrobial agents
Materials and Methods:
The preparation of the substituted 5-benzylidene-2-thiazolyimino-4-
thiazolidinones was achieved in three steps from 2-amino-5-methylthiazoline. All the compounds
have been screened in PASS antibacterial activity prediction and in a panel of bacteria and fungi
strains. Minimum inhibitory concentration and minimum bacterial concentration were both
determined by microdilution assays. Molecular modeling was conducted using Accelrys Discovery
Studio 4.0 client. ToxPredict (OPEN TOX) and ProTox were used to estimate the toxicity of the
PASS prediction revealed the potentiality antibacterial property of the designed thiazolethiazolidinone
hybrids. All tested compounds were found to kill and to inhibit the growth of a vast
variety of bacteria and fungi, and were more potent than the commercial drugs, streptomycin,
ampicillin, bifomazole and ketoconazole. Further, in silico study was carried out for prospective
molecular target identification and revealed favorable interaction with the target enzymes E. coli
MurB and CYP51B of Aspergillus fumigatus. Toxicity prediction revealed that none of the active
compounds was found toxic.
Substituted 5-benzylidene-2-thiazolyimino-4-thiazolidinones, endowing remarkable
antibacterial and antifungal properties, were identified as a novel class of antimicrobial agents and
may find a potential therapeutic use to eradicate infectious diseases.
Background:PIM-1 is a kinase which has been related to the oncogenic processes like cell survival, proliferation, and multidrug resistance (MDR). This kinase is known for its ability to phosphorylate the main extrusion pump (ABCB1) related to the MDR phenotype.Objective:In the present work, we tested a new mechanistic insight on the AZD1208 (PIM-1 specific inhibitor) under interaction with chemotherapy agents such as Daunorubicin (DNR) and Vincristine (VCR).Materials and Methods:In order to verify a potential cytotoxic effect based on pharmacological synergism, two MDR cell lines were used: Lucena (resistant to VCR) and FEPS (resistant to DNR), both derived from the K562 non-MDR cell line, by MTT analyses. The activity of Pgp was ascertained by measuring accumulation and the directional flux of Rh123. Furthermore, we performed a molecular docking simulation to delve into the molecular mechanism of PIM-1 alone, and combined with chemotherapeutic agents (VCR and DNR).Results:Our in vitro results have shown that AZD1208 alone decreases cell viability of MDR cells. However, co-exposure of AZD1208 and DNR or VCR reverses this effect. When we analyzed the ABCB1 activity AZD1208 alone was not able to affect the pump extrusion. Differently, co-exposure of AZD1208 and DNR or VCR impaired ABCB1 activity, which could be explained by compensatory expression of abcb1 or other extrusion pumps not analyzed here. Docking analysis showed that AZD1208 is capable of performing hydrophobic interactions with PIM-1 ATP- binding-site residues with stronger interaction-based negative free energy (FEB, kcal/mol) than the ATP itself, mimicking an ATP-competitive inhibitory pattern of interaction. On the same way, VCR and DNR may theoretically interact at the same biophysical environment of AZD1208 and also compete with ATP by the PIM-1 active site. These evidences suggest that AZD1208 may induce pharmacodynamic interaction with VCR and DNR, weakening its cytotoxic potential in the ATP-binding site from PIM-1 observed in the in vitro experiments.Conclusion:Finally, the current results could have a pre-clinical relevance potential in the rational polypharmacology strategies to prevent multiple-drugs resistance in human leukemia cancer therapy.
Linezolid (LNZ) induced Cutaneous Adverse Drug Reactions (CADRs) have
rare atypical presentation. Till date, there are very few published case reports on LNZ induced CADRs
among the multidrug-resistant patients suffering from Infective Endocarditis (MDR IE). Here,
we present a rare case report of LNZ induced CARs in a MDR IE patient.
A 24-year-old female patient was admitted to the hospital with chief complaints of
fever (101°C) associated with rigors, chills, and shortness of breath (grade IV) for the past 4 days.
She was diagnosed with MDR IE, having a prior history of rheumatic heart disease. She was prescribed
LNZ 600mg IV BD for MDR IE, against Staphylococcus coagulase-negative. The patient
experienced flares of cutaneous reactions with multiple hyper-pigmented maculopapular lesions all
over the body after one week of LNZ therapy. Upon causality assessment, she was found to be suffering
from LNZ induced CADRs. LNZ dose was tapered gradually and discontinued. The patient
was prescribed corticosteroids along with other supportive care. Her reactions completely subsided
and infection got controlled following 1 month of therapy.
Healthcare professionals should be vigilant for rare CADRs, while monitoring the patients
on LNZ therapy especially in MDR patients as they are exposed to multiple drugs. Moreover,
strengthened spontaneous reporting is required for better quantification.
As one of the forms of media and art most consumed in the world, Oscar-nominated movies should have their drug use representation monitored because of possibly influencing but also reflecting society’s behavior.
To investigate drug use representation in scenes from movies nominated for the Academy Awards (Oscar) from 2008-2011, through media content analysis.
437 scenes from Oscar-nominated movies (best film, best actor and best actress categories) showing drug consumption and/or its effects were assessed. Each drug represented and identified in a given scene (i.e., drug use incident) was counted as a unit for the present study (n = 515). Survey settings were used to control for over- or under-estimation of the prevalence of a variable in a given year or movie.
All the Oscar-nominated movies portrayed at least one scene of drug use. There was a massive predominance of alcohol and tobacco in movies, with a high use among men who also use drugs, habitually or occasionally, but related to stress/tension, predominantly at home. However, there was a significant progressive increase in the use of drugs other than alcohol and tobacco, multiple drugs, and by women.
These findings echo epidemiological studies on substance use in western countries, an overall trend towards greater home drug use representation and gender convergence since 1970, which increased since 2000. Monitoring drug use representation in Oscar-nominated movies may represent an important public health tool.