5 research outputs found
An observational study of adverse drug reactions reported in a rural tertiary care hospital
Background: Adverse drug reactions (ADRs) are noxious and unintended effects of a drug that occurs at doses normally used in humans. ADRs may also result in diminished quality of life, increased physician visits, hospitalizations, and even death. The objectives of this study are to analyze and assess the causality and severity of reported ADRs.Methods: A cross sectional study of ADRs reported to Pharmacovigilance cell of MNR Medical College and Hospital Sangareddy in a year. The details of the various ADRs were statistically analyzed to find out pattern of ADRs. The WHO-UMC causality category and Hartwig-Seigel Scale were used to assess causality and severity of ADRs respectively.Results: The study shows, out of 60 suspected ADRs, the majority of ADRs were adults (68.3%) and out of whom 56% were females. According to the WHO-UMC Causality categories, 43.3% of the ADRs were categorized under Probable/likely, followed by possible (35%). The Hartwig-Siegel severity assessment scale shows that the majority (90%) of suspected ADRs were of mild category.Conclusions: The pattern of ADRs reported in our study is comparable to other studies. The commonest organ system affected was gastrointestinal tract, nervous and cutaneous system. Antimicrobial agents were causing maximum ADRs and medicine and allied departments have more number of ADRs. This study provides a valuable database for ADRs due to all commonly used drugs at hospitals and also helps in creating awareness regarding safe & judicious use of drugs to prevent ADRs
Modeling the Closed and Open State Conformations of the GABAA Ion Channel - Plausible Structural Insights for Channel Gating
Recent disclosure of high resolution crystal
structures of Gloeobacter violaceus (GLIC) in open state and
Erwinia chrysanthemii (ELIC) in closed state provides newer
avenues to advance our knowledge and understanding of the
physiologically and pharmacologically important ionotropic
GABAA ion channel. The present modeling study envisions
understanding the complex molecular transitions involved in
ionic conductance, which were not evident in earlier disclosed
homology models. In particular, emphasis was put on
understanding the structural basis of gating, gating transition
from the closed to the open state on an atomic scale. Homology modeling of two different physiological states of GABAA was
carried out using their respective templates. The ability of induced fit docking in breaking the critical inter residue salt bridge
(Glu155β2 and Arg207β2) upon endogenous GABA docking reflects the perceived side chain rearrangements that occur at the
orthosteric site and consolidate the quality of the model. Biophysical calculations like electrostatic mapping, pore radius
calculation, ion solvation profile, and normal-mode analysis (NMA) were undertaken to address pertinent questions like the
following: How the change in state of the ion channel alters the electrostatic environment across the lumen; How accessible is
the Cl− ion in the open state and closed state; What structural changes regulate channel gating. A “Twist to Turn” global motion
evinced at the quaternary level accompanied by tilting and rotation of the M2 helices along the membrane normal rationalizes the
structural transition involved in gating. This perceived global motion hints toward a conserved gating mechanism among pLGIC.
To paraphrase, this modeling study proves to be a reliable framework for understanding the structure function relationship of the
hitherto unresolved GABAA ion channel. The modeled structures presented herein not only reveal the structurally distinct
conformational states of the GABAA ion channel but also explain the biophysical difference between the respective state