Scaffold Based Search on the Desferithiocin Archetype

:Iron overload disorder and diseases where iron mismanagement plays a crucial role require orally available iron chelators with favourable pharmacokinetic and toxicity profile. Desferrithiocin (DFT), a tridentate and orally available iron chelator has a favourable pharmacokinetic profile but its use has been clinically restricted due to its nephrotoxic potential. The chemical architecture of the DFT has been naturally well optimized for better iron chelation and iron clearance from human biological system. Equally they are also responsible for its toxicity. Hence, subsequent research has been devoted to develop a non-nephrotoxic analogue of DFT without losing its iron clearance ability.:The review has been designed to classify the compounds reported till date and to discuss the structure activity relationship with reference to modifications attempted at different positions over pyridine and thiazoline ring of DFT. Compounds are clustered under two major classes: (i) Pyridine analogues and (ii) phenyl analogue and further each class has been further subdivided based on the presence or absence and the number of hydroxy functional groups present over pyridine or phenyl ring of the DFT analogues. Finally a summary and few insights into the development of newer analogues are provided.

Current Perspectives on Treatment of Gram-Positive Infections in India: What Is the Way Forward?

The emerging antimicrobial resistance leading to gram-positive infections (GPIs) is one of the major public health threats worldwide. GPIs caused by multidrug resistant bacteria can result in increased morbidity and mortality rates along with escalated treatment cost and hospitalisation stay. In India, GPIs, particularly methicillin-resistant Staphylococcus aureus (MRSA) prevalence among invasive S. aureus isolates, have been reported to increase exponentially from 29% in 2009 to 47% in 2014. Apart from MRSA, rising prevalence of vancomycin-resistant enterococci (VRE), which ranges from 1 to 9% in India, has raised concerns. Moreover, the overall mortality rate among patients with multidrug resistant GPIs in India is reported to be 10.8% and in ICU settings, the mortality rate is as high as 16%. Another challenge is the spectrum of adverse effects related to the safety and tolerability profile of the currently available drugs used against GPIs which further makes the management and treatment of these multidrug resistant organisms a complex task. Judicious prescription of antimicrobial agents, implementation of antibiotic stewardship programmes, and antibiotic policies in hospitals are essential to reduce the problem of drug-resistant infections in India. The most important step is development of newer antimicrobial agents with novel mechanisms of action and favourable pharmacokinetic profile. This review provides a synopsis about the current burden, treatment options, and the challenges faced by the clinicians in the management of GPIs such as MRSA, Quinolone-resistant Staphylococcus, VRE, and drug-resistant pneumococcus in India.

Adverse effects of topiramate in patients with epilepsy in a tertiary care hospital: observational study

Background: Epilepsy is a common chronic neurological disorder characterized by paroxysmal cerebral dysrhythmia. Conventional antiepileptic drugs such as Phenytoin, carbamazepine, phenobarbitone and sodium valproate, have been proven to have good therapeutic effects. There are currently more than 10 different adjuvants which are approved for use in epileptics. Topiramate, a second-generation antiepileptic drug, is being used for several types of partial-onset and generalized-onset seizures. Effective treatment of epilepsy depends on medication compliance. The incidence of adverse effects is an important issue when antiepileptic drugs are prescribed to treat epilepsy. This study was done in Department of Neurology to observe the adverse effects of Topiramate in patients with epilepsy in a Tertiary care hospital.Methods: For this study 100 patients receiving topiramate as an adjuvant drug along with regular anti epileptic drugs were enrolled in the study for prescheduled three months. Data of the patients were collected.Results: In this study we observed that paresthesia (31%) was the commonly noted adverse effect followed by cognitive impairment (24%), sleepiness (19%), nausea (13%), anorexia (9%) and weight loss (4%).Conclusions: Topiramate is a potent antiepileptic drug effective against most seizure types and has relatively favourable pharmacokinetic profile. It is appropriate for initial monotherapy as well as for adjuvant therapy in refractory patients. The major problem limiting its use is the frequent occurrence of cognitive adverse effects, especially expressive language dysfunction, which are reversible upon discontinuation of the medication.

Topiramate: Pharmacokinetics and Pharmacodynamics

ABSTRACT:Topiramate is a structurally novel anti-epileptic drug with at least 3 postulated mechanisms of action including: 1) potentiation of GABA responses, 2) impairment of AMPA/kainate glutamate receptors and 3) suppression of high frequency action potential firing. It has a favourable pharmacokinetic profile with rapid absorption, good bio-availability, linear pharmacokinetics, relatively long half-life and limited pharmacokinetic drug interactions. However, topiramate can reduce the estrogen component of oral contraceptive medications. Women may require birth control preparations containing 50 (Xg of estrogen. Topiramate clearance is reduced in severe renal failure and increased by enzyme-inducing antiepileptic drugs. The dose of topiramate may have to be reduced in renal failure or when withdrawing enzyme inducers.