Steroidal conjugates and their pharmacological applications

Nature continues to be the main source of inspiration for synthetic chemists in their quest to make novel conjugates, which can have different physical, biological and medicinal properties. Nature makes these conjugates from mixed biosynthesis and some of these chimeras are found to exhibit unusual biological properties. During the past two decades design of such entities has been receiving increasing attention. Among the hybrid natural products, hybrids of steroid frameworks have attracted great attention due to the significant biological properties and numerous therapeutic effects of steroids. The developments made over the past few years in the isolation, design and synthesis of steroidal conjugates and their pharmacological applications are discussed in this review.     

Cataract surgery by appointment – a pilot study

Background  

"Cataract Surgery by Appointment" is a new method of delivery of cataract surgery that reduces the time a patient spends in hospital by their direct arrival at the operating theatre, having self-prepared for surgery, thus avoiding admission to the ward or time spent in the Day Case Unit. The patient can stay as little as 20 minutes from their arrival to going home. We describe the process in detail, and seek to evaluate the visual outcome, safety and patient satisfaction of same.     

Mathematical Assessment of Properties of Precursor-Dependent Indirect Pharmacodynamic Response Models

Precursor-dependent indirect response (PDIDR) models may describe the tolerance and rebound phenomenon observed for many pharmacodynamic responses where these characteristics are manifested due to the depletion or accumulation of a physiological precursor or cofactor pool responsible for generating drug effects. The purpose of this report is to extend the concepts and applications of these models and to approximate responses and limiting conditions for very large doses of drugs. Asymptotic analysis was performed for qualitative determination of various parameters, such as maximum response (R_max) and rebound (R_Bmax), time to maximum response and rebound (T_Rmax and TR_Bmax), and area under the effect and rebound curve (ABEC and ABRC) for large doses. Computer simulations were performed to assess the role of dose for both cases where drugs act either by depleting (Model V) or by blocking (Model VI) the endogenous precursor. Simulations showed that R_max, R_Bmax, T_RBmax, ABEC and ABRC increase with dose, eventually reaching a plateau when Dose/V is very large compared to the efficacy parameters (SC₅₀ or IC₅₀) of the drug. However, T_Rmax either increased or decreased with dose depending on various system and drug parameters. The limits for these parameters at large doses qualitatively determined by asymptotic analysis closely approximated the plateaus observed from the simulated curves. At large doses, the drug response could be approximated by a Bateman-like function for both Models V and VI. Qualitative analyses along with simulation studies provide a fundamental basis for understanding the temporal aspects of the PDIDR models especially at large doses to describe the tolerance and rebound phenomenon. Supported by Grant GM 57980 from National Institute of General Medical Sciences, National Institutes of Health.     

REPORT TO THE SOCIETY FOR THE STUDY OF ADDICTION

Professor Golla has recently retired from the post of Director of the Burden Neurological Institute so the time seems appropriate to review the work on alcohol carried out with the support of the Society's Monthly Bulletin Research Fund.