Perioperative and periprocedural management of GLP-1 receptor-based agonists and SGLT2 inhibitors: narrative review and the STOP-GAP and STOP DKA-2 algorithms.

The GLP-1 receptor-based agonists (GLP-1RAs) and SGLT2 inhibitors (SGLT2i) are major 21 century breakthroughs in diabetes and obesity medicine but there are important safety considerations regarding the perioperative and periprocedural management of individuals who are treated with these agents. GLP-1RAs have been linked to an increased risk of retained gastric contents and pulmonary aspiration while SGLT2i can be associated with diabetic ketoacidosis. This manuscript provides a narrative review of the available evidence for perioperative and periprocedural risks in people prescribed GLP-1RAs and SGLT2i.

Discovery of 3-(3-(4-(1-Aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (ARQ 092): An Orally Bioavailable, Selective, and Potent Allosteric AKT Inhibitor.

The work in this paper describes the optimization of the 3-(3-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine chemical series as potent, selective allosteric inhibitors of AKT kinases, leading to the discovery of ARQ 092 (21a). The cocrystal structure of compound 21a bound to full-length AKT1 confirmed the allosteric mode of inhibition of this chemical class and the role of the cyclobutylamine moiety. Compound 21a demonstrated high enzymatic potency against AKT1, AKT2, and AKT3, as well as potent cellular inhibition of AKT activation and the phosphorylation of the downstream target PRAS40.

Discovery and optimization of a series of 3-(3-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amines: orally bioavailable, selective, and potent ATP-independent Akt inhibitors.

This paper describes the implementation of a biochemical and biophysical screening strategy to identify and optimize small molecule Akt1 inhibitors that act through a mechanism distinct from that observed for kinase domain ATP-competitive inhibitors. With the aid of an unphosphorylated Akt1 cocrystal structure of 12j solved at 2.25 Å, it was possible to confirm that as a consequence of binding these novel inhibitors, the ATP binding cleft contained a number of hydrophobic residues that occlude ATP binding as expected.

The Subjective Global Assessment: a review of its use in clinical practice.

Many methods of evaluating malnutrition have been proposed that combine multiple components such as dietary and medical history, amount of weight loss, biochemical variables, and anthropometry. The Subjective Global Assessment (SGA), first described by Baker et al in 1982, SGA was introduced to assess the patient for malnutrition at the bedside, without the need for precise body composition analysis. Since it was developed, the SGA has been used in various different patient populations, including surgical and oncology patients.

Microscopic colitis-defining incidence rates and risk factors: a population-based study.

Background & Aims: The burden and determinants of microscopic colitis (MC) in North America are inadequately defined. We determined the incidence rate of and risk factors for MC in a well-defined North American population.

Methods: A population-based cohort study was conducted between April 1, 2002, and March 31, 2004.

Controlled porosity osmotic pump-based controlled release systems of pseudoephedrine. I. Cellulose acetate as a semipermeable membrane.

A controlled porosity osmotic pump-based drug delivery system has been described in this study. Unlike the elementary osmotic pump (EOP) which consists of an osmotic core with the drug surrounded by a semipermeable membrane drilled with a delivery orifice, controlled porosity of the membrane is accomplished by the use of different channeling agents in the coating. The usual dose of pseudoephedrine is 60 mg to be taken three or four times daily.

Once daily sustained release tablets of venlafaxine, a novel antidepressant.

Venlafaxine is a unique antidepressant that differs structurally from other currently available antidepressants. Sustained release tablets of venlafaxine to be taken once daily were formulated with venlafaxine hydrochloride equivalent to 75 mg of venlafaxine base. Matrix system based on swellable as well as non-swellable polymers was selected for sustaining the drug release.

Stability indicating LC method for the estimation of venlafaxine in pharmaceutical formulations.

A rapid, selective and stability indicating high performance liquid chromatographic method was developed and validated for the estimation of venlafaxine in pharmaceutical dosage forms. The analysis was done on a Spherisorb C8 (4.6 x 250 mm, 5 microm) column.