Riding a VeSPha in the classroom: A Versatile Simulation tool for effective didactic illustration of Pharmacodynamic concepts

Abstract

A solid mastery of Pharmacodynamics concepts is a cornerstone of effective pharmacology education. Understanding the meaning and appropriate use of pharmacodynamics terms such as potency, affinity, intrinsic efficacy, or receptor reserve is extremely valuable but challenging for most trainees. The onus, therefore, is on the educators to devise effective strategies and tools to facilitate the acquisition of this critical competency.When approaching pharmacodynamics, the ability of learners to explore the influence of driving parameters on the magnitude and position of concentration response curves is a powerful way to visualize and make concrete the basic concepts of pharmacodynamics. To this end, I have developed VeSPha, a Versatile Simulation tool for Pharmacodynamics based on a rapid equilibrium generalization of Furchgott’s views on agonism. Through multiple sliders, the user can vary the parameters of the system, such as the concentrations of orthosteric and allosteric ligands, their respective affinities, the allosteric coupling constant, the intrinsic efficacies of each of the receptor species, the total number of receptors and the sensitivity of the system to the stimulus. A graph panel allows the display of the resulting response curves as a function of the concentration of ligand as well as orthosteric and allosteric ligand occupancy curves. Dropdown lines with corresponding EC50 as well as apparent Kd values for each ligand are also displayed. VeSPha also includes bar graphs as well as an intuitive graphic representation of the model displaying the values of the parameters, the distribution of the receptor species at the chosen state, the total stimulus as well as the resulting responses.The tool allows easy exploration of a wide gamut of possibilities that illustrate basic concepts of affinity, intrinsic efficacy, partial agonism, constitutive activity, inverse agonism, competitive antagonism, as well as allosteric modulation of both affinity and efficacy in any combination. The tool is implemented as an easy‐to‐use Excel file. This allows for flexible standalone use and for straightforward embedding into PowerPoint presentations for real‐time illustrations during lectures. The tool also readily generates simulated data including sampling errors for composing realistic, internally consistent assessment items such as quiz, problem set and exam questions.Implementation of this didactic tool is straightforward and effective in the author’s experience across a wide range of learners spanning from undergraduates, Master’s, Ph.D. M.D. Pharm D and DDS students. The tool, including a tutorial video can be made available to the Pharmacology teaching community upon request and an online version is under development.