Pharmacological Versus Non-Pharmacological and Ancillary Mechanisms in Eye Drops Used in the Treatment of Glaucoma

Abstract

Medical Devices Made of Substances (MDMS) are increasingly used in the healthcare system alongside classic medicinal products and constitute an important field of experimentation and innovation in the biomedical field. In fact, these products are rapidly establishing themselves as a valuable therapeutic resource and are available in various forms including, but not limited to, creams, syrups, nasal or oropharyngeal sprays, and eye drops. MDMS are marketed to treat different diseases and the advantages and benefits of the use of these products can be claimed, once proven their clinical activity. What are the differences between medicinal products and MDMS? The substantial difference lies in the mechanism of action: the first case is based on pharmacological, metabolic, and immunological actions while the second one is based on mechanical, or chemical/physical action. Sometimes the boundaries are not well defined and there is a need for a reassessment and a consensus on the underlying concepts and definitions, also in the light of the increasing ability to recognize molecular mechanisms underneath the action of several substances not acting through an easy recognizable unique target (as a receptor, for example). In the present paper, we discuss the role of eye drops as an example of MDMS used in glaucoma, a widely diffused eye disease. The choice is due to the fact that some products used in this field of application and containing similar substances are marketed either as medicinal products or as medical devices or, using other dosage forms, as food supplements. Accordingly, it is important to underscore in the various cases what may be the principal mode of action and the contribution of additional mechanisms as derived, for example, from system pharmacology data. Their analysis may help to exemplify some of the problems around the sometimes fuzzy border between MDMS and medicinal products suggesting the need for new definitions and regulatory decisions about MDMS.

Characteristics of elderly diabetes patients: focus on clinical manifestation, pathogenic mechanism, and the role of traditional Chinese medicine

“…Clinical treatment focuses on alleviating clinical symptoms, improving blood glucose control and cardiovascular risk factors . Pain in the elderly need arouse attention from clinicians and patients (Marchesi et al, 2024). In pain management, anticonvulsants such as pregabalin and gabapentin are the first-line treatment of choice, followed by amitriptyline, duloxetine, and venlafaxine (Cernea and Raz, 2021).…”

“…In pain management, anticonvulsants such as pregabalin and gabapentin are the first-line treatment of choice, followed by amitriptyline, duloxetine, and venlafaxine (Cernea and Raz, 2021). Opioids and related medications are recommended for short-term use during acute exacerbations of pain (Kozma et al, 2012;Feldman et al, 2019;Marchesi et al, 2024). These interventions play an important role in diminishing DPN's symptoms and complications.…”

“…Basic interventions also include nutritional recommendations (mecobalamin, etc.) and functional exercise (Didangelos et al, 2020;Seyedizadeh et al, 2020;Shen et al, 2023b;Marchesi et al, 2024). However, diet and exercise are often neglected in the treatment of elderly patients with diabetes.…”

New regulation on medical devices made of substances: Opportunities and challenges for pharmacological and toxicological research

“…Other valuable approaches could be the ones used for target validation in drug discovery such as genetic manipulation of targets by knocking out/in strategies. However, there may be cases such as the use of citicoline in glaucoma, in which the discrimination between pharmacological and non-pharmacological mode of action is hard to demonstrate and may change according to the dose, the route of administration and target selection (Marchesi et al, 2022).…”

“…However, the practical approaches and scientific evidence that is required to demonstrate a non-pharmacological mechanism of action are still blurred: current paradigms, including system biology and network pharmacology are applied to the study of the complexity of the biological activities elicited by both drugs and mixtures of natural substances and how they can be applied to the study of the mechanism of action of MD is still uncertain. The difficulties in delineating the boundaries between pharmacological and nonpharmacological mechanism of action and the regulatory classification of even a single substance, such as citicoline in glaucoma (Marchesi et al, 2022), exponentially increase in the case of complex mixtures of substances.…”