Disambiguating "Mechanisms" in Pharmacy: Lessons from Mechanist Philosophy of Science

Abstract

Talk of mechanisms is ubiquitous in the natural sciences. Interdisciplinary fields such as biochemistry and pharmacy frequently discuss mechanisms with the assistance of diagrams. Such diagrams usually depict entities as structures or boxes and activities or interactions as arrows. While some of these arrows may indicate causal or componential relations, others may represent temporal or operational orders. Importantly, what kind of relation an arrow represents may not only vary with context but also be underdetermined by empirical data. In this manuscript, we investigate how an analysis of pharmacological mechanisms in terms of producing and underlying mechanisms-as discussed in the contemporary philosophy of science-may shed light on these issues. Specifically, we shall argue that while pharmacokinetic mechanisms usually describe causal chains of production, pharmacodynamics tends to focus on mechanisms of action underlying the in vivo effects of a drug. Considering the action of thyroid gland hormones in the human body as a case study, we further demonstrate that pharmacodynamic schemes tend to incorporate entities and interactions on multiple levels. Yet, traditional pharmacodynamic schemes are sketched "flat", i.e., non-hierarchically. We suggest that transforming flat pharmacodynamic schemes into mechanistic multi-level representations may assist in disentangling the different kinds of mechanisms and relations depicted by arrows in flat schemes. The resulting Baumkuchen model provides a powerful and practical alternative to traditional flat schemes, as it explicates the relevant mechanisms and relations more clearly. On a more general note, our discussion demonstrates how pharmacology and related disciplines may benefit from applying concepts from the new mechanist philosophy to guide the interpretation of scientific diagrams.

Keywords: Baumkuchen model; arrows; causation; mode of action; multi-level mechanisms; new mechanist philosophy; pharmacodynamics.

Figure 1

Schematic representation of the “mechanisms” regulating the blood pressure in the human body. BP: blood pressure, CO: cardiac output, PVR: peripheral vascular resistance, SV: stroke volume, HR: heart rate, BV: blood volume, FP: filling pressure (kidney), BV: blood volume, SNS: sympathetic nervous system, RAA System: renin-angiotensin-aldosterone system. This scheme has been adapted from a pharmacology textbook namely, Brenner and Stevens’ Pharmacology 5th edition p. 105) [4,5].

Figure 2

Three kinds of mechanisms; green circles depict the phenomenon to be explained (adapted from [3], p. 66) [3].

Figure 3

Production within an underlying mechanism. Please note that any component of the underlying mechanism shown in white may itself also be an explananda of another, even deeper underlying mechanism.

Figure 4

Mechanisms underlying components of a productive mechanism.

Figure 5

Schematic representation of a multi-level mechanism.

Figure 6

The biosynthesis of thyroid hormones and their impact on healthy muscle growth [5,23,26,27]. This scheme is adapted from two standard pharmacology textbooks, namely, Brenner and Stevens’ Pharmacology 5th edition p. 368 and Basic & Clinical Pharmacology 14th edition p. 688, and purely for illustration purposes, has been expanded to include some additional formulae and conversions.

Figure 7

Resonance structures of perchlorate (ClO₄^-) connected by arrows indicating mesomerism. The hooked arrows point towards “delocalized” electron pairs which are “moving” in the representation to generate four distinct structures. In contrast, this “movement” cannot be observed experimentally, as there is only one perchlorate molecule. The hooked arrows serve solely the purpose of explanation and to connect the four resonance structures required to describe perchlorate, its properties, acidity of perchloric acid, spectroscopy and reactivity fully.

Figure 8

The Baumkuchen model of the initially “flat” biochemical scheme depicted in Figure 6. Here, the different layers are clearly separated. Producing mechanisms within layers are shown in straight arrows, and underlying mechanisms depicted with cones, similar to the model in Figure 5. Please note that the Baumkuchen model avoids arrows between layers. If shown, these arrows may serve as heuristic tools rather than indicators of interlevel causation.