Introduction
The earliest version of this manual was prepared over the Thanksgiving long weekend in 2015, in a shorter and much less-polished format, as a revision guide to accompany a second year Fall term lecture course on pharmacodynamics and pharmacokinetics, part of the B.Sc. Pharmacology program at the University of Alberta. Six months later, a decision was made to replace the pharmacodynamics/pharmacokinetics course with something more entertaining and less challenging. Rather than consign the guide to the dustbin, I adapted it substantially to accompany a shorter series of related lectures presented to first year medical students in the M.D. Foundations block. For many of the medical students, these lectures represented their first exposure to the subject of pharmacology, and although most quickly became comfortable with the key concepts through the lectures, it was felt that a “belt and braces” approach might be helpful in solidifying students’ understanding of principles that, ultimately, were intended to assist in reducing drug dosing errors and patient harm.
A working familiarity with pharmacokinetics in particular is necessary if clinicians are to develop both confidence and competence in designing and modifying drug dosing regimens and interpreting clinical laboratory reports detailing drug concentration measurements in patients’ plasma or urine. Often the patients in question will have altered plasma protein levels, uraemia, hepatic insufficiency or reduced cardiac output, resulting in significant variations of a drug’s pharmacokinetic parameters from what might be considered a normal range, and necessitating calculation of personalised dosing rates, amounts and/or intervals. From predicting drug concentrations in plasma following termination of an IV infusion, to modifying a target concentration range for a drug highly bound to plasma albumin in a patient with an elevated unbound fraction, to deciding whether clearance or volume of distribution is the primary determinant of the concentration of drug in the plasma after a short infusion; the calculations and clinical decisions based upon them are countless. That approaches taken to reach these decisions are often dependent upon the drug in question adds to the complexity of the process.
This introductory guide, like the lectures it accompanies, seeks not to teach students the whole gamut of approaches used to reach clinical dosing decisions; even introductory textbooks of clinical pharmacokinetics provide flowcharts that simplify the process of selecting an approach and associated equations that are best-suited to specific clinical situations. Rather, the aim is to familiarise students with the core concepts of pharmacokinetics (and pharmacodynamics) underpinning all of these approaches, to develop an understanding in students that will allow them to have informed conversations with pharmacists about the drugs they prescribe and administer. The format of the guide also facilitates its use as a rapid reference through which students may remind themselves of concepts rusty through lack of use.
Although this document was designed originally to serve as little more than an examination revision aid, it transpired that some medical students kept a digital copy of the guide on their phones or tablets, and during their clinical training, referred back to explanations and examples provided therein. Subsequently, I made a decision to create a more permanent digital reference guide that could be published as an Open Educational Resource. During the 18 months spent creating this eBook, the lecture time allotted to pharmacokinetics and pharmacodynamics in the M.D. Foundations block has been reduced by almost half, with the result that a significant portion of the book’s content is either now not covered at all in the lectures, or is covered in far less detail in the lectures than was previously the case. However, I chose not to remove content from the eBook to remain aligned with lecture content, as this would diminish the usefulness of the guide as a reference work.
The guide is comprised of two sections, covering pharmacokinetics and pharmacodynamics, with each section containing an alphabetical listing of concepts and terms. Each listing offers a definition for the listed term or concept, and these are often followed by a more extensive explanation. Live links within the text take the reader to separate listings dedicated to related content, thereby providing a means to cross-reference material and understand context. Diagrams and graphs are used extensively to accompany text, while calculation examples are also offered where these might be helpful. For some entries, more in-depth background information is provided which might be of interest to students and which would facilitate a deeper understanding of a topic, but which is not critical. Indeed, the purpose of the guide’s content, like the lectures, is to develop a broad understanding of key principles that govern drug action, and much of the content is included not because it would be used routinely – or indeed, at all – in clinical practice, but because it enhances understanding of that content which is used routinely.
Where appropriate, clinical relevance of a concept has been outlined in a “Clinical Context” box within an entry. Details and examples included therein were provided by Marcel Romanick, a Clinical Practice Leader within Pharmacy Services at Alberta Health Services; the information is thus current and very much on-point for those working directly with patients, and these contributions represent a valuable addition to the guide.
For 2024, a new section (Section 3) has been added to the book that lists all of the core concepts identified by the International Union of Basic and Clinical Pharmacology (IUPHAR) Education Project as being key to the understanding of pharmacokinetics and pharmacodynamics. A further addition (Section 4) is planned in which commonly-prescribed drugs will be listed, along with information on the drug’s pharmacokinetic and pharmacodynamic properties.
Some of the more challenging concepts presented in lectures were explained, in part, through the use of analogies and animations which appealed to visual learners and which were widely popular among the students. Thus, many listings in this guide will include live links to short animated videos that have been (or are being) prepared specifically for this project. The original animated files may be obtained from me, on request, and repurposed for inclusion in teaching content elsewhere.
As the financial pressures on students grow to unmanageable levels, I chose to make this book freely-available as an Open Educational Resource. If you wish to express your gratitude, please do so by voting – always – for a government that understands the purpose of post-secondary education and that truly values and supports public education and public healthcare. If you wish to express your gratitude financially, please consider making a small donation to an indigenous charity, or to a charity that supports houseless persons, or that cares for sick or injured animals and birds.
Finally, this eBook is a “living document”. Content will be modified and updated on an ongoing basis. At the time of first release, in the summer of 2023, many of the links to supplementary animated videos were not yet active, or had not yet been added to the text, and one year later I have not made much progress in this regard. These deficiencies will be addressed slowly over the coming months, whenever I have an opportunity to do so.
Dr. Andy Holt
August 2024
