Pressbooks
Clinical Pharmacology and Prescribing Skills: Copyright © 2023
1
This collection of resources, titled ‘Clinical Pharmacology and Prescribing Skills: Resources for Canadian Medical Trainees’, is intended to assist medical students and residents, in understanding some key concepts in Clinical Pharmacology and Toxicology, find relevant and highly rated curricular resources, and understand the training and career opportunities in this new, smallest specialty of the Royal College of Physicians and Surgeons of Canada.
This project is made possible, in part, with funding by the Government of Ontario and through eCampus Ontario’s support of the Virtual Learning Strategy. To learn more about the Virtual Learning Strategy visit: https://vls.ecampusontario.ca.
This resource is licensed under an Ontario Commons License (Derivative Learning Object), except where otherwise noted.
2
A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z
Absorption
Adherence
Adverse drug event
Adverse drug reaction
Affinity
Agonist
Allele
Allosteric modulator
Antagonist
Apparent volume of distribution (Vd)
AUC
Bioavailability (F)
Biological marker (biomarker)
Biotransformation
Cheng-Prusoff equation
Competitive antagonist
Concentration-time curve
De-sensitization
Dose-response relationships
Drug concentration
Drug transport
Efficacy
Enteral drug administration
Equilibrium dissociation constant (Kd)
First-pass effect
Full agonist
IC50
Informed consent document
Inhibitory constant (Kj)
Inverse agonist
Irreversible antagonist
Metabolic drug tolerance
Metabolism
Metabolite
Michaelis constant (Km)
Parent compound
Parenteral drug administration
Partial agonist
Pharmacodynamics
Pharmacogenetics
Pharmacogenomics
Pharmacokinetics (PK)
Pharmacology
Potency
Prodrug
Receptor pharmacology
Reversible antagonist
3
The project team remains committed to creating an e-Book to meet requirements as set forth in the Accessibility for Ontarians with Disabilities Act (AODA) for publicly available online content. Pressbooks webbooks are designed to be accessible for users of all abilities and compatible with screen readers and other assistive technology (site maps, colour schemes, translations). As per Pressbooks accessibility recommendations, chapters, headings, and subheadings are used to organize content, described link text for links to web content are provided, and properly tagged table titles/captions and table headers/footers are available where appropriate. The webbook can be produced into two different types of PDF exports. ‘PDF (for digital distribution)’ exports use the PDF/UA-1 profile, which means that these digital PDFs will be tagged for accessibility and are designed to be read on a screen with maximal accessibility.
1
Clinical pharmacology is a medical specialty concerned with the research, teaching and clinical application of what the human body does to drugs and what drugs do to humans. The knowledge and correct application of drug therapies is a core responsibility of every physician and crosses every disease and organ group. At a population level, Canada along with every other developed country, has noted that drugs form the fastest growing component of health care budgets. This means that there is tremendous pressure to ensure that medicines are provided in the most judicious (effective, safe and cost-effective) manner to optimize health. More recently, medication safety problems have been recognized as the most prominent single source of internal medicine patient adverse events and as a common source of disciplinary action against physicians. At an international, national and local level, it has been noted that trainees receive inadequate training in clinical pharmacology and therapeutics. In addition, overdose and drug use disorders are common and require toxicology knowledge and expertise.
Clinical pharmacologists with combined clinical expertise, critical appraisal abilities, knowledge of drug action and familiarity with regulatory and reimbursement policies, influence healthcare at all levels (policy, provider and patient) and are in exceedingly short supply.
It is imperative that each practicing medicine specialist has a basic competence in safe prescribing and evidence-based therapeutics.
2
Every physician, no matter what specialty, must learn to prescribe competently, which means choosing medications based on an accurate diagnosis, indication, prior therapies, applying high levels of evidence for effectiveness, safety and cost-effectiveness. In addition, prescribing competence requires ongoing monitoring for benefit and harm, expertise in patient communications, knowledge of the regulatory and formulary environment, and an ability to de-prescribe appropriately.
3
Clinical Pharmacology and Toxicology knowledge and Prescribing competence, especially in training and early years of practice, correlates with fewer medication errors, better licensing exam results, fewer professional disciplinary complaints, and improved sustainability of health care.
Physicians and the Pharmaceutical Industry: Interests and Conflicting Interests
An interactive H5P element has been excluded from this version of the text. You can view it online here:
https://ecampusontario.pressbooks.pub/clinicalpharmacologyandprescribingskillsformedicine/?p=24#h5p-7
4
A few helpful pharmacology e-textbooks:
Links to Dr. Mitch Levine’s pharmacology talks:
*disclaimer: you need to have, and use, a Medportal login to access the links below
5
Canadians do not have universally funded Pharmacare. They do, however, in most provinces, have income-adjusted access to a formulary of approximately 4000 medications. Health Canada’s federal drug regulation system works similarly to the FDA in the USA and EMEA in Europe. Manufacturers bring drugs for approval based primarily on efficacy while demonstrating acceptable safety. Promising medications for serious conditions where there is a high need for better therapies, are sometimes granted Notice of Compliance with Conditions (NoCC) where additional evidence must be gathered to confirm initial impressions of effiacy and safety. This is an important distinction from full Notice of Compliance (NoC) as NoCC medications frequently do not turn out to be safe and effective.
Once cleared by Health Canada with NoC, medications are usually submitted to the Common Drug Review at CADTH (Canadian Agency for Drugs and Technology in Health) for recommendations regarding funding through public formularies in the provinces and territories. This requires an additional and more rigorous standard of evidence based on societal value, systematic review of the evidence with economic analysis of cost-effectiveness, and burden of illness.
The recommendations from the expert advisory committees based on the above review, are then considered by the individual provinces/territories and a formulary designation made. In Ontario, this is managed by the Ontario Public Drug Benefit Program. This program covers, seniors 65 years and older, children and youth 25 years and younger, those on disability or social assistance, and those with extreme drug expenditures relative to household income.
Drug Product Database online query (canada.ca)
The Drug Review and Approval Process in Canada
CADTH. Reimbursement Reviews. 2020.
CMPA. Medication Safety. 2021.
6
It has been shown that poor training in medical school and poor communication skills with patients, predict medicolegal trouble in practice. Trainees are referred to earlier chapters on Advice on Prescribing from the CPSO. Careful review of advice from the Canadian Medical Protective Association (CMPA), is also crucial to safe and successful practice.
7
Health Advocacy is a key role and competency for physicians in Canada, so much so that it is one of the main CanMEDS competencies.
In our discipline, typical patient advocacy roles include:
a) completing forms regarding restricted access to expensive non-formulary medications for patients meeting criteria or where there is no other option
b) continually working with patients to reduce and discontinue their exposure to harmful medications including alcohol, tobacco, cocaine and similar stimulants, high dose opioids, etc.
c) recognizing and remediating vulnerable situations where patients are at risk of lethal overdoses or poisonings.
d) participating in high quality research with patients that will address important medication-related questions.
e) discouraging use of expensive, supplements and natural health products which lack adequate evidence of effectiveness and safety, and are not regulated in terms of contamination.
8
One or more interactive elements has been excluded from this version of the text. You can view them online here: https://ecampusontario.pressbooks.pub/clinicalpharmacologyandprescribingskillsformedicine/?p=34
9
APPROPRIATENESS OF PRESCRIBING QUESTIONNAIRE (APEQ) DOMAINS
Holbrook, AM et al.
(More specific criteria are developed for each drug/drug family)
10
List curated by CPT specialists, internal medicine and pediatric specialists, regularly updated. This is modelled after the long-standing World Health Organization concept of an essential drugs list for poor countries, however our list has been modified to be relevant for Canadian practice. Most physicians will prescribe most frequently a core list of approximately 50-80 medications throughout their career. Our Essential Drugs List deliberately attempts to influence what that list should include.
Holbrook A. McMaster Essential/Core Drugs List for Medical Students. MacSphere, McMaster University: Medicine Publications collection; Hamilton ON, 2022. http://hdl.handle.net/11375/27291
An interactive H5P element has been excluded from this version of the text. You can view it online here:
https://ecampusontario.pressbooks.pub/clinicalpharmacologyandprescribingskillsformedicine/?p=38#h5p-2
11
This product of a previous eCampusOntario grant provides a curated list of key e-curriculum resources that have been evaluated by clinical, research, usability and e-learning experts. Most resources are international (for example, the Australian National Prescribing Curriculum (NPC) is excellent), therefore Canadian preambles are provided for areas of translation.
Our own work with Canadian medical students shows that many lack basic clinical pharmacology and therapeutics knowledge, and prescribing skills as schools struggle to meet all of their required curricula objectives.1, 2 Expertise in this broad-based specialty is scarce, and most medical schools no longer have dedicated clinical pharmacology courses. However, for the first time, the Medical Council of Canada has recently launched specific Prescribing Practices objectives that schools must cover.3
Safe prescribing is a complex activity requiring detailed knowledge of dozens of drug families, accurate patient diagnosis and individual risk assessment, excellent communication and interprofessional collaboration skills, and professionalism. More than 700 million prescriptions are written annually in Canada for drugs from approximately 1100 therapeutic groups.4 Medication errors are common, usually go unrecognized and can pose a serious patient safety hazard.2, 5-8 Medical students and residents are especially vulnerable, with prescribing errors on 7-10% of their prescriptions.5
Competent prescribing and medication management is even more essential as years go on, given the dozens of new medications introduced each year, primarily high-risk medications and very expensive medications, increasing numbers of patients with extreme polypharmacy, lethal problems with drug overdose and poisoning, and poor adherence with effective medications.
Holbrook A, Patel D, Yoo L. Introductory Preambles to Clinical Pharmacology and Toxicology eCurriculum Resources for Canadian Medical Students [MacSphere]. McMaster University, Department of Medicine: Hamilton, Ontario; 2022. Available from http://hdl.handle.net/11375/27381
12
Links to Australian National Prescribing Curriculum course with Canadian adaptation (eg, Choosing Wisely Canada), and Vanessa’s Law reporting obligations, with interpretation preambles for medical students.
Understanding Medication Safety
Preamble:
13
Dr. Spellberg’s video recording for grand rounds:
Short Course Antibiotic Therapy. Youtube [internet]. Los Angeles County, University of Southern California; October 13 2022 [cited October 20 2022]. Available from Short Course Antibiotic Therapy – YouTube.
Link to Dr. Spellberg’s antibiotics website: Shorter Is Better | mysite (bradspellberg.com)
Links to Australia NPC course, Canadian antibiogram data, and other Canadian resources
Australian NPC course: https://learn.nps.org.au/
Preamble:
14
Link to useful introduction on the importance of Drug Interactions to Adverse Drug Events:
Link to e-textbook on poisonings and drug overdose:
*disclaimer: you must have, and use, a Medportal login to access the link below
15
Type 2 Diabetes: Initiating Treatment
Preamble: The case description and details about symptoms, vitals, history etc. are reasonable and should be understood by the Canadian learners.
Parameter | Module | 2018 Diabetes Canada Clinical Practice Guidelines | Hamilton Regional Laboratory |
Triglycerides (TG) | < 2 mmol/L | <1.5 mmol/L | |
Albumin to Creatinine Ratio (ACR) | > 2.5 mg/mmol in men and > 3.5 mg/mmol in women is indicative of microalbuminuria | 2 – 20 mg/mmol is the range considered for microalbuminuria. uACR>20 mg/mmol is considered overt nephropathy | |
Potassium | 3.2 – 4.3 | N/A | 3.5 – 5.2 mmol/L |
Serum Creatinine | 60 – 120 | N/A | 60 – 110 umol/L |
ALT | N/A | ||
AST | N/A | ||
ALP | N/A | ||
GGT | N/A | ||
Albumin | 34 – 48 g/L | N/A | 42 – 50 g/L |
Target Blood Glucose Ranges | “Generally, the HbA1c target for most people with type 2 diabetes is ≤ 53 mmol/mol (7%) and the fasting blood glucose level is between 6 and 8 mmol/L.” | FBG: 4 – 7 mmol/L (or 4 – 5.5 mmol/L if diabetes is not well controlled) 2-hour post-prandial: 5 – 10 mmol/L (or 5 – 8 if diabetes is not well-controlled) | N/A |
Urinary Tract Infection
Preamble:
Postoperative Pain and Vomiting
Chronic obstructive pulmonary disease (COPD) exacerbation
Preamble: Important clarifications for Canadian medical students:
Prevention of Venous Thromboembolism
16
A suggested Medical Toxicology curriculum for medical students, has been suggested by a consensus group in the USA – see Table 1 in this publication.
Goldfine C, Lung D, Beauchamp G, O’Connor A, Stolbach A, Kao L, Judge B, Wax P, Patwari R, Kazzi Z. Consensus Development of a Core Content for a Standardized Medical Toxicology Curriculum for Medical Students. J Med Toxicol. 2022 Apr;18(2):139-144. doi: 10.1007/s13181-021-00874-z. Epub 2022 Jan 28. PMID: 35089533; PMCID: PMC8796743.
*disclaimer: you will need to have, and use, a Medportal login to access the links below
17
Opioids and Non-opioids in the Management of Pain: Time for Change
An interactive H5P element has been excluded from this version of the text. You can view it online here:
https://ecampusontario.pressbooks.pub/clinicalpharmacologyandprescribingskillsformedicine/?p=50#h5p-6
An interactive H5P element has been excluded from this version of the text. You can view it online here:
https://ecampusontario.pressbooks.pub/clinicalpharmacologyandprescribingskillsformedicine/?p=50#h5p-8
18
We are developing a computerized prescription writing assessment tool that will allow much broader formative practice, assessment and feedback for medical students and residents to practice their therapeutics and prescribing skills in a safe environment. This will be a form of ClinPharmTox simulation.
In the meantime, try this Prescription Writing simulation:
An interactive H5P element has been excluded from this version of the text. You can view it online here:
https://ecampusontario.pressbooks.pub/clinicalpharmacologyandprescribingskillsformedicine/?p=52#h5p-9
Click here to Download this exercise.
19
Concerns about prescribing competence are not isolated to North American medical graduates. The EQUIP study in England reviewed 124,260 medication orders finding an error rate as high as 10.3% amongst junior housestaff. In response to this study and a series of serious medication safety incidents, education leaders in clinical pharmacology and the British Pharmacological Society instituted the Prescribing Safety Assessment (PSA), an online exam that final year medical students must pass prior to their licensing exams. The full PSA consists of 60 questions and lasts for two hours, drawing on a large database of validated questions. Students participate in the PSA at the end of medical school a few months before their medical licensure examinations, and are encouraged to prepare using practice resources.(14) Approximately 53,000 students have completed the exam in the last five years, with very positive feedback on fairness and the helpfulness of the exam to their competence to practice. These students expressed appreciation for the initiative taken to address the prescription competency concerns, for increased their confidence when prescribing as a first year resident, and for making them aware of key prescribing resources such as formularies.
The Canadian PSA is a 30-question, 1 hour exam modified by Dr Holbrook from the British PSA. It has been tried consistently at McMaster University and sporadically at other Ontario medical schools over a 7-year period, with very good face validity. The exam is meant to be a formative assessment near the end of medical school as a measure of readiness for residency. Practice exams are made available for the Transitions to Clerkship period.
Recommendations to prepare for the PSA exam include:
Table 1: Prescribing Safety Assessment Question Domains
Prescription Writing | Writing a prescription requiring decisions regarding specific drug, dose, route and frequency based on clinical circumstances and supplementary information. |
Prescription Review | Deciding which components of the current prescription list are inappropriate, unsafe, or ineffective based on clinical circumstances. |
Planning Management | Deciding which combination of therapies would be the most appropriate to manage a particular clinical situation. |
Providing Information | Deciding which are the important pieces of information that should be provided to patients to allow them to choose whether to take the medication, or to enhance its safety and effectiveness. |
Calculation Skills | Making an accurate drug dosage calculation based on numerical information. |
Adverse Drug Reactions | Identifying likely adverse reactions of specific drugs, drugs that are likely to be causing specific adverse drug reactions, potentially dangerous drug interactions and deciding on the best approach to managing a clinical presentation that results from the adverse effects of a drug. |
Drug Monitoring | Deciding on how to monitor the beneficial and harmful effects of medicines. |
Data Interpretation | Deciding on the meaning of the results of investigations as they relate to decisions about on-going drug therapy. |
1
Available at: https://www.mcc.ca/objectives/expert/key/125/. Accessed June 14, 2021
PRESCRIBING PRACTICES — 125
Rationale:
Prescribing medications safely is a central component of most physicians’ activities and requires appropriate medical knowledge, skill, professional judgment, and an understanding of the applicable legislation related to prescribing.
Key Objectives:
To safely and effectively manage a patient presenting with a condition that requires prescription medication, the candidate will first undertake a thorough clinical assessment and then apply principles of evidence-based medicine and cost effectiveness in prescribing.
Enabling Objectives:
Given a patient that requires a medication to be prescribed safely and effectively, the candidate will