Part 1: PHARM 466 — Epidemiology of Aging

Topic: Epidemiology of Aging

Lecturer: Prof. Colleen Maxwell, School of Pharmacy and School of Public Health and Health Systems, University of Waterloo; Adjunct Scientist, ICES (Institute for Clinical Evaluative Sciences)

Foundational Definitions

Understanding the demographic drivers of population aging requires fluency with a small set of core concepts that recur throughout geriatric pharmacy literature.

Epidemiological Measures of Frequency

When interpreting geriatric pharmacoepidemiology literature, two fundamental measures arise repeatedly.

Prevalence is the number of existing cases of a disease or event divided by the total population, measured at a particular point in time or over a defined period. Incidence is the number of new cases of a disease or event divided by the number of persons at risk, during a specified time interval.

A critical mathematical relationship connects the two: prevalence ≈ incidence × duration. This has profound practical implications. For example, although the incidence of dementia in Canada has declined modestly — partly due to better control of vascular risk factors — those living with dementia are surviving longer with the condition. Consequently, the prevalence of dementia is increasing substantially. Understanding this distinction helps practitioners interpret apparently contradictory reports in the literature.

Canada’s Aging Population: Demographic History

Canada’s age pyramid reflects 150 years of demographic, social, and economic history. The parents of the baby boomer generation were born between 1922 and 1938; the Second World War occurred between 1939 and 1945. In the post-war period, fertility rates rose dramatically, producing the baby boomer cohort born between 1946 and 1965, with fertility rates well above the replacement level of 2.1 children per woman — peaking around 3.5. Since the early 1970s, Canada’s total fertility rate has remained below the replacement level of 2.1, meaning Canadians are not replacing themselves. Following the boom came the “baby busters” (late 1960s to early 1970s) and then a modest “echo boom” (approximately 1975–1995) — the children of the boomers.

The first baby boomers reached age 65 in 2011; the last will reach that milestone in 2030. Between 2011 and 2016, Canada saw its most rapid increase in the proportion of the population aged 65 and over, alongside a simultaneous drop in the proportion under 15. For the first time in Canadian history, the 2016 census recorded more seniors (65+) than children (under 15) in the population. By 2036, projections suggest approximately 1 in 4 Canadians will be aged 65 or older — a proportion currently resembling that of Japan, which has the world’s oldest population due to the combination of the lowest fertility rates and the highest life expectancy globally.

Centenarians (those aged 100 and over) constitute the fastest-growing segment of Canada’s population since 2011. One-third of those aged 85 and over, and two-thirds of those aged 100 and over, live in collective dwellings such as nursing homes or retirement residences.

Life Expectancy Trends and Determinants

From 1941 to 2015–2017, Canadian life expectancy at birth rose from 63 to 80 years for males, and from 66 to 84.1 years for females. Women have consistently outlived men, and in the mid-1950s this gap widened to approximately 7 years. Around 2000, however, the gap began to narrow, with males making proportionally greater gains than females. Three key contributors to this narrowing include: (1) reduced violent deaths among male teenagers and young adults; (2) significant improvements in the treatment of cardiovascular disease affecting men disproportionately; and (3) increased similarity in women’s health behaviours to those of men, particularly smoking, alcohol use, and work-related stress. The colloquial framing is that “women are dying to be like men,” meaning the adoption of unhealthy lifestyle patterns previously more common among males.

Between 2016 and 2017, for the first time in recent Canadian history, life expectancy stalled — no change was recorded. The opioid crisis was a significant contributor, with accidental drug overdose deaths offsetting gains in cardiovascular mortality reduction. The effect was particularly pronounced among men in British Columbia and Alberta, and to a lesser degree among women in those provinces. Questions about how COVID-19 will further alter these trajectories remain active concerns.

Regional Variation in Aging

Not all regions of Canada are aging at the same rate. The Atlantic provinces and Quebec, along with British Columbia, show relatively older population structures; the prairie provinces (especially Alberta) and the territories show younger profiles. The explanation lies in the interplay of fertility, life expectancy, and migration:

Alberta’s relatively young population reflects three converging factors: higher fertility rates; interprovincial in-migration of working-age individuals (historically to the oil industry) from provinces including Newfoundland and Labrador; and higher life expectancy. Nunavut’s young profile is explained predominantly by high fertility rates and low life expectancy. BC’s older profile reflects its very low fertility rate combined with high life expectancy.

Within provinces, inequalities in life expectancy are striking. In Alberta between 2000 and 2015, life expectancy decreased for First Nations populations. The gap between First Nations and non-First Nations Albertans stood at nearly 12 years. The gap between the least affluent northeast region and the most affluent part of Calgary was 13.2 years. These inequalities arise from socioeconomic factors, access to healthcare, lifestyle behaviours, and other social determinants of health.

Healthy Life Expectancy and the Disability Gap

Although women live longer than men, they spend a greater proportion of those years in relatively poor health or with some form of disability. Disability in this context encompasses impairments in mobility, agility, and sensory function (hearing, vision, etc.). This disparity is partly attributable to the mix of chronic conditions more prevalent among women, including conditions related to pain and mobility such as osteoporosis. Older women also face heightened social and economic vulnerability: they are more likely to live alone, historically have lower incomes, and are less likely to remarry after losing a partner — all factors that affect medication adherence, access to care, and the capacity to relay accurate medication histories to healthcare providers.

In practical terms, when an older woman presents to a community pharmacy or nursing home setting, the pharmacist must consider not just her biological age and diagnoses, but whether she has an advocate, whether she lives alone, and how these factors shape her capacity to manage a complex therapeutic regimen.

Topic: Multimorbidity and Therapeutic Implications

Continuing from Prof. Colleen Maxwell’s lecture series on the epidemiology of aging

Rectangularization of Mortality and the Compression of Morbidity Debate

In Canada and other developed countries, there is a phenomenon known as the rectangularization of mortality (also called the compression of mortality). As a greater proportion of individuals survive to advanced ages, the survival curve for a birth cohort takes on an increasingly rectangular shape, with more deaths concentrated at progressively older ages. By 2009–2011, 87% of Canadian males and 92% of females could be expected to reach age 65 — compared with 59% of males and 62% of females in 1931.

The central question accompanying this trend is whether the compression of mortality will be matched by a compression of morbidity — that is, whether individuals will not only live longer, but live longer in good health, with the onset of chronic disease pushed to increasingly late in life. Current evidence suggests this is not occurring uniformly. Instead, increasing longevity appears to be accompanied by increasing multimorbidity — the simultaneous burden of multiple chronic conditions.

Defining Multimorbidity

The threshold of two or more conditions is most commonly used in the literature; some studies use three or more. The number and type of conditions included also varies across studies, but the general findings are consistent: multimorbidity is common, increases with age, and is rising in prevalence over time.

Approximately 90% of Canadians aged 65 and over live with at least one chronic condition. Among those aged 65–79, two-thirds have two or more chronic conditions; among those aged 80 and over, this rises to approximately 80%. A study of all Ontario residents conducted across index dates in 2003, 2009, and 2016, examining 18 chronic conditions of high prevalence and health system burden, found that the age- and sex-adjusted prevalence of multimorbidity (two or more conditions) rose from 26.5% in 2003 to 30% in 2016. Critically, levels of higher-order multimorbidity (three, four, five or more conditions) also increased.

Complexity and Diversity of Multimorbidity

The clinical challenge deepens with increasing levels of multimorbidity because the cluster of coexisting conditions becomes progressively more heterogeneous. In Ontario data, among individuals with only one chronic condition, the top five conditions — asthma, arthritis, hypertension, depression, and cancer — accounted for 91% of that single-condition cohort. As the complexity level rose to five or more conditions, the diversity of disease clusters became extraordinary: 2,744 unique combinations of five conditions accounted for 80% of those with five or more chronic conditions, and no single cluster was present in more than about 1.4% of that group. This level of diversity renders single-disease clinical practice guidelines fundamentally inadequate for the care of these patients, because the guidelines cannot possibly account for all interaction effects.

Consequences of Multimorbidity

The health system and patient-level consequences of multimorbidity are substantial and dose-dependent: the more chronic conditions, the worse the outcomes across every dimension measured.

Those with five or more chronic conditions face approximately eight times the odds of hospitalization compared with those having only one condition. Hospitalization outcomes also worsen with increasing multimorbidity: those with five or more conditions have longer median lengths of stay (from six days for one condition to ten days for five or more), dramatically higher rates of three or more hospital visits, greater proportions of alternative level of care (ALC) days (when patients are medically stable but cannot be discharged due to lack of community supports), higher in-hospital mortality, and higher 30-day readmission rates.

Approximately 80% of all total healthcare costs in Ontario are spent on persons with two or more chronic conditions. Cost drivers include increasing contributions from continuing care, prescription drugs, and hospitalizations. Health-related quality of life falls meaningfully with increasing numbers of chronic conditions, with statistically and clinically significant declines seen starting at four or more conditions.

Drivers of Multimorbidity

Health in older age is not random. It reflects the cumulative effect of lifelong interactions between individual characteristics (sex, ethnicity, occupation, education, income) and environments (physical, social, economic). The factors most consistently associated with elevated risk for multimorbidity include:

Smoking and high body mass index have been identified as the two most significant lifestyle predictors of multimorbidity in men (in a study by Martin Fortin’s group); BMI was also significant for women. Among women, reaching a cumulative count of two or more unhealthy lifestyle behaviours (including low fruit and vegetable consumption, low physical activity, high alcohol use, smoking, and high BMI) was associated with onset of multimorbidity; in men, the threshold was four to five such factors.

Between 1980 and 2013, the percentage of obese Canadians doubled for both sexes. Data suggest smoking rates among younger women are increasing, and rates of obesity continue to rise across all ages — pointing to worsening future cohorts of multimorbidity burden.

Socioeconomic status exerts a consistent and strong gradient: lower income is associated with higher rates of multimorbidity, greater polypharmacy, and worse outcomes. This gradient has remained stable in Ontario over the 2003–2016 study period, though in some countries (notably the United States) it is widening. The mechanisms operate through differential access to healthy food, safe recreational spaces, healthcare, and through differential rates of health-harming behaviours.

Medication Use in Older Adults with Multimorbidity

Older adults are the dominant consumers of both prescription and over-the-counter medications. Despite representing only 17% of Canada’s population, those aged 65 and over account for nearly 40% of all prescription drug spending and 55% of public drug program spending (CIHI, 2016).

Approximately two-thirds of seniors take five or more drug classes — a common threshold definition of polypharmacy in the literature. About 25% take 10 or more drug classes, which is often defined as excessive polypharmacy or hyperpolypharmacy. Drug use increases with age, is higher among men, and is higher in lower socioeconomic and rural regions.

In 2016, five of the ten most commonly used drug classes in Canadian seniors were for cardiovascular conditions. Nearly half of all Canadians aged 65 and over were on a statin, raising questions about the appropriateness of statin initiation in very old or frail individuals with limited life expectancy. Almost half of the senior population was using one or more drugs from the Beers Criteria list of potentially inappropriate medications (PIMs) — a figure that rises to about two-thirds among long-term care residents.

The top ten drug classes by rate of use in seniors include: statins (number one in the community), proton pump inhibitors (PPIs), antihypertensives (including ACE inhibitors, calcium channel blockers, and diuretics), thyroid medications, oral antidiabetics, opioids for chronic pain, and benzodiazepines for agitation, anxiety, and insomnia. Sex differences exist: men are more likely to receive a statin and cardiovascular medications; women are more likely to receive a PPI, a benzodiazepine, an opioid for chronic pain, and thyroid medications.

In long-term care, the prescribing landscape shifts markedly. Other antidepressants (predominantly trazodone) become the most commonly prescribed class — prescribed four times more frequently than in the community. This appears to reflect a substitution effect: as quality improvement initiatives and quality indicators have driven down the use of antipsychotics and benzodiazepines in long-term care, prescribers have turned to trazodone for its sedative properties, despite its predominantly off-label use in this context. Simultaneously, quetiapine use has risen, and the total burden of psychoactive drug use has not necessarily fallen. PPIs, opioids, antibiotics, and all classes of antidepressants are also elevated in long-term care relative to the community.

The concern about the “pinching the balloon” phenomenon — reducing inappropriate use in one drug class only to see it expand in another — is central to quality improvement work in geriatric pharmacy. Statins, which are number one in community seniors, fall to number six in long-term care residents, raising the question of whether a preventive medication with a long time-horizon to benefit is appropriate for individuals with an average age of approximately 85 and high levels of frailty.

Adverse Drug Events and Hospitalization

The number of medications used by an older adult is the primary determinant of hospitalization for an adverse drug event. From CIHI (2016) data, hospitalization for an adverse drug event was five times more likely among individuals using 10–14 drug classes, and eight times more likely for those using 15 or more drug classes.

In American studies of emergency department visits for adverse drug events, the most common drug classes implicated in hospitalizations were not Beers-listed PIMs but rather a small cluster of drugs with narrow therapeutic indices: anticoagulants (e.g., warfarin), insulin and oral antidiabetics, and oral antiplatelets. Two-thirds of adverse drug event hospitalizations were related to these four classes. The primary failure modes identified were: failure to adjust dose appropriately for an older adult; drug-drug, drug-food, drug-alcohol, and drug-disease interactions; incomplete medication profiles (including non-prescription and self-medication); and the prescribing cascade — where a side effect of one medication is misinterpreted as a new condition and treated with an additional drug, creating a chain of compounding harm.

Drugs with moderate to severe anticholinergic effects are specifically implicated in falls, confusion, and cardiovascular deterioration in frail and vulnerable seniors.

The Treatment Burden Problem

A landmark 2005 study by Cynthia Boyd and colleagues, published in JAMA, examined nine clinical practice guidelines for common chronic conditions and found that most single-disease guidelines failed to provide guidance for patients with multimorbidity. They did not modify recommendations for those with coexisting conditions, did not address treatment burden or adherence, and did not acknowledge patient preferences or prognosis. Critically, following all applicable single-disease guidelines simultaneously could lead to suboptimal drug use, adverse drug interactions, and poor outcomes — the opposite of their intent.

Their illustrative case was a 79-year-old woman with five conditions: COPD, type 2 diabetes, osteoporosis, hypertension, and osteoarthritis. Following the most conservative comprehensive treatment plan consistent with all relevant guidelines would require: 12 separate medications, 19 daily doses at five different time points, a complex non-pharmacological regimen of 14 additional recommendations, multiple potential drug-drug and drug-disease interactions, discordant recommendations across guidelines, and an annual out-of-pocket cost of approximately $4,000 even with insurance. The conclusion was that this regimen would impose an unsustainable treatment burden adversely affecting adherence.

Principles of Care for Older Adults with Multimorbidity

The American Geriatrics Society has articulated guiding principles organized around five domains:

Patient preferences: Elicit and incorporate the values, priorities, and preferences of the patient and family. Recognize preference-sensitive decisions. Understand the role of family and social support, and revisit preferences as circumstances change (especially as end of life approaches).

Interpreting the evidence: Critically assess the quality and applicability of available evidence for patients with multimorbidity. Most trials enrolled younger or healthier patients and excluded those with complex comorbidity. Evidence gaps are substantial.

Prognosis: Frame clinical decisions within the context of the patient’s prognosis — considering quantity and quality of life together, along with functional status. This is especially important when considering the time-horizon to benefit for preventive therapies (e.g., does it make sense to newly initiate a statin in a frail 87-year-old in a nursing home?).

Clinical feasibility: Assess how complex and burdensome the treatment plan is, and whether it is sustainable. Streamline wherever possible. Use strategies to optimize benefit and minimize harm.

Optimizing therapies: Apply frameworks like deprescribing to reduce polypharmacy. Consider tools from the Canadian Deprescribing Network (with specific algorithms for benzodiazepines, antipsychotics, and PPIs), the STOPP/START criteria, and STOPP-Frail (designed for the most vulnerable, frail older adults). Resources including the Institute for Safe Medication Practices, Choosing Wisely Canada, and the Canadian Foundation for Healthcare Improvement offer evidence-based decision supports.

The challenges to enacting these principles in practice are considerable: multiple providers across multiple settings make coordinated care difficult; complexity is hard to explain to patients and families; reducing polypharmacy always carries medicolegal concerns about under-treatment; and the current reimbursement structure does not adequately compensate the time required for comprehensive medication reviews and deprescribing discussions.

Part 2: PHARM 466 — Geriatric Syndromes & Frailty

Topic: Geriatric Syndromes — Conceptual Framework

Lecturer: Prof. Colleen Maxwell

Framing Geriatric Syndromes

Against the backdrop of multimorbidity and polypharmacy, geriatric syndromes add another layer of clinical complexity for older adults. These syndromes share a set of defining features that distinguish them from standard disease categories:

They are extremely prevalent, cause considerable disability, are costly to the healthcare system, are clinically complex, and are multifactorial — arising from the interaction of multiple risk factors across multiple organ systems, rather than from a single pathological cause.

The recognized geriatric syndromes include delirium, falls, pressure ulcers, urinary incontinence, frailty, sleep disorders, dizziness, and syncope. They exhibit unusual clinical presentations where the presenting complaint often points away from — rather than toward — the underlying pathological change. For example, a urinary tract infection may present as delirium in a vulnerable older adult rather than as dysuria or frequency. They are thought to involve dysregulation of homeostatic mechanisms, with loss of the complexity and reserve that normally maintain physiological balance.

Medications play a dual role with respect to geriatric syndromes: they can be modifiable risk factors for the onset or progression of syndromes (e.g., sedatives precipitating falls or delirium); they may interact with other vulnerability or precipitating factors; and they represent a potential — if still investigational — avenue for prevention or treatment of selected syndromes.

Shared Risk Factors and Pathophysiology

Geriatrician Sharon Inouye conducted seminal work identifying common risk factors shared by five geriatric syndromes (pressure ulcers, incontinence, falls, functional decline, and delirium). Four common risk factors emerged: older age, baseline cognitive impairment, baseline functional impairment, and impaired mobility. Encouragingly, three of these four factors are amenable to intervention.

Inouye proposed a conceptual model of a self-sustaining cycle: shared risk factors lead to the onset of geriatric syndromes; accumulated geriatric syndromes lead to frailty; frailty in turn predisposes to new or worsening geriatric syndromes; and this downward spiral accelerates toward greater disability, nursing home placement, and death. Once far along this trajectory, the potential for intervention to meaningfully reverse course diminishes.

Potential shared pathophysiological mechanisms across geriatric syndromes include: multi-system dysregulation, inflammatory dysregulation, onset of sarcopenia (loss of muscle mass and strength), and atherosclerotic processes. If these shared mechanisms are confirmed, a unified prevention approach targeting multiple syndromes simultaneously might be achievable — though the social and economic context that compounds the risk cannot be separated from the biological.

Delirium: An Acute Geriatric Emergency

Delirium is a medical emergency. It is extremely prevalent and life-threatening: among older hospitalized patients, up to 25% have delirium on admission, and new-onset (incident) delirium occurs in up to 50% of inpatients. The incidence rises in high-acuity settings: up to 50% post-operative, up to 87% in the ICU, up to 60% in nursing homes, and up to 83% in palliative care populations. Despite this prevalence, delirium is under-recognized in up to 70% of cases and is rarely documented when present.

The reason for poor recognition is partly clinical: the most common subtype in older adults is hypoactive (quiet) delirium, characterized by sedation, lethargy, slow responses, and little spontaneous movement — features that are easily mistaken for progressive cognitive decline or depression, especially when delirium is superimposed on pre-existing dementia. Hyperactive delirium — with agitation, restlessness, hypervigilance, hallucinations, and delusions — is more dramatic but less common (15–47% of cases). A mixed subtype combines features of both.

The importance of recognition cannot be overstated: approximately 40% of delirium is preventable, and even non-preventable delirium can be shortened in duration or severity through targeted intervention.

Outcomes of delirium are severe. In-hospital consequences include aspiration and pneumonia, pressure ulcers, pulmonary emboli, and decreased oral intake. Long-term consequences include persistent cognitive impairment, increased risk of subsequent dementia, functional impairment, falls, poor rehabilitation outcomes, prolonged hospital stays, and long-term care placement. Estimated costs are approximately $60,000 per patient per year with delirium. Patient distress is significant — a substantial proportion of those who survive delirium remember it, particularly if they experienced delusions.

Risk Factors: Predisposing and Precipitating

Delirium risk is conceptualized as the product of predisposing (vulnerability) factors and precipitating (triggering) factors. A highly vulnerable individual may develop delirium from a single low-level trigger (e.g., one dose of a sedative); a less vulnerable individual requires multiple and more severe precipitants.

Predisposing factors include: dementia (the most common, underlying delirium in two-thirds of all cases — dementia and delirium share common mechanisms including decreased cerebral blood flow, cholinergic deficiency, and inflammatory processes), advanced age, history of stroke or prior delirium, multimorbidity, chronic renal or hepatic disease, frailty, and male sex.

Precipitating factors include: sensory impairment (hearing or vision); immobilization (physical restraints or catheters); medications (responsible in approximately 40% of cases — key culprits include sedatives, hypnotics, opiates/narcotics, anticholinergic drugs, corticosteroids, any polypharmacy, and abrupt withdrawal from benzodiazepines or alcohol); acute neurological events (stroke, hemorrhage, CNS infection); acute intercurrent illness (infections, iatrogenic complications, anemia, dehydration, malnutrition, fracture, trauma); metabolic derangement; surgery; pain; emotional distress; and sustained sleep deprivation.

Pathophysiology of Delirium

The pathophysiology is not fully understood and likely involves multiple overlapping mechanisms converging on acute brain failure. Key proposed mechanisms include:

Neurotransmitter abnormalities: A cholinergic deficiency is well-supported — anticholinergic drugs reliably induce delirium, generating interest in cholinesterase inhibitors as potential preventive agents (though trial evidence remains insufficient). Elevated dopaminergic activity is also implicated — anti-Parkinsonian drugs can cause delirium, while dopamine antagonists (antipsychotics) may help control symptoms. Other neurotransmitter systems are also under investigation.

Inflammatory dysregulation: Pro-inflammatory cytokines (released following infection, trauma, or surgery) are implicated, with research focusing on cytokine biomarkers as predictors of delirium.

Acute stress response: Elevated cortisol levels from acute stressors may precipitate or sustain delirium. Direct neuronal injury can impair neurotransmitter synthesis and release.

Structural brain changes associated with delirium vulnerability — including cortical atrophy, ventricular dilatation, and white matter lesions — suggest a background of pre-existing neurological vulnerability that makes the brain susceptible to acute insults.

Diagnosis: DSM-IV Criteria

The formal clinical diagnosis of delirium requires meeting the following DSM-IV criteria (DSM-5 retains essentially the same framework):

A: Disturbance of consciousness — reduced clarity of awareness of the environment, or reduced ability to focus, sustain, or shift attention.

B: Acute change in cognition — memory deficit, disorientation, language disturbance, or perceptual disturbance not better accounted for by a pre-existing dementia.

C: Acute onset and fluctuating course — development over a short period (hours to days), with tendency to fluctuate in severity during the day, typically worse at night.

D: Evidence of a causative medical factor — from history, physical examination, or laboratory findings, suggesting the disturbance is due to a general medical condition, substance intoxication, substance withdrawal, or multiple etiologies.

Differentiating delirium from dementia, psychotic disorders, and depression requires careful attention to the acuity of onset (sudden in delirium, insidious in dementia), the fluctuating course (characteristic of delirium), and the level of consciousness (typically altered in delirium). Diagnosis requires clinical history, neurological examination, cognitive assessment, and — critically — information from someone who knows the patient well, to establish what their baseline was and whether the current presentation represents an acute change.

Screening and Severity Assessment

The most widely used screening tool is the Confusion Assessment Method (CAM), which evaluates four features: (1) acute onset and fluctuating course; (2) inattention; (3) disorganized thinking or (4) altered level of consciousness. Positive screening on the CAM requires features 1 and 2, plus either 3 or 4. The tool has high sensitivity, specificity, and inter-rater reliability when used by trained evaluators. Adaptations exist for the ICU (CAM-ICU) and for family proxy reporting (CAM-FAM). For severity rating, the Memorial Delirium Assessment Scale (10-item) and the CAM-S scoring system are validated options.

Management and Prevention of Delirium

The first priority is prevention. All patients at risk for delirium (identified by vulnerability factors) should receive a comprehensive medication review conducted by an experienced healthcare professional — examining recent additions, withdrawals, dose changes, and the possibility of enhanced pharmacokinetic alterations related to aging, frailty, or new acute illness. Clinicians should exercise caution before initiating any new psychoactive medication in patients vulnerable to delirium. Limiting the use of benzodiazepines and drugs with moderate to severe anticholinergic effects wherever possible is foundational.

The HELP (Hospital Elder Life Program), developed by Sharon Inouye, is a multi-component, cost-effective intervention proven to prevent delirium and functional decline in hospital settings. It addresses: orientation (to person, place, and time); nutrition and hydration; sleep; early mobility; and sensory adaptations (glasses, hearing aids). Proactive comprehensive geriatric assessment (especially following acute hip fracture) and home rehabilitation programs after hospitalization also reduce delirium incidence.

Pharmacological prevention is not currently recommended. Small trials of haloperidol and cholinesterase inhibitors as preventive agents in surgical populations have been inconclusive, with insufficient evidence to support routine use.

For treatment, the first-line approach is non-pharmacological and multi-component: reorientation; sensory cues; behavioural interventions for agitation; early mobilization; clear and frequent communication; ensuring adequate hydration, nutrition, and pain control; avoiding physical restraints; environmental optimization (low noise, consistent staff); and a non-pharmacological sleep protocol.

Pharmacological treatment is reserved for exceptional cases of hyperactive delirium where the patient’s behaviour compromises their own safety or the safety of others, or where agitation prevents necessary medical treatment. In these rare circumstances, a low-dose antipsychotic (e.g., haloperidol or atypical antipsychotics such as quetiapine) may be considered, with the principle of “start low, go slow” and for the shortest possible duration. Atypical antipsychotics may have lower risk of extrapyramidal syndrome, but all antipsychotics pose risks of cognitive worsening, stroke, and QTc prolongation. Benzodiazepines are reserved specifically for delirium caused by alcohol or benzodiazepine withdrawal, with a preference for monotherapy and short-acting agents (e.g., lorazepam).

A persistent challenge is the gap between what we know works and what is actually implemented in clinical practice. Very few hospital units have formal delirium risk reduction programs. The barriers are the same as those encountered in geriatric care more broadly: complexity requiring multi-component, coordinated approaches; inadequate resources, interdisciplinary communication, and reimbursement structures; and insufficient geriatric training among clinical staff.

Topic: Frailty

Lecturer: Prof. Colleen Maxwell (Part 2 of Geriatric Syndromes & Frailty)

Defining and Conceptualizing Frailty

Despite a lack of consensus on a standardized operational definition, frailty is clinically useful across care settings because knowing a patient’s chronological age and disease burden alone often fails to explain the observed variation in health outcomes and treatment responses. Frailty captures an additional dimension of vulnerability — it explains why two patients of the same age and similar diagnoses may respond very differently to the same drug or intervention.

Frailty is not equivalent to disability or multimorbidity, though it overlaps with both. An individual can be frail without being disabled, and frail without having many chronic conditions. Importantly, frailty is also associated with obesity (in part through its relationship with sarcopenia), not only with the stereotypical image of a thin, petite older woman.

The conceptual model of frailty centres on a loss of resiliency and reserve: the same minor stressor (a minor illness, a minor surgical procedure, a new drug) that causes only a modest, transient drop in a fit older adult will cause a disproportionately larger and more prolonged decline in a frail older adult — one from which they never fully recover to baseline. This distinction has profound implications for therapeutic decision-making.

Why Frailty Matters Clinically

Prevalence: Frailty increases with age, affecting upwards of 45–50% of those aged 85 and over, and approximately a quarter of those aged 65 and over. It is generally more common among women, though in very old populations receiving home care or nursing home care, the sex difference diminishes.

Dynamics: Frailty exists on a continuum from robust to pre-frail to frail. Progression is not inevitable or unidirectional — evidence shows that individuals can improve from more frail to less frail states, though this is less common than progression. This dynamism is what makes measurement and intervention both meaningful and feasible.

Adverse outcomes: Frailty predicts, in a dose-response relationship, increased risk of falls, disability, reduced quality of life, hospitalization, poor post-hospitalization recovery, long-term care admission, and mortality.

Atypical presentations: Frail older adults often present atypically. Delirium and cognitive impairment, depression, gait impairment and reduced walking speed, incontinence, and social support vulnerability are all common features of frailty and complicate standard clinical assessment.

Adverse drug events: Frail individuals are predisposed to adverse drug events because of their compromised multi-system physiological reserve. They are susceptible to complications of care generally, and specifically to drug-related side effects and interactions that would be well-tolerated in more robust adults.

Frailty and Pharmacokinetics

Building on age-related pharmacokinetic changes, frailty may produce exaggerated pharmacokinetic alterations over and above those attributable to aging alone. As frailty is associated with increased relative body fat, decreased lean body mass and body water, lower serum albumin, and declining renal and hepatic function, the predicted pharmacokinetic consequences include:

For lipophilic drugs: increased volume of distribution, lower plasma concentrations, and prolonged half-life. For hydrophilic drugs: decreased volume of distribution and potentially higher plasma concentrations. Clearance may be further reduced by declines in plasma esterase activity, hepatic metabolism (including cytochrome P450 enzyme activity), and renal function (glomerular filtration rate). A small study by Sarah Hilmer demonstrated altered clearance of gentamicin in frail patients, providing early empirical support for this theoretical framework. Much more research is needed.

Beyond pharmacokinetics, frailty’s cognitive and social components directly affect medication management: patients with greater cognitive or social vulnerability face barriers to accessing, understanding, and correctly taking medications — all dimensions of medication adherence that fall within the pharmacist’s scope of influence.

Measuring Frailty: The Two Major Models

There are numerous approaches to measuring frailty in the literature. The two most influential are the Physical Frailty Phenotype by Linda Fried (the Cardiovascular Health Study model) and the Frailty Index (accumulation of deficits model) by Ken Rockwood.

The Physical Frailty Phenotype (Fried) identifies frailty using five criteria: (1) unintentional weight loss; (2) slow gait speed (lowest quintile); (3) weak grip strength (lowest quintile); (4) low energy expenditure (low physical activity); and (5) self-reported exhaustion (based on two items from a clinical depression scale, an acknowledged limitation). An individual meeting three or more criteria is classified as frail; meeting one or two is pre-frail; meeting none is robust. In Fried’s original cohort: 7% were frail, approximately 47% pre-frail, and 46% not frail. This phenotype predicted falls, functional decline, hospitalization, and death over three years.

Limitations: The model is heavily physically oriented, relies on items that may not be feasible in the most vulnerable populations (e.g., gait speed testing is impractical in a nursing home), and explicitly excluded individuals with dementia or depression from its derivation study — meaning it neglects the cognitive and psychosocial dimensions of frailty that many researchers consider essential.

The Frailty Index (Rockwood) is a continuous ratio: the number of health deficits present in an individual divided by the total number of deficits assessed. A minimum of 40 items is recommended to ensure robustness. Items span biomedical, clinical, functional, and psychosocial domains — symptoms, signs, diseases, functional impairments, cognitive impairments, depression, social vulnerability, and abnormal laboratory values. An individual with 30 impairments out of 72 items assessed would have a frailty index of 30/72 ≈ 0.42.

An intriguing mathematical property of the frailty index, replicated across populations worldwide regardless of which specific items are included, is that no individual scores above approximately 0.7. This upper limit — consistent across North America, Europe, and China — appears to represent a biological threshold beyond which the accumulation of deficits becomes incompatible with continued life.

Advantages: The frailty index is comprehensive, captures cognitive and social domains, and functions as a continuous variable preserving gradations of frailty. Disadvantages: Collecting 40+ items is resource-intensive unless automated data are available (e.g., comprehensive geriatric assessment databases); and the large number of possible items makes it harder to target specific interventions.

Clinical frailty scale: A simpler, subjective approach — a 1–9 scale from “very fit” to “severely frail/terminally ill” — is used for rapid bedside assessment (e.g., by ICU physicians in Alberta). While easy to administer, it is inherently open to assessor bias and reliability concerns.

Single physical performance measures such as gait speed and grip strength (dynamometry) are easy to perform in community settings but may not be feasible in nursing home or hospital populations.

Pathophysiology of Frailty

The physiological systems most consistently implicated in frailty are the skeletal muscle system, the endocrine system, and the immune system, which are intimately interconnected.

Sarcopenia — the progressive loss of skeletal muscle mass, strength, and power — is considered a fundamental marker and driver of frailty. Sarcopenia is reinforced by neuroendocrine and immune dysfunction, and by inadequate nutrition (whether cause or consequence of frailty remains under investigation).

Neuroendocrine dysregulation includes declining hormone synthesis and release. Low testosterone levels and corresponding elevation of luteinizing hormone, loss of sex hormones, and dysregulation across the hypothalamic-pituitary-adrenal axis contribute to muscle wasting and reduced energetics.

Chronic low-grade inflammation (sometimes termed “inflammaging”) — characterized by elevated pro-inflammatory cytokines — is consistently observed in frail individuals. Differentiating whether this reflects frailty itself versus underlying chronic conditions is challenging, as both produce elevated inflammatory markers. Research has focused on combined endocrine-immune biomarker profiles — such as low IGF-1 combined with high cytokines, or combinations of coagulation markers and inflammatory mediators — as the most robust predictors of frailty, consistent with the multi-system nature of the syndrome.

Nutrition plays a role in frailty that is not yet fully characterized in its temporal relationship — it may cause, perpetuate, or be a consequence of frailty. Chronic inflammation can drive anorexia and muscle protein catabolism, exacerbating sarcopenia in a vicious cycle.

Linda Fried’s group’s cycle of frailty model integrates these pathways: neuroendocrine dysregulation, immune dysfunction, and declining muscle mass and energetics create a self-reinforcing cycle expressed clinically as unintentional weight loss, slowed walking speed, reduced grip strength, exhaustion, and low physical activity — the five phenotypic criteria.

Frailty and Drug Use: Clinical Implications

The relationship between frailty, multimorbidity, and polypharmacy is bidirectional and self-reinforcing:

Polypharmacy may be a risk factor for the onset or progression of frailty. Frailty is associated with polypharmacy, and both contribute to increased risk of adverse drug events. Non-adherence to medications is elevated in frail patients — the cognitive, social, and physical barriers to adherence accumulate with frailty.

The presence of frailty may directly increase the risk or severity of adverse drug events through its association with delirium, falls, orthostatic hypotension, and altered pharmacokinetics. Frailty may also lead to undertreatment if clinicians form a subjective judgment that a patient is “too frail” for an intervention without rigorously evaluating eligibility and potential benefit.

A study by Prof. Maxwell’s group in an assisted living population examined hospitalization risk among users of antipsychotics stratified by frailty level (using both the frailty index and the Fried phenotype). Regardless of which measure of frailty was used, individuals classified as robust had a lower hospitalization risk when taking antipsychotics, while those classified as frail had a substantially higher hospitalization risk — demonstrating empirically that frailty status modifies the risk associated with specific drug classes.

Because frail older adults have rarely been included in the randomized controlled trials that underpin clinical practice guidelines, clinicians are often working without adequate evidence for this population. The emerging consensus in pharmacoepidemiology is that frailty measures should be routinely incorporated into clinical trials of medications used in older adults.

Prevention and Treatment of Frailty

Prevention has focused on: modifiable predisposing factors (physical inactivity, overweight, smoking); precipitating triggers (infections, hip fractures); and modulators of recovery (depression, nutritional status, barriers to healthcare access).

Exercise interventions — particularly home-based physical therapy and resistance training — have shown positive effects on reducing fall risk and preserving mobility in pre-frail populations. Combinations of nutrition and exercise have demonstrated potential to prevent or slow sarcopenia. Comprehensive geriatric assessment targeted to the most vulnerable individuals reduces the risk of functional and cognitive decline. Evidence for nutritional supplementation alone (without exercise) is weak. Compliance to exercise regimens in older adults remains a persistent challenge, and optimal exercise frequency and intensity for frail populations is not fully established.

Treatment research has explored: exercise for its effects on inflammatory biomarkers (elevated in overweight and sedentary individuals); dietary interventions; vitamin D and antioxidant supplementation (largely without definitive positive findings); hormone replacement (experimental, limited evidence); cytokine inhibition strategies; and ACE inhibitors, which have attracted interest for their potential dual benefits of inhibiting inflammatory cytokines and improving the efficiency of skeletal muscle cells — a pathway connecting cardiovascular pharmacology to frailty biology.

The care of older adults across the frailty spectrum requires a growing, geriatrically expert, adequately reimbursed workforce of healthcare providers — including pharmacists trained in geriatric pharmacotherapy — to manage the time-intensive, comprehensive, and longitudinal care that frail older adults require.

Part 3: PHARM 491 — Pharmacy Seminar

Topic: Course Introduction

Coordinator: Prof. Colleen Maxwell, PHARM 491 Seminars in Pharmacy 3, Winter 2021

Topic: Therapeutic Developments in Respiratory Diseases

Presenter: Angie Shaw, Registered Respiratory Therapist and Certified Respiratory Educator, Airway Clinic, St. Mary’s Hospital, Kitchener (January 28, 2021)

Disclosure: Past single-presentation funding from AstraZeneca, Boehringer Ingelheim, and GSK on separate occasions for COPD management and inhaler education. No brand-specific recommendations made in this session.

Clinical Context and Diagnostic Principles

Angie Shaw has worked as a respiratory therapist since 2000 and as a certified respiratory educator, with experience in Alberta and in the Airway Clinic at St. Mary’s Hospital, Kitchener since 2007. The clinic serves outpatient populations with COPD, asthma, cystic fibrosis, and long-term ventilation needs, and operates a full pulmonary function and diagnostics laboratory.

A fundamental principle underlying all respiratory drug therapy is that confirming the diagnosis is the essential first step. Not everything that wheezes is asthma; not everything that coughs is COPD. Spirometry confirming reversible or irreversible airflow obstruction is required for both diagnoses. Spirometry cannot be reliably performed in children under age 6.

The guidelines governing practice in Canada and globally include: the Canadian Asthma Guidelines (2017, with 2021 updates anticipated); the GINA (Global Initiative for Asthma) Guidelines (2019); the Severe Asthma Guidelines; and the Canadian COPD Guidelines. The 2021 Canadian guidelines were expected to align closely with the GINA 2019 guidelines, particularly around the re-positioning of ICS-formoterol as first-line treatment.

Short-Acting Beta-2 Agonists (SABAs)

The prototypical SABA is salbutamol (trade names: Ventolin, Airomir) or terbutaline (Bricanyl). These are rapid-onset bronchodilators, relaxing smooth muscle around the bronchi with onset within one minute. Side effects include tremors, palpitations, and headache.

Formoterol (Foradil, Oxeze) occupies an intermediate position: it is technically classified as a long-acting beta-2 agonist but has a rapid onset of approximately 3 minutes — close to the SABAs — which is the pharmacokinetic property that enables its role as a rescue inhaler when combined with an inhaled corticosteroid in Symbicort (see below).

A major paradigm shift in asthma management is the de-emphasis of SABA monotherapy as first-line treatment for adults and adolescents (12 years and older) in the GINA 2019 guidelines, with full adoption expected in the 2021 Canadian guidelines. The problem with SABA-first management is that patients preferentially reach for the SABA (producing quick symptom relief) while neglecting the inhaled corticosteroid that addresses the underlying inflammation. This pattern has been associated with asthma deaths, where repeated bronchodilator use in the absence of anti-inflammatory treatment fails to control the inflammatory cascade — by the time a patient arrives at hospital, even intravenous corticosteroids take hours to begin working. For preschoolers, SABA remains an initial treatment based on presentation.

SABA use in COPD: SABAs remain first-line therapy in COPD, used as rescue medication. Therapy is advanced when symptoms persist despite as-needed short-acting bronchodilator use (typically defined as use more than twice weekly).

Short-Acting Anticholinergics (SABAs/SAMAs)

Ipratropium bromide (Atrovent) is a short-acting muscarinic antagonist (SAMA). It is a bronchodilator with a longer onset of action than salbutamol — not an appropriate first choice for acute rescue — but a useful option for patients who cannot tolerate the tremors and palpitations of beta-2 agonists. Side effects include dry mouth, mild tremors and palpitations (less than SABAs), and increased intraocular pressure if the aerosol contacts the eye (relevant warning: do not spray toward eyes; nebulizer delivery carries the highest risk of ocular exposure).

Combivent (salbutamol + ipratropium) is a SABA/SAMA combination that demonstrates superior outcomes in COPD compared to SABA alone. However, it is not covered on the Ontario provincial formulary, limiting its use due to out-of-pocket cost.

Ipratropium has no role in routine outpatient asthma management (possible use in the emergency room only), while in COPD it can be first-line therapy for patients intolerant of SABAs.

Long-Acting Muscarinic Antagonists (LAMAs)

LAMAs (long-acting muscarinic antagonists — the preferred terminology over “long-acting anticholinergics”) available in Canada include:

• Tiotropium (Spiriva, HandiHaler, Respimat) — once daily
• Glycopyrronium (Seebri) — once daily
• Aclidinium (Tudorza) — twice daily
• Umeclidinium (Incruse) — once daily

Side effects are consistent with the class: dry mouth, urinary retention (rare but profound when it occurs), constipation, and risk of glaucoma exacerbation (intraocular pressure elevation). If a patient is started on a LAMA, the short-acting ipratropium (Atrovent) should be stopped to avoid compounding anticholinergic side effects.

LAMA in asthma: Add-on therapy only, when inhaled corticosteroid alone is insufficient. For severe asthma or near-fatal asthma history, it can be a daily treatment. Only tiotropium is currently approved for asthma management. For children aged 12 and older, LAMA can be added when ICS alone is inadequate.

LAMA in COPD: LAMAs are typically the first-line daily therapy in COPD once a patient requires regular treatment beyond rescue SABAs. Head-to-head studies show LAMAs slightly outperform LABAs in symptom relief and duration of effect in COPD.

Asthma-COPD overlap (ACO): Patients with both conditions should begin with an ICS-LABA combination as first-line therapy, to address both the asthmatic inflammation and the COPD component; a LAMA can be added if control remains inadequate.

Long-Acting Beta-2 Agonists (LABAs)

LABAs available in Canada include formoterol (Foradil, Oxeze — 12-hour, rapid onset), indacaterol (Onbrez — 24-hour), and salmeterol (Serevent — 12-hour, slow onset of 20 minutes, not suitable as a reliever). Side effects mirror SABAs but may be more pronounced given longer systemic exposure.

Critical safety rule for LABAs in asthma: never use a LABA alone in asthma. A prominent black box warning exists for LABA monotherapy in asthma due to increased risk of asthma-related deaths. LABAs must always be used in combination with an inhaled corticosteroid. Using combination inhalers (ICS-LABA in one device) prevents patients from inadvertently using the LABA without the steroid.

LABA in asthma: Add-on to ICS when ICS alone is insufficient. In severe asthma, it is a common first-line daily therapy in conjunction with ICS.

LABA in COPD: Can be used as first-line daily therapy (alongside LAMA), but LAMAs are generally preferred in head-to-head comparisons.

ICS-LABA Combination Inhalers and the SMART Protocol

ICS-LABA combination inhalers available in Canada:

• Advair (fluticasone propionate + salmeterol) — Diskus or MDI
• Symbicort (budesonide + formoterol) — Turbuhaler
• Zenhale (mometasone + formoterol) — MDI
• Breo (fluticasone furoate + vilanterol) — Ellipta (once daily)

A landmark paradigm shift, reflected in GINA 2019 and anticipated in the 2021 Canadian guidelines, is the use of Symbicort as both a controller and a reliever — formally termed SMART (Symbicort Maintenance and Reliever Therapy) or sometimes MART in the literature. The rationale: when a patient uses their reliever because they are symptomatic, they have airway inflammation. By delivering formoterol (fast bronchodilation) alongside budesonide (steroid reducing inflammation) in the same puff, the reliever simultaneously treats the symptom and the underlying pathology. This approach also breaks the unhealthy emotional attachment patients develop to their blue SABA inhaler. Only Symbicort among Canadian ICS-LABAs is suitable for this role, because of formoterol’s rapid onset; Advair’s salmeterol has too slow an onset (20 minutes); Zenhale has formoterol but Merck has not released supporting efficacy data for as-needed use; Breo’s vilanterol has not been adequately studied in this context.

For children aged 6–11 in Canada, Symbicort is not indicated. The interim recommendation from GINA is that any time a child uses a SABA, they should also take a dose of ICS — requiring two separate inhalers. A SABA-ICS combination inhaler exists elsewhere in the world but not yet in Canada.

For COPD, ICS-LABA combinations (Advair, Symbicort, Breo) are used as add-on therapy only — when long-acting bronchodilators and pulmonary rehabilitation have not achieved adequate control, or in patients with asthma-COPD overlap. ICS alone is not used in COPD (unlike in asthma), because COPD inflammation typically does not respond well to corticosteroids. Zenhale has no COPD indication due to absence of supporting Merck studies.

Inhaled Corticosteroids (ICS)

ICS available in Canada include:

• Beclomethasone (QVAR)
• Budesonide (Pulmicort)
• Ciclesonide (Alvesco)
• Fluticasone propionate (Flovent)
• Fluticasone furoate (Arnuity)
• Mometasone (Asmanex)

ICS are the cornerstone of asthma maintenance therapy — addressing the underlying inflammation that SABA use alone fails to treat. Common local side effects include oral thrush (candidiasis), dysphonia (voice changes), and sore throat. The standard mitigation strategy is to rinse and gargle with water after every use. Rare systemic effects from prolonged high-dose use include easy bruising, dermal thinning, bone weakening (osteoporosis risk), and adrenal suppression (cortisol level changes).

Ciclesonide (Alvesco) is a prodrug ICS — the steroid molecule is not activated until it reacts with respiratory tract enzymes in the lung. It therefore has minimal systemic absorption or oral deposition, substantially reducing the risk of oral thrush, dysphonia, and systemic effects. This makes it a preferred option for patients who experience troublesome ICS side effects.

ICS in asthma: First-line daily maintenance therapy, starting at low dose and stepping up as needed. The approach is to avoid high-dose ICS by adding on LABA or LAMA before escalating steroid dose.

ICS in COPD: Not used alone. Only used in combination with LABA (and potentially LAMA in triple therapy) in moderate-to-severe COPD or asthma-COPD overlap.

For asthma exacerbations, the recommendation is a short-term fourfold increase in the patient’s ICS dose (not a small increment) — pharmacists should not be surprised to see this on prescriptions.

LAMA-LABA Combination Inhalers

Available in Canada: Ultibro (indacaterol + glycopyrronium), Inspiolto (tiotropium + olodaterol, Respimat), Anoro (umeclidinium + vilanterol, Ellipta), and Duaklir (aclidinium + formoterol, 12-hour, twice daily). All others are once-daily.

These drugs are for convenience and adherence optimization — consolidating two bronchodilators into one device. Once COPD is more than very mild, most patients benefit from dual bronchodilation. Studies consistently show that LAMA-LABA combinations outperform either component alone. In clinical practice, very few patients remain on LAMA or LABA monotherapy; most advance to the combination.

No role in asthma (LAMA-LABA combinations are not indicated for asthma).

Triple Therapy: ICS-LABA-LAMA

Canada’s current triple therapy option is Trelegy (fluticasone furoate + vilanterol + umeclidinium, Ellipta), a once-daily inhaler. It comes in only one ICS strength, which may be insufficient for patients requiring higher steroid doses (particularly in asthma-COPD overlap). It is not indicated for asthma, though studies are underway.

Triple therapy is used in moderate-to-severe COPD when LAMA-LABA dual bronchodilation is insufficient, or in asthma-COPD overlap when ICS-LABA alone does not achieve control. Additional triple therapy options were anticipated to reach Canada within one to two years of the January 2021 session.

Non-Inhaler Add-On Therapies

In asthma: Montelukast (Singulair) — a leukotriene receptor antagonist — can be an add-on therapy from as young as 2 years of age. Omalizumab (anti-IgE, Xolair) is used in allergic asthma. Oral corticosteroids (prednisone) are used for exacerbations. Theophylline is an older option, rarely used now but retained for cases of treatment failure or cost-prohibitive circumstances. Macrolides (notably azithromycin three days per week) are used in severe asthma for their anti-inflammatory properties. Anti-IL-5 biologics (three available in Canada as of 2021) are reserved for severe eosinophilic asthma under specialist care.

In COPD: Roflumilast (Daxas) — a PDE4 inhibitor — has a role in severe COPD with frequent exacerbations; widely used internationally but less commonly in Canada. Macrolides (azithromycin) are increasingly used in COPD for their anti-inflammatory and potentially antimicrobial effects. Standing antibiotic prescriptions (typically azithromycin or doxycycline) are given to higher-risk COPD patients, who are instructed to self-initiate therapy and notify their physician if a purulent exacerbation develops. A standing oral corticosteroid prescription is similarly provided for non-infective COPD exacerbations.

Inhaler Devices: Technique and Selection

Correct inhaler technique is a major determinant of therapeutic effectiveness. Pharmacists share responsibility with other healthcare providers for assessing and teaching inhaler technique at the point of dispensing.

Metered Dose Inhaler (MDI) with spacer/chamber: The MDI with a spacer (valved holding chamber) is recommended over MDI alone for all patients. Spacer use improves lung deposition, eliminates the coordination challenge of pressing the canister simultaneously with inhalation, and substantially reduces oropharyngeal deposition of ICS, decreasing the risk of oral thrush and voice changes.

Available spacer devices in Ontario include the AeroChamber (most common, most expensive, approximately $20–50 without mask), Opti Chamber, Pocket Chamber (most compact), and Slide Chamber. All come with mouthpiece and optional mask attachments (adult, pediatric, and infant). Coverage is typically through third-party drug plans, not the Ontario Drug Benefit (ODB) formulary. Spacers should be cleaned weekly in warm soapy water and air-dried (not towel-dried, to avoid fiber residue).

Technique for MDI with spacer: (1) Shake vigorously at least 10 times; (2) insert MDI into chamber; (3) place chamber mouthpiece in mouth with teeth open; (4) actuate once; (5) inhale slowly and deeply over 3–5 seconds; (6) hold breath for a count of 10; (7) exhale gently; (8) wait at least 30 seconds between actuations (time for propellant pressure to recharge). The 30-second wait is unique to MDIs — Respimat is spring-loaded and does not require this delay.

The chamber whistle (built into most devices) indicates the patient is inhaling too fast. Teeth-closed inhalation is a common error causing medication to impact the teeth rather than entering the airway. A multi-breath technique (six normal breaths rather than one large breath) is used for children, patients with severe breathlessness, and those who cannot seal lips around the mouthpiece (a masked chamber is used in those cases).

MDI canister fullness: Counters are present on some devices. Without a counter, gently shaking the detached canister — if the feeling of liquid movement is absent, it is empty. Never float canisters in water (blocks the nozzle). If a canister sounds full but delivers nothing, the boot (actuator) may be clogged; wash the boot in hot soapy water and allow to air dry.

Diskus (Dry Powder Inhaler): A simple four-step device — open until click, pull lever to load dose, exhale gently away from device, deep strong inhalation. The key error to avoid is exhaling into the device (blowing away the dry powder). Do not lift the tab when done — close the whole device to reset it. The Diskus has a dose counter. Wixela (generic Advair, Diskus-style device) follows the same steps. Important dosing note: Advair MDI delivers twice the puff of Advair Diskus for the LABA salmeterol component — maximum dose for MDI is 2 puffs twice daily; for Diskus it is 1 puff twice daily.

Turbuhaler: Requires a good strong deep inhalation — it has the highest resistance of all dry powder inhalers. Loading: rotate base fully one way then back the other (two turns; a click is audible). Exhale away from device, then deep strong breath. A test whistle device (available from AstraZeneca at no charge) mimics the Turbuhaler’s resistance and allows clinicians to confirm a patient can generate sufficient inspiratory force. If they cannot trigger the whistle, the Turbuhaler is not an appropriate device for them. Note that the desiccant inside the Turbuhaler makes a rattle sound even when the medication is exhausted — patients must watch the dose counter, not listen for sound.

Twisthaler: Similar resistance to Turbuhaler. Opening the cap both loads the dose (counter drops immediately) and makes the device ready to use — just remove cap and inhale. When empty, the device locks, preventing continued use.

HandiHaler (tiotropium capsule inhaler): Capsule-based device. A strip of foil-wrapped capsules is peeled one at a time; the remainder must remain in the dark. Capsule is loaded, device closed and clicked, pierced once by the button, then the patient inhales twice (to ensure complete emptying of the capsule powder). After use, the device is opened and the capsule is discarded away from the hands (due to anticholinergic residue). Gradually being replaced by Respimat. Note: patients should never open the capsule by hand or pour powder into their palm; the residue risk from touching the eyes applies here.

Breezhaler (glycopyrronium/indacaterol/aclidinium): Similar capsule concept but with a translucent capsule, allowing visual inspection for remaining powder. Has a lower resistance than the Turbuhaler, making it more accessible for patients with weaker inspiratory effort. The device has two buttons (pinched simultaneously). Design flaw: the wide loading chamber opening has led patients to accidentally drop capsules into the inhalation path — a counselling point.

Ellipta: Among the simplest devices — slide until click, breathe out, deep breath in, slide closed. Very low resistance. All medications in the Ellipta are once-daily. The counter turns red when empty but does not lock. Must not block the ventilation slot (needed for venturi airflow mechanism).

Respimat (soft mist inhaler): Requires assembly and priming upon first use (four primes). Once opened, valid for 60 days only. Unlike MDIs, it is spring-loaded — no 30-second wait between doses. Delivers medication as a slow, fine mist, requiring coordination between actuation and inhalation. The mist moves slowly enough to exit the mouth if breath-hold is not maintained — a critical counselling point. For patients with poor coordination, the Respimat can be inserted into a chamber (some companies offer a purpose-made adapter). Contains LAMAs; avoid ocular exposure.

Aerochamber with positive expiratory pressure (AerobiKa/Acapella/Flutter): Briefly mentioned in Q&A — these are positive expiratory pressure (PEP) devices used to mobilize secretions (mucus clearance). They contain a vibrating fan or mechanism; as the patient exhales, vibration is transmitted to the chest. Useful in COPD, bronchiectasis, and cystic fibrosis. Not a first-line therapy in well-controlled asthma.

Key Practical Counselling Points

Rinse and gargle after every ICS use. Use a chamber with every MDI, regardless of patient age or perceived ability. Limit the number of inhaler device types a patient needs to use — ideally one or two devices — to reduce confusion and improve adherence. Once-daily dosing options should be preferred when clinically appropriate. Adherence is a major challenge: at least 50% of prescriptions are not filled or not used correctly. Combination inhalers (ICS-LABA, LAMA-LABA, or triple) substantially improve adherence by consolidating multiple therapies.

Nebulizers: Since the SARS outbreak in 2003, it has been recognized that nebulizers aerosolize airborne particles and have potential for viral spread. The respiratory therapy community has been advocating for reducing nebulizer use in favour of MDI with spacer (which achieves equivalent or superior drug delivery) ever since — a transition made more urgent by COVID-19.

Topic: Continuing Education and Your Five-Year Plan

Presenter: Megan Shippey Quinlan, BScKin, BScPhm, PharmD (Rx 2012, University of Waterloo); Inpatient Pharmacy Manager, Juravinski Hospital, Hamilton Health Sciences; guest introduced by Dr. Rosemary Killeen (February 22, 2021)

Career Trajectory and the Meaning of Planning

Megan Shippey Quinlan’s presentation offers a retrospective examination of how a five-year career plan from 2012 unfolded across nearly a decade of pharmacy practice, from community hospital clinical pharmacist to inpatient oncology pharmacy manager.

Upon graduating from the University of Waterloo in December 2012, Megan’s stated goals were: full-time employment with benefits and pension in a community hospital as a clinical pharmacist; achievement of an antimicrobial stewardship certification (through ASHP); a certified geriatric specialist designation; continued CSHP membership; possible fellowship in the United States; and a post-baccalaureate PharmD. She had no interest in residency or teaching hospital settings — a fact she found “rather funny” in retrospect given that she now manages a pharmacy within a tertiary academic teaching hospital.

Her co-op placements shaped these goals significantly: Medication Reconciliation Coordinator at Grand River Hospital; IV compounding at Brantford General Hospital (during the early rollout of NAPRA sterile compounding standards, prompted by patient safety incidents at Marchese Hospital and London Health Sciences); Antimicrobial Stewardship Coordinator at Grand River Hospital (working with Dr. Brett Barrett); and Clinical Coordinator at a PharmaSave/methadone clinic in Woodstock.

Location vs. Job Potential

The first real-world tension she encountered was between location and job potential. She had internship offers in community pharmacy (with a position after), in locations she didn’t want to live in, and at Grand River Hospital (without a subsequent position). She chose Brantford General Hospital for the internship, which transitioned immediately into a full-time clinical pharmacist role — achieving her stated five-year goal within four months of graduation.

Her early clinical work at Brantford involved a medicine floor with infectious disease, palliative, and mental health patients, combined with a second role as a relief pharmacist and part-time methadone pharmacist. She subsequently assumed a Professional Practice Lead position alongside her clinical pharmacist role at Brantford, becoming involved in Accreditation Canada standards, scope of practice implementations directed by the Ontario College of Pharmacists (OCP), pre-printed order review/CPOE, Lean management, medication error analysis, and medical directives. A teaching opportunity with McMaster University’s Family Physician Residency Program emerged from this work.

Adaptability and Lifelong Learning

In 2014, she became a telepharmacist with Northwest Telepharmacy Solutions (a subgroup of the Northwest Company, which serves northern Canada). This enabled her and her husband to relocate to the Yukon while her husband completed residency placements, and she managed remote clinical pharmacy services for West Parry Sound Health Centre (Ontario). A subsequent assignment in Nunavut provided professional and personal experience with healthcare challenges specific to Canada’s north — tuberculosis, diabetes, and mental health in remote and underserved communities.

Her educational goals evolved significantly based on employer direction rather than her original plan. Her PharmD was completed at the suggestion of her employer at Hamilton Health Sciences. Project management certification emerged as unexpectedly valuable given the volume of implementation work in hospital pharmacy. Leadership certification, management conferences, antimicrobial stewardship programming, and methadone education all happened in response to practice context rather than pre-planned intention.

In September 2016, four years after graduation, she took the Inpatient Pharmacy Manager position at Juravinski Hospital, Hamilton Health Sciences. As of 2021, the department comprised 56 pharmacy technicians and 33 pharmacists, with recent expansion including a 15-million-dollar stem cell transplant centre pharmacy with NAPRA-compliant IV and hazardous compounding suites, five pharmacy robots, and 11 IV and hazardous hoods. Services include 50 inpatient malignant hematology beds, 42 inpatient oncology beds, medicine, ortho, and surgical oncology.

Lessons for Graduating Pharmacists

Several themes crystallized across her decade of practice:

Document everything: OCP requires a learning portfolio (one peer review and three self-assessments in the first five years; evolving toward practice assessments). Continuing education is lifelong — all formal and informal learning, peer presentations, committee work, and self-directed study should be documented.

Take every opportunity: Projects she undertook — including leading the non-sterile compounding implementation at Hamilton Health Sciences — led unexpectedly to appointment as a national subject matter expert on the National Non-Sterile Compounding Implementation Working Group and to teaching opportunities through the Ontario Pharmacists Association. Involvement in MAID (medical assistance in dying) rollout at Hamilton likewise opened further professional development avenues.

Interview preparation: Interview as often as possible; know the organization you are applying to; know what you can offer; prepare questions. University of Waterloo graduates are sought after and have more to offer than they often recognize, given the co-op experience and clinical training.

Financial planning: Student loans, mortgage, family obligations, and location-dependent wage differences (e.g., higher wages in Hamilton and smaller centres than Toronto) all affect career decisions. Further postgraduate education can be expensive. Planning financial goals alongside professional goals is essential.

COVID-19 and adaptability: The pandemic illustrated how quickly even well-developed plans must change. The Juravinski Hospital had been in outbreak (COVID-19) since December 10, 2020 — with 11 outbreaks — impacting planned oncology surgeries, stem cell transplants, and ICU capacity planning. Pharmacy pandemic response required rapid adaptation: pharmacists covered medication distribution (“meds to beds”) when staff shortages arose. The key competencies highlighted by the pandemic — and identified by the World Economic Forum as critical for the near-term future — are flexibility, critical thinking, and the ability to adapt — the same non-technical skills that Dr. Rosemary Killeen emphasized in her theoretical framing of continuing professional development.

Continuing Education Resources and Pathways

For pharmacists interested in specialty certification and advanced training, options discussed in this session include:

The Board of Pharmacy Specialties (BPS) in the United States offers board certification in areas including pharmacotherapy, oncology, infectious diseases, and others — recognized broadly in North America. ASHP’s fellowship programs offer one- and two-year structured fellowships in specialty areas. Some of these are accessible to Canadian PharmD graduates who obtain US licensure. The Master of Pharmacy (MPharm/MPharm) program at the University of Waterloo provides a pathway to clinical specialization for Canadian pharmacists without requiring US licensure. The Canadian ASHP antimicrobial stewardship and primary care CPD programs and the Society of Infectious Diseases Pharmacists certificate program (recognized broadly in North America) are available domestically. For informal educational development, specialty networks, working pharmacists in the area of interest, and direct institutional outreach often yield the most actionable leads.

The overarching message of this session, as synthesized by Prof. Colleen Maxwell in closing remarks: a pharmacist’s career path rarely follows the plan laid out at graduation. The non-pharmacy skills — leadership, project management, adaptability, communication — become as important as clinical knowledge. Life experience (including personal decisions about geography, family, and risk-taking with novel opportunities) enriches professional development. The essential posture is to recognize when goals need revision, to remain curious, and to understand that the profession of pharmacy offers broader opportunity than any single fixed plan can capture.