De-coding prescribing cascades

Case 1: Amlodipine-induced edema misinterpreted as heart failure

Patient: Linda, 78 years old

Setting: Community pharmacy

Pharmacist: Joaquim (15 years in practice)

Medical history: Hypertension, osteoarthritis, hyperlipidemia

Medications:

• Amlodipine 10 mg daily (started 1 month ago)
• Atorvastatin 20 mg daily (ongoing since 2019)
• Acetaminophen, as needed (infrequent use)

Scenario:

Linda presents with bilateral lower extremity swelling and some exertional shortness of breath. Her family physician, suspecting fluid overload, prescribes furosemide 20 mg daily. Linda states that she is to follow-up with her family physician in two weeks and has a requisition to do a blood test a day prior to that follow-up appointment.

Pharmacist reflections:

Upon reviewing Linda’s prescription profile, Joaquim wonders about the following. Could the edema be a medication side effect from amlodipine rather than fluid overload? Is furosemide appropriate in this context, or is this a preventable prescribing cascade? Joaquim also wonders, “should I really bother the doctor about this? I’m sure they have thought about this as well, and it’s not my job to diagnose. Doctors always complain about too many pharmacy faxes and I recently read derogatory remarks on social media about pharmacist’s scope of practice made by the prescribing physician. What’s the worst that can happen if I dispense the furosemide? After all, the patient is seeing the doctor in two weeks.”

What would you do if you were in Joaquim’s position?

Key points:

Amlodipine commonly causes peripheral edema, particularly at higher doses, through arteriolar dilation without matching venous dilation. The edema is not due to fluid retention, so diuretic therapy offers no clinical benefit and can cause electrolyte imbalance, dehydration, acute kidney injury and falls.¹⁴ While we can’t fully predict whether this patient will have an adverse event, such as a fall, from the addition of furosemide, we may wish to consider how risks may be mitigated. How would we assess risk or counsel the patient? Reflect on personal biases and experiences, for example, one’s individual confidence and comfort in working to their full scope of practice and the strength of collaborative relationships with physicians.

Pharmacist actions: what did Joaquim do?

Joaquim spoke with the patient about peripheral edema being a common side effect of amlodipine and explained why a diuretic may not help. Joaquim reviewed the risks of furosemide, including fall risk and effects on electrolytes and renal function. Joaquim explained to the patient that the side effect from amlodipine may improve with reducing the dose of amlodipine or switching to another antihypertensive. Joaquim offered the patient the choice to try the furosemide as prescribed by the physician, or Joaquim could contact the physician to review the concern. The patient revealed to Joaquim that the physician didn’t mention that the swelling could be a side effect of the amlodipine, so she asked Joaquim to contact the prescriber. Joaquim faxed the clinic and followed-up with a phone call to review the importance of the prescriber reviewing the fax. Joaquim recommended reducing the amlodipine dose or switching to an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB).

Do you agree with Joaquim’s approach? Would you have done anything differently?

Case 2: Cholinesterase inhibitor-induced incontinence treated with an anticholinergic

Patient: Bharath, 84 years old

Setting: Community pharmacy

Pharmacist: Hannah (one year in practice)

Medical history: Mild Alzheimer’s disease, benign prostatic hypertrophy (BPH), hypertension

Medications:

• Donepezil 5 mg daily (started 3 weeks ago)
• Tamsulosin 0.4 mg daily (ongoing since 2023)
• Amlodipine 5 mg daily (ongoing since 2001)

Scenario:

Bharath’s daughter, Priyanka, presents a new prescription for oxybutynin 5 mg twice daily from an after-hours walk-in-clinic physician, after Bharath began experiencing urinary urgency and occasional incontinence. Priyanka shares that her dad is extremely distressed by the episodes of urinary incontinence as this has occurred in social situations. She is hoping this new medication “does the trick” to reduce these episodes.

Pharmacist reflections:

Hannah is aware that oxybutynin has anticholinergic properties. She is wondering, would oxybutynin worsen Bharath’s cognition? Or perhaps, could donepezil be contributing to Bharath’s urinary symptoms? Is there a risk in combining a cholinesterase inhibitor (donepezil) with oxybutynin? Hannah also notes that Bharath is on tamsulosin. She wonders whether his symptoms might be more consistent with worsening BPH, and whether his BPH management needs reassessment. Hannah also notes on Bharath’s profile that there are multiple prescribers involved—donepezil is prescribed by a geriatrician, tamsulosin prescribed by a urologist, and amlodipine prescribed by a family physician.

What would you do if you were in Hannah’s position?

Key points:

Donepezil, a cholinesterase inhibitor, can increase bladder contractility via cholinergic effects, leading to urgency or incontinence. Oxybutynin is a potent anticholinergic, which may worsen cognition, delirium risk and fall risk in older adults. This combination represents a pharmacologic conflict—where one drug’s side effect is treated with a counteractive agent.¹⁵ There may also be underlying medical issues that may confound the assessment, and questions around continuity with medical follow-up.

Pharmacist actions: what did Hannah do?

Hannah explained to Priyanka that she is concerned that the oxybutynin could be associated with worsening confusion, agitation and fall risk. She also explained that donepezil might be associated with urinary side effects, but there might be other issues as well, such as worsening signs or symptoms of BPH, or even a urinary tract infection (UTI). Hannah is clear to Priyanka that she does not feel comfortable dispensing the oxybutynin without speaking to the prescribing physician to help better understand the diagnosis. Hannah contacted the walk-in-clinic physician who felt that Bharath’s symptoms were not in keeping with an acute UTI, but cancelled the prescription for oxybutynin and advised that the patient follow-up with their family physician to consider whether the donepezil should be reassessed, or further review his BPH. Hannah states to Priyanka that it is not in her scope of practice to instruct Bharath to discontinue the donepezil, but advises Priyanka to schedule follow-up with the geriatrician and/or family physician to review further. Priyanka agrees to do so.

Do you agree with Hannah’s approach? Would you have done anything differently?

Case 3: NSAID-induced hypertension and renal impairment

Patient: Catalina, 71 years old

Setting: Interprofessional primary care team

Pharmacist: Jamie (18 years in practice)

Medical history:

• Rheumatoid arthritis (RA) (diagnosed in 2025)
• Type 2 diabetes (latest glycated hemoglobin [A1C] 8%)
• Hypertension (previously well-controlled on monotherapy)
• Stage 2 chronic kidney disease (CKD) (eGFR ~65 mL/min/1.73 m²)

Medications:

• Lisinopril 10 mg daily (ongoing since 1998)
• Metformin 500 mg twice a day (ongoing since 1995)
• Naproxen 500 mg twice a day (prescribed 8 weeks ago by rheumatologist for worsening RA symptoms)
• Acetaminophen 325 mg twice a day, as needed (since 2025)
• Vitamin D 1000 IU daily

Scenario:

Catalina was referred to the primary care team pharmacist, Jamie, by the clinic’s nurse practitioner to review medications, specifically regarding consideration of initiating a sodium–glucose cotransporter 2 (SGLT2) inhibitor for diabetes and renoprotection. During this medication review, Jamie notes that Catalina’s blood pressure (BP) has increased over the past two recent clinic visits (now averaging 158/92 mmHg). Recent labs show a rise in serum creatinine (from baseline 85 to 112 µmol/L) and an eGFR drop to 54 mL/min/1.73 m². The clinic’s nurse practitioner recently initiated amlodipine 5 mg daily to manage the elevated blood pressure.

Pharmacist reflections:

Jamie wonders, could the new antihypertensive be treating a side effect of another medication? Is the patient’s kidney function decline and elevated BP potentially NSAID-induced?

Key points:

Naproxen, like other NSAIDs, can raise blood pressure and impair renal function by reducing renal perfusion and sodium excretion, particularly in patients with diabetes, hypertension or pre-existing CKD.^3,4 The combination of an NSAID with an ACE inhibitor (naproxen plus lisinopril in this case) can increase the risk of renal injury. Adding a new antihypertensive may mask the problem, escalating polypharmacy without addressing the root cause.

Pharmacist actions: what did Jamie do?

Jamie educated Catalina on how naproxen may be worsening her blood pressure control and kidney function. Catalina shared that the rheumatologist did offer her other options, specifically, hydroxychloroquine, but Catalina felt that naproxen was the most familiar option to her, and thus the safest. This led to further education of the patient concerning the safety profile of hydroxychloroquine compared to naproxen. Jamie spoke with the clinic nurse practitioner highlighting the temporal relationship between starting naproxen and the rise in BP and creatinine. Jamie wondered whether the naproxen could be stopped or the dose reduced to 250 mg twice a day and then renal function and BP reassessed. Jamie also suggested the patient may wish to revisit hydroxychloroquine with the rheumatologist, as Catalina may now be more open to considering this option. Jamie and the nurse practitioner reviewed what pain management strategies they felt comfortable offering the patient in primary care, while awaiting follow-up with rheumatology. For example, optimizing the acetaminophen dose, topical diclofenac for local pain, and nonpharmacologic supports for pain management. Jamie and the nurse practitioner also reviewed considering a trial of NSAID dose reduction, with a repeat serum creatinine and blood pressure check to be done one month later.

Do you agree with Jamie’s approach? Would you have done anything differently?

Case 4: Antipsychotic-induced parkinsonism treated with an anticholinergic

Patient: Dimitri, 82 years old

Setting: Community pharmacy serving a retirement home

Pharmacist: Mei (3 years in practice)

Medical history: Dementia with behavioural symptoms, hypertension, chronic constipation

Medications:

Risperidone 0.5 mg twice a day (initiated 8 weeks ago for agitation)

Trihexyphenidyl 1 mg twice a day (started 3 weeks ago to manage risperidone-induced parkinsonism)

Irbesartan 150 mg daily (ongoing since 2000)

PEG 3350 17g daily (ongoing since 2015)

Scenario:

Dimitri’s son and power of attorney, Mikhail, phones the pharmacy asking to speak with the pharmacy manager. He is upset. He reports that his father suffered a fall last week, which resulted in an intracranial hemorrhage, leading to Dimitri’s death. Mikhail expresses shock, stating that his father had no prior history of falls. He recently discovered online that trihexyphenidyl is considered high-risk in elderly patients, especially those with dementia. Mikhail questions why the pharmacy dispensed a medication that is known to cause confusion and increased fall risk in seniors and demands an explanation.

Pharmacist reflection:

Mei realizes that Dimitri is grieving the loss of his father, and is questioning whether his death was medication-related or preventable. Mei is conflicted on how best to respond to Dimitri, and feels pressure to defend that what the pharmacy dispensed was appropriate, but she is unsure if she has all the information at hand. She wonders, however, was the fall preventable? There is a strong possibility that a prescribing cascade contributed to the adverse outcome. What triggered the cascade? Risperidone, an antipsychotic often used for behavioural symptoms in dementia, can cause extrapyramidal symptoms such as parkinsonism. Was trihexyphenidyl appropriate to treat these symptoms?

Key points:

A prescribing cascade occurred. Risperidone-induced parkinsonism led to treatment with trihexyphenidyl, which may have contributed to the fall and fatal injury.¹⁶ The use of trihexyphenidyl in an elderly patient with dementia and constipation was high-risk and potentially avoidable. This medication is listed on the Beers Criteria as potentially inappropriate in older adults due to the risk of worsening cognitive impairment, increased sedation, exacerbation of constipation and higher fall risk.¹⁷ Nonpharmacologic strategies, including environmental or behavioural interventions to address agitation, and reassessing the need for risperidone may have been safer alternatives.

Pharmacist actions: what did Mei do?

Mei felt her first priority was to express condolences and acknowledge the seriousness of this event. Mei contacted the pharmacy manager so that they could speak with the patient’s son. Mei recognized this as a learning opportunity for the entire pharmacy team to reflect on what pharmacy processes were implemented to review Dimitri’s medications. For example, were concerns about trihexyphenidyl identified by the dispensing pharmacist? Were any electronic flags noted by the pharmacy’s computer system? How were these risks communicated by the pharmacist to the patient, or in this case, power of attorney? Or to the prescriber? Was there any documentation around a discussion of other therapeutic approaches, or suggestions around reassessing the use of risperidone? What can be learned from this case? Do any processes and procedures need to change at the pharmacy? How would you have handled this case if you were in Mei’s position?

Discussion

These cases highlight the significant clinical impact of prescribing cascades and the essential role pharmacists practising in community settings play in their identification and prevention. Key to identifying a cascade is recognizing the temporal relationship between medication changes and new symptoms. In Linda’s case, amlodipine-induced edema was misinterpreted as fluid overload, prompting an unnecessary diuretic. Similarly, Jamie identified that naproxen likely contributed to rising blood pressure and renal decline, challenging the addition of an antihypertensive.

These examples show how pharmacists can prevent harm by questioning medication changes and considering iatrogenic causes. Barriers, however, remain. Pharmacists may hesitate to engage in proactive inquiries with prescribers, especially in fragmented care environments involving multiple clinicians. Confidence, professional experience and access to structured tools, such as ThinkCascades and the international PIPC list, can influence whether and how pharmacists act. Newer pharmacists, like Hannah, may feel less certain but can still play a critical role by advocating for safer care and appropriate follow-up.

Dimitri’s case, involving a potentially fatal prescribing cascade, underscores the high stakes of inaction. It also highlights the importance of system-level processes, including documentation, interprofessional communication and pharmacist-led medication safety reviews.^7-13

Summary

To reduce the harm from prescribing cascades, pharmacists must remain vigilant, supported by robust tools, collaborative relationships and a culture that values their clinical insights. Early recognition and timely intervention can reduce unnecessary drug use, prevent adverse events and, ultimately, improve patient outcomes. These cases reinforce that pharmacist action—sometimes as simple as asking a question—can make a critical difference.

Suzanne Singh ([email protected]) is a pharmacist at the Mount Sinai Academic Family Health Team and an Adjunct Lecturer at the Department of Family and Community Medicine at the University of Toronto. She is an advocate for enhancing the role of the pharmacist within integrated and innovative primary care practice models.

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