Unveiling a Prescribing Cascade in an Older Man

Abstract

To the Editor: A 70-year-old man was admitted to the intensive care unit with a subdural hemorrhage and bilateral frontal lobe contusions sustained after an unwitnessed fall in his home. Arterial blood gas measurement revealed anion gap metabolic acidosis with a serum salicylate level of 4.59 mmol/L (normal range <1.5 mmol/L). Other laboratory investigations were unremarkable. X-ray imaging identified opaque contrast material throughout the colon, despite no antecedent oral contrast administration (Figure 1). Because collateral history was unavailable, the salicylate toxicity was presumed to be secondary to medication misadministration, possibly owing to his memory loss. His pharmacy confirmed that he was neither prescribed acetylsalicylic acid, nor had it been purchased over the counter (OTC). He was self-administering donepezil, calcium carbonate, alendronate, pravastatin, ezetimibe, omeprazole, and perindopril, with no history of medication overdose. All of these medications were long-standing, except the cholinesterase inhibitor, donepezil, which a consultant had prescribed when the man had been diagnosed with mild Alzheimer's disease 2 months earlier. Shortly after initiating donepezil, he visited his family physician complaining of persistent abdominal discomfort and diarrhea, for which he was referred to a gastroenterologist. Although not apparent when the initial medication history was obtained, his friend revealed that, while awaiting his gastroenterology appointment, the patient had self-medicated with large amounts of bismuth subsalicylate (Pepto-Bismol) because it provided temporary relief of his gastrointestinal symptoms. Bismuth subsalicylate contains 8.7 mg of salicylic acid per mL and can cause acute or chronic salicylate toxicity when consumed in excess.1 The friend observed symptoms consistent with salicylate toxicity and specifically recalled that the man's cognition had acutely and progressively worsened shortly after bismuth subsalicylate was started. His gait and functional impairment concurrently deteriorated and culminated in the traumatic fall. Bismuth is also slightly radiopaque, explaining the contrast material visualized throughout the colon on pelvic X-ray.2 This case involves three relevant medication issues: a prescribing cascade, salicylate toxicity, and bismuth neurotoxicity. The salicylate toxicity and subsequent traumatic fall were probably secondary to self-medication with OTC bismuth subsalicylate for gastrointestinal symptoms temporally related to the initiation of a cholinesterase inhibitor. This pattern represents a prescribing cascade, in which an adverse drug reaction to a medication is misinterpreted as a new medical condition, leading to another drug being prescribed to treat the adverse effect.3, 4 In the current case, the man and his physician misinterpreted the adverse gastrointestinal effects of the cholinesterase inhibitor as a new medical condition, leading to self-medicating with an additional OTC drug at toxic doses. Cholinesterase inhibitors are associated with adverse gastrointestinal events, most commonly abdominal pain, nausea, anorexia, diarrhea, and weight loss.5 Given that many older adults with dementia are malnourished, physicians prescribing cholinesterase inhibitors need to inform them about these potential adverse events and consider the possible contributing role of cholinesterase inhibitors in new-onset gastrointestinal symptoms or weight loss. Furthermore, the possibility of an adverse drug event presenting as a prescribing cascade should always be carefully considered when evaluating an older adult, and any new symptom should be considered to be drug related until proven otherwise.3 The neurotoxicity of bismuth subsalicylate is often underappreciated, despite its long history of use for a variety of gastrointestinal disorders. Two distinct toxicities must be considered: salicylate toxicity and bismuth toxicity. Salicylate toxicity is detailed in the case presentation above. Bismuth neurotoxicity can provoke delirium, psychosis, ataxia, myoclonus, and seizures and is reversible over several weeks, when bismuth intake is stopped.6, 7 It is hoped that this case presentation will increase recognition of the adverse effects of cholinesterase inhibitors and salicylate and bismuth neurotoxicity with OTC medications. In addition, this case highlights the potential for prescribing cascades involving OTC preparations that are sometimes missed when taking a medication history. This work was supported by Team Grant OTG-88591 from the Canadian Institutes of Health Research (CIHR) Institute of Nutrition, Metabolism, and Diabetes. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: All authors contributed equally. Ethics committee approval and patient consent were obtained. Sponsor's Role: There was no sponsor involved in the management of the patient or preparation of the paper.