Hidden harms: A clinical review of drug toxicity in palliative medicine

Abstract

Pharmacological therapy is central to symptom control in palliative medicine; however, polypharmacy, altered physiology, and multi-system disease place patients at high risk of drug toxicity and accidental overdose. Adverse drug effects are frequently under-recognized and may be misinterpreted as disease progression, leading to morbidity and compromised quality of life. This narrative review aims to synthesize existing evidence on toxicity and overdose associated with commonly used palliative medications, with particular emphasis on opioids, paracetamol, tricyclic antidepressants, and psychotropic drugs. The review also explores mechanisms of toxicity, clinical manifestations, management strategies, and ethical considerations relevant to palliative practice. A narrative review was conducted using PubMed, Scopus, Embase, Google Scholar, and the Cochrane Library for English-language publications from 2000 to 2024. Clinical studies, reviews, guidelines, and pharmacological literature addressing drug toxicity, overdose, and management in palliative populations were included. Data were synthesized thematically with a focus on clinical relevance rather than quantitative comparison. Opioid toxicity is commonly presented with sedation, delirium, respiratory depression, and neurotoxicity, particularly in the presence of renal impairment or drug interactions. Paracetamol toxicity, often due to repeated supratherapeutic dosing, may progress to acute liver failure, especially in malnourished or cachectic patients. Tricyclic antidepressants are associated with life-threatening cardiotoxicity, including QRS prolongation and malignant arrhythmias. Several drugs frequently used in palliative care—such as methadone, antipsychotics, antidepressants, and antiemetics— contribute to QT prolongation and risk of torsades de pointes. Management relies on early recognition, supportive care, rational description, and judicious use of antidotes. Drug toxicity in palliative medicine is not predictable. Clinicians must balance symptom relief with patient safety while respecting goals of care and ethical principles. A structured, patient-centered approach to prescribing and toxicity management is essential to preserve comfort, dignity, and quality of life at the end of life.