Anaes · Applied cardiovascular & respiratory physiology

Drug toxicity and adverse drug reactions

Also known as Adverse drug reaction · ADR · Drug toxicity · Type A and Type B reactions · LAST · Pharmacovigilance

An adverse drug reaction is any noxious, unintended response to a drug given at standard doses; toxicity is harm from excessive exposure. Together they are among the commonest causes of iatrogenic injury and a major focus of perioperative safety. The framework rests on six exam-critical ideas. First, adverse drug reactions are classified by predictability into Type A (Augmented) reactions, which are dose-dependent, predictable from the drug's pharmacology and common (e.g. bleeding with warfarin, bradycardia with a beta-blocker, respiratory depression with an opioid), and Type B (Bizarre) reactions, which are dose-independent, unpredictable, uncommon and often immune-mediated or idiosyncratic (e.g. anaphylaxis, malignant hyperthermia, idiosyncratic drug-induced liver injury); Type A accounts for about 80 percent of all reactions. Second, the four mechanistic classes of toxicity are on-target (an exaggerated but expected pharmacological effect), off-target (an effect at a different receptor), immune (hypersensitivity — IgE, immune complex, T-cell) and idiosyncratic (a genetically determined, unpredictable reaction, often reactive-metabolite mediated). Third, organ-specific toxicity has recognisable signatures: hepatotoxicity (paracetamol via the reactive metabolite NAPQI depleting glutathione; halothane; idiosyncratic DILI), nephrotoxicity (NSAIDs, aminoglycosides, radiocontrast), cardiotoxicity (the local anaesthetics, causing local-anaesthetic systemic toxicity LAST; the anthracyclines), and neurotoxicity. Fourth, several toxicity syndromes are high-stakes in anaesthesia: local-anaesthetic systemic toxicity (seizures and cardiovascular collapse from bupivacaine, rescued by intravenous lipid emulsion), perioperative anaphylaxis (most often a neuromuscular blocker, treated with intravenous adrenaline), drug-induced long-QT and torsades de pointes (prolonged repolarisation from a wide range of agents), serotonin syndrome, neuroleptic malignant syndrome, malignant hyperthermia and propofol infusion syndrome. Fifth, drug toxicity can be delayed and remote from the dose: teratogenicity (harm to the fetus — thalidomide, valproate, retinoids, mycophenolate), carcinogenicity and mutagenicity. Sixth, management is to stop the drug, provide supportive care, and use specific antidotes where they exist (N-acetylcysteine for paracetamol, flumazenil for benzodiazepines, naloxone for opioids, lipid emulsion for LAST, dantrolene for malignant hyperthermia), and to report the reaction for pharmacovigilance. Built on the adverse-drug-reaction reporting study (Dubrall 2026), the acetaminophen-liver-injury redox study (Guo 2026), the long-acting local-anaesthetic safety review (Pham 2026), the perioperative immediate-hypersensitivity guidelines (Michel 2026), the remimazolam-anaphylaxis report (Jo 2026), the drug-induced QT-prolongation report (Sapkota 2026), the sodium-valproate teratogenicity review (McLaughlin 2026), and the drug-induced-liver-injury incidence study (Pocurull 2026).