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Hydrocodone functions as an opioid receptor agonist and activates mu-opioid receptors to produce analgesic effects. In addition, hydrocodone activates delta- and kappa-opioid receptors as the plasma drug concentration increases beyond the starting doses. This activity focuses on single-ingredient hydrocodone for pain relief. This activity outlines the indications, mechanism of action, significant adverse effects, contraindications, monitoring, toxicity, and other critical elements of hydrocodone therapy in the clinical setting. These details are essential for the interprofessional healthcare teams responsible for managing the care of patients with pain and related conditions and sequelae.