The Sound of Evolution
Hydromorphone
Mechanism of action:
Hydromorphone is an opioid and a semi-synthetic morphinan derivative. Hydromorphone binds to and activates μ-opioid receptors in the central nervous system. These receptors are Gi/o protein-coupled receptors. After receptor activation, adenylyl cyclase is inhibited, cAMP production decreases, and presynaptic voltage-gated Ca²⁺ channels are suppressed, preventing calcium influx and reducing the release of pain-related neurotransmitters such as glutamate and substance P. At the same time, postsynaptic K⁺ channels are activated, promoting potassium efflux and causing neuronal hyperpolarization.
Reference(s):
1. Kumar MG et al. (2007). Hydromorphone in the management of cancer-related pain: an update on routes of administration and dosage forms. J Pharm Pharm Sci.
2. Trescot AM et al. (2008). Opioid pharmacology. Pain Physician.
3. Overholser BR et al. (2011). Opioid pharmacokinetic drug–drug interactions. Am J Manag Care.