The Sound of Evolution
Hydrocodone
Mechanism of action:
Hydrocodone is an opioid. Hydrocodone binds to and activates μ-opioid receptors in the spinal cord, brainstem, and cerebral cortex. 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. Melhem MR et al. (2013). Population pharmacokinetic analysis for hydrocodone following the administration of hydrocodone bitartrate extended-release capsules. Clin Pharmacokinet.
2. Linares OA et al. (2015). Individualized hydrocodone therapy based on phenotype, pharmacogenetics, and pharmacokinetic dosing. Clin J Pain.
3. Liu W et al. (2015). Pharmacokinetics of hydrocodone/acetaminophen combination product in children ages 6–17 with moderate to moderately severe postoperative pain. J Clin Pharmacol.