Atomoxetine is a nonstimulant medication used to treat attention-deficit/hyperactivity disorder (ADHD). Cytochrome P450 (CYP)2D6 polymorphisms influence the metabolism of atomoxetine thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for atomoxetine based on CYP2D6 genotype (updates at www. cpicpgx.org).
Much of the toxicity associated with drugs such as clonidine, guanfacine, and tetrahydrozoline are due to their binding to imidazoline receptors. Knowledge of the imidazoline receptors may lead to new therapeutic agents and inform management of patients with imidazoline overdose.
Objective
Pupillometry has been used to assess both pain intensity and response to analgesic medications in adults. The aim of this observational study was to explore proof-of-concept for the use of this technique in paediatric patients. Changes in pupil parameters before and after opioid exposure also were evaluated.
Design and Setting
This was a single-center, prospective study conducted at an academic paediatric medical center.
Patients
Children 9-17 years of age undergoing elective surgical correction of pectusexcavatum were enrolled into a protocol approved by the human ethical committee (IRB).
Interventions
Pupil size and reactivity were measured using a hand-held pupillometer. Pain was assessed using age-appropriate, validated pain self-report scales.
Results
Thirty patients were enrolled. Each point change on a 10 cm visual analog pain intensity scale was associated with a statistically significant mean change of 0.11 mm/s in maximum pupil constriction velocity, and of approximately 0.4% in pupil diameter. As expected, there was an association between total opioid dose (expressed as morphine equivalents) and pupil diameter. Age, sex, and baseline anxiety scores did not correlate significantly with pupillary response.
Conclusion
The association of both maximum pupillary constriction velocity and diameter with pain scores illustrates the potential for using pupillometry as a non-invasive method to objectively quantitate pain response/intensity in children. The technique holds promise as a pharmacodynamic “tool” to assess opioid response in paediatric patients.
Pupil size and reactivity show little correlation with age and are therefore suitable for further exploration in using pupillometry as a biomarker across the pediatric age range. Differences in race should be taken into consideration when pupillometry is used in mixed populations.
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