The Pupillary Effects of Intravenous Morphine, Codeine, and Tramadol in Volunteers

Abstract

Opioid analgesics have pharmacological effects in many organ systems, including the eye. Because the metabolites of morphine and codeine contribute to their overall pharmacological effect pupil diameter measurements were made over a 6-h period. We studied the pupillary effects of IV morphine (0.125 mg/kg), codeine (1 mg/kg), tramadol (1.25 mg/kg), or placebo (10 mL 0.9% w/v sodium chloride) in 10 healthy volunteers. Pupil diameter was measured every 30 min using a pupil densitometer. Comparisons of the change in pupil diameter for each drug were made using analysis of variance with repeated measures. No significant change in pupil diameter was observed after placebo. After IV morphine and codeine administration there was a 26% decrease in pupil diameter (P < 0.001). Over the course of the study period, pupil diameter gradually returned to baseline values. After administration of tramadol there were no significant changes in pupil diameter until 150 min after administration, after which there was a significant reduction for the remainder of the study period (P < 0.01). The changes in pupil diameter may be explained in part by the pharmacokinetic profiles of the opioids studied. Measurement of pupil diameter may have a place in monitoring the central effect of opioids.

Comparison of pupil diameter and tear production in dogs treated with acepromazine, tramadol and their combination

“…The same result was observed by Knaggs et al (2004) in a study wherein tramadol did not change the PD in human patients. According to Branson & Gross (2003) and Duthie (2008), tramadol does not bind to all kinds of receptors like other opioids, which may be reason why it does not change the PD, unlike the total opioid agonists.…”

“…In general, they tend to produce mydriasis in cats, rats and monkeys and miosis in dogs, rabbits and humans (Lamont & Mathews, 2007). However, tramadol does not significantly alter the human pupil diameter (Knaggs et al, 2004). Parrilha et al (2009) reported that tramadol does not significantly alter the cardiovascular, respiratory and thermoregulatory parameters of dogs.…”

Impact of Intravenous Naltrexone on Intravenous Morphine-Induced High, Drug Liking, and Euphoric Effects in Experienced, Nondependent Male Opioid Users

“…As morphine causes miosis, [29,32,33] pupillometry measurements were introduced as an objective measure of opioid effect. The geometric mean E min was significantly smaller after intravenous morphine than after placebo or after morphine plus naltrexone.…”

“…Pupil diameter was measured using a pupil densitometer, [29] with smaller values (pupillary miosis or constriction) indicating a greater morphine effect. End-tidal carbon dioxide levels, measured by noninvasive capnography, were assessed not as a safety endpoint but as an additional exploratory pharmacodynamic endpoint and are not included in this report.…”

Dysfunction of the pupillary light reflex in experimental autoimmune autonomic ganglionopathy

“…Modern pupillometry systems use infrared digital video systems that automatically detect and measure pupil diameter with high temporal resolution. This technique has been increasingly used in research and clinical applications, including preoperative assessment before ocular surgery (Rosen et al, 2002, Wickremasinghe et al, 2005, clinical assessment of coma after closed head injury (Larson and Muhiudeen, 1995), studies of drug metabolism (Bitsios et al, 1999, Knaggs et al, 2004, psychology (Fukuda et al, 2005, Steinhauer andHakerem, 1992) and behavioral disorders (Granholm et al, 2003). Pupillometry can detect subtle abnormalities when the pupil response appears normal or may demonstrate a small pupillary light reflex when no pupil response is apparent clinically.…”