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LETTER TO THE EDITOR

Differential Effects of Morphine and Codeine on Pupil Size: Dosing Issues

Department of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois, jzacny{at}dacc.uchicago.edu

To the Editor:

The article by Knaggs et al. (1) showing that different opioids have different profiles and durations of effect on the measure of pupil size is interesting, in that tramadol had a delayed effect relative to morphine and codeine. However, there appears to be a problem in the design of the study. The authors found that morphine had a more marked effect on miosis than did codeine, and posited that this was due to codeine’s weaker affinity than morphine for mu-opioid receptors. However, equianalgesic doses of the two drugs were not tested, and this certainly could be an alternative explanation for the results obtained. The dose of morphine used in the study was 0.125 mg/kg, and according to analgesic potency tables (2), an equianalgesic dose of codeine would be 1.63 mg/kg. Rather, a codeine dose of 1 mg/kg was tested. Therefore, it is not surprising that morphine generated a larger magnitude of effect. The authors also made a comment that there is limited data on the duration of opioid-induced miosis in the literature. In fact, the Knaggs et al. (1) study is preceded by many studies, some conducted over 25 years ago, examining the time course (up to 6 hours and longer) and magnitude of miotic effects of different opioids, both in opioid abusers (3) and in volunteers with a limited history of recreational drug usage (4).

References

1. Knaggs RD, Crighton IM, Cobby TF, et al. The pupillary effects of intravenous morphine, codeine and tramadol in volunteers. Anesth Analg 2004;99:108–12.[Abstract/Free Full Text]
2. Reisine T, Pasternak G. Opioid analgesics and antagonists. In: Hardman JG, Gilman AG, Limbird LE, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 9th ed. New York: Pergamon Press, 1996:521–55.
3. Fraser HF, Van Horn GD, Martin WR, et al. Methods for evaluating addiction liability: (A) "Attitude" of opiate addicts toward opiate-like drugs. (B) a short-term "direct" addiction test. J Pharmacol Exp Ther 1961;33:371–87.
4. Zacny JP, Lichtor JL, Binstock W, et al. Subjective, behavioral and physiological responses to intravenous meperidine in healthy volunteers. Psychopharmacology 1993;111:306–14.[Medline]

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