The analgesic meperidine has been reported to produce signs of central nervous system excitation in human beings. To determine the relationship between signs and symptoms of central nervous system excitation and plasma levels of meperidine and normeperidine, we studied 67 patients receiving meperidine for the relief of postoperative or chronic pain. In 48 patients, excitatory effects ranging from mild nervousness to tremors, twitches, multifocal myoclonus, and seizures were directly correlated with accumulation of normeperidine in plasma. Evidence of compromised renal function occurred in only 14 of the 48 symptomatic patients, suggesting that renal dysfunction may contribute to but is not the sole factor in the accumulation of normeperidine or its relation to adverse neurological signs. In a second study we surveyed mood alterations in 47 patients receiving meperidine and 29 receiving other narcotic analgesics for postoperative pain. The repeated administration of meperidine was associated with adverse alterations in various elements of mood (e.g., apprehension, sadness, restlessness).

References

1 Andrews HL: Cortical effects of Demerol. J Pharmacol Exp Ther 76: 89–94, 1942
CAS Web of Science® Google Scholar
2 Burns JJ, Berger BL, Lief PA, Wollack A, Papper EM, Brodie BB: The physiological disposition and fate of meperidine (Demerol) in man and a method for its estimation in plasma. J Pharmacol Exp Ther 114: 289–298, 1955
CAS PubMed Web of Science® Google Scholar
3 Cowan A, Geller EB, Adler MW: Classification of opioids on the basis of change in seizure threshold in rats. Science 206: 465–467, 1979
10.1126/science.504986
CAS PubMed Web of Science® Google Scholar
4 Deneau GA, Nakai K: The toxicity of meperidine in the monkey as influenced by its rate of absorption. Bull Drug Addict Narcot Appendix 6: 2460–2469, 1961
Google Scholar
5 Elliott HW, Gottschalk LA, Uliana RL: Relationship of plasma meperidine levels to changes in anxiety and hostility. Compr Psychiatry 15: 249–254, 1974
10.1016/0010-440X(74)90023-6
CAS PubMed Web of Science® Google Scholar
6 Foldes FF, Swerdlow M, Siker ES: Narcotics and Narcotic Antagonists. Springfield, IL, Thomas, 1964, p 44
Web of Science® Google Scholar
7 Gilbert PE, Martin WR: Antagonism of the convulsant effects of heroin, d-propoxyphene, meperidine, normeperidine and thebaine by naloxone in mice. J Pharmacol Exp Ther 192: 538–541, 1975
CAS PubMed Web of Science® Google Scholar
8 Himmelsbach CK: Studies of the addiction liability of “Dem-erol” (D-140). J Pharmacol Exp Ther 75: 64–68, 1942
CAS Web of Science® Google Scholar
9 Himmelsbach CK: Further studies of the addiction liability of Demerol. J Pharmacol Exp Ther 79: 5–6, 1943
CAS Google Scholar
10 Houde RW, Wallenstein SL, Rogers A: Clinical pharmacology of analgesics: 1. A method of assaying analgesic effect. Clin Pharmacol Ther 1: 163–174, 1960
10.1002/cpt196012163
CAS PubMed Web of Science® Google Scholar
11 Jaffe JH, Martin WR: Narcotic analgesics. In AG Gilman, LS Goodman, A Gilman (eds): The Pharmacologic Basis of Therapeutics. Sixth edition. New York, Toronto, and London, Macmillan, 1980, p 515
Google Scholar
12 Jasinski DR, Nutt JG: Progress report on the clinical assessment program of the Addiction Research Center. In Proceedings of the Committee on Problems of Drug Dependence. Washington, DC, National Research Council, 1973, pp 108–130
Google Scholar
13 Kaiko RF, Wallenstein SL, Rogers AG, Grabinski PY, Houde RW: Analgesic and mood effects of heroin and morphine in cancer patients with postoperative pain. N Engl J Med 304: 1501–1505, 1981
10.1056/NEJM198106183042501
CAS PubMed Web of Science® Google Scholar
14 Klotz U, McHorse TS, Wilkinson GR, et al: The effect of cirrhosis on the disposition and elimination of meperidine in man. Clin Pharmacol Ther 16: 667–675, 1974
10.1002/cpt1974164667
CAS PubMed Web of Science® Google Scholar
15 Lambertsen CJ, Wendel H, Longenkazen JB: The separate and combined respiratory effects of chlorpromazine and meperidine in normal men controlled at 46 mm Hg alveolar pCO₂. J Pharmacol Exp Ther 131: 381–393, 1961
CAS PubMed Web of Science® Google Scholar
16 Lasagna L, Von Felsinger JM, Beecher HK: Drug-induced mood changes in man. 1. Observations on healthy subjects, chronically ill patients and postaddicts. JAMA 157: 1006–1020, 1955
10.1001/jama.1955.02950290026009
CAS PubMed Web of Science® Google Scholar
17 MacDonald AD, Woolfe G, Bergel F, Morrison AL, Rinderknecht H: Analgesic action of pethidine derivatives and related compounds. Br J Pharmacol 1: 4–14, 1946
10.1111/j.1476-5381.1946.tb00022.x
CAS PubMed Web of Science® Google Scholar
18 Mather LE, Lindop MJ, Tucker GT, et al: Pethidine revisited: plasma concentrations and effects after intramuscular injection. Br J Anaesth 47: 1269–1275, 1975
10.1093/bja/47.12.1269
CAS PubMed Web of Science® Google Scholar
19 Mather LE, Tucker GT, Pflug AE, et al: Meperidine kinetics in man; intravenous injection in surgical patients and volunteers. Clin Pharmacol Ther 17: 21–30, 1975
10.1002/cpt197517121
CAS PubMed Web of Science® Google Scholar
20 Miller JW, Anderson HH: The effect of N-demethylation on certain pharmacologic actions of morphine, codeine, and meperidine in the mouse. J Pharmacol Exp Ther 112: 191–196, 1954
CAS PubMed Web of Science® Google Scholar
21 Miller RR, Jick H: Clinical effects of meperidine in hospitalized medical patients. J Clin Pharmacol 18: 180–189, 1978
10.1002/j.1552-4604.1978.tb01591.x
CAS PubMed Web of Science® Google Scholar
22 Plotnikoff NP, Elliot HW, Way EL: The metabolism of N-C¹⁴H₃ labeled meperidine. J Pharmacol Exp Ther 104: 377–386, 1952
CAS PubMed Web of Science® Google Scholar
23 Plotnikoff NP, Way EL, Elliot HW: Biotransformation products of meperidine excreted in the urine of man. J Pharmacol Exp Ther 117: 414–419, 1956
CAS PubMed Web of Science® Google Scholar
24 Seitner PG, Martin BC: Survey of analgesic drug prescribing patterns. Washington, DC, The Drug Abuse Council, 1975, pp 6–7
Google Scholar
25 Shee JC: Dangerous potentiation of pethidine by iproniazid and its treatment. Br Med J 2: 507–509, 1960
10.1136/bmj.2.5197.507
CAS PubMed Web of Science® Google Scholar
26 Stambaugh JE, Wainer IW: Drug interaction: meperidine and chlorpromazine, a toxic combination. J Clin Pharmacol 21: 140–146, 1981
10.1002/j.1552-4604.1981.tb05691.x
CAS PubMed Web of Science® Google Scholar
27 Stambaugh JE, Wainer IW, Hemphill DM, et al: A potentially toxic drug interaction between pethidine (meperidine) and phenobarbitone. Lancet 1: 398–399, 1977
10.1016/S0140-6736(77)92606-X
CAS PubMed Web of Science® Google Scholar
28 Szeto HH, Inturrisi CE: Simultaneous determination of meperidine and normeperidine in biofluids. J Chromatogr 125: 503–510, 1976
10.1016/S0021-9673(00)85713-1
CAS PubMed Web of Science® Google Scholar
29 Szeto HH, Inturrisi CE, Houde R, et al: Accumulation of normeperidine, an active metabolite of meperidine, in patients with renal failure or cancer. Ann Intern Med 86: 738–740, 1977
10.7326/0003-4819-86-6-738
CAS PubMed Web of Science® Google Scholar
30 Umans JG, Inturrisi CE: Antinociceptive activity and toxicity of meperidine and normeperidine in mice. J Pharmacol Exp Ther (in press)
Google Scholar
31 Way EL, Gimble AI, McKelway WP, Ross H, et al: The absorption, distribution and excretion of isonipecaine (Demerol). J Pharmacol Exp Ther 96: 477–484, 1949
CAS PubMed Web of Science® Google Scholar

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Volume13, Issue2

February 1983

Pages 180-185

Central nervous system excitatory effects of meperidine in cancer patients

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Central nervous system excitatory effects of meperidine in cancer patients

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