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Comparative Evaluation of the Analgesic Properties of a New Drug and Codeine

G.D. Allen, G.L. Freedman and E.C. Funk J DENT RES 1969 48: 410 DOI: 10.1177/00220345690480031301 The online version of this article can be found at: http://jdr.sagepub.com/content/48/3/410

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Comparative Evaluation of the Analgesic Properties of a New Drug and Codeine

G. D. ALLEN, G. L. FREEDMAN, and E. C. FUNK Departments of Oral Surgery and Anesthesiology, University of Washington. Seattle, Washington 98105
A clinical study was made of the analgesic effectiveness of a new drug, Flucarbril (100 mg), and its statistical comparison to codeine (30 mg). Neither drug when used alone in the doses indicated was found useful for the relief of pain after the surgical removal of impacted third molars.

Flucarbril, 1-methyl-6 trifluromethylcarbostyril, is a new drug with muscle relaxant, analgesic, and anti-inflammatory properties.* Its use for postoperative dental trismus, pain, and edema has been suggested. The recommended dosage of Flucarbril is 300 to 400 mg daily in divided doses when side effects are not noted. Codeine has been claimed to be effective in the relief of pain and is used frequently for analgesia in dentistry. Its effect has been compared with that of other drugs in previous studies of pain thresholds.1-3 In this investigation, 30 mg codeine was used as a control to preclude the development of unfavorable side effects which occur with
a

developed prior to leaving the clinic. The second dose was to be taken within one-half hour, and subsequent doses were to be taken as needed. To determine placebo effect, the first of the four capsules administered was separately assigned. A questionnaire was provided on which the patient was to record the following information:
1. Time of each dose 2. Degree of pain when tablet taken (mild, moderate, severe) 3. Time for development of relief (in minutes) 4. Degree of relief: a) 100% b) Over 50% c) Below 50% d) None 5. Duration of relief 6. Overall effect: a) Satisfactory

higher dosage. 14

Materials and Methods Postoperative pain relief was evaluated in 52 healthy patients who had undergone surgical removal of impacted third molars under general anesthesia: 26 patients received 30 mg codeine phosphate and 26 patients received 100 mg Flucarbril. The medications were dispensed as four identical capsules in a double-blind study; selection of medication was by random assignment. The patients were given the first capsule at the onset of pain, which always
This investigation was supported by NIDR Research Grant #ROlDEO-2419-02 and a grant-in-aid from Smith, Kline & French Laboratories, Philadelphia, Pa. Received for publication August 2, 1968. Smith, Kline & French Laboratories, Philadelphia. Pa.
*

b) Unsatisfactory The patient was to list also any other medications taken and whether or not sleep was disturbed by pain. In addition, any side effects of the medication were to be noted. These cards were returned on the postoperative visit, and the results were assessed by one of the investigators in conference with the patient. Eight cards were not returned, and effectiveness was evaluated by consultation only. The 44 questionnaires returned showed that the first capsules administered were: placebo to 15 patients, Flucarbril to 16, and codeine to 13. Results were statistically analyzed by X2 test. Results The first dose response (Table 1) indicated no significant differences between Flucarbril, codeine, and placebo. In the relief of severe pain (Table 2), Flucarbril was twice as effective as codeine. Differences in severe pain relief in excess of 50% were significant to 0.05 level. In the overall as-

410
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Vol 48 No. 3

ANALGESIC PROPERTIES OF A NEW DRUG

411

TABLE 1 PLACEBO RESPONSE TO THE FIRST CAPSULE

Pain Relief

TABLE 3 INVESTIGATORS' ASSESSMENT OF RESULTS

Pain Relief

Flucarbril

Codeine

Placebo

Flucarbril, 100 mg

Codeine, 30 mg

100% >50% <50%

0

1 3 3 9

4 2 2 5

1 2 5 7

100% >50% <50% 0

0 11 3

0 8 6

12

12

16

13

15

TABLE 2 NUMBER OF PATIENTS COMPLAINING OF SEVERE PAIN WITH RELIEF EXPERIENCED

Pain Relief

Flucarbril

Codeine

100% >50% <50%

0

0 9 1 9

3 2 5 7 17
no sigcodeine

larger dose of codeine is required, which, however, results in an increase in side effects. The activity of other narcotic analgesics can also be intensified by aspirin. Although codeine is the drug most frequently chosen for pain relief (used in low dosage to minimize side effects), this study indicated that codeine alone is inadequate for relief of severe pain after oral surgery.

19

sessment of pain relief (Table 3),

nificant difference of Flucarbril was noted.

over

Discussion It was necessary to discontinue this study because of the inability of the tested drugs to relieve significantly the severe pain of the majority of patients. Indeed, the investigators' assessment indicated no relief in almost half the patients (Table 3). Three patients did not require any pain-relief medication. Half the patients had some placebo effect (Table 1), but only three patients had good pain relief. A possible explanation of this unusually high placebo effect is that the first dose was given within half an hour after surgery at which time residual anesthetic effects would have been present. The particular finding of interest was that when either drug was used alone, it was inadequate to relieve severe postoperative pain. In discussions with the patients, it was learned that pain relief was greatly heightened when patients added aspirin to either medication. To achieve postoperative pain relief under these circumstances, a

Summary The significant feature of the investigation was that neither of these oral analgesics was adequate to relieve postoperative pain after surgical removal of third molars unless it was combined with aspirin. The reported severity of pain was greater than anticipated. Further investigations of the effects of larger doses of codeine and dihydromorphinone in combination with aspirin for the relief of postoperative pain will be reported.
References
1. BONICA, J.J., and ALLEN, G.D.: "Drugs for the Relief of Pain," Drugs of Choice, chap xiii, St. Louis: C. V. Mosby Co., 1966-1967. 2. HOLLIDAY, A.R., and DILLE, J.M.: An Experimental Investigation of the Change Effected by the Ingestion of Carisoprodal, Aspirin, Codeine and a Placebo upon the Threshold for Deep Aching Pain Induced by Ultrasonic Stimulation, Ann NY Acad Sci 86: 147, 1960. 3. GRUBER, C.M.: Codeine Phosphate, Propoxyphene Hydrochloride and Placebo, JAMA 164:966, 1957. 4. GRUBER, C.M.; MILLER, C.L.; FINNERAN, J.; and CHERNISH, S.M.: The Effectiveness of D-Propoxyphene Hydrochloride and Codeine Phosphate as Determined by Two Methods of Clinical Testing for Relief of Chronic Pain, Arch Int Pharmacodyn 104:156, 1955.

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