Analgesic and antiinflammatory effects of glucamet hacin (a nonsteroidal antiinflammatory analgesic) after the removal of impacted third molars Fernando Gallardo, Santiago, Chile UNIVERSITY

DDS,” Mariana

Carstens, DDS,b and Marina

Ayarza, DDS,


A double-blind study was undertaken to compare the effects of glucamethacin, aspirin, and placebo in the control of pain, trismus, and postoperative swelling of 59 outpatients who underwent the surgical removal of impacted lower third molars. Aspirin (1000 mg three times a day) was superior to placebo in one of the analgesic parameters studied, whereas glucamethacin (140 mg three times a day) was not superior to placebo. Both drugs significantly reduced the occurrence of trismus on the day after surgery, but no differences with placebo were found 48 hours postoperatively. In the study of postoperative swelling, no significant differences were found between the medications and the placebo in the postoperative period. It is concluded that glucamethacin, a nonsteroidal antiinflammatory drug, produces a minimal analgesic effect and does not relieve postoperative swelling in the dental patient undergoing surgical removal of impacted third molars.



t is well known that the natural metabolites of arachidonic acid, prostaglandins, and leukotrienes play a key role in the inflammatory process, since they act as mediators and modulators of that reaction by causing vascular dilatation, by increasing capillary permeability, by producing hyperalgesia, and by promoting the migration of leukocytes and macrophages to the site of inflammation.‘-4 Since nonsteroidal antiinflammatory drugs inhibit cyclooxigenase and thus reduce the synthesis of prostaglandins, particularly PGE, and PG12,‘,2those drugs can be used for the control of pain, trismus, and swelling, the usual sequelae of oral surgery procedures such as removal of impacted third molars and other more invasive techniques such as those performed in orthognatic surgery. For the oral surgeon it is often difficult to choose a drug for the treatment of those symptoms from “School of Medicine, Department of Pharmacology. %School of Dentistry, Department of Oral Surgery. ‘Intern resident in Clinical Pharmacology, 1986.


among the large number of nonsteroidal antiinflammatory agents, presently available in therapy. Usually the efficacy of drugs in dentistry has been extrapolated from the experience gathered in rheumatology in the treatment of osteoarthritis, rheumatoid arthritis, osteoarthrosis, and related conditions. However, more reliable data can be obtained by assessingthose drugs in dental patients undergoing oral surgery procedures, and a number of such studies, largely those designed to test analgesic efficacy, are currently reported in the dental literature. However, fewer studies are conducted to evaluate the antiinflammatory efficacy of those drugs because of the inherent difficulty in objectively assessing the postoperative edema of the dental patient. In the present article we report a double-blind evaluation aimed to study the efficacy of glucamethatin, a relatively new nonsteroidal antiinflammatory drug, as compared to aspirin and to placebo in the control of pain, trismus, and swelling of young adult outpatients who underwent the surgical removal of impacted third molars. 157



Carstens, and Ayarza


February 1990 Table I

Age (yr) Mean Range Sex Male Female Length of surgical time (min)

28.6 lo-42 8 (47.1%) 9 (52.9%) 42.3

30.4 13-40

32.6 16-41

10 (45.4%) 8 (44.4%) 12 (54.6%) 10 (55.6%) 40.8 39.0

eye and the angle of the lower jaw were also measured, by means of a silk suture, along the natural convexity of each patient’s face. The patients were reexamined 24 and 48 hours after surgery, and the same measurements of jaw opening and distance on the side of the face were taken. The percent of trismus was calculated as follows: preoperativemeasurepercent of _ postoperativemeasure trismus - preoperativemeasure x 100 Facial swelling was calculated as follows: Facial measure =


The present investigation was undertaken on 59 young outpatients, 17 to 40 years old, who underwent the surgical removal of a lower impacted third molar. Once surgery with local anesthesia was completed, the patients received, under double-blind conditions, a plastic bag containing twelve identical capsules of either aspirin (500 mg), glucamethacin (70 mg), or placebo. The patients were instructed to take two capsuleseach 8 hours for 2 days, starting 1 hour after surgery. For ethical reasons they were requested to resort to a conventional analgesic such as acetaminophen or aspirin when adequate relief from pain was not achieved with the study medication. Patients with a past history of gastric or duodenal ulcers were excluded from this investigation. Likewise were excluded all pregnant or lactating patients and those who reported the existence of hypersensitivity reactions either to aspirin or to glucamethacin or other nonsteroidal antiinflammatory drugs. Study of the analgesic


The patients were requested to rate pain intensity as absent (0), slight (l), moderate (2) or intense (3) on the day of surgery and 24 hours later. To compare the pain-relieving properties of each drug, the number of patients experiencing severe or moderate pain was compared to the number reporting slight or no pain in the 24- and 48-hour periods. Nonparametric statistical analysis of the results was done by means of a chi-square test. Study of trismus and swelling

The study of trismus and swelling was done by the method described by Amin and Laskin.5 Before surgery the maximum mouth opening was recorded between the incisal edges of the upper and lower central incisors. A horizontal distance from the corner of the mouth to the lobe of the ear and a vertical distance between the outer canthus of the

horizontal + vertical measure 2


preoperative measure x loo facia’ swe11ing = preoperative measure


The Student t test was used for comparison between treatment groups in the statistical analysis of these parameters. RESULTS

The demographic study, variable relative to the surgical procedure and the distribution of patients with regard to the drug received, appears in Table I. Table II summarizes data on the analgesic efficacy of the studied drugs on the day of surgery and 24 hours after surgery. As can be seen, glucamethacin was not superior to placebo, whereas aspirin proved to be superior to placebo in the need for other analgesic drugs on the day of surgery (p < 0.025) but was not statistically superior to glucamethacin in this parameter. The effects of the studied drugs on trismus and postoperative swelling appear in Table III, which shows that both glucamethacin and aspirin significantly reduced the postoperative trismus 24 hours after surgery (p < 0.005 and p < 0.025, respectively), but they were not superior to placebo 48 hours after surgery. In terms of the effects on postoperative swelling, Table III shows that the drugs did not have a significant effect on this parameter when compared to placebo. The incidence of adverse effects reported by the patients who took the medications supplied and who did not resort to another analgesic drug appears in Table IV. As can be seen, there was no significant difference between glucamethacin, aspirin, and placebo. Unexpectedly, a patient who took placebo had a macular rash, a finding quite difficult to account for becauseof the low antigenic potential of the placebo (lactose plus excipients).

Analgesic and antiinflammatory

Volume 69 Number 2

eJ&ectsof glucamethacin


Table II. Summary of the analgesic actvity of glucamethacin, aspirin, and placebo on the parameters

studied* Pain intensity

Need for other analgesic drugs Day after surgery

Day of surgery Mild or absent

Drug Glucamethacin (n = 19) Aspirin (II = 22) Placebo (n = 18)

Day after surgery

Day of surgery

Moderate or intense

Mild or absent

Moderate or intense





























*Statistical analysis of each drug as compared to placebo. TSuperior to placebo (x’ = 6.2: p < 0.025).

Table Ill. Effects of glucamethacin, aspirin, and placebo on trismus and postoperative swelling (comparative analysis of each drug versus placebo) Parameter

Glucamethacin (n = 19)

Aspirin (n = 22)

Placebo (n = 18)

Percent of trismus reduction + SE Control 24.89 f 3.36* 31.63 k 3.74t 42.54 24 hr Control 20.07 + 4.48 27.34 t 4.41 33.17 48 hr Percent of increase of postoperative swelling + SE Control 5.87 f 1.1 1 4.20 t 0.55 8.08 24 hr 3.74 t 0.94 4.07 k 0.73 Control 4.57 48 hr _____-.

2 3.41 f 5.01

f 1.37 _t 0.96

Table IV. Adverse effects reported by patients after treatment with each medication Adverse effect Epigastric pain Nausea Diarrhea Constipation Dry mouth Cutaneous rash Headache Drowsiness Insomnia Dizziness Orthostatic hypotension Hemorrhage



2 1

3 1 1 -



2 6 2 I


3 7 2 6

3 1 4 8 2 2 1

*p < 0.005.

tp c 0.025.


Glucamethacin (N-p-chlorobenzoyl-2 methyl-5 metoxi-indol3-acetic monohydrate glucosamine) is a nonsteroidal drug with analgesic and antiinflammatory properties. This drug has been evaluated largely in rheumatologic studies for the treatment of rheumatoid arthritis, osteoarthritis, and related conditions. The drug is an indole derivative that is less toxic to the gastrointestinal tract and exhibits a lower degree of symptoms in the central nervous system than indomethacin, the parent compound.6-9 As far as we know, there is only one report on the use of glucamethacin in the dental patient. In that experience glucamethacin (70 mg four times a day) was superior to placebo but not to aspirin (500 mg four times a day) for the control of postoperative trismus 24 hours after surgery in a sample of patients who underwent surgical removal of either impacted

or semiimpacted third molars.1° Additionally, no significant differences were found between the drugs and the placebo in the study of the parameters postoperative swelling and analgesic activity of the medications. The present investigation was undertaken to determine whether a higher dosageof glucamethacin (140 mg three times a dayj in a more homogeneous patient sample (only impacted third molars) could be a useful approach for the control of pain, trismus, and postoperative swelling of dental patients. However, our results were similar to those reported earlier (i.e., glucamethacin reduced postoperative trismus but was not superior to placebo for the relief of pain and for the control of postoperative swelling). These data are, however, in agreement with those reported in the current literature with the use of different antiinflammatory drugs in the dental patient. For instance, Bazerque and coworkers” found a minimal effect of indomethacin on postoper-



Carstens, and Ayarza



February 1990

ative edema as judged by a subjective assessment.By using the same drug and a subjective measurement, PetersenI demonstrated a significant reduction of pain and trismus, but the drug had no effect on edema. Van Der Zwan and colleaguesi reported a slight reduction on postoperative swelling (10% to IS%) or of trismus (20%) in a multiple comparative study of indomethacin, ibuprofen, naproxen, niflumic acid, and oxyphenbutazone. However, in that study the use of betamethasone resulted in a significant reduction of trismus (40%) and edema (65%) as compared to placebo. More recently Sisk and Bonningtoni4 compared the effects of flurbiprofen, methylprednisolone, and placebo administered before the surgical removal of impacted third molars. It was shown that flurbiprofen significantly reduced pain but was not superior to placebo in reducing postoperative swelling, parameter that was significantly reduced by methylprednisolone. In fact, the report of Amin and Laskin’ in which indomethacin was given preoperatively and postoperatively (total dose = 100 mg) is the only one in which a single drug was effecive for relieving pain and swelling 48 hours after surgery. In conclusion, the data presently available indicate that no single class of drugs administered either before or after surgery is effective in controlling pain, trismus, and swelling, since nonsteroidal antiinflammatory drugs relieve pain but are not able to decrease postoperative swelling and trismus, symptoms that can be properly treated with steroids. Consequently, most surgical teams involved in oral surgery procedures use a combination of a nonsteroidal antiinflammatory drug (usually a phenylpropionic acid derivative such as ibuprofen, naproxen, or flurbiprofen) to control pain and a steroid agent to reduce trismus and postoperative swelling. REFERENCES 1. Ferreira SH, Moncada S, Vane JR. Indomethacin and aspirin abolish prostaglandin release from the spleen. Nature; New Biology 1971;231:237-9.

2. Juan J. Prostaglandins as modulators of pain. Gen Pharmacol 1978;9:403-4. 3. Samuelsson B. Leukotrienes: mediators of allergic reactions

and inflammation. Int Arch Allergy Appl lmmunol 1981; 1):98-106. 4. Higgs GA, Moncada S. Leukotrienes in disease. Implications for drug development. Drugs 1985;30: l-5. 5. Amin MM, Laskin DM. Prophylactic use of indomethacin for prevention of postsurgical complications after removal of impacted third molars. ORAL SURG ORAL Mm ORAL PATHOL 66(suppl


6. Giordano M, Capelli L, Chianese U. The therapeutic activity of I -(p-chlorobenzoyl)5-methoxy-2-methylindole-3-acetic acid monohydrate glucosemide in rheumatoid arthritis. Arszneimittel Forschung Drug Research 1975;25:435-40. 7. Capelli L, Chianese V, Montagna LA, Giordano M. Further studies on glucamethacin in rheumatoid arthritis and other chronic types of rheumatism. Current Medical Research Opinion 1981;7:227-33. 8. Guerciolini R, Cecconi M, Toraldo P, Michetti F. Gastrointestinal blood loss in subjects receiving glucamethacin (Teoremac) or indomethacin. A comparative evalution. Clinical Trials Journal 1982;20:53-8. 9. Mirelli E, Fichara G, Della Volpe A, Lasola M. Endoscopic study of the gastrointestinal tolerance of glucamethacin. Current Medical Research Opinion 1978;5:648-54. 10. Carstens M, Ligueros 0, Lobo R, et al. Estudio comparative doble-ciego de la actividad analgtsica y antiinflamatoria de la glucametacina, aspirina y placebo en cirugia oral. Odontologia Chilena 1987;35:31-9. 11. Bazerque P, Garfinquel M, Costa OC. Use of indomethacin as an anti-inflammatory agent in patients subjected to exodontia. Rev Asoc Odont Argent 1967;55:526-8. 12. Petersen JK. Antiinflammatory and analgesic effects of indomethacin following removal of impacted mandibular third molar. Int J Oral-Surg 1975;4:267-76. 13. Van Der Zwan J, Boering G, Wesseling H, et al. The lower third molar and antiphlogististics. Int J Oral Surg 1982;l I :34050. 14. Sisk AL,

Bonnington GJ. Evaluation of methylprednisolone and flurbiprofen for inhibition of the postoperative inflammatory response. ORAL SURG ORAL MED ORAL PATHOL 1985; 13:137-41.

Reprint requests to: Dr. Fernando Gallardo Department of Pharmacology University of Chile School of Medicine P.O. Box 70.000, Santiago 7, Chile

Analgesic and antiinflammatory effects of glucamethacin (a nonsteroidal antiinflammatory analgesic) after the removal of impacted third molars.

A double-blind study was undertaken to compare the effects of glucamethacin, aspirin, and placebo in the control of pain, trismus, and postoperative s...
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