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Caffeine as an Analgesic Adjuvant: A Double-blind Study Comparing Aspirin With Caffeine to Aspirin and Placebo in Patients With Sore Throat

Caffeine as an Analgesic Adjuvant: A Double-blind Study Comparing Aspirin With Caffeine to... Abstract Despite its frequent clinical use in analgesic agents, caffeine has not been accepted unequivocally as an analgesic adjuvant. To evaluate this activity of caffeine, we used new study methods in a randomized controlled trial on patients with acute sore throat due to tonsillopharyngitis. Patients were randomly assigned to receive a single dose of one of three treatments: 800 mg of aspirin with 64 mg of caffeine (n 70), 800 mg of aspirin (n 68), or placebo (n = 69). Under double-blind conditions, during a 2-hour evaluation period, patients used different rating scales to assess pain intensity, change in pain, relief, and two qualities of throat pain, how swollen the throat felt, and difficulty swallowing. Aspirin with caffeine and aspirin alone were significantly more effective than placebo for all efficacy measurements from 30 minutes through 2 hours and overall. The aspirin-caffeine combination also showed evidence of activity at 15 minutes on the relief scale. Aspirin with caffeine was more effective than aspirin alone after 30 minutes and over the entire study period. For patients with fever, both active treatments were equally effective antipyretic agents. We conclude, therefore, that 800 mg of aspirin, given alone or with 64 mg of caffeine, is an effective analgesic and antipyretic agent. Because the aspirin-caffeine combination is significantly more effective than aspirin alone as an analgesic, we also conclude that 64 mg of caffeine is an analgesic adjuvant. (Arch Intern Med. 1991;151:733-737) References 1. Beaver WT. Mild analgesics: a review of their clinical pharmacology . J Med Sci. 1966;251(pt (2) ):576-599.Crossref 2. Beaver WT. Aspirin and acetaminophen as constituents of analgesic combinations . Arch Intern Med. 1981;141:293-300.Crossref 3. Over-the-counter drugs: establishment of a monograph for OTC internal analgesic, antipyretic and antirheumatic products . Fed Register. 1988;53:46244. 4. Williams MW. Analgesic effects of the APC combination in rat . Toxicol Appl Pharmacol. 1959;1:447-453.Crossref 5. Siegers CP. Effects of caffeine on the absorption and analgesic efficacy of paracetamol in rats . Pharmacology. 1973;10:19-27.Crossref 6. Vinegar R, Truax JF, Selph JL, Welch RM, White HL. Potentiation of the anti-inflammatory and analgesic activity of aspirin by caffeine in the rat . Proc Soc Exp Biol Med. 1976;151:556-560.Crossref 7. Seegers AJM, Jager LP, Zandberg P, Van Noordwijk J. The anti-inflammatory, analgesic and antipyretic activities of non-narcotic analgesic drug mixtures in rats . Arch Int Pharmacodyn. 1981;251:237-254. 8. Giertz H, Jurna I. Effects des Caffeins in analgeticsgemischen . Naturwissenschaften. 1957;44:445.Crossref 9. Fuchs HR, Giertz H. Analgetisch wirksome Arzneimittelgemisch . Arzneimittelforsch. 1960;10:526-530. 10. Gregg EC Jr. Effect of non-opiate analgesics and other drugs on the vibratory threshold . J Pharm Exp Ther. 1952;106:1-13. 11. Lim RKS, Miller DG, Guzman F, et al. Pain and analgesia evaluated by the intraperitoneal bradykinin-evoked pain method in man . Clin Pharmacol Ther. 1967;8:521-542. 12. Booy RH. Pain-relieving with simple analgesics in dentistry . Ned Tijdschr Tandheelkinde. 1972;79:69-75. 13. Wojcicki J, Samochowiec L, Lawczynski L, Szwed G, Olszewska M. A double-blind comparative evaluation of aspirin, paracetamol and paracetamol with caffeine (Finimal) for their analgesic effectiveness . Arch Immunol Ther Exp. 1977;25:175-179. 14. Wallenstein SL. Analgesic studies of aspirin in cancer patients . In: Proceedings of the Aspirin Symposium . London, England: The Aspirin Foundation; 1975:5-10. 15. Jain AK, McMahon FG, Ryan JR, Unger D, Richard W. Aspirin and aspirin-caffeine in postpartum pain relief . Clin Pharmacol Ther. 1978;24:69-75. 16. Rubin A, Winter L. A double-blind randomized study of an aspirin/caffeine combination versus acetaminophen/aspirin combination versus acetaminophen versus placebo in patients with moderate to severe post-partum pain . J Int Med Res. 1984;12:338-345. 17. Laska EM, Sunshine A, Zighelboim I, et al. Effect of caffeine on acetaminophen analgesia . Clin Pharmacol Ther. 1983;33:498-509.Crossref 18. Laska EM, Sunshine A, Mueller F, Elvers WB, Siegel C, Rubin A. Caffeine as an analgesic adjuvant . JAMA. 1984;251:1711-1718.Crossref 19. Beaver WT. Caffeine revisited . JAMA. 1984;251:1732-1733.Crossref 20. Schachtel BP, Fillingim JM, Beiter DJ, Lane AC, Schwartz LA. Rating scales for analgesics in sore throat . Clin Pharmacol Ther. 1984;36:151-156.Crossref 21. Schachtel BP, Paull B, Baybutt R. Qualities of pain in the evaluation of a combination analgesic . Acta Pharmacol Toxicol. 1986;59:268. 22. Schachtel BP, Fillingim JM, Thoden WR, Lane AC, Baybutt RI. Sore throat pain in the evaluation of mild analgesics . Clin Pharmacol Ther. 1988;44:707-711.Crossref 23. Dascombe MJ, Milton AS. The effect of caffeine on the antipyretic action of aspirin administered during endotoxin fever . Br J Pharmacol. 1972;46:548P-549P. 24. Schachtel BP, Fillingim JM, Beiter DJ, Lane AC, Schwartz LA. Subjective and objective features of sore throat . Arch Intern Med. 1984;144:497-500.Crossref 25. Steel RGD, Torrie JH. Principles and Procedures of Statistics: A Biometrical Approach. 2nd ed. New York, NY: McGraw-Hill International Book Co; 1980:186-187. 26. Wallenstein SL, Heidrich G, Kaiko R, Houde RW. Clinical evaluation of mild analgesics: the measurement of clinical pain . Br J Clin Pharmacol. 1980;10:319S-327S.Crossref 27. Huskisson EC. Measurement of pain . Lancet. 1974;2:1127-1131.Crossref 28. Joyce CRB, Zutski DW, Hrubes V, Mason RM. Comparison of fixed internal and visual analogue scales for rating chronic pain . Eur J Clin Pharmacol. 1975;8:415-420.Crossref 29. Scott J, Huskisson EC. Graphic representation of pain . Pain. 1976;2:175-184.Crossref 30. Revill SI, Robinson JO, Rosen M, Hogg MIJ. The reliability of a linear analysis for evaluating pain . Anesthesia. 1976;31:1191-1198.Crossref 31. Downie WW, Leatham PA, Rhind VM, Wright V, Branco JA, Anderson JA. Studies with pain rating scales . Ann Rheum Dis. 1978;37:378-381.Crossref 32. Dixon JS, Bird HA. Reproducibility along a 10-cm vertical visual analog scale . Ann Rheum Dis. 1981;40:87-89.Crossref 33. Sriwatanakul K, Kelvie W, Lasagna L, Calmlim JF, Weis OF, Mehta G. Studies with different types of visual analog scales for measurement of pain . Clin Pharmacol Ther. 1983;34:234-239.Crossref 34. Schachtel BP, Sorrentino JV, Wooley BH, Davis B, Brown J. Qualities of pain rated as indicators of therapeutic response . Clin Pharmacol Ther. 1985;37:226. 35. Melzack R, Torgerson WS. On the language of pain . Anesthesiology. 1971;34:50-59.Crossref 36. Melzack R. The McGill pain questionnaire: major properties and scoring methods . Pain. 1975;1:277-299.Crossref 37. Debas HT, Cohen MM, Holubitsky IB, Harrison KC. Caffeine stimulated gastric acid and pepsin secretion dose-response studies . Scand J Gastroenterol. 1971;6:453-457.Crossref 38. Butcher RW, Sutherland EW. Adenosine 3, 5, phosphate in biological materials . J Biol Chem. 1962;287:1244-1250. 39. Dahanukar SA, Pohujani S, Sheth UK. Bioavailability . Med Res. 1978;68:844-848. 40. Yoovathaworn KC, Sriwatanakul K, Thithapandha A. Influence of caffeine on aspirin pharmacokinetics . Eur J Drug Metab Pharmacokinet. 1986;11:71-76.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Caffeine as an Analgesic Adjuvant: A Double-blind Study Comparing Aspirin With Caffeine to Aspirin and Placebo in Patients With Sore Throat

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Publisher
American Medical Association
Copyright
Copyright © 1991 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1991.00400040081017
Publisher site
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Abstract

Abstract Despite its frequent clinical use in analgesic agents, caffeine has not been accepted unequivocally as an analgesic adjuvant. To evaluate this activity of caffeine, we used new study methods in a randomized controlled trial on patients with acute sore throat due to tonsillopharyngitis. Patients were randomly assigned to receive a single dose of one of three treatments: 800 mg of aspirin with 64 mg of caffeine (n 70), 800 mg of aspirin (n 68), or placebo (n = 69). Under double-blind conditions, during a 2-hour evaluation period, patients used different rating scales to assess pain intensity, change in pain, relief, and two qualities of throat pain, how swollen the throat felt, and difficulty swallowing. Aspirin with caffeine and aspirin alone were significantly more effective than placebo for all efficacy measurements from 30 minutes through 2 hours and overall. The aspirin-caffeine combination also showed evidence of activity at 15 minutes on the relief scale. Aspirin with caffeine was more effective than aspirin alone after 30 minutes and over the entire study period. For patients with fever, both active treatments were equally effective antipyretic agents. We conclude, therefore, that 800 mg of aspirin, given alone or with 64 mg of caffeine, is an effective analgesic and antipyretic agent. Because the aspirin-caffeine combination is significantly more effective than aspirin alone as an analgesic, we also conclude that 64 mg of caffeine is an analgesic adjuvant. (Arch Intern Med. 1991;151:733-737) References 1. Beaver WT. Mild analgesics: a review of their clinical pharmacology . J Med Sci. 1966;251(pt (2) ):576-599.Crossref 2. Beaver WT. Aspirin and acetaminophen as constituents of analgesic combinations . Arch Intern Med. 1981;141:293-300.Crossref 3. Over-the-counter drugs: establishment of a monograph for OTC internal analgesic, antipyretic and antirheumatic products . Fed Register. 1988;53:46244. 4. Williams MW. Analgesic effects of the APC combination in rat . Toxicol Appl Pharmacol. 1959;1:447-453.Crossref 5. Siegers CP. Effects of caffeine on the absorption and analgesic efficacy of paracetamol in rats . Pharmacology. 1973;10:19-27.Crossref 6. Vinegar R, Truax JF, Selph JL, Welch RM, White HL. Potentiation of the anti-inflammatory and analgesic activity of aspirin by caffeine in the rat . Proc Soc Exp Biol Med. 1976;151:556-560.Crossref 7. Seegers AJM, Jager LP, Zandberg P, Van Noordwijk J. The anti-inflammatory, analgesic and antipyretic activities of non-narcotic analgesic drug mixtures in rats . Arch Int Pharmacodyn. 1981;251:237-254. 8. Giertz H, Jurna I. Effects des Caffeins in analgeticsgemischen . Naturwissenschaften. 1957;44:445.Crossref 9. Fuchs HR, Giertz H. Analgetisch wirksome Arzneimittelgemisch . Arzneimittelforsch. 1960;10:526-530. 10. Gregg EC Jr. Effect of non-opiate analgesics and other drugs on the vibratory threshold . J Pharm Exp Ther. 1952;106:1-13. 11. Lim RKS, Miller DG, Guzman F, et al. Pain and analgesia evaluated by the intraperitoneal bradykinin-evoked pain method in man . Clin Pharmacol Ther. 1967;8:521-542. 12. Booy RH. Pain-relieving with simple analgesics in dentistry . Ned Tijdschr Tandheelkinde. 1972;79:69-75. 13. Wojcicki J, Samochowiec L, Lawczynski L, Szwed G, Olszewska M. A double-blind comparative evaluation of aspirin, paracetamol and paracetamol with caffeine (Finimal) for their analgesic effectiveness . Arch Immunol Ther Exp. 1977;25:175-179. 14. Wallenstein SL. Analgesic studies of aspirin in cancer patients . In: Proceedings of the Aspirin Symposium . London, England: The Aspirin Foundation; 1975:5-10. 15. Jain AK, McMahon FG, Ryan JR, Unger D, Richard W. Aspirin and aspirin-caffeine in postpartum pain relief . Clin Pharmacol Ther. 1978;24:69-75. 16. Rubin A, Winter L. A double-blind randomized study of an aspirin/caffeine combination versus acetaminophen/aspirin combination versus acetaminophen versus placebo in patients with moderate to severe post-partum pain . J Int Med Res. 1984;12:338-345. 17. Laska EM, Sunshine A, Zighelboim I, et al. Effect of caffeine on acetaminophen analgesia . Clin Pharmacol Ther. 1983;33:498-509.Crossref 18. Laska EM, Sunshine A, Mueller F, Elvers WB, Siegel C, Rubin A. Caffeine as an analgesic adjuvant . JAMA. 1984;251:1711-1718.Crossref 19. Beaver WT. Caffeine revisited . JAMA. 1984;251:1732-1733.Crossref 20. Schachtel BP, Fillingim JM, Beiter DJ, Lane AC, Schwartz LA. Rating scales for analgesics in sore throat . Clin Pharmacol Ther. 1984;36:151-156.Crossref 21. Schachtel BP, Paull B, Baybutt R. Qualities of pain in the evaluation of a combination analgesic . Acta Pharmacol Toxicol. 1986;59:268. 22. Schachtel BP, Fillingim JM, Thoden WR, Lane AC, Baybutt RI. Sore throat pain in the evaluation of mild analgesics . Clin Pharmacol Ther. 1988;44:707-711.Crossref 23. Dascombe MJ, Milton AS. The effect of caffeine on the antipyretic action of aspirin administered during endotoxin fever . Br J Pharmacol. 1972;46:548P-549P. 24. Schachtel BP, Fillingim JM, Beiter DJ, Lane AC, Schwartz LA. Subjective and objective features of sore throat . Arch Intern Med. 1984;144:497-500.Crossref 25. Steel RGD, Torrie JH. Principles and Procedures of Statistics: A Biometrical Approach. 2nd ed. New York, NY: McGraw-Hill International Book Co; 1980:186-187. 26. Wallenstein SL, Heidrich G, Kaiko R, Houde RW. Clinical evaluation of mild analgesics: the measurement of clinical pain . Br J Clin Pharmacol. 1980;10:319S-327S.Crossref 27. Huskisson EC. Measurement of pain . Lancet. 1974;2:1127-1131.Crossref 28. Joyce CRB, Zutski DW, Hrubes V, Mason RM. Comparison of fixed internal and visual analogue scales for rating chronic pain . Eur J Clin Pharmacol. 1975;8:415-420.Crossref 29. Scott J, Huskisson EC. Graphic representation of pain . Pain. 1976;2:175-184.Crossref 30. Revill SI, Robinson JO, Rosen M, Hogg MIJ. The reliability of a linear analysis for evaluating pain . Anesthesia. 1976;31:1191-1198.Crossref 31. Downie WW, Leatham PA, Rhind VM, Wright V, Branco JA, Anderson JA. Studies with pain rating scales . Ann Rheum Dis. 1978;37:378-381.Crossref 32. Dixon JS, Bird HA. Reproducibility along a 10-cm vertical visual analog scale . Ann Rheum Dis. 1981;40:87-89.Crossref 33. Sriwatanakul K, Kelvie W, Lasagna L, Calmlim JF, Weis OF, Mehta G. Studies with different types of visual analog scales for measurement of pain . Clin Pharmacol Ther. 1983;34:234-239.Crossref 34. Schachtel BP, Sorrentino JV, Wooley BH, Davis B, Brown J. Qualities of pain rated as indicators of therapeutic response . Clin Pharmacol Ther. 1985;37:226. 35. Melzack R, Torgerson WS. On the language of pain . Anesthesiology. 1971;34:50-59.Crossref 36. Melzack R. The McGill pain questionnaire: major properties and scoring methods . Pain. 1975;1:277-299.Crossref 37. Debas HT, Cohen MM, Holubitsky IB, Harrison KC. Caffeine stimulated gastric acid and pepsin secretion dose-response studies . Scand J Gastroenterol. 1971;6:453-457.Crossref 38. Butcher RW, Sutherland EW. Adenosine 3, 5, phosphate in biological materials . J Biol Chem. 1962;287:1244-1250. 39. Dahanukar SA, Pohujani S, Sheth UK. Bioavailability . Med Res. 1978;68:844-848. 40. Yoovathaworn KC, Sriwatanakul K, Thithapandha A. Influence of caffeine on aspirin pharmacokinetics . Eur J Drug Metab Pharmacokinet. 1986;11:71-76.Crossref

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Apr 1, 1991

References

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