Comparison of analgesic, anti-inflammatory and anti-pyretic efficacy of diclofenac, paracetamol and their combination in experimental animals
Keywords:
Analgesic, Anti-inflammatory, Anti-pyretic, Combination, Diclofenac, ParacetamolAbstract
Background: Various combinations of analgesics antipyretic drugs are available in the market for treatment of various musculoskeletal disorders and pain relief. Diclofenac and paracetamol combination is most commonly used combination and its rationality is questionable. The objective of this study was to compare the analgesic, anti-inflammatory and anti-pyretic activities of diclofenac, paracetamol and their combination.
Methods: Experimental animals were divided into 4 different groups – control, diclofenac, paracetamol and their combination. Analgesic activity was compared by using tail-clip method in rats and writhing test in mice, anti-inflammatory activity was compared by carrageenan paw edema method using plethysmometer and anti-pyretic action was compared using TAB vaccine induced pyrexia and measuring the rectal temperature. Different doses of diclofenac (1mg/kg and 2mg/kg) and paracetamol (10mg/kg and 20mg/kg) used and same doses were used in combination group.
Results: Diclofenac sodium (1mg/kg) showed significantly higher analgesic activity using tail-clip and writhing method compared to paracetamol (10mg/kg) (p<0.0001) and the combination group (p<0.05). Diclofenac sodium (2mg/kg) showed significantly higher analgesic activity using tail-clip and writhing method compared to paracetamol (20mg/kg) (p<0.0001) and the combination group (p<0.1). Diclofenac has no significant difference in anti-inflammatory activity using carrageenan induced paw edema when compared to the combination group (p<0.1) for both doses. But diclofenac when compared to paracetamol for anti-inflammatory effect, it was highly significant (p<0.0001 and p<0.0004) for both doses at 1st and 3rd hour. Paracetamol 20mg/kg was superior antipyretic (p<0.05,0.01 and 0.01 ) when compared to the combination group at 1hr, 2hr and 3hr duration after injecting TAB vaccine.
Conclusion: Diclofenac and paracetamol combination was either equal or inferior in all three activities studied as compared to the individual drugs.
References
Yadav P, Kanase V, Lacchiramka P, Jain S. Drug utilization trends in ENT outpatient department in a Teaching hospital. Int J Pharm Biol Sci 2010;1:153-60.
Jeevangi SR, Patil RB, Avanti S, Manjunath S, Patil B, Devi K. Drug utilization study in a burn care unit of a tertiary care hospital. Asian Pac J Trop Dis 2011;1:41-6.
Ong CK, Seymour RA, Lirk P, Merry AF. Combining Paracetamol (Acetaminophen) with Nonsteroidal Antiinflammatory Drugs: A Qualitative Systematic Review of Analgesic Efficacy for Acute Postoperative Pain. Anesth Analg 2010;110(4):1170-9.
Munishankar, Fettes P, Moore C, McLeod GA. A double-blind randomized controlled trial of paracetamol, diclofenac or the combination for pain relief after caesarean section. Int J Obstet Anesth 2008;17:9-14.
Beaver WT. Combination analgesics. Am J Med 1984;77:38-53.
J. Demeules, V. Rollason, V. Piguet, P. Dayer. Clinical Pharmacology and rationale of analgesic combinations. Eur J Anaesthesiol Suppl. 2003;28:7-11.
Bianchi C. & Francheschini J. Experimental observations on Haffner’s method for testing analgesic drugs. Brit J Pharmacol 1954;9(3):280-4.
Witkin LB, Hebner CF, Gaddi F, O'Keefe E, Spitaletta P, Plumer AJ. Pharmacology of 2-aminoindane hydrochloride (SU-8629): A potent non-narcotic analgesic. J Pharmacol Exp Ther. 1961;133:400-8.
Winter CA, Risley EA, Nuss GW. Carrageenan-induced oedema in hind paw of the rats as an assay for anti-inflammatory drugs. Proc Soc Exp Biol Med. 1962;111:544-7.
Dange SV, Shah KU, Ghongane BB, Ranade RS. Potentiation of antipyretic effect of acetaminophen by concomitant administration of ascorbic acid. Indian J Physiol Pharmacol. 1985 Apr-Jun;29(2):129-31.
Festing MF and Altman DG.Guidelines for the Design and Statistical Analysis of Experiments Using Laboratory Animals. ILAR J. 2002;43(4):244-58.
Dahanukar SA, Regs N N. Focus on NSAID combinations. The Indian Practitioner 1998;51(1):43-7.
Bhattacharya SK, Goel RK, Bhattacharya SK, Tandon R. Potentiation of gastric toxicity of ibuprofen by paracetamol in the rat. J Pharm Pharmacol 1991;43(7):520-1.
H O Collier, L C Dinneen, C A Johnson, and C Schneider. The abdominal constriction response and its suppression by analgesic drugs in the mouse. Br J Pharmacol Chemother. 1968 February; 32(2): 295-310.
Björkman R. Central antinociceptive effects of non-steroidal anti-inflammatory drugs and paracetamol. Experimental studies in the rat. Acta Anaesthesiologica Scandinavica. Supplementum 1995;103:1-44.
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 Ther 1981;251:237-54.
Flower R, Gryglewski R, Herbaczyńska-Cedro K, Vane JR. Effects of anti-inflammatory drugs on prostaglandin biosynthesis. Nat New Biol 1972;238:104-6.
Feldberg W, Saxena PN. Prostaglandins, endotoxin and lipid A on body temperature in rats. J Physiol 1975;249:601-15.
Levi S, Shaw-Smith C. Non-steroidal anti-inflammatory drugs: how do they damage the gut? Br J Rheumatol. 1994;33(7):605-12.
Duggin GG. Combination analgesic-induced kidney disease: the Australian experience. Am J Kidney Dis. 1996 Jul;28(1 Suppl 1):S39-47.
Radford MG Jr, Holley KE, Grande JP, Larson TS, Wagoner RD, Donadio JV, McCarthy JT. Reversible membranous nephropathy associated with the use of nonsteroidal anti-inflammatory drugs. JAMA 1996 Aug 14;276(6):466-9.
Rømsing J, Møiniche S, Dahl JB. Rectal and parenteral paracetamol and paracetamol in combination with NSAIDs, for postoperative analgesia. Br J Anaesth. 2002 Feb;88(2):215-26.
Hyllested M, Jones S, Pedersen JL, Kehlet H. Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review. Br J Anaesth. 2002 Feb;88(2):199-214.
Zezi, Abdulkadir Umar. Some pharmacological studies of paracetamol and paracetamol co-formulated with either aspirin, caffeine, diclofenac or ibuprofen. Jun-2006 [dissertation]. Available at http://kubanni.abu.edu.ng:8080/jspui/handle/123456789/1798. Accessed 14 January 2013.