Combining diclofenac with acetaminophen or acetaminophen-codeine after oral surgery: A randomized, double-blind single-dose study

Breivik, Else Kristine; Barkvoll, Pål; Skovlund, Eva

doi:10.1053/cp.1999.v66.103629001

Cited by 110 publications

(33 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results obtained confirm the potential benefit of combining paracetamol with NSAIDs as it is usually carried out clinically. This is in accordance with the evidence regarding a boosted analgesic effect of combining paracetamol and NSAIDs available from animal studies, experimental pain models in human being [28,41] and clinical studies of pain on osteoarthritis [42], dental surgery [43] or other selected surgical procedures [2,3]. However, the exact and quantitative nature of the interaction (additive or supra-additive) and its mechanisms are still under debate.…”

Section: Discussionsupporting

confidence: 84%

A Randomized, Controlled Trial Validates a Peripheral Supra-Additive Antihyperalgesic Effect of a Paracetamol-Ketorolac Combination

Lorenzini¹,

Besson²,

Daali³

et al. 2011

Basic &Amp; Clinical Pharmacology &Amp; Toxicology

View full text Add to dashboard Cite

The combination of paracetamol with non-steroidal anti-inflammatory drugs (NSAIDs) is widely used; however, the nature and mechanism of their interaction are still debated. A double-blind, pharmacokinetic ⁄ pharmacodynamic, randomized, cross-over, placebo-controlled study was carried out in human healthy volunteers. The aim was to explore the existence of a positive interaction between paracetamol 1 g and ketorolac 20 mg administered intravenously on experimental pain models in human beings. The effects of the paracetamol-ketotolac combination were compared with similar doses of respective single analgesic and to placebo on the sunburn model (UVB-induced inflammation), cold pain tolerance and the nociceptive flexion reflex. The kinetics of the plasma concentrations of paracetamol and ketorolac were measured using 2D-liquid chromatography-mass spectrometry. Thirteen volunteers were screened, and 11 completed the study. Ketorolac significantly decreased primary hyperalgesia to heat stimuli compared with paracetamol (p < 0.014). The combination performed better than paracetamol (p < 0.001) and placebo (p < 0.042), increasing heat pain threshold by 1.5°C. The combination radically reduced primary hyperalgesia to mechanical stimulation (39%) compared with placebo (p < 0.002) and single agents (paracetamol p < 0.024 and ketorolac p < 0.032). The combination also reduced, slightly although significantly, the intensity of pain (10%) for the cold pressor test (versus placebo: p < 0.012, paracetamol: p < 0.019 and ketorolac p < 0.004). None of the treatments significantly affected the central models of pain at this dosage level. No pharmacokinetic interactions were observed. These results suggest a supra-additive pharmacodynamic interaction between paracetamol and ketorolac in an inflammatory pain model. The mechanism of this interaction could mainly rely on a peripheral contribution of paracetamol to the effect of NSAIDs.Multimodal analgesia involves a combination of different classes of analgesics to improve pain relief and reduce the adverse effects of drugs [1]. The combination of paracetamol with non-steroidal anti-inflammatory drugs (NSAIDs) is widely used in clinical practice although it has been demonstrated to be effective in pain management only in few clinical studies [2][3][4]. The putative rationale underlying this association is their different site and ⁄ or mode of action (central versus peripheral, serotonin and ⁄ or cannabinoid systems versus prostaglandin synthesis) [5]. The mechanism of action of paracetamol is yet to be fully elucidated [6]. Much evidence supports the hypothesis of a central analgesic effect [7], while the other evidence supports a peripheral effect [8]. The prostaglandin H 2 synthase (PGHS) [9], the serotoninergic system [10,11] and ⁄ or the cannabinoid system [12,13] have been proposed as potential targets. NSAIDs essentially act by inhibiting prostaglandin biosynthesis at the site of the inflammation [14]. However, some NSAIDs also exhibit a central action [15]. Experiment...

show abstract

Section: Discussionsupporting

confidence: 84%

A Randomized, Controlled Trial Validates a Peripheral Supra-Additive Antihyperalgesic Effect of a Paracetamol-Ketorolac Combination

Lorenzini¹,

Besson²,

Daali³

et al. 2011

Basic &Amp; Clinical Pharmacology &Amp; Toxicology

View full text Add to dashboard Cite

show abstract

“…Our study did not show the same additive effect of combining rofecoxib and paracetamol as in a study by Breivik et al in which they combined diclofenac and paracetamol (18). These authors demonstrated an additive effect of paracetamol over the whole study period of 8 h. Their study also showed less use of rescue medication in the combination group compared with the patients treated with diclofenac alone, something also found in a study by Matthews et al (19).…”

Section: Discussionsupporting

confidence: 65%

“…Research on paracetamol has not been able to delineate a clear mechanism of action, but it is suggested to lie predominantly in the central nervous system (17). Some studies indicate that combining a traditional NSAID and paracetamol after oral surgery may enhance the analgesic effect compared with single drug regimes (18,19).…”

mentioning

confidence: 99%

Combining paracetamol with a selective cyclooxygenase‐2 inhibitor for acute pain relief after third molar surgery: a randomized, double‐blind, placebo‐controlled study

Haglund

Bültzingslöwen

2006

European J Oral Sciences

View full text Add to dashboard Cite

Severe pain after third molar surgery is often encountered and more effective treatment regimes are warranted. The objective of this study was to evaluate if the combination of paracetamol and rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, improves analgesic effects following third molar surgery compared with rofecoxib alone. Paracetamol alone was also evaluated. Altogether 120 patients with moderate to severe pain after third molar surgery were given a single postoperative dose of one of the following treatments: rofecoxib + paracetamol; rofecoxib alone; paracetamol alone; or placebo. Patients assessed level of pain and pain relief every 30 min for 8 h after surgery, and made a global evaluation of the medication 4 and 8 h after surgery. Paracetamol and rofecoxib combined improved the analgesic effect compared with rofecoxib alone for the first 1.5 h. Rofecoxib alone and the combination of paracetamol and rofecoxib had a significantly better analgesic effect than paracetamol alone from 3 h onwards. The early onset of pain relief for the combination of paracetamol and rofecoxib, compared with rofecoxib alone, could be of great importance when treating acute pain after third molar surgery. After data collection for this study, rofecoxib was withdrawn from the market as a result of reported fatal cardiovascular events. Whether this is relevant for short-term use is unknown, but it has to be considered before rofecoxib may be used for pain relief following third molar surgery.

show abstract

“…Ibuprofen 600 mg taken every 6 h is optimal for managing pulpal and periradicular pain of inflammatory origin (103). The combination of a NSAID and acetominophen taken together show additive analgesia for treating dental pain (103,105,(149)(150)(151). However, for those patients that cannot tolerate this drug class one should consider 1000 mg acetominophen (103,104).…”

Section: (B) Non-narcotic Analgesicsmentioning

confidence: 99%

Interappointment pain: mechanisms, diagnosis, and treatment

Siqueira¹,

Barnett²

2004

Endodontic Topics

103

View full text Add to dashboard Cite

Knowledge on the causes of and the mechanisms behind interappointment pain in endodontics is of utmost importance for the clinician to properly prevent or manage this undesirable condition. The causative factors of interappointment pain encompass mechanical, chemical, and/or microbial injury to the pulp or periradicular tissues, which are induced or exacerbated during root canal treatment. Microorganisms can participate in causation of interappointment pain in the following situations: apical extrusion of debris; incomplete instrumentation leading to changes in the endodontic microbiota or in environmental conditions; and secondary intraradicular infections. Interappointment pain is almost exclusively due to the development of acute inflammation at the periradicular tissues in response to an increase in the intensity of injury coming from the root canal system. When an interappointment emergency occurs, proper diagnosis and active treatment are required for the clinician to succeed in solving the problem. This review focuses on the mechanisms of interappointment pain, with special emphasis placed on the causative agents and the host response to injury that can precipitate pain. In addition, diagnostic measures and treatment approaches to manage interappointment pain are also discussed.

show abstract

Combining diclofenac with acetaminophen or acetaminophen-codeine after oral surgery: A randomized, double-blind single-dose study

Cited by 110 publications

References 36 publications

A Randomized, Controlled Trial Validates a Peripheral Supra-Additive Antihyperalgesic Effect of a Paracetamol-Ketorolac Combination

A Randomized, Controlled Trial Validates a Peripheral Supra-Additive Antihyperalgesic Effect of a Paracetamol-Ketorolac Combination

Combining paracetamol with a selective cyclooxygenase‐2 inhibitor for acute pain relief after third molar surgery: a randomized, double‐blind, placebo‐controlled study

Interappointment pain: mechanisms, diagnosis, and treatment

Contact Info

Product

Resources

About