Non-steroidal anti-inflammatory drugs antagonise the constipating effects of tramadol

Planas, Eulalia; Poveda, Raquel; Sánchez, Sílvia; Romero, Asunción; Puig, Margarita M.

doi:10.1016/j.ejphar.2003.09.048

Cited by 13 publications

(7 citation statements)

References 11 publications

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“…On the inhibition of GIT, our results confirm previous results obtained by our group with TRAM [11,18], although other authors have been unable to detect this effect [28]. The dual mechanism of action of TRAM (weak opioid and inhibition of norepinephrine and serotonin reuptake), implicated in the inhibition of GIT [29,30], together with the clinical experience with the drug support our findings on the inhibitory effects of TRAM on GIT in mice.…”

Section: Discussionsupporting

confidence: 91%

“…In our experiments, DEX showed a weak inhibition of the GIT at low doses, but we could not obtain a consistent dose-response curve because of the toxicity of the drugs (increased motor activity), when administered at high doses. Nevertheless, the study of the interaction between DEX and TRAM by using the fixed-dose methods clearly shows antagonism, a fact that confirms previous studies carried out by our group [11].…”

Section: Discussionsupporting

confidence: 89%

“…For antinociception, the analysis of the interaction was carried out by isobolograms and interaction indexes (I.I. ), while for GIT, we used the fixed-dose method [11].…”

Section: Introductionmentioning

confidence: 99%

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Effects of tramadol and dexketoprofen on analgesia and gastrointestinal transit in mice

Miranda

Puig

Romero

et al. 2009

Fundamemntal Clinical Pharma

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The purpose of the present study was to evaluate the nature of the antinociceptive interaction among dexketoprofen (DEX), a mixed inhibitor of the cyclo-oxygenases, and tramadol (TRAM), a weak opioid with monoaminergic activity that inhibits norepinephrine and serotonin re-uptake. We assessed antinociception in the acetic acid writhing test, the tail flick and the formalin (FT) tests, and gastrointestinal transit (GIT) after the administration of a charcoal meal. The analysis of the interaction was carried out using isobolograms and interaction indexes or the fixed-dose method GIT. The administration of DEX or TRAM individually induced dose-dependent antinociception in all the algesiometric tests. In the three tests, TRAM was between 5.2 (FT, phase I) and 35 times (FT, Phase II) more potent than DEX. When testing combinations at different potency ratios (1 : 1, 1 : 3, 3 : 1), we could demonstrate synergy in all algesiometric tests, only when drugs were combined in a 1 : 1 proportion. Interestingly, the proportion of the drugs in the combination could change the type of interaction from synergy to antagonism. On the inhibition of GIT, a dose-related inhibition was established for TRAM, but not for DEX. Using a fixed-dose protocol, we could demonstrate antagonism between DEX and TRAM on the inhibition of GIT. The results of the present study suggest that a combination of DEX and TRAM in a 1 : 1 proportion could be adequate to use in future clinical trials in humans.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 89%

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Effects of tramadol and dexketoprofen on analgesia and gastrointestinal transit in mice

Miranda

Puig

Romero

et al. 2009

Fundamemntal Clinical Pharma

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“…Most subjects had, for example, NSAID as a concomitant medication with a similar frequency across the study groups. This is an important point as experimental data indicate that NSAIDs may antagonize the constipation effects of some opioid analgesics [22]. Secondly, gabapentinoids were used in 20 patients to continue patients’ preoperative medications.…”

Section: Discussionmentioning

confidence: 99%

Opioid-Induced Bowel Dysfunction in Patients Undergoing Spine Surgery: Comparison of Oxycodone and Oxycodone-Naloxone Treatment

et al. 2016

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IntroductionOpioids are needed for postoperative pain in spine surgery patients, but opioid-induced constipation is a harmful adverse event. The aim of this clinical trial was to compare the use of a controlled-release oxycodone-naloxone combination product with oxycodone controlled-release tablets in these patients. The main outcome measure was the prevalence of constipation at 7 days postoperatively assessed with a Bowel Function Index questionnaire. A follow-up assessment at 21 days after surgery was also included.MethodsA total of 180 patients undergoing spine surgery, 91 having preoperative opioids in use and 89 opioid-naïve, were randomized to receive twice-daily oxycodone 10 mg or oxycodone-naloxone 10/5 mg controlled-release tablets for the first 7 postoperative days. Patients were followed-up for 21 days after surgery.ResultsAt baseline, prevalence of constipation was common both in the opioid-naïve—25/87 (29%) and on-opioid groups 43/90 (48%) (P = 0.009). This increased at 7 days postoperatively with no difference between the groups, 54/89 with oxycodone and 54/88 with oxycodone-naloxone had constipation. At 21 days, constipation was less than in the baseline in both groups, in the opioid-naïve group the prevalence of constipation was 3/43 (7%) in patients with oxycodone-naloxone compared to 9/44 (21%) with oxycodone (effect size 0.68; P = 0.068). Both study compounds provided similar pain relief and were well tolerated.ConclusionIn patients presented for back surgery, the prevalence of constipation was significantly higher than that in the community. In opioid-naïve subjects, oxycodone-naloxone was beneficial concerning constipation; but this was not distinguishable in subjects with chronic opioid use. The analgesic efficacy of oxycodone and oxycodone-naloxone was similar. Trial registration: European Clinical Trials Database (EudraCT no. 2012-001816-42) and ClinicalTrials.gov database (Identifier: NCT02573922).

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“…Opioid-induced bowel dysfunction is common, and represents a significant barrier to achieving optimal pain management 74 . Animal studies suggested that NSAIDswhen combined with tramadol-may limit constipation 75 . Accordingly, dexketoprofen was found to be able to counteract tramadol-induced inhibition of GI transit 72 .…”

Section: Dexketoprofen/tramadol Fdc For Acute Painmentioning

confidence: 99%

Multimodal analgesia in moderate-to-severe pain: a role for a new fixed combination of dexketoprofen and tramadol

Varrassi

Hanna

Macheras

et al. 2017

Current Medical Research and Opinion

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Dexketoprofen/tramadol (25 mg/75 mg) is a new oral fixed-dose combination offering a comprehensive multimodal approach to moderate-to-severe acute pain that encompasses central analgesic action, peripheral analgesic effect and anti-inflammatory activity, together with a good tolerability profile. The analgesic efficacy of dexketoprofen/tramadol combination is complemented by a favorable pharmacokinetic and pharmacodynamic profile, characterized by rapid onset and long duration of action. This has been well documented in both somatic- and visceral-pain human models. This review discusses the available clinical evidence and the future possible applications of dexketoprofen/tramadol fixed-dose combination that may play an important role in the management of moderate-to-severe acute pain.

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Non-steroidal anti-inflammatory drugs antagonise the constipating effects of tramadol

Cited by 13 publications

References 11 publications

Effects of tramadol and dexketoprofen on analgesia and gastrointestinal transit in mice

Effects of tramadol and dexketoprofen on analgesia and gastrointestinal transit in mice

Opioid-Induced Bowel Dysfunction in Patients Undergoing Spine Surgery: Comparison of Oxycodone and Oxycodone-Naloxone Treatment

Multimodal analgesia in moderate-to-severe pain: a role for a new fixed combination of dexketoprofen and tramadol

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