Combination strategies for pain management

Raffa, Robert B.; Clark-Vetri, Rachel; Tallarida, Ronald J.; Wertheimer, Albert I.

doi:10.1517/14656566.4.10.1697

Cited by 63 publications

(32 citation statements)

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“…In a study conducted in advanced cancer patients receiving a stable dose of opioids, the addition of 5 g of acetaminophen daily resulted in significant improvement in pain compared with placebo [42]. Combination opioid products confer better pain control than do individual components given at the same doses, owing to the concept of additive synergistic analgesia [43][44][45]. However, whether acetaminophen exhibits a ceiling effect at higher doses is unknown [46][47][48], and such an effect could explain the lower MEDD-hydrocodone ratio for higher doses of hydrocodone.…”

Section: Discussionmentioning

confidence: 99%

The Opioid Rotation Ratio of Hydrocodone to Strong Opioids in Cancer Patients

et al. 2014

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Purpose. Cancer pain management guidelines recommend initial treatment with intermediate‐strength analgesics such as hydrocodone and subsequent escalation to stronger opioids such as morphine. There are no published studies on the process of opioid rotation (OR) from hydrocodone to strong opioids in cancer patients. Our aim was to determine the opioid rotation ratio (ORR) of hydrocodone to morphine equivalent daily dose (MEDD) in cancer outpatients. Patients and Methods. We reviewed the records of consecutive patient visits at our supportive care center in 2011–2012 for OR from hydrocodone to stronger opioids. Data regarding demographics, Edmonton Symptom Assessment Scale (ESAS), and MEDD were collected from patients who returned for follow‐up within 6 weeks. Linear regression analysis was used to estimate the ORR between hydrocodone and MEDD. Successful OR was defined as 2‐point or 30% reduction in the pain score and continuation of the new opioid at follow‐up. Results. Overall, 170 patients underwent OR from hydrocodone to stronger opioid. The median age was 59 years, and 81% had advanced cancer. The median time between OR and follow‐up was 21 days. We found 53% had a successful OR with significant improvement in the ESAS pain and symptom distress scores. In 100 patients with complete OR and no worsening of pain at follow‐up, the median ORR from hydrocodone to MEDD was 1.5 (quintiles 1–3: 0.9–2). The ORR was associated with hydrocodone dose (r = −.52; p < .0001) and was lower in patients receiving ≥40 mg of hydrocodone per day (p < .0001). The median ORR of hydrocodone to morphine was 1.5 (n = 44) and hydrocodone to oxycodone was 0.9 (n = 24). Conclusion. The median ORR from hydrocodone to MEDD was 1.5 and varied according to hydrocodone dose.

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Section: Discussionmentioning

confidence: 99%

The Opioid Rotation Ratio of Hydrocodone to Strong Opioids in Cancer Patients

et al. 2014

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“…Opioid use may cause constipation, respiratory depression and the development of tolerance and dependence, while cannabinoid drugs elicit central side effects including psychomotor impairment and sedation (Ashton, 2001). Synergistic drug combinations may improve effective pharmacotherapy of pain as the lower clinical dose requirements for each agent will minimise drugspecific adverse effects (Raffa et al, 2003).…”

Section: Sm Tham Et Almentioning

confidence: 99%

Synergistic and additive interactions of the cannabinoid agonist CP55,940 with μ opioid receptor and α₂‐adrenoceptor agonists in acute pain models in mice

Tham

Angus

Tudor

et al. 2005

British J Pharmacology

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1 Cannabinoid receptor agonists elicit analgesic effects in acute and chronic pain states via spinal and supraspinal pathways. We investigated whether the combination of a cannabinoid agonist with other classes of antinociceptive drugs exerted supra-additive (synergistic) or additive effects in acute pain models in mice. 2 The interactions between the cannabinoid agonist CP55,940, a 2 -adrenoceptor agonist dexmedetomidine and m-opioid receptor agonist morphine were evaluated by isobolographic analysis of antinociception in hot plate (551C) and tail flick assays in conscious male Swiss mice. Drug interactions were examined by administering fixed-ratio combinations of agonists (s.c.) in 1 : 1, 3 : 1 and 1 : 3 ratios of their respective ED 50 fractions. 3 CP55,940, dexmedetomidine and morphine all caused dose-dependent antinociception. In the hot plate and tail flick assays, ED 50 values (mg kg À1 ) were CP55,940 1.13 and 0.51, dexmedetomidine 0.066 and 0.023, and morphine 29.4 and 11.3, respectively. Synergistic interactions existed between CP55,940 and dexmedetomidine in the hot plate assay, and CP55,940 and morphine in both assays. Additive interactions were found for CP55,940 and dexmedetomidine in the tail flick assay, and dexmedetomidine and morphine in both assays. 4 Thus, an a 2 -adrenoceptor agonist or m opioid receptor agonist when combined with a cannabinoid receptor agonist showed significant synergy in antinociception in the hot plate test. However, for the tail flick nociceptive response to heat, only cannabinoid and m opioid receptor antinociceptive synergy was demonstrated. If these results translate to humans, then prudent selection of dose and receptorspecific agonists may allow an improved therapeutic separation from unwanted side effects.

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“…Furthermore, drug combinations often are characterized by an increased activity and tolerability compared to that of monotherapy. Therefore, drug combinations are widely used in the treatment of infectious diseases (e.g., malaria, HIV, and tuberculosis), cancer, and chronic disorders (e.g., cardiovascular disease, diabetes, and pain management) (5,8,12,30,39). Combination chemotherapy has been tested in experimental studies using triclabendazole-susceptible and -resistant strains of F. hepatica.…”

mentioning

confidence: 99%

In Vivo and In Vitro Sensitivity of Fasciola hepatica to Triclabendazole Combined with Artesunate, Artemether, or OZ78

Duthaler

Smith

Keiser

2010

Antimicrob Agents Chemother

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Triclabendazole resistance is continually documented from livestock, and hence new treatment strategies for Fasciola hepatica infections are needed. We investigated the effect of triclabendazole combined with artesunate, artemether, or OZ78 compared to that of monotherapy against adult and juvenile F. hepatica in rats. In vitro experiments with triclabendazole and its sulfoxide and sulfone metabolites, each in combination with the peroxides, complemented our study. F. hepatica-infected rats were subjected to single drugs or drug combinations 3 to 4 weeks (juvenile flukes) and >8 weeks (adult flukes) postinfection. Negative binomial regressions of worm and egg counts were used to analyze dose-response relationships and whether the effects of drug combinations were synergistic or antagonistic. The in vitro assays were evaluated by means of viability scales based on fluke motility. Fifty percent effective dose values of 113.0, 77.7, 22.9, and 2.7 mg/kg of body weight were calculated for monotherapy with artesunate, artemether, OZ78, and triclabendazole, respectively, against adult F. hepatica. Likelihood ratio tests revealed synergistic interactions (P < 0.05) of combinations of triclabendazole (2.5 mg/kg) plus artesunate or artemether on adult worm burden. Antagonistic effects on the adult burden and egg output were observed when a lower triclabendazole dose (1.25 mg/kg) was combined with the artemisinins. No significant interactions (P ‫؍‬ 0.07) were observed for OZ78 and triclabendazole combinations and between the triclabendazole effect and the effects of the other partner drugs on juvenile worms. Our in vitro studies of adult worms agreed with the in vivo results, while the in vitro analysis of juvenile worms revealed greater interactions than observed in vivo. In conclusion, single-agent triclabendazole demonstrated a more potent in vivo and in vitro fasciocidal activity than the experimental drugs artesunate, artemether, and OZ78. When combined, synergistic but also antagonistic effects depending on the doses administered were observed, which should be elucidated in more detail in future studies.

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Combination strategies for pain management

Cited by 63 publications

References 9 publications

The Opioid Rotation Ratio of Hydrocodone to Strong Opioids in Cancer Patients

The Opioid Rotation Ratio of Hydrocodone to Strong Opioids in Cancer Patients

Synergistic and additive interactions of the cannabinoid agonist CP55,940 with μ opioid receptor and α₂‐adrenoceptor agonists in acute pain models in mice

In Vivo and In Vitro Sensitivity of Fasciola hepatica to Triclabendazole Combined with Artesunate, Artemether, or OZ78

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Combination strategies for pain management

Cited by 63 publications

References 9 publications

The Opioid Rotation Ratio of Hydrocodone to Strong Opioids in Cancer Patients

The Opioid Rotation Ratio of Hydrocodone to Strong Opioids in Cancer Patients

Synergistic and additive interactions of the cannabinoid agonist CP55,940 with μ opioid receptor and α2‐adrenoceptor agonists in acute pain models in mice

In Vivo and In Vitro Sensitivity of Fasciola hepatica to Triclabendazole Combined with Artesunate, Artemether, or OZ78

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Synergistic and additive interactions of the cannabinoid agonist CP55,940 with μ opioid receptor and α₂‐adrenoceptor agonists in acute pain models in mice