Opioids and Cancer Mortality.

OPINION STATEMENT: Opioids are the gold standard for the treatment of cancer-related pain. Preclinical studies have associated opioids with cancer progression and overall survival. In mice models, opioids have been shown to possess pro-tumor activity secondary to immunosuppression, migration of tumor cells, increased activity of vascular endothelial growth factor receptors, and angiogenesis leading to tumor progression. In contrast, opioids have also been associated with having antitumor activity by activation of apoptosis and phagocytosis. However, high-quality randomized controlled trials in humans that are focused on the association between opioids and survival in cancer patients are lacking, which underscores the importance of being cautious when interpreting the results of the preclinical studies. Cancer-related pain is complex and multifactorial and may worsen as the disease progresses leading to higher opioid utilization. Moreover, cancer pain by itself has been associated with poor survival. The survival in these advanced cancer patients taking opioids may be more likely to be associated with cancer progression and not the opioid use. Adequate treatment of cancer pain has the potential to improve quality of life and performance status, highlighting the importance of continuing to use opioids to manage pain efficiently. More research is clearly needed.

The effects of radio-frequency radiation (RFR) exposure on the analgesic efficacy of morphine in healthy rats and rats with inflammation.

OBJECTIVES: The aim of this study, conducted at the Military Institute of Hygiene and Epidemiology in Warsaw in 2017, was to evaluate the effects of a single (15 min) and repeated (5 times for 15 min) radio-frequency radiation (RFR) exposure of 1800 MHz frequency on the analgesic efficacy of morphine in healthy rats and rats with complete Freund's adjuvant (CFA) induced inflammation. MATERIAL AND METHODS: Rats were injected intraperitoneally with morphine (MF) in the dose of 8 mg/kg or drug vehicle 15 min before RFR exposure. The authors used the plantar analgesia meter and the radiant heat paw-withdrawal test to assess the pain threshold. RESULTS: A single RFR exposure slightly influenced paw withdrawal latency (PWL) in healthy rats in the single exposure baseline group, and influenced PWL, 30 and 60 min after morphine or vehicle injection, in the repeated exposure group. There were differences between the sham-exposed groups (vehicle), 30, 60 and 90 min after injection, both in the single and repeated RFR-exposure groups. The antinociceptive effect of morphine in healthy rats was slightly decreased by RFR exposure at 60 and 90 min, both in the single and repeated exposure groups. The PWL was slightly decreased, both in the single and repeated exposure groups with inflammation (CFA and CFA/MF), at 30, 60 and 90 min, and PWL was increased in the sham-exposed groups (CFA and CFA/MF), both in the single and repeated exposure groups, at 30, 60 and 90 min. The antinociceptive effect of morphine in healthy rats was significantly increased by RFR exposure at 30 min after drug injection in the single exposure group, and increased at 30 and 60 min in the repeated exposure group. CONCLUSIONS: The authors observed a minor influence of RFR exposure on the antinociceptive effects of morphine in healthy rats after repeated exposures and a statistically significant influence of repeated exposure on morphine mediated antinociceptive effects in the inflammation group. Int J Occup Med Environ Health. 2019;32(4):465-74.

[Shelf-lives of morphine and pethidine solutions stored in patient-controlled analgesia devices: physico-chemical and microbiological stability study]. / Durée de péremption des solutions de morphine et de la péthidine présentées dans des dispositifs pour analgésie autocontrôlée: étude de stabilité physicochimique et microbiologique.

Morphine and meperidine in Patient-Controlled Analgesic devices are commonly used to treat chronic pain patients. These devices deliver a programmed amount of drug and allow self-administration by the patient depending on the pain. In our department of pharmacy, 300 devices were manufactured in 2003. The aim of this study was to assess their shelf-life. The devices were filled aseptically and without preservatives with 1 and 40 mg/ml morphine solution and 5 and 20 mg/ml meperidine and stored over 30 days at room temperature and protected from light. Culture assay of the solutions showed that they remained sterile for 30 days. No turbidity of any solutions from samples collected twice a week was noticed. pH and osmolarity remained constant. Drug concentrations were determined using stability indicating HPLC method, as we showed that degradation products can be separated from the drugs. Little loss of meperidine occurred within 21 days (<5%) and morphine concentration, which increased, because of solvent evaporation, remained lower than 5% within 21 days but increased up to 10% after 30 days. No traces of degradation products (pseudomorphine or pethidic acid) were detected. The physicochemical and microbiological stability of morphine and meperidine hydrochlorides stored in such devices has been established for 21 days at room temperature and protected from light.

Compatibility of ketamine and morphine injections.

The compatibility of ketamine and morphine mixture was studied. In addition, pH adjustment to minimise local tissue irritation led to no change in stability of the mixture up to pH 5.9. It appears that ketamine and morphine mixtures are stable over a 24 h period.

Stability of morphine solutions in plastic syringes determined by reversed-phase ion-pair liquid chromatography.

A reversed-phase ion-pair HPLC assay has been developed for quantitating morphine, codeine, apomorphine, and pseudomorphine in aqueous solutions. Using two types of plastic syringes, the effect of light (25 W) and temperature (22 and 3 degrees C) on the stability of morphine, over a 12-week period, has been investigated in the presence and absence of preservative and antioxidant. The leaching of contaminants from the plastic syringes to water stored in them, for a period of up to 12 weeks, has also been investigated. The results indicate that less than 3% of the morphine is degraded in both types of plastic syringes, stored in light at 22 +/- 2 degrees C. The degradation is even less prominent in the dark or at 3 degrees C. Pseudomorphine has been identified as the major degradation product. Using 5% degradation of drug as the criterion for the determination of the shelf-life of morphine, it was found that in one brand of plastic syringes, morphine has a shelf-life of the order of 20 and 33 weeks, in the absence and presence of preservative and antioxidant, respectively. In the other brand of plastic syringe, the drug has a shelf-life of greater than 1 year. Some unidentified leached contaminants have been detected in water stored in both brands of syringes.