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The Journal of Burn Care &... 1992Morphine sulfate (MS Contin), a proven analgesic in the treatment of cancer pain and chronic benign pain, seems to be a good analgesic for the treatment of burn pain. MS... (Clinical Trial)
Clinical Trial Comparative Study
Morphine sulfate (MS Contin), a proven analgesic in the treatment of cancer pain and chronic benign pain, seems to be a good analgesic for the treatment of burn pain. MS Contin is morphine sulfate incorporated in a wax cellulose matrix delivery system. This wax cellulose delivery system gives MS Contin its duration of action. Ten patients were enrolled in an open-labeled, nonrandomized study. The study was designed to examine the analgesic efficacy of MS Contin in the burn population. Each patient remained in the study for 6 days. The efficacy of the analgesic regimen was subjectively measured by the visual pain scale. The MS Contin group was retrospectively compared with a group of patients who were given continuous intravenous infusions of morphine. The two groups were matched according to age, burn size, surgical procedures, and hospital stay. The analgesic qualities of MS Contin were comparable to those of continuous intravenous morphine sulfate infusions. MS Contin is a possible candidate for the treatment of patients with burn pain because of its analgesic qualities, oral dosing, and duration of action.
Topics: Adolescent; Adult; Aged; Burns; Child; Drug Delivery Systems; Humans; Infusions, Intravenous; Middle Aged; Morphine; Pain; Pilot Projects; Retrospective Studies
PubMed: 1452594
DOI: 10.1097/00004630-199209000-00013 -
Canadian Journal of Veterinary Research... Oct 1997The pharmacokinetics and bioavailability (F) of single dose sustained release morphine sulfate (OSRMS) and nonsustained release morphine sulfate (NSRMS) were compared to... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
The pharmacokinetics and bioavailability (F) of single dose sustained release morphine sulfate (OSRMS) and nonsustained release morphine sulfate (NSRMS) were compared to each other and to a bolus injection of morphine sulfate (MS) intravenously (i.v.) in dogs. Beagles (n = 6) were randomly assigned to 3 treatment groups: namely, OSRMS 15 mg orally, NSRMS 15 mg orally, and 15 mg i.v. Serum samples were drawn at intervals up to 480 min following oral and 420 min following i.v. administration. Serum was analysed for morphine concentration using a radioimmunoassay. Data were analysed using non-compartmental pharmacokinetics. The only statistically significant difference between OSRMS and NSRMS was maximum serum concentration (Cmax). There were trends toward longer time to maximum serum concentration (Tmax) and longer mean absorption time (MAT) for OSRMS when compared to NSRMS, but the differences were not statistically significant (P < 0.05). Pharmacokinetic parameters for both oral formulations exhibited large variability in the rate of absorption of MS from the gastrointestinal tract. Bioavailability of both OSRMS and NSRMS was low (15%-17%). As expected, the area under the concentration vs time curve (AUC) and Cmax for the i.v. data was significantly greater than for both oral groups, and Tmax and mean residence time (MRT) were significantly less following i.v. administration. There were no statistically significant differences among the 3 treatment groups for apparent volume of distribution at steady state (Vdss) or elimination parameters. The OSRMS formulation used in this study provided equivalent bioavailability to NSRMS in dogs, accompanied by large individual variability in drug absorption. It also did not appear that the sustained release formulation provided sufficiently prolonged release of morphine sulfate from the tablet matrix in dogs to allow prolonged dosing intervals compared to NSRMS.
Topics: Administration, Oral; Analgesics, Opioid; Analysis of Variance; Animals; Area Under Curve; Biological Availability; Delayed-Action Preparations; Dogs; Female; Injections, Intravenous; Morphine; Radioimmunoassay; Time Factors
PubMed: 9342447
DOI: No ID Found -
Clinical Pharmacology and Therapeutics May 1987Ketorolac tromethamine, a nonnarcotic, prostaglandin synthesis-inhibiting analgesic, was compared with morphine sulfate for relief of moderate to severe postoperative... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Ketorolac tromethamine, a nonnarcotic, prostaglandin synthesis-inhibiting analgesic, was compared with morphine sulfate for relief of moderate to severe postoperative pain. The 155 patient participants received single intramuscular doses of either ketorolac, 10, 30, or 90 mg, or morphine, 6 or 12 mg, administered in a double-blind, randomized fashion. Pain scores (verbal and visual analog) were recorded at baseline and assessed at 30 minutes and then hourly to 6 hours. Pain relief was rated at the same times. Ketorolac, 90 and 30 mg, was rated significantly better than morphine, 6 mg, at each assessment interval after 1 hour. Ketorolac, 90 and 30 mg, was rated similarly to morphine, 12 mg, for the first 3 hours and better than morphine, 12 mg, 4 hours after injection. There were no serious side effects reported. The only side effect reported in more than 3% of patients was 8% somnolence with morphine. This study shows ketorolac to be a safe and effective analgesic for relief of postoperative pain.
Topics: Adult; Aged; Drug Combinations; Female; Humans; Injections, Intramuscular; Ketorolac Tromethamine; Male; Middle Aged; Morphine; Pain, Postoperative; Pyrroles; Tolmetin; Tromethamine
PubMed: 3568540
DOI: 10.1038/clpt.1987.71 -
Neurosurgery Jun 1986A total of 24 patients with intractable cancer pain were evaluated as candidates for spinal morphine therapy. Temporary trials were carried out with bolus injections of... (Clinical Trial)
Clinical Trial
A total of 24 patients with intractable cancer pain were evaluated as candidates for spinal morphine therapy. Temporary trials were carried out with bolus injections of preservative-free morphine sulfate via percutaneously inserted epidural catheters. Fourteen patients felt that pain relief was sufficient to warrant long term morphine application, and permanent drug delivery systems were implanted. These consisted of an Ommaya reservoir and an epidural spinal catheter in 6 patients and an Infusaid pump with either an epidural or subarachnoid spinal catheter in 8 patients. Pain relief with these systems was felt to be excellent in 7 patients, good in 4 patients, and fair in 3 patients. There was a statistically significant reduction in supplemental narcotic use between the pre- and postoperative periods (P less than 0.001). Median survival after operation was 3.0 months (mean, 5.0 months), with a range of 1 to 23 months. Tolerance was seen in all patients regardless of the mode of drug delivery, but it occurred more quickly with bolus injections than with continuous infusion (statistically significant difference, P less than 0.05). A persistent cerebrospinal fluid fistula developed in 1 patient; this required wound revision. No other serious complications or episodes of respiratory depression occurred. We conclude that intraspinal morphine sulfate is a beneficial treatment option for cancer patients in whom pain has become debilitating and unresponsive to oral or parenteral narcotic regimes.
Topics: Aged; Anesthesia, Epidural; Anesthesia, Spinal; Clinical Trials as Topic; Drug Administration Schedule; Female; Humans; Long-Term Care; Male; Middle Aged; Morphine; Neoplasms; Pain, Intractable; Time Factors
PubMed: 3090473
DOI: 10.1227/00006123-198606000-00011 -
Neuroscience Letters Jan 2015Neuropeptide FF (NPFF) modulates opiate actions. It has pro-nociceptive effects, primarily through the NPFF receptor 1 subtype, and anti-nociceptive effects, primarily...
Neuropeptide FF (NPFF) modulates opiate actions. It has pro-nociceptive effects, primarily through the NPFF receptor 1 subtype, and anti-nociceptive effects, primarily through the NPFFR2 subtype. AC-263093 is a small l, organic, systemically active molecule that was previously shown to functionally activate NPFFR2, but not NPFFR1. It was hypothesized that AC-263093 would attenuate morphine tolerance. Rats were tested for radiant heat tail-flick latency before and after 5 mg/kg morphine sulfate s.c. They were then rendered morphine-tolerant by continuous subcutaneous infusion of 17.52 mg/kg/day morphine sulfate. On the seventh day of infusion, they were retested for analgesia 10 and 20 min after 5mg/kg morphine sulfate s.c. Tolerance was indicated by reduction of morphine analgesia from the pre-infusion test. Fifty minutes prior to morphine challenge, rats received either 10 mg/kg i.p. AC-263093 or injection vehicle alone. AC-2623093-treated rats had far smaller tolerance scores than control rats. This drug effect was significant, p = 0.015. The same dose of AC-263093 had almost no analgesic effect in non-tolerant, saline-infused rats. In vitro experiments revealed that AC-263093 had equal affinity for NPFFR1 and NPFFR2, and functionally inactivated NPFFR1, in addition to its previously shown ability to activate NPFFR2. Thus, altering the balance between activation of NPFF receptor subtypes may provide one approach to reversing opiate tolerance.
Topics: Analgesics, Opioid; Animals; Drug Interactions; Drug Tolerance; Hydrazines; Male; Morphine; Oligopeptides; Radioligand Assay; Rats, Sprague-Dawley; Receptors, Neuropeptide
PubMed: 25459291
DOI: 10.1016/j.neulet.2014.10.018 -
American Journal of Hospital Pharmacy Jul 1989The stability of four concentrations of morphine sulfate injection in prefilled reservoirs for portable infusion pumps was studied after storage for 30 days at...
The stability of four concentrations of morphine sulfate injection in prefilled reservoirs for portable infusion pumps was studied after storage for 30 days at refrigerated and room temperature and after a three-day simulated administration period at body temperature. Thirty-milliliter samples of morphine sulfate injections in four concentrations--1, 5, 15, and 25 mg/mL--were loaded into a pump reservoir. The reservoirs were stored in the dark at 5 degrees C and 25 degrees C for 30 days. Samples were taken from each reservoir immediately after loading and after 7, 14, and 30 days of storage. The reservoirs were then connected to portable infusion pumps, which were run for three days at a flow rate of 0.4 mL/hr at 37 degrees C. The last sample was collected at the end of the three-day period. Samples were assayed for morphine sulfate content by high-performance liquid chromatography. The concentration of morphine sulfate increased up to 6% (for the 5-mg/mL sample) at refrigerated temperature and up to 16% (for the 15-mg/mL sample) at room temperature after 30 days' storage in the reservoirs. Evaporation of water from the reservoirs may have accounted for this phenomenon. No absolute relationship was found between the initial concentration of morphine sulfate and the percentage concentration increase after storage for 30 days. The change in morphine sulfate concentration before and after the three-day pumping period was not significant. Injectable solutions of morphine sulfate in concentrations ranging from 1 to 25 mg/mL are stable when stored at refrigerated temperature for 30 days in a prefilled drug reservoir.
Topics: Chromatography, High Pressure Liquid; Drug Stability; Drug Storage; Infusion Pumps; Morphine
PubMed: 2757049
DOI: No ID Found -
Veterinary Ophthalmology May 2018To evaluate whether topical ocular application of 1% morphine sulfate would change corneal sensitivity and to identify the duration of action. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate whether topical ocular application of 1% morphine sulfate would change corneal sensitivity and to identify the duration of action.
ANIMAL STUDIED
Eight healthy adult horses.
PROCEDURE
Corneal touch threshold (CTT) was measured in the center of one randomly selected eye of each horse by Cochet-Bonnet esthesiometer (Luneau Cochet-Bonnet Esthesiometer; Western Ophthalmics, Lynnwood, WA, USA). Immediately following baseline CTT measurement, 0.3 ml of 1.0% preservative-free morphine sulfate (Morphine Sulfate 25 mg/ml Preservative-free; Hospira, Lake Forest, IL, USA) (3 mg) was applied to the tested eye. The same volume of artificial tear (LiquiTears; Major Pharmacauticals, Livonia, MI, USA) solution was then applied to the control eye following acquisition of baseline CTT. Corneal touch threshold was then subsequently measured at 1 min after medication application, followed by every 5 min until 60 min post administration. If the corneal touch threshold had not returned to baseline by 60 min, measurements were continued at 15-min intervals until corneal sensitivity returned to baseline CTT measurement up to 180 min post administration if needed. The control eye was treated identically and measurements on the control eye stopped when the corresponding treated eye returned to baseline.
RESULTS
Mean baseline CTT of both eyes was 21.8 mm with an identical range of 15-30 mm. Mean corneal touch threshold was not statistically different between morphine-treated and control eyes (P = 0.22). There was a large degree of inter- and intrasubject variation in the CTT measurements obtained. All but three horses were considered to be at baseline values by 60 min.
CONCLUSIONS
Topical ophthalmic 1% morphine sulfate did not have a clinically significant analgesic effect on the corneal touch threshold of intact healthy equine corneas.
Topics: Analgesics, Opioid; Anesthesia, Local; Anesthetics, Local; Animals; Female; Horses; Morphine; Ophthalmic Solutions
PubMed: 28714189
DOI: 10.1111/vop.12494 -
Circulatory Shock 1987In previous work, morphine sulfate was shown to decrease heart rate (HR) and cardiac output (CO) in a dose-related fashion. It was hypothesized that this effect was...
In previous work, morphine sulfate was shown to decrease heart rate (HR) and cardiac output (CO) in a dose-related fashion. It was hypothesized that this effect was mediated by opiate receptors located in the myocardium. The present study evaluated the effect of opiate receptor antagonism with naloxone using a modified Langendorff rat heart perfusion apparatus. Sixty-five rat hearts were excised and perfused with Krebs-Henseleit buffer (KHB) solution, to which morphine sulfate and naloxone (NAL) were added in different concentrations. In the initial studies, NAL (10(-5) M) was added to the perfusate prior to the incremental additions of morphine. This resulted in no antagonism of the previously described opiate agonist effects. Norepinephrine (NE; 10(-9) M) was then added to the perfusate prior to the NAL or morphine. The NE did not affect the dose-related decrease in HR and CO when morphine was added but did permit the attenuation of the morphine effect by the addition of increasing concentrations of NAL up to 10(-5) M. These results suggest that the agonist effect can be attenuated by opiate receptor antagonism with NAL; the data also suggest a possible interrelationship between opiate and catecholamine receptor activity in the myocardium.
Topics: Animals; Cardiac Output; Heart; Heart Rate; In Vitro Techniques; Morphine; Naloxone; Rats; Rats, Inbred Strains; Receptors, Opioid
PubMed: 2827907
DOI: No ID Found -
The American Journal of Medicine Sep 1985Despite a lack of clinical data in this area, conventional wisdom holds that morphine sulfate induces vagally mediated conduction defects, especially in patients with...
Despite a lack of clinical data in this area, conventional wisdom holds that morphine sulfate induces vagally mediated conduction defects, especially in patients with inferior myocardial infarction. To assess the accuracy of this "clinical pearl," the records of 244 patients admitted to the Barnes Hospital Cardiac Care Unit with suspected acute myocardial infarction were reviewed to determine the frequency of deleterious cardiovascular effects related to the administration of morphine sulfate. Of 184 patients (156 subsequently documented to have infarction) who received morphine sulfate, four patients had symptomatic hypotension temporally associated with morphine sulfate administration. This represented a frequency of 2.2 percent for all patients treated with morphine sulfate and a frequency of 2.6 percent in those with proved infarction. In each instance, the heart rate response was inappropriate, i.e., decreased or less markedly accelerated than might be expected given the reduced blood pressure, suggesting a vagal mechanism for the adverse effects. Only one of the four patients had inferior infarction, and in three of four instances, the adverse effect occurred after the first dose. All patients subsequently received morphine sulfate without evidence of toxicity. No case of narcotic-induced conduction abnormality was identified. This series, which is the most extensive evaluation of the topic, documents that adverse cardiovascular effects due to morphine sulfate are rare and do not conform to preconceived clinical doctrine. They consist of inappropriate heart rate responses to hypotension rather than conduction defects and are not particularly associated with inferior myocardial infarction.
Topics: Aged; Heart Rate; Humans; Hypotension; Middle Aged; Morphine; Myocardial Infarction; Pain
PubMed: 4036983
DOI: 10.1016/0002-9343(85)90311-0 -
Life Sciences Sep 2017Slow-release morphine sulfate pellets and osmotic pumps are common routes of chronic morphine delivery in mouse models, but direct comparisons of these drug delivery... (Comparative Study)
Comparative Study
AIMS
Slow-release morphine sulfate pellets and osmotic pumps are common routes of chronic morphine delivery in mouse models, but direct comparisons of these drug delivery systems are lacking. In this study, we assessed the efficacy of slow-release pellets versus osmotic pumps in delivering morphine to adult mice.
MAIN METHODS
Male C57BL/6NCr mice (8weeksold) were implanted subcutaneously with slow-release pellets (25mg morphine sulfate) or osmotic pumps (64mg/mL, 1.0μL/h). Plasma morphine concentrations were quantified via LC-MS/MS, analgesic efficacy was determined by tail flick assay, and dependence was assessed with naloxone-precipitated withdrawal behaviors (jumping) and physiological effects (excretion, weight loss).
KEY FINDINGS
Morphine pellets delivered significantly higher plasma drug concentrations compared to osmotic pumps, which were limited by the solubility of the morphine sulfate and pump volume/flow rate. Within 96h post-implantation, plasma morphine concentrations were indistinguishable in pellet vs. pump-treated samples. While osmotic pump did not have an antinociceptive effect in the tail flick assay, pumps and pellets induced comparable dependence symptoms (naloxone-precipitated jumping behavior) from 24-72h post-implantation.
SIGNIFICANCE
In this study, we compared slow-release morphine pellets to osmotic minipumps for morphine delivery in mice. We found that osmotic pumps and subcutaneous morphine sulfate pellets yielded significantly different pharmacokinetics over a 7-day period, and as a result significantly different antinociceptive efficacy. Nonetheless, both delivery methods induced dependence as measured by naloxone-precipitated withdrawal.
Topics: Analgesics, Opioid; Animals; Chromatography, Liquid; Delayed-Action Preparations; Drug Delivery Systems; Drug Implants; Male; Mice; Mice, Inbred C57BL; Morphine; Naloxone; Narcotic Antagonists; Osmosis; Substance Withdrawal Syndrome; Tandem Mass Spectrometry; Time Factors
PubMed: 28723417
DOI: 10.1016/j.lfs.2017.07.016