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American Journal of Veterinary Research Jul 2015To establish the minimum alveolar concentration (MAC) of desflurane and evaluate the effects of 2 opioids on MAC in sheep. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To establish the minimum alveolar concentration (MAC) of desflurane and evaluate the effects of 2 opioids on MAC in sheep.
ANIMALS
8 adult nulliparous mixed-breed sheep.
PROCEDURES
A randomized crossover design was used. Each sheep was evaluated individually on 2 occasions (to allow assessment of the effects of each of 2 opioids), separated by a minimum of 10 days. On each occasion, sheep were anesthetized with desflurane in 100% oxygen, MAC of desflurane was determined, oxymorphone (0.05 mg/kg) or hydromorphone (0.10 mg/kg) was administered IV, and MAC was redetermined. Physiologic variables and arterial blood gas and electrolyte concentrations were measured at baseline (before MAC determination, with end-tidal desflurane concentration maintained at 10%) and each time MAC was determined. Timing of various stages of anesthesia was recorded for both occasions.
RESULTS
Mean ± SEM MAC of desflurane was 8.6 ± 0.2%. Oxymorphone or hydromorphone administration resulted in significantly lower MAC (7.6 ± 0.4% and 7.9 ± 0.2%, respectively). Cardiac output at MAC determination for desflurane alone and for desflurane with opioid administration was higher than that at baseline. No difference was identified among hematologic values at any point. Effects of oxymorphone and hydromorphone on durations of various stages of anesthesia did not differ significantly.
CONCLUSIONS AND CLINICAL RELEVANCE
MAC of desflurane in nulliparous adult sheep was established. Intravenous administration of oxymorphone or hydromorphone led to a decrease in MAC; however, the clinical importance of that decrease was minor relative to the effect in other species.
Topics: Adjuvants, Anesthesia; Analgesics, Opioid; Anesthetics, Inhalation; Animals; Blood Gas Analysis; Cardiac Output; Cross-Over Studies; Desflurane; Female; Hydromorphone; Infusions, Intravenous; Isoflurane; Oxymorphone; Pulmonary Alveoli; Sheep
PubMed: 26111087
DOI: 10.2460/ajvr.76.7.583 -
Veterinary Surgery : VS 1990The effects of naloxone (0.4 mg and 1.2 mg intravenously [IV]), nalmefene (0.03 mg/kg IV) and butorphanol (0.2 mg/kg IV and 0.4 mg/kg IV) on oxymorphone-induced sedation... (Comparative Study)
Comparative Study
The effects of naloxone (0.4 mg and 1.2 mg intravenously [IV]), nalmefene (0.03 mg/kg IV) and butorphanol (0.2 mg/kg IV and 0.4 mg/kg IV) on oxymorphone-induced sedation were studied in six dogs over a 4-hour observation period. The same dogs were observed for 4 hours untreated (unsedated control) and with oxymorphone sedation followed by saline solution (sedated control). The reversal drug or saline placebo was administered IV 20 minutes after oxymorphone (4.5 mg IV). Blinded observers evaluated the dogs for positional and attitudinal responses, heart rate, and respiratory rate. Sedated dogs treated with nalmefene most closely resembled unsedated dogs in all observed variables. Naloxone was most effective when administered at the higher dose. Mild renarcotization occurred in two dogs at hour 2, even after the higher naloxone dose. Residual sedation was observed in all dogs treated with 0.4 mg naloxone. Butorphanol resulted in partial reversal of sedation at both dosage levels. However, the degree of sedation was significantly less than that observed in the saline-treated controls, and it appeared that 0.4 mg/kg butorphanol may be clinically useful for opiate reversal in some situations.
Topics: Animals; Behavior, Animal; Butorphanol; Dogs; Female; Heart Rate; Male; Naloxone; Naltrexone; Narcotic Antagonists; Oxymorphone; Respiration
PubMed: 2219678
DOI: 10.1111/j.1532-950x.1990.tb01217.x -
American Journal of Obstetrics and... Jan 1962
Topics: Anesthesia; Anesthesia, Obstetrical; Anesthesiology; Hydromorphone; Obstetrics; Oxymorphone
PubMed: 13914618
DOI: 10.1016/0002-9378(62)90282-x -
Anaesthesia Oct 1966
Clinical Trial Comparative Study Randomized Controlled Trial
Topics: Analgesia; Anesthesia, Obstetrical; Clinical Trials as Topic; Female; Humans; Meperidine; Oxymorphone; Pregnancy
PubMed: 5331992
DOI: 10.1111/j.1365-2044.1966.tb02651.x -
Journal of Medicinal Chemistry Jul 1985Ethylketocyclazocine (1) has greater kappa/mu selectivity than cyclazocine in brain binding assays. 10-Ketonaltrexone (11) and 10-ketooxymorphone (10) were prepared from... (Comparative Study)
Comparative Study
Ethylketocyclazocine (1) has greater kappa/mu selectivity than cyclazocine in brain binding assays. 10-Ketonaltrexone (11) and 10-ketooxymorphone (10) were prepared from naltrexone 3-methyl ether and oxycodone, respectively. Bioassays in the myenteric plexus longitudinal muscle preparation of the guinea pig ileum and in the mouse vas deferens, in addition to brain binding assays, demonstrated that 10 and 11 were far less potent than naltrexone (2) and oxymorphone (3) at mu sites and also had little affinity for kappa and delta sites. It is concluded that introduction of the 10-keto group in naltrexone and oxymorphone diminished opioid effects at all binding sites.
Topics: Animals; Biological Assay; Brain; Chemical Phenomena; Chemistry; Guinea Pigs; Hydromorphone; Ileum; Male; Mice; Naloxone; Naltrexone; Oxymorphone; Receptors, Opioid; Structure-Activity Relationship; Vas Deferens
PubMed: 2409281
DOI: 10.1021/jm00145a024 -
Journal of Clinical Pharmacology Apr 1977The relative analgesic potency of oral and intramuscular oxymorphone was evaluated in a double-blind crossover comparison of graded single doses in patients with chronic... (Clinical Trial)
Clinical Trial Comparative Study
The relative analgesic potency of oral and intramuscular oxymorphone was evaluated in a double-blind crossover comparison of graded single doses in patients with chronic pain due to cancer. When both duration and intensity of analgesia are considered (total effect), oral oxymorphone was 1/6 as potent as the intramuscular form. In terms of peak effect, however, oral oxymorphone was only 1/14 as potent. These values are almost identical to those obtained in a previous study comparing oral with intramuscular morphine. The analgesic effect of oral oxymorphone rose to a peak later and had a longer duration than the effect of intramuscular oxymorphone. Intramuscular oxymorphone and morphine were also compared in a similar patient group. Intramuscular oxymorphone proved to be 8.7 times as potent as morphine in terms of total analgesic effect and 13 times as potent in terms of peak effect. In roughly equinalgesic doses, the occurrence of side effects was qualitatively and quantitatively similar for oral and intramuscular oxymorphone and for intramuscular oxymorphone and morphine.
Topics: Administration, Oral; Adult; Aged; Analgesics; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Evaluation; Female; Humans; Hydromorphone; Injections, Intramuscular; Male; Middle Aged; Morphine; Neoplasms; Oxymorphone; Pain; Placebos; Time Factors
PubMed: 66240
DOI: 10.1177/009127007701700402 -
Clinical Pharmacokinetics Jul 2016Abuse-deterrent formulations (ADFs) are technologically sophisticated pharmaceutical formulations that impede manipulation and extraction of opioids and/or provoke... (Review)
Review
Abuse-deterrent formulations (ADFs) are technologically sophisticated pharmaceutical formulations that impede manipulation and extraction of opioids and/or provoke unpleasant effects when they are taken in excessive quantity. This is implemented by creating physical barriers, inseparably combining the opioid with an opioid antagonist or adding aversive agents to the formulation. These pharmaceutical changes may potentially alter the pharmacokinetics and consequently the pharmacodynamics of the opioid. In this review, comparative evidence on pharmacokinetic differences between abuse-deterrent and classical formulations of the same opioids is summarized; furthermore, pharmacodynamic differences, with a focus on analgesia and abuse-related symptoms, are addressed. Most of the 12 studies comparing opioid pharmacokinetics have judged the physically intact ADF as being bioequivalent to the corresponding classical formulation. Pharmacokinetic differences have, however, been reported with physically manipulated ADFs and have ranged from moderate deviations from bioequivalence to complete changes in the pharmacokinetic profile (e.g. from a sustained-release formulation to a fast-release formulation). Pharmacodynamic effects were assessed in 14 comparative studies, which reported that intact ADFs usually provided clinically equivalent analgesia and clear advantages with respect to their addiction potential. However, withdrawal symptoms could be induced by the ADFs, although rarely and, in particular, when the ADFs had been physically altered. This evidence suggests that opioid ADFs are a working concept resulting in mostly minor pharmacokinetic and pharmacodynamic differences in comparison with classical formulations; however, they may deviate from this equivalence when physically altered.
Topics: Analgesics, Opioid; Buprenorphine; Chemistry, Pharmaceutical; Humans; Morphine; Oxycodone; Oxymorphone; Pain
PubMed: 26719075
DOI: 10.1007/s40262-015-0362-3 -
Journal of Analytical Toxicology May 2008A minor pathway for the biotransformation of morphine to hydromorphone has been identified in humans. Recently, an unsubstantiated claim that morphine is metabolized to... (Clinical Trial)
Clinical Trial
A minor pathway for the biotransformation of morphine to hydromorphone has been identified in humans. Recently, an unsubstantiated claim that morphine is metabolized to hydromorphone and then to oxymorphone was published. The goal of this study was to determine if credible evidence that oxymorphone is a metabolite of either morphine or hydromorphone exists. Urine specimens from pain patients who were treated exclusively with high daily doses of morphine (N = 34) or hydromorphone (N = 26) were analyzed by liquid chromatography-tandem mass spectrometry for oxymorphone, hydromorphone, and morphine (LOD = 25 ng/mL). Specimens were also tested for a variety of other medications. Criteria for inclusion of patients' specimens were as follows: 1. patients were undergoing exclusive dosing with either morphine or hydromorphone; 2. non-prescribed medications were not detected; and 3. urine concentrations of morphine were > 100,000 ng/mL for the high-dose morphine group and > 1,000 ng/mL of hydromorphone for the high-dose hydromorphone group. Consistent with earlier reports, hydromorphone was detected in patients treated with high-dose morphine. The ratio of hydromorphone to morphine ranged from 0.2 to 2.2%. Oxymorphone was not detected in any specimen from high-dose morphine or high-dose hydromorphone patients. The authors conclude, based on these data, that oxymorphone is not a metabolite of morphine or hydromorphone.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Hydromorphone; Male; Middle Aged; Morphine; Oxymorphone; Pain
PubMed: 18430301
DOI: 10.1093/jat/32.4.319 -
Journal of Opioid Management 2010To evaluate the long-term safety, tolerability, and effectiveness of oxymorphone extended release (ER) in patients with cancer-related pain. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the long-term safety, tolerability, and effectiveness of oxymorphone extended release (ER) in patients with cancer-related pain.
DESIGN
Post hoc analysis of two-1-year open-label extension studies.
SETTING
Multiple US cancer treatment facilities.
PATIENTS
Patients with cancer pain who had participated in two short-term crossover comparator trials of oxymorphone ER: one open-label and one double-blind randomized.
INTERVENTIONS
Patients who had been taking oxymorphone ER continued the dose established in the previous study. Patients who had been taking a comparator opioid were switched to an equianalgesic dose of oxymorphone ER. All patients underwent individualized oxymorphone ER dose titration to optimize effectiveness and tolerability.
ASSESSMENTS
Current, average, worst, and least pain scores were normalized to a 100-point scale. Patients rated treatment on a five-point global assessment of study medication (Poor = 1 to Excellent = 5). All adverse events (AEs) were recorded.
RESULTS
Of the 80 patients who entered the extension trials, 26 completed 52 weeks, 7 discontinued owing to loss of effectiveness, and 20 discontinued owing to AEs, most of which were unrelated to study drug. No significant increase in mean (standard deviation [SDD average pain intensity was observed from baseline (30.5 [19.6], 100-point scale) to final visit (35.9 [21.1], p = 0.37). The most common AEs were concomitant disease progression (28.8 percent, n=23), nausea (22.5 percent, n=18), dyspnea (16.3 percent, n=13), fatigue (16.3 percent, n=13), and edema of the lower limb (15 percent, n=12).
CONCLUSIONS
In these patients with pain related to cancer, oxymorphone ER was generally well tolerated and provided stable long-term pain control.
Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Middle Aged; Neoplasms; Oxymorphone; Pain, Intractable
PubMed: 20642247
DOI: 10.5055/jom.2010.0016 -
Journal of Analytical Toxicology Oct 2007Human urine specimens that were determined to be presumptively positive for oxycodone and its metabolite, oxymorphone, by immunoassay screening were assayed using fast...
Human urine specimens that were determined to be presumptively positive for oxycodone and its metabolite, oxymorphone, by immunoassay screening were assayed using fast gas chromatography-mass spectrometry to positively identify and quantify the oxycodone and oxymorphone present. Urine specimens were first spiked with deuterated internal standards, oxycodone-d(3) and oxymorphone-d(3), subjected to acid hydrolysis, and then extracted using a positive-pressure manifold and mixed-bed solid-phase cartridge extraction methodology. Extracts were derivatized using methoxylamine and acetic anhydride. The acetylated-oxime derivatives of oxycodone and oxymorphone were identified and quantified using a selective ion monitoring (SIM). The method was found to be linear for both analytes to 1600 ng/mL, and limits of detection for oxycodone and oxymorphone were found to be 40 ng/mL and 20 ng/mL, respectively. Interlaboratory data comparisons (n = 40) showed correlation coefficients of 0.9999 and 0.9997 for oxycodone and oxymorphone, respectively. Twelve semisynthetic, structurally similar compounds at concentrations of 5000 ng/mL were assayed in the presence of oxycodone and oxymorphone and found not to interfere with identification and quantitation by this method. Finally, exact mass and tandem mass spectrometry techniques were employed to elucidate the structures of the SIM ions.
Topics: Gas Chromatography-Mass Spectrometry; Humans; Narcotics; Oxycodone; Oxymorphone; Solid Phase Extraction; Substance Abuse Detection; Tandem Mass Spectrometry
PubMed: 17988456
DOI: 10.1093/jat/31.8.434