oxymorphone and Substance-Withdrawal-Syndrome

While the risk of opioid overdose is widely accepted, the dangers of opioid withdrawal are far less clearly defined. The purpose of this publication is to provide evidence against the erroneous clinical dictum that opioid withdrawal is never life-threatening.. This case report (N = 1) illustrates an unfortunate, common scenario of a man abusing prescription opioids and heroin. His attempt at self-detoxification with buprenorphine-naloxone resulted in life-threatening opioid withdrawal. A detailed account of each day of his withdrawal period was documented by patient and family report and review of all medical records. The patient was contacted three months after hospitalization to verify information and determine progress in treatment and abstinence from drugs and alcohol.. A review of the literature was completed on severe cases of precipitated and spontaneous opioid withdrawal followed by a discussion of the significance as it relates to this case.. Given the widespread use of prescription opioids and opioid maintenance treatment, physicians should be aware of the complications of acute opioid withdrawal and should be equipped to treat these complications.

Topics: Acute Kidney Injury; Administration, Intranasal; Administration, Oral; Administration, Sublingual; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Intensive Care Units; Male; Opioid-Related Disorders; Oxycodone; Oxymorphone; Prescription Drugs; Rhabdomyolysis; Self Medication; Substance Withdrawal Syndrome; Young Adult

To evaluate the influence of age, sex, and previous opioid experience on the likelihood of successfully titrating opioid-naive and experienced patients with chronic low back pain (CLBP) to an effective and well-tolerated dose of oxymorphone extended release (ER).. Post hoc analysis of open-label titration phases of two enriched-enrollment randomized-withdrawal phase III trials in 575 adults with moderate-to-severe CLBP. Opioid-naive patients (n = 325) initiated oxymorphone ER at 10 mg/day (5 mg q12 h). Opioid-experienced patients (n = 250) initiated at a dose equianalgesic to their previous opioid and were allowed doses of 5 mg oxymorphone immediate-release rescue medication every 4-6 h, as needed. Oxymorphone ER was gradually titrated to a dose that reduced pain to or=65 years were less likely than patients aged <65 years to complete titration (45 vs. 63%; p = 0.002; 95% CI, -0.30 to -0.06) and more likely to discontinue owing to adverse events (40 vs. 15%; p < 0.001; 95% CI, 0.14-0.36). Oxycodone-experienced patients were less likely than hydrocodone-experienced patients to complete titration (46 vs. 62%, p = 0.03; 95% CI,-0.30 to -0.02). Among successfully titrated patients, pain decreased regardless of prior opioid therapy, sex, or age.. Most patients with CLBP were titrated to an effective, generally well-tolerated oxymorphone ER dose. Older patients and those converted from oxycodone may require more gradual titration. A study limitation is that patients initiated oxymorphone ER to comply with protocol, whereas treatment failure typically motivates opioid initiation or switching in clinical practice.

Topics: Aged; Analgesics, Opioid; Chronic Disease; Clinical Trials, Phase III as Topic; Delayed-Action Preparations; Dose-Response Relationship, Drug; Female; Humans; Hydromorphone; Low Back Pain; Male; Middle Aged; Oxycodone; Oxymorphone; Pain Measurement; Patient Acceptance of Health Care; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Treatment Outcome

We studied the effect of peripheral opioid receptor antagonist methylnaloxone on the development of withdrawal syndrome in morphine-dependent rats. Intraperitoneal injections of methylnaloxone iodide in a daily dose of 2 mg/kg over 3 days after morphine withdrawal reduced the severity of withdrawal symptoms. The mean total score of withdrawal syndrome in treated rats (3.20 +/- 0.13) was 2-fold lower compared to the control, mainly due to less pronounced wet dog shake behavior, limb and head shakes, dyspnea, ptosis, and teeth chattering. Methylnaloxone iodide in the specified dose had no effect on such symptoms of withdrawal syndrome as diarrhea and writhing. Our results indicate that modulation of the peripheral opioid system can reduce the severity of opioid withdrawal syndrome. Methylnaloxone-induced variations in the function of peripheral opioid receptors are probably accompanied by changes in the central nervous system, which prevents the development of withdrawal syndrome.

Topics: Animals; Male; Morphine; Opioid-Related Disorders; Oxymorphone; Rats; Rats, Wistar; Substance Withdrawal Syndrome

A series of eight (-)-14-methoxymorphinan-6-ones was synthesized and biologically evaluated. The morphinanones 3-7 were prepared from 3-desoxy-7,8-dihydro-14-hydroxymorphinone (1). The key step in this synthetic sequence, O-methylation in position 14, was accomplished with dimethyl sulfate. Hydrolysis followed by reductive opening of the 4,5-oxygen bridge afforded the phenol 4, which was O-methylated to give 5. Removal of the 4-OH group yielded the aromatic unsubstituted morphinan 7. The synthesis of 9 and 10 was accomplished by starting from 14-methoxy-7,8-dihydrocodeinone and involved a similar reaction sequence. The compounds 12-15 were synthesized from oxymorphone (11), which was 3-O-benzylated, 6,14-bis-O-methylated with dimethyl sulfate, hydrolyzed, and hydrogenated to yield the oxymorphone 14-O-methyl ether 15. The derivatives 3, 4, 5, 7, 9, 10, 14, and 15 exhibited high antinociceptive potency in the hot-plate assay in mice, after both subcutaneous and oral administration. The most potent derivative in this series (15) showed a potency (sc) about 400 times higher than that of morphine and about 40 times higher than its 14-OH analogue oxymorphone (11). The 14-OCH3 series also exhibited a considerably higher affinity to opioid receptors in binding studies using [3H]naloxone as ligand when compared to their 14-OH analogues.

Topics: Analgesia; Animals; Binding, Competitive; Biological Assay; Brain; Cell Membrane; Drug Evaluation, Preclinical; Humans; Indicators and Reagents; Mice; Morphinans; Morphine; Naloxone; Narcotic Antagonists; Rabbits; Rats; Receptors, Opioid; Respiration; Structure-Activity Relationship; Substance Withdrawal Syndrome

Butorphanol, a new, totally synthetic morphinan, which is chemically related to naloxone, has been demonstrated to have both analgesic and narcotic antagonist properties. In rodent antiwrithing analgesic tests, butorphanol was 4 to 30 times more potent than morphine and dl-pentazocine, respectively. As an antagonist, butorphanol was about equivalent to nalorphine and 30 times more potent than dl-pentazocine. On the basis of the naloxone-induced mouse jumping test and the lack of substitution in withdrawn morphine-dependent mice, it is estimated that the potential for physical dependence of butorphanol will be less than that of dl-pentazocine but greater than that of nalorphine and dl-cyclazocine. Animal data also show that agonistic actions of butorphanol, such as respiratory depression and miosis, reach ceiling effects which are lower than those seen with morphine with an increase in dosage. Thus, butorphanol differed from morphine which exhibited agonist effects in a dose-related manner. Butorphanol showed weak to moderate central depressant properties at doses which were considerably higher (greater than 100 X) than those producing analgesia. Minimal cardiovascular and respiratory effects were seen with butorphanol in conscious dogs.

Topics: Analgesics; Animals; Behavior, Animal; Cyclobutanes; Dogs; Drug Tolerance; Female; Haplorhini; Hemodynamics; Histamine Release; Humans; Male; Mice; Morphinans; Motor Skills; Narcotic Antagonists; Oxymorphone; Pentylenetetrazole; Pupil; Rats; Reaction Time; Respiration; Saimiri; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Analgesics; Animals; Benzazepines; Crystallization; Dose-Response Relationship, Drug; Female; Humans; Locomotion; Male; Mice; Morphine; Mydriatics; Nalorphine; Naloxone; Narcotic Antagonists; Oxymorphone; Pentazocine; Rabbits; Reflex; Respiration; Structure-Activity Relationship; Substance Withdrawal Syndrome; Tail; Time Factors