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PubMed1980

Reversible suppression of spermiogenesis in beagle dogs following overdosage with the narcotic analgesic cogazocine lactate.

Acute single overdosage (1.0 mg/kg, i.m.) with the novel benzmorphan narcotic analgesic agent Cogazocine lactate lowered serum LH and testosterone concentrations of Beagle dogs. The effect was rapidly reversible and persisted for less than 24 h after drug administration. Repeated administration (1.0 mg/kg, i.m.) induced reversible suppression of spermatid maturation with subsequent effects on semen characteristics. Examination of circulating LH and testosterone concentrations, together with pituitary and prostate morphology, suggested that the changes were due to inhibition of LH release. It is probable that the underlying mechanism is an exaggerated pharmacological response to repeated overdosage, common to many potent narcotic analgesic agents.

Analgesics, Opioid↗
PubMed1975

Conditioning of narcotic abstinence symptoms in human subjects.

Clinical evidence suggests the possibility of conditioning of narcotic abstinence symptoms. Addicts report subjective and objective signs of withdrawal/craving when exposed to certain stimuli. This may partially explain the high rate of relapse to drug seeking behavior when treated addicts return to their home environment. Conditioning of narcotic abstinence symptoms was produced experimentally in five of eight volunteer subjects. Brief naloxone precipitated abstinence was the unconditioned response. The conditioned stimulus was a tone and odor. After an average of seven training trials, the tone and odor produced a conditioned abstinence response. The conditioned response consisted of subjective components (feelings of sickness, nausea, cramps, craving) and objective components (yawning, tearing, rhinorrhea, irregular respiration and transiently increased blood pressure). These laboratory findings support the anecdotal evidence regarding the existence of conditioned abstinence phenomena.

Acoustic Stimulation↗
PubMed1995

Drug users' spiritual beliefs, locus of control and the disease concept in relation to Narcotics Anonymous attendance and six-month outcomes.

Narcotics Anonymous (NA) is an important support network for drug users emerging from abstinence based treatments. However, the views of NA on 'spirituality' and the 'disease' nature of addiction could be seen as encouraging an external attributional style and have been cited as reasons for non-attendance. After 6 months ninety percent of 101 drug users in treatment were followed up. Narcotics Anonymous attendance was inversely related to drug use for those who had left residential care. We found that spiritual beliefs and disease concept beliefs were not prerequisites for attendance of NA. Spiritual beliefs were not found to cause external attributions for previous drug use or possible future lapse events. It emerged that the most powerful predictors of non-attendance were positive attitudes to the use of alcohol. Treatment implications are discussed.

Adult↗
PubMed1985

Crime as a source of income for narcotic addicts.

Although it has been well documented that narcotic addicts derive the bulk of their income from criminal activities and that there are major differences between black and white addicts, interview data presented in this paper show little difference between the two races with respect to the degree of dependence on criminal income. However, the results also highlight the diversity among narcotic addicts in that there are some individuals who derive none of their funds from illegal sources, thus suggesting that not all addicts should be treated in the same manner.

Black or African American↗
PubMed1987

Narcotic addiction and family process: death wish or countertransference.

This article critically examines the literature which suggests that families of narcotic addicts push their addicted member toward death. Following an overview of the conventional literature on the family treatment of drug addiction, an alternative perspective is proposed to more fully understand how these families are preoccupied with death. The "suicide-like" quality of addiction is probed both in terms of the intention to die and the countertransference possibilities. The notion of a family "death wish" has the potential to be misinterpreted by the countertransference response of an unseasoned treatment provider. Clinicians are cautioned that this notion can be a potential threat to the patient's life. Implications are presented for the supervision of the family treatment of narcotic addiction.

Attitude to Death↗
PubMed1989

A comparison of oxymorphone and fentanyl as narcotic supplements in general anesthesia.

The safety and efficacy of two potent opiate analgesics, fentanyl and oxymorphone, used as adjuncts in general anesthesia, were studied in 39 patients undergoing elective gynecologic surgery of at least 2 hours duration. Based on a potency ratio of 10:1, patients received either fentanyl 6.5 micrograms/kg or oxymorphone 65 micrograms/kg prior to a thiopental 2 to 3 mg/kg succinylcholine induction and endotracheal intubation. Additional maintenance narcotic and isoflurane were administered as required by the "blinded" anesthesiologist in response to hemodynamic alterations 15% above a presurgical baseline. Overall analysis included hemodynamic response at preset intraoperative intervals, total anesthetic requirements, and stability of vital signs in the recovery room. Blood pressure and heart rate were reliably controlled with either agent; however, less narcotic (ml) and recovery room analgesics were required in the oxymorphone-treated group (p less than 0.05). Decreased naloxone requirements (p less than 0.05) and a more rapid emergence suggested that fentanyl was a safer agent when administered in relatively unrestricted fashion.

Anesthesia, General↗
PubMed2003

A randomized, controlled trial to compare ketorolac tromethamine versus placebo after cesarean section to reduce pain and narcotic usage.

OBJECTIVE: The purpose of this study was to determine whether postcesarean section administration of ketorolac tromethamine reduces pain and narcotic usage. STUDY DESIGN: A double-blinded randomized, placebo-controlled trial of ketorolac tromethamine was performed. Patients were randomly assigned to receive either ketorolac tromethamine or placebo. Patient-controlled analgesia (PCA) was used for pain control. Visual analog scales (VAS) were administered postoperatively to assess pain levels. Morphine equivalents and attempts were recorded. RESULTS: There were 22 patients in each arm of the study. There was no significant difference between patient demographics, blood loss, and type of anesthesia. Pain scores were significantly different at 2, 3, 4, 6, 12, and 24 hours by analysis of variance (ANOVA) (P=.033). There was a significant decrease in pain medication usage (P=.008) in the study group. CONCLUSION: Ketorolac tromethamine is efficacious in reducing postoperative pain and narcotics usage after cesarean section.

Adult↗
PubMed2006

The combined toxic effects of nonpolar narcotic chemicals to Pseudokirchneriella subcapitata.

This paper presents the toxicity data of 10 nonpolar narcotic chemicals on Pseudokirchneriella subcapitata (green algae) assessed by a new algal toxicity testing technique conducted under air-tight environment. Based on DO production, median effective concentration (EC50) varies from 1.73 mg/L (1-octanol) to 8,040 mg/L (2-propanol). The endpoint of algal growth rate reveals similar sensitivity as that from DO production. Compared to literature data, Pseudokirchneriella subcapitata and Nitrosomonas are apparently more sensitive to nonpolar narcotics than other organisms such as minnow, daphnia, and Tetrahymena pyriformis. Furthermore, good correlations between toxic effects observed from Pseudokirchneriella subcapitata and other aquatic organisms were found. Hence, algal toxicity test can be considered as a surrogate test for estimating the toxicity of nonpolar chemicals to fathead minnow, Microtox, activated sludge, Daphina magna, and Tetrahymena pyriformis. The combined effects of 13 binary mixtures of nonpolar chemicals were investigated using both additive-index method and isobologram analysis. Overall speaking, the joint actions between these chemicals are strictly additive. Model analyses indicate that these compounds act on identical reaction sites or receptors, which verify that these chemicals are of the same toxicity mechanism (narcosis).

Alcohols↗
PubMed1998

Hepatotoxicity of non-narcotic analgesics.

The central role of the liver in drug metabolism sets the stage for drug-related hepatotoxicity. The incidence of hepatotoxicity associated with non-narcotic analgesics is low, but their widespread use both prescription and over-the-counter-makes analgesic-associated hepatotoxicity a clinically and economically important problem. Hepatotoxicity is considered a class characteristic of nonsteroidal anti-inflammatory drugs (NSAIDs), despite the fact that they are a widely diverse group of chemicals. In fact, there are many differences in the incidence, histologic pattern, and mechanisms of hepatotoxicity between, as well as within, chemical classes. Most NSAID reactions are hepatocellular and occur because of individual patient susceptibility (idiosyncrasy). Aspirin, however, is a dose-related intrinsic hepatotoxin. Acetaminophen is also an intrinsic hepatotoxin but rarely demonstrates hepatotoxicity at therapeutic doses. It does cause hepatotoxicity with massive overdoses and with therapeutic doses in susceptible patients such as chronic users of alcohol. No hepatotoxicity has been reported to date with tramadol, another non-narcotic analgesic.

Acetaminophen↗
PubMed1993

Comparison of patient-controlled analgesia versus intramuscular narcotics in resolution of postoperative ileus after radical retropubic prostatectomy.

Patient-controlled analgesia has become standard practice after major abdominal operations. The benefits of patient-controlled analgesia have been well documented. However, its possible effect of prolonging postoperative ileus has not been well examined. To determine if patient-controlled analgesia prolongs postoperative ileus when compared to conventional intramuscular narcotics, a retrospective review of length of postoperative ileus in 98 consecutive patients (62 using patient-controlled analgesia and 36 using intramuscular narcotics) undergoing bilateral pelvic lymphadenectomy and radical retropubic prostatectomy was done. The patients receiving patient-controlled analgesia resolved the postoperative ileus an average of 1.0 day later than the intramuscular injection group (5.2 days versus 4.2 days p < 0.0001). Overall hospital stay was not significantly affected. Our results show that patient-controlled analgesia use prolongs postoperative ileus.

Analgesia, Patient-Controlled↗
PubMed1987

Role of epidural and intrathecal narcotics and peptides in the management of cancer pain.

The spinal administration of opioids may provide analgesia of long duration to patients with bilateral or midline lower abdominal or pelvic cancer pain. However, cross-tolerance to orally and parenterally administered narcotics and the rapid development of tolerance to spinal narcotics have limited their usefulness. Opioids have extensive distribution in the CSF and plasma when administered into the epidural or intrathecal space, and delivery of drug to brain stem sites may account for many of the toxic and therapeutic effects of spinal opioids. Further clinical and pharmacokinetic studies are required to provide the information regarding: the optimal opioids for use as spinal analgesics; equieffective dose ratios of spinal opioids in comparison to parenteral or oral opioids; strategies useful to forestall the development of tolerance of spinally administered opioids; the analgesic efficacy of this therapy in opioid-tolerant patients; and the role of spinally administered nonopioid analgesics in the management of cancer pain in the tolerant patient. These questions will need resolution before this therapy can be recommended for routine use in the management of cancer pain.

Analgesia↗
PubMed1992

Ketorolac for sickle cell vaso-occlusive crisis pain in the emergency department: lack of a narcotic-sparing effect.

STUDY OBJECTIVE: To determine if a single dose of intramuscular ketorolac given on presentation to the emergency department has a narcotic-sparing effect in adult patients with sickle cell vaso-occlusive crisis pain. DESIGN: A prospective, randomized, single-dose, double-blind study. SETTING: ED of a university hospital and an affiliated county hospital. TYPE OF PARTICIPANTS: Eighteen adult patients who presented to the ED with sickle cell crisis pain a total of 24 times. INTERVENTIONS: Patients were randomized to receive either ketorolac 60 mg IM or placebo on presentation to the ED. Subjects were administered meperidine on presentation and then received a standardized dose of meperidine every 30 minutes during the four-hour observation period based on the severity of pain. MEASUREMENTS AND MAIN RESULTS: The 12 subjects in the ketorolac group received an average of 231 +/- 92 mg meperidine, whereas the 12 subjects in the placebo group received an average meperidine dose of 250 +/- 85 mg (P = .61). CONCLUSION: The use of intramuscular ketorolac did not lead to a clinically significant reduction in the requirement for narcotics during the four-hour ED treatment period.

Acute Disease↗
PubMed1998

Differential contributions of family and peer factors to the etiology of narcotic addiction.

This retrospective study investigated relationships among early family circumstances, peer associations, and narcotic addiction in a sample of 601 urban males. Results of logistic regression analyses indicated that the extent of deviant behavior among close friends at ages 12-14 and disruption in family structure (parental divorce/separation) prior to age 11 were significantly associated with narcotic addiction. Additional regression analyses indicated that deviant behavior among family members, as well as family disruption, experienced prior to age 11, also increased the probability of association with deviant peers and a negative home atmosphere at ages 12-14. Implications of these findings for preventive interventions and for future research are presented.

Adolescent↗
PubMed1977

N-(2,4,5-Trihydroxyphenehtyl)normetazocine, a potential irreversible inhibitor of the narcotic receptor.

The reaction of N-2,4,5-tribenzyloxyphenyl)ethyl methanesulfonate, prepared in a seven-step sequence, with normetazocine followed by hydrogenolysis of the benzyloxy-protecting groups, gave N-(2,4,5-trihydroxyphenethyl)normetazocine. This compound was prepared to study the effect of a narcotic analgesic containing a functional group which could be activated in situ to a moiety potentially capable of reacting irreversibly with the narcotic receptor. This 6-hydroxydopamin derivative of normetazocine did not prove to be a useful affinity label. Its low toxicity could indicate the necessity for the formation of an aminochrome system for the expression of toxicity by 6-hydroxydopamine.

Adenylyl Cyclases↗
PubMed1988

Solubility and related physicochemical properties of narcotic analgesics.

The physicochemical properties of select opioid and anilinopiperidine narcotic analgesics were investigated. The solubilities of the narcotics in hexane and water and, for morphine, in other organic solvents were determined. Regular solution theory seems to be applicable to the solubility behavior of morphine in solvents that lack strong dipoles and hydrogen bonds. A best-fit solubility parameter of 13.2 (cal/cm3)1/2 for morphine was determined from its solubilities in London solvents and its ideal solubility. Calculation of morphine's solubility parameter from its hexane solubility alone and its melting properties gave a corresponding delta 2 value. These measured solubility parameters were appreciably larger than the solubility parameter estimated from molar attraction constants. Solubility parameters of hydromorphone, codeine, fentanyl, and sufentanil were also calculated from respective hexane solubilities, melting points, and heats of fusion and were 11.7, 10.9, 9.8, and 9.7 (cal/cm3)1/2. For these compounds, experimental solubility parameters agreed with solubility parameters estimated from molar attraction constants. Because meperidine, fentanyl, and sufentanil exhibit low levels of intracrystalline cohesion, as reflected in low melting points and relatively modest heats of fusion, theoretically projected ideal solubilities and actual solubilities in organic solvents measured for them were considerably higher than determined for morphine and its analogues. Consistent with the solubilities, the octanol-water partition coefficients of the two 4-anilinopiperidine analogues and of meperidine were several orders of magnitude larger than those of the opioids, evidencing the fact that meperidine, fentanyl, and sufentanil are substantially more lipophilic than the opioids.

Analgesics, Opioid↗
PubMed1983

Anticipatory hyperexcitability and tolerance to the narcotizing effect of morphine in the rat.

The role of Pavlovian conditioning in tolerance to the narcotizing effect of a high dose of morphine in the rat was examined. Initially, two groups received nine injections of morphine (40 mg/kg), and two groups received nine injections of saline. One group administered each substance was injected in one of two distinctive environments: the animal colony or a distinctive room. Subsequently, rats in all groups received five morphine injections in the distinctive room. Analyses of videotape records of postinjection behavior indicated that rats tested in the presence of the usual predrug cues were more tolerant to the narcotizing effect of morphine than rats tested with cues different from those previously associated with morphine. In addition, rats tested with the usual predrug cues exhibited more anticipatory "hyperexcitable" behavior than rats tested in the absence of the usual predrug cues. These results provide further evidence that compensatory pharmacological conditional responses partially mediate tolerance, and they suggest that these drug-anticipatory responses contribute to so-called "withdrawal symptoms."

Animals↗
PubMed2001

Ketorolac reduces postoperative narcotic requirements.

BACKGROUND/PURPOSE: Adverse effects from narcotics complicate pain management in children. Ketorolac, a potent nonsteroidal antiinflammatory agent can be used as an adjuvant analgesic, yet concerns of bleeding and nephrotoxicity have limited routine use. The authors hypothesized that postoperative use of ketorolac in healthy pediatric surgical patients would limit narcotic requirements without increasing morbidity. METHODS: A case-control clinical trial was conducted of 29 pediatric surgical cases prospectively administered ketorolac (0.5 mg/kg intravenously every 6 hours) supplemented with morphine. Controls receiving morphine only were matched for age (+/- 6 months) and surgical procedure. Incidence of respiratory depression, urinary retention, emesis, nephrotoxicity, and bleeding were recorded. RESULTS: Patients receiving ketorolac plus morphine had significantly less morphine requirements in the first 48 postoperative hours (Ketorolac plus Morphine: 0.36+/-0.16 mg/kg/d, Morphine only: 1.08+/-0.16 mg/kg/d [P<.05, analysis by paired t test]). This decrease was noted despite mode of analgesia (patient controlled or nurse administered). Adverse effects of morphine including respiratory depression, emesis, and urinary retention were not affected by ketorolac. Patients administered ketorolac had no significant increase in bleeding or nephrotoxicity. CONCLUSION: Ketorolac exhibits significant opiate-sparing effects in the immediate postoperative period without introducing additional morbidity to pediatric surgical procedures.

Analgesics, Opioid↗
PubMed1973

Stereospecific binding of the potent narcotic analgesic (3H) Etorphine to rat-brain homogenate.

Etorphine, the most potent narcotic analgesic known, was labeled with tritium by catalytic exchange. This drug exhibits stereospecific, saturable binding to rat-brain homogenate. At saturation, the stereospecific binding is 0.1-0.15 pmol/mg of protein. Specific binding is inhibited high salt concentrations, sulfhydryl reagents, and proteolytic enzymes, but is unaffected by phospholipases A and C, sodium azide, sodium fluoride, and prostaglandins E(1) and E(2). Competition for binding of [(3)H]etorphine correlates with agonist and antagonist potencies. The stable, stereospecific binding of an active narcotic analgesic supports the existence of opiate receptors.

Acetamides↗