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5-Hydroxytryptamine and narcotic-analgesics interactions in the intestine.

The effects of 5-hydroxytriptamine (5-HT), 5-HT blocking agents, morphine, narcotic-antagonists and ganglionic blocking agents were tested in the dog intestine by close intra-arterial injection. Morphine, as 5-HT, induced an immediate increase in the intestinal tonus followed by phasic contractions. When 5-HT was injected immediately after cessation of morphine induced phasic contractions, a significant potentiation of the 5-HT induced intestinal contraction could be observed. The potentiation could be demonstrated for other narcotic-analgesics like dextromoramide and it is specific for 5-HT. 5-HT blocking agents like LSD, BOL, and cyproheptadine did not block either 5-HT or morphine. However, bufotenidine, a neural tryptaminergic blocking agent, blocked the effects of both 5-HT and morphine. The effects of 5-HT and morphine upon intestinal motility were also diminished by ganglionic depolarizing agents such as nicotine and DMPP. This effect could, however, be prevented by the pretreatment with hexamethonium. These results seem to confirm the hypothesis of a 5-HT mediator role in the intestinal contractile effect induced by the narcotic-analgesics. On the other hand, narcotic-antagonists such as nalorphine and cyclazocine, not only lacked the 5-HT potentiation effect but also prevented the 5-HT potentiation induced by morphine. Cyclazocine also showed a long lasting 5-HT blocking effect. These results seem to show that the 5-HT potentiating effect of morphine in vivo is very specific and characteristic of the narcotics and thus could be implicated in some of their central effects.

Analgesics, Opioid↗

Control of breathing in babies of narcotic- and cocaine-abusing mothers.

To learn if chemoreceptor control of breathing is abnormal in babies whose mothers took narcotics, cocaine, or both drugs during pregnancy, we performed hypoxia and hypercapnia challenges on 28 babies (greater than or equal to 36 weeks gestation). Six babies were exposed to narcotics, six to cocaine, nine to both drugs, and seven babies were controls. Studies were done at 3 and 8 weeks and 3 and 5 months of age. Gestational ages were similar, but birth weight was lower in the cocaine group. Respiratory rate was higher in both groups of cocaine-exposed babies at 3 weeks. End-tidal partial pressure of CO2 (PCO2) was decreased and partial pressure of O2 (PO2) increased at 3 and 8 weeks in babies exposed to narcotics plus cocaine. At 3 weeks, babies exposed to narcotics plus cocaine had a shift to the left in CO2 response with a normal slope; at 8 weeks, both intercept and slope were decreased. Responses to hypoxia were similar among the four groups. Babies exposed to narcotics plus cocaine before birth have abnormalities in control of breathing in the first months after birth.

Birth Weight↗

The incidence of narcotic-induced emesis.

Epidemiologic studies of the incidence of emesis induced by narcotic analgesics are lacking. The histories of 260 cancer patients receiving oral narcotic analgesics prescribed at the Pain Clinic of our Institute from December 1988 to December 1989 were reviewed. Of the 260 patients, 120 were women, median age 61 (range 30-90) yr and 140 were men, median age 62 (range 30-82) yr. Nausea and vomiting associated with assumption of the various narcotics were buprenorphine 8.3% and 22.7%, morphine 18.3% and 28%, codeine 16.2% and 29.7%, and oxycodone 10% and 40%, respectively. Since the use of narcotic analgesics can effectively relieve pain and improve quality of life in cancer patients, it is important to be aware of the incidence of narcotic-induced emesis in order to use appropriate prophylactic antiemetic therapy.

Adult↗

Potential adverse outcomes of psychotropic and narcotic drug use in Canadian seniors.

Potential adverse outcomes (falls, impaired cognition, impaired self-care) of psychotropic (benzodiazepines, antidepressants, antipsychotics) and narcotic medication use were examined in a large sample of Canadians 65 years of age and older. We examined rates of reported falls, Digit Symbol Substitution Test (DSST) scores, and mean number of self-care impairments for those consuming psychotropic and/or narcotic drugs as compared to non-users. Use of psychotropic drugs and/or narcotics was associated with an increased prevalence of falls, lower DSST scores, and/or number of self-care difficulties. For example, in subjects who were cognitively normal, the frequency of falls was 60% greater in benzodiazepine users and 120% greater in users of antidepressants as compared to non-users. Adverse outcomes increased with the number of classes of psychotropic or narcotic medications used. These effects were most pronounced in cognitively normal subjects where the prevalence of falls increased from 13.9% in those consuming none of the medication classes to 42.6% for users of two or more classes. In subjects with mild dementia the use of these medications was not associated with any significant differences in the outcomes measured. Regression models showed that benzodiazepine, antidepressant, and narcotic use remained significant explanatory variables for potential adverse outcomes even after simultaneously considering the effects of several other variables. Although further work is necessary, our results suggest that individuals with better cognitive function may be at particular risk for adverse effects with use of these medications.

Accidental Falls↗

Epidural narcotics for postoperative pain: nursing implications.

The use of epidural narcotics is fast becoming an accepted technique for postoperative pain relief. Reduction of the patient's narcotic requirements, increased movement in bed and cooperation with postoperative exercises are the major advantages of this type of therapy for pain relief. Knowledge of the anatomy and physiology of pain transmission is essential in understanding how narcotics affect the central nervous system and provide pain relief. Nurses should also be knowledgeable about the technical aspects of the procedure for catheter insertion and the narcotics that might be used for postoperative pain relief. Nursing implications for patients receiving epidural narcotics for postoperative pain relief are presented.

Analgesia, Epidural↗

Continuous infusion of naloxone in the treatment of narcotic overdose.

Based on the pharmacokinetic parameters of naloxone and the clinical studies discussed in this paper, it is evident that naloxone infusion may be useful in cases of opiate overdose. The infusion protocol presented in Appendix I was formulated based on the pharmacokinetic data available from the literature including Nelson's animal data. An infusion of naloxone was used with apparent success in the two cases presented. Both patients presented with narcotic overdose; although immediate patient history could not be obtained, the presentations were classic for narcotic overdose. It is of note that it may be possible to keep a patient from relapsing into narcosis after overdose by the use of naloxone infusion. Additionally, the extreme safety of naloxone is certainly an advantage with any administration technique. We feel that the administration of continuous infusion of naloxone is an especially important advance in the overdose treatment of longer-acting agents such as methadone, as well as of other narcotics. Therefore, it is recommended that further clinical trials of naloxone by infusion be undertaken, as suggested by J. Nelson, et al. (A protocol for treatment with continuous infusion of naloxone [Narcan] in selected cases of opiate [narcotic] overdose. Austin: University of Texas; May, 1976, unpublished), to further document the effectiveness of an infusion of naloxone in narcotic overdose.

Adult↗

Acute pulmonary alveolitis in narcotics abuse.

Lungs of 17 narcotic abusers from medical-legal autopsies were studied to determine the pathological basis for regional alterations of ventilation and perfusion. Postmortem pulmonary angiographic and histological techniques demonstrated acute alveolar wall inflammation with exudation of fluid and cells into the alveoli in all eight abusers dying of narcotism and in six of nine dying of other causes. All abusers had extensive focal chronic intersititial inflammatory infiltrates. Vascular obstruction due to foreign material occurred only with intravenous use of oral pharmaceuticals, and then only in the microcirculation. Lungs of ten young adults dying suddenly with no history or evidence of narcotics abuse showed no acute alveolitis or intravascular foreign material. Intravenous narcotics injection produces transient acute alveolar inflammation that may account for respiratory manifestations and death. Permanent injury to the lung parenchyma or larger vessels with the usual forms of narcotic abuse is not common.

Acute Disease↗

Narcotic abuse among homicide victims in Detroit.

A record of 751 homicides occurred in Detroit in 1973. An attempt was made to explore the relationship between narcotics and a random sample of these homicides. It was demonstrated that in the group studied, 43% were narcotic users. It is suggested that if one includes pushers and dealers (possibly victims of a "drug war"), people killed by addicts, and those cases where a narcotic might not be detected in the biological sample, the percentage of homicide victims associated with narcotics traffic could be as high as 60 to 70%. An investigation into the manner (executed, killed in a robbery attempt, etc) helps substantiate this suggestion. Finally, unlike the majority of homicide victims, ethanol is infrequently found in the victim using narcotics.

Adult↗

A four year survey of neonatal narcotic withdrawal: evaluation and treatment.

BACKGROUND: Narcotic abuse has steadily become more prevalent in Israel and may result in an increasing number of children exposed prenatally to narcotics, with a consequent increase in the number of infants born with neonatal abstinence syndrome. OBJECTIVE: To report our experience with infants born to narcotic-addicted women between the years 1995 and 1998 at the Soroka University Medical Center. METHODS: The medical records of 24 newborns and their drug-addicted mothers admitted to our Medical Center for parturition were analyzed retrospectively. A diagnosis of NAS was established on the basis of the clinical presentation and anamnesis. The Finnegan Neonatal Abstinence Scoring System was used to assess drug withdrawal. Urine toxicological analysis for narcotics was done only for the year 1998. RESULTS: Of the 24 newborn infants exposed prenatally to narcotics 23 (96%) developed NAS, and 78% (18 of the 23) had a Finnegan score of 8 or more. These 18 infants were treated pharmacologically (tincture of opium and/or phenobarbital) until the score was reduced to less than 8, after which they received supportive treatment. In one child who became lethargic after the first dose of tincture of opium, the medication was stopped and supportive treatment alone was given. Four of the five neonates with scores of 7 and less were given supportive treatment. One of five infants who had a low Finnegan score at birth nevertheless received pharmacological therapy to prevent further deterioration of his physical state since he was born with severe dyspnea. Ten of the 24 children (42%) were followed for lengths of time ranging from 6 to 22 months after discharge, all of whom showed normal development. CONCLUSIONS: About three-quarters of newborns exhibiting withdrawal syndrome required pharmacological therapy. Previous information on maternal drug abuse is a crucial criterion for early detection and treatment.

Adult↗

[The use of narcotics in veterinary practice and hospitals in the Federal Republic of Germany including Berlin-West].

An inquiry on the use of narcotics was carried through among practising veterinary surgeons and in animal hospitals. Of 5907 questionnaires sent out 2725 (46.1%) were returned; 86.3% of these stated the use of narcotics. There was a negative correlation between the use of narcotics and the age of the veterinary surgeons. Levomethadone, pentobarbital and fentanyl were used most often, the other narcotics were only mentioned in 1-2% of the questionnaires or not at all. Narcotics were primarily ordered for the veterinary "house pharmacy" and for use in practice, prescriptions for the individual patient being the exception.

Animals↗

Rectal, buccal, and sublingual narcotics for the management of cancer pain.

We review current knowledge on the rectal, buccal, and sublingual routes of narcotic administration as potential alternatives to oral, intramuscular, intravenous, and subcutaneous administrations of narcotics for the management of cancer pain. Most of the experience reported in the literature is based on the use of rectal, sublingual, and buccal narcotics for the management of acute pain syndromes. Preliminary evidence suggests that both morphine sulfate and chlorhydrate can be administered rectally because there is acceptable absorption with this route even if considerable interpersonal variation exists. There are no controlled trials on the long-term use of rectal morphine for cancer pain. There are very few reports on the clinical effects of sublingual and buccal morphine, and pharmacokinetic data are often debatable. There is evidence to justify further research into all three routes of narcotic administration. At the moment rectal use is justified in clinical trials in cancer patients, but there are not enough data on the pharmacokinetics of different narcotics when administered by the buccal or sublingual routes.

Administration, Buccal↗

Selection of implantable narcotic delivery systems.

Intraspinal narcotics have dramatically influenced the way pain of malignant origin is managed. There has been a rapid acceptance of this modality within the anesthesia community to treat a wide variety of cancer pain problems. In tandem the development of various implantable narcotic delivery systems has complemented and facilitated the expanded role of intraspinal narcotics in the treatment of cancer pain. Appropriate patient selection is crucial if optimal results are to be achieved. Factors to be considered in patient selection should include the results of the preimplantation spinal narcotic trial, infection trial, infection and local conditions, hematologic status, physiologic and behavioral abnormalities, cost, patient support systems and life expectancy. By interfacing these factors with the unique profiles that each of the five types of implantable narcotic delivery systems offer, improved results both in terms of pain relief and patient satisfaction can be expected.

Catheters, Indwelling↗

Pharmacological analysis of the phencyclidine-like discriminative stimulus properties of narcotic derivatives in rats.

The purpose of the present experiments was to evaluate the phencyclidine (PCP)-like discriminative stimulus properties of narcotic derivatives in the rat. Rats were trained to discriminate between saline and 3.0 mg/kg of PCP in a two-choice, shock-avoidance procedure. PCP-like stimulus control of behavior was produced by (in order of relative molar potency): l-cyclazocine greater than PCP greater than dl-cyclazocine greater than SKF 10,047 greater than MeO-cyclazocine greater than dextrorphan greater than d-cyclazocine. Metazocine and levalorphan also occasioned appreciable percentages of PCP-appropriate responding. Ten other narcotic derivatives, including pentazocine and nalorphine, occasioned only saline-appropriate responding. Among enantiomeric pairs, levocyclazocine was more potent than dextrocyclazocine, and dextrorphan but not levorphanol produced PCP-like discriminative effects. The specific narcotic antagonist naloxone failed to antagonize these PCP-like effects but rather increased the relative potency of cyclazocine and "unmasked" PCP-like effects of higher doses of metazocine. These results demonstrate that PCP and selected narcotic derivatives have similar components of action which appear to be mediated by sigma receptors rather than receptors which subserve the characteristic opioid actions of narcotic analgesics.

Animals↗

Hepatitis B serologic studies in narcotic users with chronic liver disease.

Hepatitis B surface antigen (HBsAG) and antibody (anti-HBs), and antibody to the hepatitis B core antigen ( anti-HBc) were measured by radioimmunoassay in 46 current or former narcotic users who underwent liver biopsy for evaluation of chronic liver disease. Significant alcohol abuse was found in 38 narcotic users (82.6%). On liver biopsy, 24 had cirrhosis (52.2%), nine had chronic active hepatitis (19.6%), five had lipid accumulation (10.9%) and eight had other diagnoses (17.4%). At least one marker for hepatitis B was found in 45 of 46 narcotic users (97.8%). Five had HBsAg and anti HBc (10.9%), one had anti-HBs alone (2.2%), 30 had anti-HBs and anti-HBc (65.2%) and nine had anti-HBc alone. Although almost all narcotic users with chronic liver disease have active or resolved hepatitis B infection, alcohol abuse appears to be the major factor in the development of cirrhosis in the subset of narcotic users studied.

Adult↗

Narcotic antagonists. Treatment tool for addiction.

Narcotic antagonists have recently gained attention through research aimed at evaluating both biochemical effects and treatment potential for opiate addiction. Narcotic antagonists are a classification of drugs which block the euphoric (and all other) effects of opiates. Naltrexone is the most promising narcotic antagonist based on ability to produce blockade, length of duration, and relative absence of side effects. The narcotic antagonists offer an adjunctive or alternative method of treatment for opiate addicts based on Wikler's biobehavioral theory of conditioned abstinence. Narcotic antagonists are presently being investigated at seven research centers throughout the United States and may be available for clinical use in the future.

History, 20th Century↗

A 24-year follow-up of California narcotics addicts.

OBJECTIVE: This study examined longitudinal patterns of narcotics use, other substance use, criminal involvement, morbidity, and mortality among narcotics addicts. DESIGN: A 24-year follow-up study. Data were obtained from admission records and two face-to-face interviews conducted in 1974-1975 and 1985-1986. PARTICIPANTS: Five hundred eighty-one narcotics addicts admitted to the California Civil Addict Program during the years 1962 through 1964. RESULTS: Most of this sample initiated narcotics use before age 20 years and had a mean age at program admission of 25.4 years. In 1974-1975, 13.8% of the sample died and 28.6% tested negative for opiates. Corresponding rates in 1985-1986 were 27.7% and 25.0%, respectively. Substance use and criminal involvement remained high among this sample into their late 40s. In any given year during the 10 years prior to the 1985-1986 interview, less than 10% of the sample participated in community-based treatment programs such as methadone maintenance. Disability, long periods of heavy alcohol use, heavy criminal involvement, and tobacco use were among the strongest correlates of mortality. CONCLUSIONS: The results suggest that the eventual cessation of narcotics use is a very slow process, unlikely to occur for some addicts, especially if they have not ceased use by their late 30s.

Adult↗

Long-term use of narcotic analgesics in chronic pain.

The use of narcotic analgesics have been avoided by clinicians in patients with chronic pain syndromes. Uncertainty as to the etiological cause of chronic pain, development of addiction and habituation and associated psychological and behavioral symptoms found in chronic pain states which are not amenable to narcotic medications are the major reasons narcotics are not prescribed. This communication describes the long-term use of low dose narcotic analgesics as a treatment component of a comprehensive pain management program and addresses the questions of whether or not narcotic efficacy is maintained in long-term use, improvement of patients' function is continued and side effects develop as a result of this treatment.

Adolescent↗

Factors associated with insulin and narcotic independence after islet autotransplantation in patients with severe chronic pancreatitis.

BACKGROUND: For patients who suffer from severe chronic pancreatitis, total pancreatectomy can alleviate pain, and islet autotransplantation (IAT) might preserve endocrine function and circumvent the complications of diabetes. Factors that determine success after this operation have not been clearly defined. STUDY DESIGN: From 2000 to 2004, 45 total or subtotal pancreatectomies with IAT were performed. Patient characteristics, narcotic usage and insulin requirements were recorded at routine followup. Narcotic usage was standardized by conversion to morphine equivalents (MEs). Univariate and multivariate statistical analyses were performed to determine factors associated with insulin and narcotic independence. RESULTS: Forty-five patients (30 women, 15 men), with a mean age of 39 years (range 16 to 62 years) underwent total or completion (n=41) or subtotal (n=4) pancreatectomies with IAT. Forty percent of patients were insulin free after a mean followup of 18months (range 1 to 46months). Factors associated in univariate analyses with insulin independence included female gender (p=0.004), lower body weight (kg) (p=0.04), more islet equivalents per kg body weight (IEQ/kg) transfused (<0.05), lower mean insulin requirement for the first 24hours postoperation (p=0.002), and lower mean insulin requirement at discharge (p=0.0005). A multiple logistic regression using gender, body mass index, and IEQ/kg identified female gender as the only notable variable associated with insulin independence. There was a notable reduction (p < 0.0001) of postoperative MEs (mean 90 mg) compared with preoperative MEs (mean 206 mg) for the entire cohort; 58% of patients are narcotic independent. In the subset of patients with>5months followup (n=32), 23 (72%) are narcotic free, with a substantial decrease in ME usage (p=0.01). CONCLUSIONS: The likelihood of glycemic control after IAT is related to both patient characteristics and islet cell mass. Based on these data, more islet cells may be required for insulin independence than previously thought.

Adolescent↗