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Intrabiliary pressure changes produced by narcotic drugs and inhalation anesthetics in guinea pigs.

The effects of narcotic agents and two inhalation anesthetics on intrabiliary pressure (IBP) were measured before and after morphine (0.2 mg/kg), meperidine (2 mg/kg), fentanyl (0.002 mg/kg), or pentazocine (1 mg/kg) given intramuscularly to guinea pigs, and after halothane (0.5, 1.0, 1.5, or 2.0 MAC) or enflurane (same range of MAC) administered by inhalation. All narcotics except pentazocine significantly increase IBP, the increases ranging from 85.7% for meperidine to 143.4% for fentanyl. Pentazocine had no effect on IBP. Peak IBP increases occurred between 9 and 18 minutes after administration. The elevation of IBP produced by narcotics was reversed by atropine (0.05 mg/kg). No statistically significant alterations of IBP were noted during halothane or enflurane anesthesia.

Analgesics, Opioid↗

Post-marketing management of the use of non-narcotic analgesics.

While the use of non-narcotic analgesics is of considerable health benefit to people everywhere, they also represent a health problem. This problem has to do more with the risks associated with individual courses of treatment than with the commonality of those treatments. The public health challenge in post-marketing management of non-narcotic analgesic use, is to promote a pattern of use such that the risks are justifiable by the benefits and are the lowest that can be attained. To achieve such goals it is essential to have scientific knowledge about the benefits and risks and to be able to determine the quality of use in the population as to how proper it is. Current post-marketing management programmes focus largely on regulation, overlooking other equally important basic methods of public health intervention, namely education and service. If it is accepted that mass education is the key element in the proper management of non-narcotic analgesic use, the present emphasis on regulation needs amendment. Such changes will take time, but it is conceivable that ultimately the management goal can be achieved with minimal regulatory intervention.

Analgesics↗

Role played by narcotics laboratories in the campaign against drug abuse and drug trafficking: a view from a developing country.

The narcotics laboratory at the national level identifies drugs for abuse and their accompanying substances in suspected samples, determines the purity and the possible origin of illicit drugs, carries out drug-related research, particularly on new sources of drugs liable to abuse, and, when required by the police or courts of law, provides supportive expertise in drug trafficking cases. Precaution must be taken to ensure that samples to be examined are representative. The university is a particularly appropriate setting for the location of a narcotics laboratory, especially if such a laboratory carries out complex work requiring assistance from other professional disciplines. Before new laboratory equipment is purchased, a careful study of requirements and financial resources should be made to ensure economical and optimum utilization of such equipment. In some situations the use of simple techniques, such as thin-layer chromatography, can be sufficient, while in others more sophisticated techniques may be required. Appropriate training of personnel is of particular importance for the effective functioning of a narcotics laboratory. The laboratory of the Department of Toxicology and Forensic Chemistry, University of Buenos Aires, provides for the training of personnel at three levels: The first level consists of basic training, which includes the use of kits for rapid identification of drugs in field conditions, for personnel from the police, gendarmerie, prefecture, customs and other agencies which deal with drug problems, but which have no previous skills in laboratory techniques; The second level is provided for professional laboratory personnel and usually lasts six months; The third level consists of two years' postgraduate university training for students who are expected to carry out complex laboratory work; an additional year is provided for trainees who are expected to assume responsibility in a laboratory unit.

Cannabis↗

Narcotic effects on hepatic disposition of sulfobromophthalein in rats.

Ascending morphine doses above 5 mg/kg s.c. progressively reduced plasma clearance of sulfobromophthalein (BSP) and raised hepatic levels of this dye in rats. The narcotic reduced the elimination constant of BSP without affecting its volume of distribution. Because abdominal surgery markedly reduced plasma clearance of BSP, no further effect of morphine could be shown in rats with bile cannulas. In duct-cannulated animals morphine had no effect on BSP concentration in bile, but did raise hepatic BSP levels while reducing bile flow and biliary BSP content. The narcotic also lowered the biliary transport maximum of BSP. The effects on BSP disposition were demonstrated acutely after morphine administration but had subsided completely by 1 and 2 days after giving narcotic. The present findings suggest that morphine impaired the secretion of BSP into bile by a mechanism not involving biliary occlusion and thereby enhanced retention of this dye in liver and plasma.

Animals↗

The effect of incisional infiltration of bupivacaine hydrochloride upon pulmonary functions, atelectasis and narcotic need following elective cholecystectomy.

Forty randomly selected patients admitted for elective cholecystectomy were entered into the study after they have given informed consent. Arterial blood gas analysis, FVC and FEV1 were measured preoperatively and on the second postoperative day. Preoperatively and on the third postoperative day, roentgenograms of the chest were obtained. The frequency of administration of narcotics was recorded through day 3. The double-blind method selected 17 patients for infiltration of 50 milliliters of 0.25 per cent bupivacaine hydrochloride into the wound and 23 patients for infiltration of 50 milliliters of normal saline solution at the time of closure of the incision. In the saline solution group, postoperative FVC and FEV1 values were only 50 per cent of the preoperative levels (p less than 0.005), while in the bupivacaine hydrochloride group, the FEV1 value was 72 per cent of the preoperative values (p less than 0.05) and the FVC, 78 per cent (p less than 0.05). Roentgenographic evidence of atelectasis occurred postoperatively in four patients of the saline solution group and in only nine patients of the bupivacaine hydrochloride group (p less than 0.001). The saline solution group required 10.8 doses of narcotic through day 3 in contrast with 6.5 doses for the bupivacaine hydrochloride group (p less than 0.05). The hospital stay was 6.6 days for those in the saline solution group and 5.9 days for those in the bupivacaine hydrochloride group (p value, not significant). No complications occurred. Intraoperative infiltration of bupivacaine hydrochloride into the wound improves pulmonary function, reduces the incidence of atelectases and lessens the use of narcotics following cholecystectomy.

Adult↗

Multiplicative interaction between narcotic agonisms expressed at spinal and supraspinal sites of antinociceptive action as revealed by concurrent intrathecal and intracerebroventricular injections of morphine.

In rats in which the fourth ventricular exits had been acutely occluded, morphine sulfate was injected concomitantly into the spinal subarachnoid space (0-10 micrograms/4 microliter) and into the third cerebral ventricle (0-50 micrograms/5 microliter). The combinations of intrathecal (i.t.) and intracerebroventricular (i.v.t.) dosages used were selected to yield particular ratios of supraspinal to spinal (SS:S) agonisms. Dose-response lines for both the tail-flick and hot plate responses were constructed for each SS:S ratio, with the abscissa representing i.v.t. morphine dosage. It was observed that the analgetic potency of morphine injected i.v.t. was profoundly potentiated by the concurrent administration of morphine i.t. Dose-response lines for i.v.t. morphine were shifted progressively to the left as the spinal dose of morphine was increased. At the optimal balance of spinal and supraspinal dosage (SS:S = 1:1), the ED50 values for i.v.t. morphine for the hot plate and tail-flick tests were reduced by factors of 45 and 29, respectively. A similar, but less profound, potentiation of the analgetic potency of morphine injected i.t. by concurrent administration of morphine i.v.t. was observed. Isobolographic analysis of the data revealed that the isobols were hyperbolas having extreme negative curvature of all effect levels. Inspection of the isobols indicated that, at all ratios of spinal to supraspinal agonism which could conceivably be obtained when morphine is given systemically, the spinal-supraspinal interaction is multiplicative. The results suggest that narcotic agonism at both spinal and supraspinal narcotic-sensitive sites is essential to the production of analgesia by systemically administered morphine and that neither site can logically be deemed the "primary" site of narcotic action.

Animals↗

The use of intrapartum intrathecal narcotic analgesia in a community-based hospital.

OBJECTIVE: To evaluate the use of intrapartum intrathecal narcotic analgesia in the obstetric population of our community-based hospital. METHODS: A protocol to administer intrapartum intrathecal narcotic analgesia was established at our institution in December 1992. All patients consenting to this procedure received a single lumbar intrathecal injection of 25 micrograms fentanyl and 0.25 mg morphine sulfate through a 25-gauge spinal needle. Only those patients with singleton pregnancies in the vertex presentation were included in this study. The study group was matched by gravidity and parity with singleton pregnancies delivered during the study period. Patients in the study group were asked to complete an analgesia satisfaction survey using a five-point Likert scale ranging from 0 for total dissatisfaction to 5 for total satisfaction. RESULTS: A total of 75 patients were assigned to each group; the control and study groups were similar with respect to age, race, estimated gestational age, infant birth weight, interval between rupture of membranes and delivery, and mode of delivery. The length of the first and second stages of labor and the incidence of fetal malposition were not significantly different between the two groups. Frequent side effects of this analgesia included complaints of pruritus (81.3%), urinary retention (53.3%), and nausea and vomiting (44.0%). Headaches were less common (9.3%), with two (2.7%) of seven patients requiring an epidural blood patch for relief. Infrequent side effects included respiratory depression (1.3%) and oversedation (1.3%). Patients were generally satisfied with the degree of pain relief obtained, rating it highly during the first and second stages of labor and in comparison to their previous labor experience. CONCLUSION: The use of intrapartum intrathecal narcotic analgesia provides a satisfactory level of pain relief without disrupting the normal course of labor.

Analgesia, Obstetrical↗

Flunixin meglumine: a non-narcotic analgesic.

The N-methyl-d-glucamine salt of flunixin (flunixin meglumine) is a potent non-narcotic analgesic agent after parenteral administration in mice, rats and monkeys. It is significantly more potent than pentazocine, meperidine and codeine in the rat yeast paw test after subcutaneous administration in saline. Activity on intramuscular administration is comparable to that after subcutaneous administration and is enhanced when dissolved in buffered saline as compared to nonbuffered saline. In addition, flunixin meglumine also had oral activity and differs from indomethacin in having more analgesic activity per unit of anti-inflammatory activity. In mice, flunixin meglumine is equipotent to pentazocine and more potent than meperidine and codeine in the abdominal constriction test. In primates, flunixin meglumine at 10 mg/kg i.m., produced a degree of analgesic efficacy comparable to that of a clinically effective dose of morphine (0.3 mg/kg). In contrast to codeine, tolerance to the analgesic action of flunixin meglumine was not observed. Furthermore, flunixin meglumine retained its activity in rats made tolerant to codeine. Unlike narcotics, the analgesic effect of flunixin meglumine is not antagonized by naloxone after acute administration in rats. These results indicate that flunixin meglumine is a parenterally and orally effective analgesic in animals and is unlikely to have narcotic or drug dependence liability.

Analgesics↗

Psychosocial and biomedical aspects of deaths associated with heroin and other narcotics.

Our findings point to sizable intercity differences in the United States among certain psychosocial and biomedical aspects of deaths associated with narcotics. Secondly, narcotic-involved deaths are not purely accidental, but many are motivated by suicidal goals and a smaller percentage by homicidal intentions. And finally, in addition to the errors that have been surmised to occur in estimates of psychoactive drug deaths from heroin and other narcotics owing to inadequate reporting or other shortcomings in data collection, there are biomedical errors due to variations in the quality control of toxicological laboratories.

Adult↗

Anti-nociceptive activity of narcotic agonists and partial agonists in mice given biogenic amines by intracerebroventricular injection.

Using a tail immersion technique in mice, the anti-nociceptive activity of some narcotic agonists (diamorphine, etorphine, morphine and pethidine), partial agonists (cyclazocine, nalorphine and pentazocine) and naloxone have been determined alone, and after the intracerbroventricular (ICV) injection of 5-hydroxytryptamine (5-HT) or noradrenaline (NA). In common with morphine, the anti-nociceptive effects of each agonist and partial agonist studied were significantly increased by ICV 5-HT, and significantly attenuated by ICV NA. The marginal anti-nociceptive activity of naloxone was not significantly affected by the ICV injection of either amine. It is concluded that the anti-nociceptive effects of all narcotic agonist and partial agonist agents are determined by the balance within the brain of the activities of the two amines, 5-HT and NA.

Analgesia↗

Effectiveness and safety of intravenous nalmefene for emergency department patients with suspected narcotic overdose: a pilot study.

STUDY OBJECTIVE: To evaluate the efficacy and safety of nalmefene, an investigational narcotic antagonist that has potential advantages over naloxone because of its four- to eight-hour half-life, in emergency department patients with possible narcotic overdose. DESIGN: Multi-institutional, prospective, phase II, open-label study. TYPE OF PARTICIPANTS: Complete data were available for 53 cases from two teaching hospitals. Men 18 years old or older who would otherwise receive naloxone were eligible (two women were enrolled inadvertently). METHODS: Over four hours, one to ten boluses (median, one) of 0.5 or 1.0 mg nalmefene IV were given as often as every two minutes based on clinical need. Respirations, blood pressure, pulse, pupil size, and overall clinical response were monitored. Overall clinical response (1, no change; 2, partial response; 3, complete response), first assessed at two minutes, was analyzed by the Mann-Whitney U test. RESULTS: Fifteen of 25 (0.5 mg) and nine of 28 (1.0 mg) cases were opiate positive. Twelve of 15 (0.5 mg) and six of nine (1.0 mg) opiate-positive cases had a rapid complete response. Coincident causes of depressed sensorium were identified in the remaining six opiate-positive cases. No difference in initial overall clinical response was seen between 0.5-mg and 1.0-mg opiate-positive cases (P = .59). No deterioration requiring repeat nalmefene occurred in opiate-positive cases, even if methadone (four), codeine (two), or pentazocine (one) was found. No serious adverse events were judged to be related to nalmefene. CONCLUSION: Nalmefene is effective in the reversal of opiate overdose and appears to be safe in the management of patients with altered sensorium.

Adolescent↗

Synthesis and structure-activity relationships of 1-substituted 4-(1,2-diphenylethyl)piperazine derivatives having narcotic agonist and antagonist activity.

Racemates and enantiomers of 1-substituted 4-[2-(3-hydroxyphenyl)-1-phenylethyl]piperazine derivatives (3-18) were synthesized, and their analgesic and other pharmacological activities and structure-activity relationships were investigated. The S-(+) enantiomers of 2a, 5, 7, 9, 10, and 15-18 had a stronger analgesic activity than their R-(-) enantiomers; analgesic activity of the strongest one [(S)-(+)-10] was 105 times as potent as that of morphine. The S-(+) enantiomers of these compounds had the opposite configuration to that of morphine with respect to its (C-9) asymmetric center but the same configuration to that of the tyrosine residue of Met5-enkephalin. The R-(-) enantiomers of 16 and 18 showed narcotic antagonist activity, but the S-(+) enantiomers did not. (R)-(-)-18 had analgesic and narcotic antagonist activities comparable to pentazocine but showed no significant physical dependence liability. From these results, it is suggested that these compounds show an uncommon enantioselectivity in comparison with morphine and its surrogates, and belong to a new series of compounds having a potent analgesic activity.

Analgesia↗

Nalmefene to prevent epidural narcotic side effects in pediatric patients: a pharmacokinetic and safety study.

STUDY OBJECTIVE: To determine the pharmacokinetics and preliminary efficacy of nalmefene in children in preventing epidural-induced narcotic side effects. DESIGN: Double-blind, placebo-controlled study. SETTING: University-affiliated children's hospital. PATIENTS: Thirty-four children (aged 2-12 yrs) undergoing cardiothoracic surgery with epidural anesthesia. INTERVENTIONS: Patients were randomized to receive intravenous bolus nalmefene 1 microg/kg or placebo. MEASUREMENTS AND MAIN RESULTS: Six blood samples (one before nalmefene administration and five from 13 randomly designated time points) from each patient were assayed to determine plasma nalmefene concentrations. Patients were assessed for pain, nausea, vomiting, and urinary retention for 24 hours after administration. Concentration-time data were analyzed by a limited sampling strategy with adult pharmacokinetic parameters used as Bayesian priors. A two-compartment, first-order model was fitted to the data using ADAPT II. Pharmacokinetic parameter estimates in these patients were similar to values reported in adults. The initial disposition half-life (t(1/2alpha)) was 0.36+/-0.11 hour, the terminal elimination half-life (t(1/2beta)) 8.7+/-2.3 hours, clearance 0.729+/-0.172 L/kg/hr, and steady-state volume of distribution 7.21+/-2.49 L/kg. Ability to prevent epidural narcotic-induced side effects could not be documented at the 1-microg/kg dose. No statistically significant differences were noted between study and placebo groups with regard to pain, nausea, vomiting, or urinary retention. CONCLUSION: Nalmefene has similar pharmacokinetics in children as in adults. It was administered safely to these patients and did not produce unmanageable pain.

Analgesia, Epidural↗

Statutory classification of cocaine as a narcotic: an illogical anachronism.

Although cocaine is pharmacologically not a narcotic, federal and state drug control laws have classified it as one from 1922 through the present. In many states and under federal law, the classification is part of a statutory scheme that imposes substantially more severe penalties for offenses involving cocaine than for offenses involving other nonnarcotic drugs. This Note examines the circumstances surrounding the adoption and maintenance of the legal classification of cocaine as a narcotic. It then reviews two of the many cases that have rejected claims that the classification is unconstitutional. The Note concludes that, despite its constitutionality, the inaccurate classification is not only illogical and unnecessary to a legislative goal of strictly penalizing cocaine offenses, but is counterproductive as well.

Cocaine↗

Narcotic use in southeast Asia and afterward. An interview study of 898 Vietnam returnees.

From all US Army enlistees leaving Vietnam in September 1971, a random sample of 943 men was selected. Of these, 470 represented a "general" sample of all enlistees returning at that time, and 495 represented a "drug positive" sample whose urine samples had been positive for opiates at the time of departure. We attempted to locate and personally interview all of the men in the samples. Results indicate that before arrival, hard drug use was largely casual, and less than 1% had ever been addicted to narcotics. In Vietnam, almost half of the general sample tried narcotics and 20% reported opiate addiction. After return, usage and addiction essentially decreased to pre-Vietnam levels. We discuss the use of nonnarcotic drugs, predictors and correlates of drug use in the samples, and the relationship of drugs to post-Vietnam social adjustment.

Age Factors↗

Management of pain in the terminally ill by administration of epidural narcotics.

Fifteen patients with chronic malignant intractable pain were given epidural narcotics for periods of up to 280 days. The majority were treated at home. The patients self-administered the narcotics through an indwelling epidural catheter that had been tunneled and brought out onto the anterior abdominal wall. The results are presented together with the problems encountered.

Administration, Oral↗

Residue-based interpretation of toxicity and bioconcentration QSARs from aquatic bioassays: polar narcotic organics.

Bioconcentration and toxicity estimation for a group of substituted phenols often categorized as "polar narcotics" can be confounded by pH-dependent ionization. Two methods of correction for ionization were applied to toxicity data obtained by U.S. EPA-Duluth for fathead minnows exposed to 30 different phenols in 37 bioassays. Toxicity QSARs with corrected data were substantially different from those obtained with raw toxicity data. When ionization-corrected toxicity data were used in the critical body residue (CBR) estimation process previously successful with neutral narcotic organics, several categories of CBR, apparently related to different modes of toxic action, resulted. Published data on lethal CBR for substituted phenols were in general agreement, although such information is limited. Elimination half-life rate constants, estimated from nonlinear curve fitting to time-toxicity information, were relatively constant for the Duluth bioassay data, averaging 0.3 days. Half-life information for small aquatic organisms, both from toxicity- and bioconcentration-based tests in the literature, was in a similar range. Much of the relatively high variability encountered experimental data for substituted phenols may in large part be due to differences in metabolic degradation between chemicals and species.

Animals↗

A comparative analysis of the effects of narcotics, alcohol and the barbiturates on the hypothalamic-pituitary-gonadal axis.

The purpose of this paper is to provide an overview of our current state of knowledge regarding the effects of alcohol, the narcotics and the barbiturates on the hypothalamic-pituitary-gonadal axis in the male. Three facets of this problem will be considered: acute drug effects; chronic effects, particularly with respect to the development of tolerance and physical dependence; and, finally, an attempt will be made to indicate the way in which these three substances of abuse are similar and/or dissimilar in their effects on this system. The effects of acute and chronic treatment with narcotics, alcohol and the barbiturates will be discussed first and then an attempt will be made, in a General Discussion, to summarize the data, make general comparisons between the drugs and suggest future lines of research.

Animals↗