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Muscular fibrosis due to chronic intramuscular administration of narcotic analgesics.

Chronic intramuscular injections, particularly of narcotic analgesics, are an uncommon cause of myopathy. We report two patients with pentazocine- and meperidine-related myopathy. Narcotic-induced muscular fibrosis and contractures must be considered in patients with a pattern of muscle involvement that does not conform to any recognized myopathy, but allows for self-administration of injections. Trauma due to needle puncture, repetitive infections and a local myotoxic effect of the drugs probably contribute to these lesions.

Adult↗

Unusual pathogens in narcotic-associated endocarditis.

We report the cases of three adults with a history of intravenous drug abuse who developed endocarditis caused by Corynebacterium xerosis, Neisseria subflava, and Neisseria flavescens, respectively. No cases of endocarditis caused by C. xerosis or N. flavescens and only one case caused by N. subflava have previously been reported in association with narcotic addiction. The prominent clinical features in all patients included poor response to antibiotic therapy, persistent fever, and major embolic events. Stigmata of infection with human immunodeficiency virus, as manifested by oral candidiasis, cervical lymphadenopathy, and serologic evidence, were present in two of the three patients. At our institution, where Staphylococcus aureus remains the most frequent etiologic agent of narcotic-associated endocarditis, the occurrence of these three cases in a 9-month period is striking. We speculate that infection with human immunodeficiency virus may play a role in the pathogenesis of endocarditis caused by these unusual organisms.

Adult↗

Bacteremia in narcotic addicts at the Detroit Medical Center. II. Infectious endocarditis: a prospective comparative study.

For one year all narcotic addicts admitted to the Detroit Medical Center with infectious endocarditis (74 cases) were compared with a control group of bacteremic addicts who had other infections (106 cases). Endocarditis was caused by Staphylococcus aureus (60.8% of cases), streptococci (16.2%), Pseudomonas aeruginosa (13.5%), mixed bacteria (8.1%), and Corynebacterium JK (1.4%). S. aureus endocarditis most frequently involved the tricuspid valve; streptococci infected left-sided valves significantly more often than other organisms (P = .001). Biventricular and multiple-valve infections were commonest in patients with pseudomonas endocarditis (P = .05). Two-dimensional echocardiography, when combined with an abnormal chest roentgenogram, was highly predictive of endocarditis. Bacteremia in the absence of endocarditis was associated with primary skin and soft tissue infection, mycotic aneurysm at the site of narcotic injection, septic arthritis, septic thrombophlebitis, pneumonia, osteomyelitis, mediastinal abscess, and unclassified infection. Polymicrobial bacteremia in the nonendocarditis group was associated with markedly increased morbidity. Mild hyponatremia occurred in 41% of all patients and was also associated with significantly increased morbidity. Analysis of the two groups disclosed similarities and differences with implications for the pathophysiology and treatment of addicts with bacteremic infection.

Adult↗

Nitrogen at raised pressure interacts with the GABA(A) receptor to produce its narcotic pharmacological effect in the rat.

BACKGROUND: Strong evidence supports the concept that conventional anesthetics, including inhalational agents and inert gases, such as xenon and nitrous oxide, interact directly with ion channel neurotransmitter receptors. However, there is no evidence that nitrogen, which only exhibits narcotic potency at increased pressure, may act by a similar mechanism. METHODS: We compared the inhibitory and sedative effects of gamma-aminobutyric acid (GABA) and nitrogen pressure on locomotor activity and striatal dopamine release in freely moving rats and investigated the pharmacologic properties of the GABA-induced and nitrogen pressure-induced narcotic action using the highly selective competitive GABA(A) receptor antagonist bicuculine. RESULTS: Intracerebroventricular GABA infusion up to 60 micromol or exposure to nitrogen pressure up to 3 MPa decreased to a similar extent striatal dopamine release (r2= 0.899, df = 4, P < 0.01) and locomotor activity (r2 = 0.996, df = 28, P < 0.001). However, both agents only showed small effects on striatal dopamine release, reducing dopamine currents by only 12-13% at sedative concentrations. Pretreatment with bicuculline at 0.5, 1, and 2.5 pmol reduced the sedative action of GABA on locomotor activity by 10, 20, and 41%, respectively. Bicuculline in the nanomole range at 1, 2.5, and 5 nmol but not in the picomole range reduced the sedative action of nitrogen pressure by 5, 37, and 73%, respectively. Schild plot analysis is consistent with the fact that bicuculline is a competitive antagonist of both GABA and nitrogen at pressure. CONCLUSIONS: These results suggest (1) that the presynaptic effects of both GABA and nitrogen pressure on striatal dopamine transmission are modest and not mainly involved in their sedative action and (2) that nitrogen at increased pressure may interact directly with the GABA(A) receptor. However, because the antagonistic effect of bicuculline on nitrogen sedation only occurred at much higher bicuculline concentrations than seen with GABA, it is suggested that nitrogen does not compete for the same site as GABA.

Air Pressure↗

Narcotic dependence in inflammatory bowel disease.

Thirteen of 43 patients (30%) with inflammatory bowel disease referred for psychiatric consultation were found to be drug dependent, most commonly on oral narcotics. Drug dependence was more frequent in patients with Crohn's disease than ulcerative colitis and many had a borderline personality disorder. The study suggests that drug dependence is not recognized often enough in patients with inflammatory bowel disease and that patients with certain psychiatric disorders are at higher risk of developing it. Recognition of drug dependence is aided by interviewing family members. It is best prevented by seeking and treating the specific cause of pain and by having only one physician assigned to prescribe and manage narcotics.

Adult↗

Attitudes toward narcotic addiction.

In an effort to isolate the major dimensions of attitude and expectation regarding narcotic addiction and its treatment and to compare different groups of addict/clients and agency staff on these factors, a comprehensive questionnaire was administered to 900 addict/clients and 237 agency personnel in 25 drug treatment clinics in six states. Results of a factor analysis, which used questionnaire data from all of the 1137 subjects so that direct group comparisons could be made, indicated the presence of 10 major dimensions of attitude and expectation. Results also suggested considerable variation, particularly by status (client vs. staff) and ethnic group, on these dimensions. An additional analysis of staff attitudes and expectations revealed correlations with years of education, ex-addict status, and years of work experience. Such findings suggest the need to consider client/staff characteristics and attitudes in the planning of treatment services for narcotic addicts. An abbreviated (53-item) attitude and expectation questionnaire was developed for this purpose.

Adult↗

Differences among treatment clinic types in attitudes toward narcotic addiction.

Factor analysis of data from a general survey of attitudes and opinions concerning narcotic addiction and its treatment revealed 10 major dimensions, five of which were likely to have significant implications for drug abuse intervention strategies. For these latter dimensions, differences were determined among clients and staff according to type of treatment clinic (three types involving the provision of methadone maintenance in various combinations with other treatments and one involving the use of abstinence only). The most pronounced differences were between the methadone clinics and those offering abstinence only. Both the clients and staff of abstinence clinics were more skeptical concerning treatment effectiveness, were more negative regarding the use of narcotic drugs, and were more disposed to the use of ex-addict counselors and group procedures in treatment.

Black or African American↗

Perceptions of social pathology in the neighborhood and the etiology of narcotic addiction. A retrospective study.

In this study, we examined whether differential perceptions of poor urban neighborhoods may contribute to narcotic addiction in individuals who grow up in these neighborhoods. Three groups of adult males provided retrospective perceptions of the neighborhoods where they lived at ages 12 to 14. The groups, matched on neighborhood, age, and race, were: narcotic addicts, peer controls--a never-addicted control sample of age-11 associates of the addicts, and community controls--a never-addicted control sample of age-11 peers who did not associate with the addicts. Results suggested clear group differences in perceptions of neighborhood deviance, with addicts perceiving the greatest and community controls the least amount of deviance. However, within groups, subjects who lived in more socially deviant areas, as determined by official records, tended to view their neighborhoods as more deviant than did subjects who lived in less deviant neighborhoods.

Adolescent↗

Religious life of narcotic addicts.

Because of the unstructured life-style of most narcotic addicts, we have inquired into the religious and social backgrounds and experiences of a group of narcotic addicts. It was observed that the subjects' parents were far less involved in religious practices than were a group of parents of nonaddicts. The addicts' fathers were found to be frequently absent from the home and uninvolved in the addicts' early religious training. The addicts came from broken homes and often their marriages also ended in divorce. The addicts, as compared to both their parents and the control subjects, were underachievers in both social and religious accomplishments.

Black or African American↗

Medication-induced performance deficits: analgesics and narcotics.

Pain is the most common medical complaint, and analgesic drugs are often used for its management. Seven out of 10 Americans took nonprescription pain relievers in the last year. Analgesics are classified as nonnarcotics (acetaminophen, aspirin, and nonsteroidal anti-inflammatory drugs), narcotics (which include the morphine-like drugs), and analgesic adjuvants (a heterogeneous group of drugs, including antihistamines, phenothiazines, anticonvulsants, calcium channel blockers, and tricyclic antidepressants), which may have intrinsic analgesic efficacy for specific pain syndromes or may be used as co-analgesics in combination with the traditional nonnarcotic and narcotic agents. Although these agents can be used safely most of the time by patients with acute or chronic pain, all classes of analgesics may impair cardiovascular and neuropsychiatric functioning, which may influence job performance in specific instances.

Adjuvants, Pharmaceutic↗

Alfentanyl (R39209): initial clinical experience with a new narcotic analgesic.

R39209 (Alfentanyl), a new narcotic analgesic with a uniquely short duration of effect, was used to supplement nitrous oxide and oxygen for the maintenance of anaesthesia. Twenty-two patients undergoing minor surgery were studied. Clinical anaesthesia was excellent or good in most (16) of the patients, and recovery was excellent or good in 18 patients, waking time being less than one minute in 15 patients. However the incidence of complications and side-effects, mainly movement, apnoea, difficulty in assisting ventilation, nausea and vomiting was high. Intravenous administration of R39209 during anaesthesia induced significant depression of respiratory rate and minute volume during the second, third and fourth minutes after injection. There was an unexplained significant rise in respiratory rate and minute volume in the first 30 seconds after the first injection. The first administration of R39209 also caused an unexplained, significant reduction in cardiac rate. An insignificant rise in mean systolic blood pressure followed injection of the drug. The transient effect of R39209 was confirmed in clinical practice, and the drug exhibited the features of a typical narcotic analgesic. It is concluded that R39209 will have a useful place in anaesthetic practice, and that better clinical results will be obtained with more experience of the drug, and better selection of indications for its use.

Adult↗

Narcotic addiction in patients with chronic pain.

The notes of 717 patients attending the Regional Pain Relief Unit, Abingdon, were reviewed. One hundred and thirty patients (18%) were taking narcotic analgesics. Of these, 74 were suffering from cancer and 56 (9.7%) had chronic benign pain. Nine patients were considered to be addicted to their analgesics. Nine men and five women were able to discontinue their narcotic analgesics as a result of therapy. All of these patients had been receiving oral agents for more than one year.

Adult↗

The role of naloxone infusions in the treatment of overdoses of long half-life narcotic agonists: application to nor-methadone.

This report describes the use of a naloxone infusion at a rate of 300 micrograms/h to provide constant antagonism of the respiratory depressant effects of a near fatal nor-methadone dose in a 2 year old boy. The terminal half-life for nor-methadone was calculated to be 13.5 h. The results indicate that a single dose of a narcotic antagonist with a short half-life (e.g. naloxone) will probably be inadequate to provide long lasting reversal of the effects of overdoses of long half-life narcotic agonists, and that continuous infusion may be the preferable to repeated bolus doses.

Apnea↗

The effects of alfentanil and selected narcotic analgesics on the rate of action potential discharge of medullary respiratory neurones in anaesthetized rats.

The effects of intravenous injections of alfentanil, fentanyl, phenoperidine or morphine on respiratory and peak inspiratory air flow rate, the diaphragm electromyogram (EMG), the activity recorded extracellularly from respiratory neurones located in the ventral respiratory group and the cardiovascular system were examined in anaesthetized rats. Alfentanil produced dose-dependent changes in peripheral and central respiratory parameters, which were prevented by naloxone pretreatment. Minimal effects were produced on the cardiovascular system. The bradypnoea was principally due to a prolongation of the inspiratory phase and was accompanied by a comparable decrease in the peak inspiratory air flow rate. Alfentanil prolonged the discharge duration of inspiratory neurones such that it still maintained a strict phase correlation with the diaphragm EMG, but changes in firing frequency were inconsistent and negligible. The action on expiratory neuronal discharge was analogous to that on inspiratory neuronal discharge but delayed in onset. Hypotension produced by morphine limited the dose used but the respiratory responses to morphine and other selected narcotic analgesics were otherwise similar to that of alfentanil, differing mainly in time-course and magnitude. From the respiratory parameters assessed, the order of duration of effect was morphine greater than phenoperidine greater than fentanyl greater than alfentanil and the relative potencies were 0.1, 0.5, 2.5 and 1 respectively. The selective prolongation of inspiration and the immediate action on inspiratory neurones suggests that systemically administered narcotic analgesics may alter the mechanisms within the central respiratory rhythm generator which determine the cessation of inspiration.

Action Potentials↗

Maternal narcotic addiction: pregnancy outcome in patients managed by a specialized drug-dependency antenatal clinic.

A retrospective analysis has been made of the outcome of pregnancy in 174 women abusing narcotics, managed by a specialist team from a drug-dependency antenatal clinic. These women were cared for through 182 pregnancies of greater than 20 weeks' gestation, resulting in 183 live and 5 stillbirths. The majority of patients were enrolled in a methadone programme and stabilized on the drug before the third trimester. The group was characterized by a high prevalence of previous obstetric and medical problems. The most common antenatal complications were preterm labour (24%) and anaemia (12%). Preterm delivery and small-for-gestational-age each occurred in a quarter of pregnancies. The mean birth-weight for the group was 2,746 g +/- 721 g; mean +/- S.D. Eight perinatal deaths occurred (5 stillbirths, 3 neonatal deaths), giving a perinatal mortality rate of 43/1,000. The data on narcotic abusers have been compared with similar data obtained from randomly selected public antenatal clinic patients who delivered during the same period.

Adolescent↗

Antagonism of stimulation-produced analgesia by naloxone, a narcotic antagonist.

Analgesia produced by focal electrical stimulation of the brain is partially reversed by the narcotic antagonist naloxone. The absence of complete reversal does not appear to be caused by inadequate doses of naloxone since doses higher than 1 milligram per kilogram of body weight did not increase the antagonism. It is suggested that stimulation-produced analgesia may result, at least in part, from release of an endogenous, narcotic-like substance, such as that recently reported by other investigators.

Analgesia↗

Narcotic analgesia: fentanyl reduces the intensity but not the unpleasantness of painful tooth pulp sensations.

Forty subjects rated the magnitude of painful electrical stimulation of tooth pulp before and after the intravenous administration of either fentanyl, a short-acting narcotic, or a saline placebo. The responses were choices of verbal descriptors from randomized lists of either sensory intensity (that is, weak, mild, intense) or unpleasantness (annoying, unpleasant, distressing) descriptors. The fentanyl significantly reduced the sensory intensity without reducing the unpleasantness of the tooth pulp stimuli, indicating that the mechanisms of narcotic analgesia may include a significant attenuation in pain sensation in addition to effects on pain reaction. These results stress the importance of using multiple measures of pain.

Dental Pulp↗

Conditioned narcotic withdrawal in humans.

Subjective and physiological manifestations of the narcotic withdrawal syndrome were produced as a conditioned response. Withdrawal reactions precipitated by the narcotic antagonist naloxone in methadone-dependent volunteers were the unconditioned response. These data support clinical anecdotes of withdrawal symptoms occurring in former addicts when they return to their drug-related environment.

Adult↗