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Narcotic analgesics are the most effective oral agents available for treatment of acute pain. A familiarity with the salient characteristics of the various agents enables physicians to choose the most effective one for use in the outpatient setting.
The properties of the giant axon of the squid Loligo pealii were studied at different hydrostatic pressures from 14.7 to 16,000 psi. At 4000 psi the resting potential, the membrane resistance, membrane capacity, the conduction velocity, the amplitude of the action potential, and the maximal change in the membrane impedance during activity were only slightly affected. At the same pressure the duration of the falling phase of the action potential was increased by about 40 to 60 per cent and the duration of the rising phase by about 20 to 35 per cent. The duration of the membrane impedance change during activity was increased by 50 to 100 per cent at 4000 psi. At pressures even slightly above atmospheric the threshold membrane current was appreciably reduced. At about 3000 to 7000 psi the fiber fired spontaneously. At pressures considerably above 5000 psi the membrane resistance decreased to about one-half to one-third the original value. The narcotizing effect upon the nerve fiber of 3 to 7 per cent ethanol was partly or almost completely opposed by low temperatures or high pressures.
The protection of workers from the potential harmful effects of active pharmaceutical ingredients (APIs) poses a significant challenge for the drug manufacturing industry. The actual pathways through which pharmaceutical production workers are exposed to potent drugs and the processes resulting in actual uptake are up till now virtually unknown. In this study, a detailed exposure assessment survey was conducted in a pharmaceutical 'primary manufacturing' production facility during which environmental and biological exposure monitoring for potent opioid narcotic drugs was performed. On the occasion of multiple consecutive production days, personal half-shift air samples were collected and hand wipes were taken at the end of each half-shift and analysed for fentanyl. All environmental samples showed detectable amounts of fentanyl (>0.1 ng per sample), indicating a potential for both inhalation and dermal exposure. Spatial distribution of fentanyl dermal contamination was further investigated by means of patch samplers placed on five anatomical regions of the body. Body locations showing the highest level of fentanyl contamination were identified as the hands, the neck and lower arms. The effective uptake of fentanyl was demonstrated by the detection of this opioid in urine samples of the workers involved. Individual and group-level analysis of combined external and internal fentanyl exposure measures revealed a positive and significant correlation between fentanyl hand exposure and urinary excretion, while it seemed that the effect of inhalation exposure was largely due to its correlation with dermal exposure. The results of the established individual linear and mixed effects models strongly suggest that in most workers the dermal pathway is actually the primary route of fentanyl exposure.
It has been shown in both mice and rats that the LD50 value for doxapram is reduced in rodents treated with narcotic analgesics. In both species the site of the toxic interaction appears to be the cardiovascular system. Doxapram alone, in sub-lethal doses, appears to cause conduction defects in the heart and this action of doxapram is increased in rodents treated with morphine. The enhancement of the toxicity of doxapram by morphine appears to involve an action in the central nervous system probably not related to respiratory depression.
The changing microbiology of bacteremia among narcotic addicts in Detroit raised concerns about current presumptive antimicrobial therapy. In a one-year study of incidence, microbiology, sites, and risk factors, 180 bacteremic addicts (15% of addict-related admissions) were followed prospectively. Cases of bacteremia were caused by methicillin-sensitive Staphylococcus aureus (33%), methicillin-resistant S. aureus (MRSA, 24%), streptococci (20%), mixed organisms (11%), Pseudomonas aeruginosa (9%), and miscellaneous other single organisms (3%). Endocarditis (41%) and abscess or cellulitis (34%) were usually found. Multivariate analysis of host factors and addiction habits yielded results predictive of bacterial species but not of infection sites. Previous hospitalization, long-term addiction, and nonprescribed antibiotic use were associated with MRSA acquisition (odds ratio, 8.6:1). All addicts with polymicrobial or P. aeruginosa bacteremia abused pentazocine and tripelennamine (P = .05). Many of the addicts with streptococcal bacteremia were women who did not abuse antibiotics (odds ratio, 20.7:1). Physicians inappropriately prescribed empiric antibiotics for 67 of 72 addicts with MRSA, P. aeruginosa, or polymicrobial infection. The results of regression analysis suggest that, guided by the patient's history, the physician can prescribe appropriate empiric antimicrobial therapy for bacteremia in the febrile addict in Detroit.
Administration of the narcotic antagonist naloxone results in an elevation of serum luteinizing hormone (LH) levels in 10-day-old female, but not male, rats. Previous studies from this laboratory indicated a role for neonatal gonadal steroids in the development of this sex-specific response. In this study, the estrogen receptor antagonist OH-Tamoxifen or the androgen-receptor antagonist flutamide were injected on Days 1 or 9 of life, and the LH responses of male and female pups to naloxone were assessed on Day 10. Flutamide did not produce a response different from that seen in vehicle-treated pups, discounting a role for androgen receptors. OH-Tamoxifen on Day 9 caused an increase in basal levels of LH; neither sex showed a response to naloxone. However, OH-Tamoxifen treatment of 1-day-old males resulted in an enhanced release of LH upon challenge with naloxone on Day 10 of life; similar treatment of 1-day-old females resulted in a normal female-type response to the opioid antagonist. These results show that blockade of estrogen receptors in males during the "critical period" of sexual differentiation results in a female phenotypic response to naloxone. Therefore, estrogen receptors play a critical role in the sexual differentiation of the LH response to naloxone in neonatal male rats.
The effects of fentanyl and sufentanil with and without N2O on left ventricular myocardium supplied by a critically narrowed and a normal coronary artery were studied in 16 dogs. Regional ventricular function was measured by recording ventricular segment length with the use of ultrasonic length detectors in the left anterior descending (LAD) and the left circumflex (LC) coronary artery territories before and during critical stenosis of the LAD. Critical stenosis was documented by the absence of a hyperemic response following a 10-s total occlusion of the LAD. Hemodynamic variables (aortic flow and pressure, left ventricular pressure, heart rate, and coronary blood flow) were measured and the first derivative of left ventricular pressure (LVdP/dt) and coronary perfusion pressure derived. Eight dogs received fentanyl 100 micrograms X kg-1 followed by an infusion of 1 microgram X kg-1 X min-1 while ventilated with O2:N2 (1:2), and eight dogs received sufentanil 30 micrograms X kg-1 with an infusion of 0.3 micrograms X kg-1 X min-1. Replacement of N2 with N2O produced evidence of mild systolic myocardial depression but no dysfunction in either group. After application of the critical constriction, the addition of N2O rapidly produced evidence of dysfunction with significant postsystolic shortening only in the LAD territory. This was not accompanied by hypotension or a decrease in coronary flow and was not always reversible. Higher infusion rates of either narcotic (fentanyl 2 micrograms X kg-1 X min-1, 4 micrograms X kg-1 X min-1; sufentanil 0.6 micrograms X kg-1 X min-1, 1.2 micrograms X kg-1 X min-1) in the absence of N2O did not produce dysfunction but had no protective effect when N2O was added.(ABSTRACT TRUNCATED AT 250 WORDS)
The profound analgesic properties of intrathecal narcotics without motor blockade make them an excellent choice for pain relief during the first stage of labor. Recent studies have attempted to define more clearly the pharmacology of commonly used agents. In this review we shall outline some of these advances and discuss their impact on labor.
OBJECTIVE: To examine differences in the incidence and spectrum of diseases, as well as duration of inpatient stay, between HIV-seronegative and HIV-seropositive narcotic drug, users (NDU). DESIGN: Retrospective analysis of 9 years of experience. Data collection by chart review using preset criteria for diagnoses. Estimation of hospital admission densities by assuming a dynamic but stable population of 2000 NDU (with a mean HIV-seroprevalence of 25%) throughout the study period. PATIENTS: Comprising 314 HIV-seronegative NDU. 217 HIV-seropositive NDU, and 10 NDU with admissions registered in either group (from a total of 1011 admissions). RESULTS: The overall admission incidence density was 35 and 120 per 1000 person-years among HIV-seronegative NDU and HIV-seropositive NDU, respectively [risk ratio (RR) 3.5, 95% confidence interval (CI) 3.2-3.7]. Compared with seronegative NDU, HIV-seropositive NDU were more frequently admitted for various non-opportunistic infections (RR 7.2, 95% CI 6.1-8.4), including pneumonia (RR 10.9, 95% CI 7.6-16.6), tuberculosis (RR 30.0, 95% CI 3.6-233.8), soft-tissue infections (RR 3.5, 95% CI 1.7-7.2), osteoarticular infections (RR 6.0, 95% CI 1.5-23.9), endocarditis (RR 5.3, 95% CI 1.5-17.9), and various other infections (RR 5.8, 95% CI 3.2-10.5). HIV-seropositive NDU were also more frequently admitted for non-infectious medical complications (RR 2.3, 95% CI 1.8-3.0). Seronegative NDU had a shorter median inpatient stay (2 versus 9 days, P < 0.00001). HIV infection accounted for an estimated excess burden of at least 2700 inpatient care days in 9 years among the 500 local HIV-seropositive NDU. CONCLUSIONS: Among NDU, HIV infection adds considerable excess burden in terms of severe complications needing inpatient care.
Children with femur fractures can have severe pain after elastic nail fixation. The purpose of this paper is to test the effectiveness of an intraoperative hematoma block in controlling postoperative pain in children that underwent elastic nail fixation of isolated femur fractures. We compared 13 children who received an intraoperative bupivacaine hematoma block after elastic nail fixation of a femur fracture with a concurrent control group of 22 children with similar femur fractures that did not receive a hematoma block. The time to first narcotic dose after surgery was over 5 hours later in the hematoma block group versus the control group (P =.008). The hematoma block did not significantly lengthen the time of surgery. This study demonstrates that an intra-operative hematoma block is a simple, quick and effective method of postoperative pain control after elastic femoral nailing in children.
The purpose of this study was to determine the effect of one dose of a common narcotic-based pain reliever (Vicodin) on a battery of oral sensitivity tests across time in women. Fifteen Caucasian women randomly were given an oral dose of 10 mg of hydrocodone/1000 mg of acetaminophen or placebo in a double-blind, cross-over design. At baseline (before drug) and after 2, 4, and 8 h each subject was evaluated for sensitivity thresholds with four tests around an experimental tooth: (a) electric pulp tester applied to exposed root; (b) electric pulp tester on adjacent mucosa; (c) increasing probe pressure (grams) on adjacent mucosa; and (d) decreasing cold probe (degrees C) on the exposed root. The outcomes of all tests were not statistically different between drug and placebo treatments at any time point (p > 0.05). These results suggest that a systemic dose of hydrocodone/acetaminophen has little impact on healthy pulp or mucosa sensitivity in women as measured by common diagnostic tests.
In a 54-month retrospective review, we compared the clinical features of 26 narcotic addicts with staphylococcal endocarditis (group 1) and ten other addicts with nonstaphylococcal endocarditis (group 2). The admission temperature and the respiratory rate of patients in group 1 were significantly higher (P less thn .05 and less than .02 respectively) than those of patients in group 2. Group 1 also differed from group 2 in the following variables: (1) bilateral multiple pulmonary infiltrates in 46% vs none in group 2; (2) greater incidence of symptoms referable to the central nervous system (50% vs none in group 2); and (3) gastrointestinal symptoms of vomiting, diarrhea, or constipation in 62% vs 10% in group 2. Serious cardiovascular, renal, and other complications were more frequent in staphylococcal endocarditis. Tricuspid regurgitation occurred with equal frequency in both groups and was of no value in differentiating staphylococcal from nonstaphylococcal endocarditis.
Hyperamylasemia after narcotic administration is found in some patients. To determine the source of the amylase, serum isoamylases were separated by column chromatography in a group of patients with response to a Prostigmin-morphine challenge. The increment of amylase activity was pancreatic amylase.
Alfentanyl is a new narcotic analgesic with a rapid onset and very short duration of effect, and a potency about one third of that of fentanyl. The respiratory effects of 1.6, 3.2 and 6.4 micrograms/kg Alfentanyl were studied in a randomised controlled trial in five volunteers. Alfentanyl 6.4 micrograms/kg induced a significant increase in respiration at 1 minute, then significant depression of mean minute volume 3 and 4 minutes after slow intravenous injection, compared with saline control, and pre-injection values. Mean end-expired carbon dioxide concentration was increased after Alfentanyl 6.4 micrograms/kg, significantly from 2 to 9 min after injection, and highly significantly at 3, 4 and 5 minutes. Examination of the effect on expired CO2 concentration at 4 minutes reveals a highly significant dose-response relationship with the three doses of Alfentanyl. The transient effect of ALfentanyl was confirmed by the fact that no change in mean ventilatory response to carbon dioxide was demonstrable 30 or 50 minutes after any dose. When Alfentanyl was given 1 minute before testing the ventilatory response to carbon dioxide the response curves showed a highly significant dose-related shift to the right. There were no significant changes in heart rate or blood pressure after Alfentanyl, but the drug produces the typical subjective effects of the opiates.
A case of central nervous system depression which developed 7 hours after an intrathecal injection of 4 mg of morphine is described. The patient lapsed into coma with bradypnoea and "pin-point' pupils and there was no response to naloxone 0.4 mg. Treatment was continued for 3 hours. No postoperative analgesics were required for 126 hours. The problems associated with the use of intrathecal opiates are reviewed, delay in onset being the usual feature. Use of hyperbaric solutions of the narcotic and maintenance of a head-up posture may protect against respiratory depression.
A case report of biliary colic induced by narcotic premedication and reversed by naloxone administration is described and the literature reviewed.
1. Running activity and brain levorphanol concentration were measured in nontolerant and tolerant mice given various doses of (3)H-levorphanol.2. The principal factor responsible for tolerance in the mouse is a loss of sensitivity to the narcotic drug at the cellular level in brain; despite adequate brain concentrations, the pharmacological effects are diminished or absent.3. There is also metabolic tolerance; a given dose establishes a lower brain concentration in tolerant than in non-tolerant animals.4. The two kinds of tolerance are distinguished here and the contribution of each is assessed.
1 The activity pattern of analogues of the enkephalins was determined in four parallel assays, the inhibition of the electrically evoked contraction of the guinea-pig ileum and mouse vas deferens at 36 degrees C and the inhibition of [(3)H]-naltrexone and [(3)H]-leucine-enkephalin binding at 0 to 4 degrees C in homogenates of guinea-pig brain.2 The activity pattern was best characterized by the ratio of the potency in the guinea-pig ileum to that in the mouse vas deferens (G.p.i./M.v.d.) and the ratio of the potency in inhibiting [(3)H]-naltrexone binding to that in inhibiting [(3)H]-leucine-enkephalin binding (Nal/Leu).3 The enkephalins had low G.p.i./M.v.d. (0.02 to 0.09) and low Nal/Leu (0.05 to 0.18) ratios whereas the corresponding values for morphine were 7.0 and 7.5.4 Analogues obtained by substituting D-Ala for Gly(2) and D-Met or D-Leu for L-Met(5) or L-Leu(5) showed only minor changes in G.p.i./M.v.d. (0.01 to 0.11) and in Nal/Leu (0.06 to 0.13) ratios.5 Analogues in which resistance to enzymatic degradation was brought about by amidation of the C-terminal carboxylic group or methylation of the amino group of tyrosine or both modifications, had G.p.i./M.v.d. ratios of 1.2 to 5.5 and Nal/Leu ratios of 0.5 to 21. High values (2.1 and 3.4) were found for the potent antinociceptive analogue of Sandoz, Tyr-D-Ala-Gly-NCH(3)Phe-Met(O)-ol.6 In the mouse vas deferens, some of the analogues with high G.p.i./M.v.d. and Nal/Leu ratios were tested for antagonism by naloxone and found to require less than the high concentration needed for the natural enkephalins. C57/BL mice, which have a lowered sensitivity to morphine but a normal response to peptides with low G.p.i./M.v.d. and Nal/Leu ratios, had a lowered sensitivity to analogues with high ratios.7 In the alkaloid-like series of narcotic analgesic drugs, ketobemidone, levorphanol, methadone, etorphine and the antagonist Mr 2266 had lower Nal/Leu ratios (1.0 to 2.8) than morphine, normorphine, naloxone and naltrexone (8 to 12).8 It would appear that compounds with low G.p.i./M.v.d. and Nal/Leu ratios interact mainly with delta-receptors in the brain and peripheral nervous system while compounds with high ratios interact mainly with mu-receptors. For antinociceptive action mu-receptors may be more important than delta-receptors.