RESUMEN
The maintenance of adequate hemodialysis vascular access is frequently complicated in the patient with polytetrafluoroethylene (PTFE) A-V hemodialysis grafts by venous anastomotic stenosis. This stenosis is caused by neointimal hyperplasia (NIH), a response to vascular injury. In this study, the authors prospectively analyzed the effect of a short-term regimen consisting of administration of two medications, heparin and low molecular weight dextran, on the development of NIH at the venous anastomosis in 79 patients with PTFE A-V hemodialysis grafts. In addition, they evaluated other parameters' effects on the development of NIH. In comparison with control subjects, heparin had some effect in minimizing the development of NIH in the PTFE grafts when evaluated radiologically at 3 months, although this effect was not statistically significant. Low molecular weight dextran, however, had no trend or statistically significant effect on this venous anastomotic narrowing. Interestingly, patient age, use of calcium channel blockers, and presence of diabetes mellitus (DM) all appeared to affect the development of NIH. Increasing age and use of calcium channel blockers was associated with decreased development of NIH; conversely, DM was associated with worsened NIH. In evaluation of access survival (time to first access failure), degree of venous anastomosis stenosis at 3 months was not predictive. Patient time on dialysis pre graft placement was the only measured parameter related to access failure. The method of dialysis pre graft placement (hemodialysis versus peritoneal dialysis) was not a significant factor in early access failure. Pharmacologic treatment of venous anastomotic narrowing in PTFE hemodialysis grafts due to NIH continues to be difficult. Short-term treatment with the tested medication failed to statistically affect NIH. Patient age, use of calcium channel blockers, and presence of DM were all factors in the development of NIH. Of measured parameters, time on dialysis pre graft placement was the only factor correlated with early access failure. In future treatment regimens, one should consider more prolonged treatment. In addition, noted risk factors should be considered when determining type of renal replacement therapy.
Asunto(s)
Anticoagulantes/uso terapéutico , Anastomosis Arteriovenosa/fisiopatología , Catéteres de Permanencia/normas , Endotelio Vascular/patología , Fibrinolíticos/uso terapéutico , Diálisis Renal/normas , Adulto , Anciano , Envejecimiento/metabolismo , Análisis de Varianza , Anticoagulantes/administración & dosificación , Anticoagulantes/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Catéteres de Permanencia/efectos adversos , Constricción Patológica/etiología , Constricción Patológica/fisiopatología , Constricción Patológica/prevención & control , Dextranos/administración & dosificación , Dextranos/farmacología , Dextranos/uso terapéutico , Diabetes Mellitus/fisiopatología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/lesiones , Femenino , Fibrinolíticos/administración & dosificación , Fibrinolíticos/farmacología , Heparina/administración & dosificación , Heparina/farmacología , Heparina/uso terapéutico , Humanos , Hiperplasia/complicaciones , Hiperplasia/fisiopatología , Hiperplasia/prevención & control , Trasplante de Riñón , Modelos Lineales , Masculino , Persona de Mediana Edad , Peso Molecular , Politetrafluoroetileno/efectos adversos , Diálisis Renal/efectos adversos , Factores de Riesgo , Resultado del TratamientoRESUMEN
After one adaptation night, the sleep of seven male nondependent opiate addicts was studied following intramuscular cyclazocine (0.125; 0.25; 0.50 mg/70 kg) or placebo at weekly intervals in a randomized double-blind crossover design. Drug effects were measured on sleep stages and several episodic phenomena. Cyclazocine caused dose-related increases in sleep latency, REMS latency, percent spindle sleep, and a marked increase over placebo in wakefulness, drowsiness, and shifts in sleep-waking states. Cyclazocine produced a dose-related decrease in all measures of delta sleep, and some measures of REMS, and a marked decrease below placebo of sleep efficiency and total REMS. All doses of cyclazocine caused sustained periods of waking with little muscle tension. Cyclazocine (0.5mg) consistently caused urination during periods of extended arousal; urination has not been seen after morphine or other opioids of the mu type. These studies indicate that cyclazocine has effects on human sleep which are in some ways similar and other ways dissimilar to morphine type analgesics. The results are consistent with the concept that cyclazocine is a mixed agonist-antagonist of the opioid type with agonist actions at the kappa receptor.
Asunto(s)
Ciclazocina/efectos adversos , Trastornos Relacionados con Opioides/rehabilitación , Trastornos del Sueño-Vigilia/inducido químicamente , Adulto , Nivel de Alerta/efectos de los fármacos , Diuresis/efectos de los fármacos , Método Doble Ciego , Humanos , Masculino , Persona de Mediana Edad , Receptores Adrenérgicos/efectos de los fármacos , Receptores Opioides/efectos de los fármacos , Receptores Opioides kappaRESUMEN
Methadone was investigated to see if it induced an insomnia comparable to that after single doses of morphine. After one adaptation night, the sleep of seven male nondependent opiate addicts was studied after intramuscular methadone (7.5, 15, or 30 mg/70 kg), morphine (10 or 20 mg/70 kg), and placebo at weekly intervals in a randomized double-blind crossover design. Drug effects were measured on several sleep and wakefulness patterns. Methadone is equipotent to morphine in its increase of wakefulness, drowsiness, muscle tension, shifts in sleep-waking state, and latency to rapid eye movement sleep (REMS) and its decrease of sleep efficiency, delta sleep, and REMS. This similarity of methadone to morphine in acute arousal from sleep is in contrast to the differences between these two drugs during long-term administration, when morphine induces a small but persistent arousal and methadone does not.
Asunto(s)
Nivel de Alerta/efectos de los fármacos , Metadona/farmacología , Morfina/farmacología , Sueño/efectos de los fármacos , Adulto , Método Doble Ciego , Humanos , Masculino , Persona de Mediana Edad , Contracción Muscular/efectos de los fármacos , Trastornos Relacionados con Opioides , Distribución Aleatoria , Trastornos del Inicio y del Mantenimiento del Sueño/inducido químicamente , Factores de TiempoRESUMEN
1 This study was performed because dose-related effects of heroin on human sleep had not been described previously, and to discover if heroin produces a morphine-like insomnia. 2 After three adaptation nights, the sleep of seven male nondependent opiate addicts was studied following i.m. doses of heroin (3, 6, 12 mg/70 kg), morphine (10, 20 mg/70 kg) or placebo at weekly intervals in a randomized double-blind crossover design. 3 Heroin produces a dose-related increase in wakefulness, drowsiness episodes, muscle tension, and shifts in sleep-waking states. 4 Heroin produces a dose-related decrease in total sleep, sleep efficiency, delta sleep and REM sleep (REMS). 5 Heroin is about twice as potent as morphine in producing this type of insomnia. 6 'Morphine insomnia' appears to be a characteristic initial effect of several opioids, at least in nondependent opiate addicts, and might serve as a model insomnia for evaluation of hypnotics.
Asunto(s)
Heroína/farmacología , Trastornos Relacionados con Opioides/fisiopatología , Trastornos del Inicio y del Mantenimiento del Sueño/inducido químicamente , Adulto , Nivel de Alerta/efectos de los fármacos , Humanos , Masculino , Morfina/farmacología , Sueño REM/efectos de los fármacosRESUMEN
Defeated and Joyless scales were developed from a questionnaire given to 54 normal, 53 alcoholic, and 28 opiate addict subjects. The Defeated scale differentiates the alcoholics and addicts from normals but not from each other, whereas the Joyless scale differentiates addicts from both alcoholics and normals. When shown to 48 college students, a film about poverty increased the Joyless score, as well as other measures, but had little effect on the Defeated score. These scales appear to distinguish between self-concept (Defeated) and mood (Joyless) components of hypophoria, an affective disorder hypothesized to be associated with drug abuse.
Asunto(s)
Síntomas Afectivos/psicología , Alcoholismo/psicología , Trastornos Relacionados con Opioides/psicología , Adulto , Euforia , Humanos , Masculino , Persona de Mediana Edad , Pruebas PsicológicasAsunto(s)
Narcóticos/metabolismo , Síndrome de Abstinencia a Sustancias/fisiopatología , Administración Oral , Animales , Biotransformación , Peso Corporal/efectos de los fármacos , Codeína/metabolismo , Remoción de Radical Alquila , Dextropropoxifeno/metabolismo , Perros , Cobayas , Humanos , Inyecciones Subcutáneas , Levorfanol/metabolismo , Meperidina/metabolismo , Acetato de Metadil/metabolismo , Morfina/metabolismo , Narcóticos/administración & dosificación , Narcóticos/farmacología , Conejos , Ratas , Trastornos Relacionados con Sustancias/etiología , Factores de TiempoRESUMEN
After one adaptation night, intramuscular doses of methadone (7.5, 15, 30 mg/70 kg), morphine (10 or 20 mg/70 kg), or placebo were given to seven male nondependent opiate addicts at weekly intervals in a randomized cross-over design. After three adaptation nights, heroin (3, 6, 12 mg/70 kg) was compared with morphine and placebo by means of a similar design in seven other subjects. Using electroencephalogram (EEG) bisector analysis, tape recordings of sleep were analyzed for two beta, three alpha, three theta, and two delta EEG patterns, as well as for detections of sleep spindles, K-complexes, eye movements, body movements, average electromyogram (EMG), and calculation of seven sleep-waking stages. All three opioids produce a dose-related arousal: they increase EMG and EEG measures of muscle activity, as well as body movements and EEG alpha, while decreasing EEG theta and spindling. These opioids also increase measures of waking state and decrease measures of spindle sleep and REM sleep. Although the 1974 version of the EEG bisector analysis is not exactly comparable to visual analysis, in this design it defined significant drug effects on sleep and EEG. Distinctive bisector analysis patterns are positively correlated with each sleep--waking stage.
Asunto(s)
Dependencia de Heroína/psicología , Metadona/uso terapéutico , Dependencia de Morfina/psicología , Fases del Sueño/efectos de los fármacos , Adulto , Nivel de Alerta/efectos de los fármacos , Computadores , Relación Dosis-Respuesta a Droga , Electroencefalografía/instrumentación , Humanos , Masculino , Persona de Mediana Edad , Sueño REM/efectos de los fármacos , Vigilia/efectos de los fármacosRESUMEN
When an opioid capable of forming active metabolites is administered, the total pharmacology is the result of interactions of the opioid and such metabolites, especially normetabolites. Normetabolites may affect the morphine-like characteristics of certain opioids and thus influence their reinforcement in animals and man. Most opioids, when administered in single doses, are positively reinforcing in addicts. Oral administration, as compared with parenteral, facilitates the formation of normetabolites. When chronically administered, many opioids, including acetylmethadol, meperidine, morphine, codeine, propoxyphene, and levorphanol, show evidence of a longer half-life for their normetabolites. Normetabolites may have aversive characteristics and thus impair positive reinforcement of the parent drug in animals and man. For example, addicts do not like chronic oral morphine or chronic oral codeine. Conversely, methadone, the normetabolites of which are inactive, is well accepted during chronic oral administration. Drugs which inhibit N-demethylation will increase the agonist potency of opioids having inactive normetabolites (e.g., methadone) but will decrease the agonist potency of opioids having more potent normetabolites than the parent (e.g., acetylmethadol). The divergent responses of addicts to single doses of opiates as compared with chronic doses indicate that chronic addiction tests in man are needed befored relative abuse liability can be predicted.
Asunto(s)
Narcóticos/farmacología , Refuerzo en Psicología , Animales , Remoción de Radical Alquila , Dextropropoxifeno/administración & dosificación , Perros , Haplorrinos , Dependencia de Heroína/psicología , Humanos , Metadona/administración & dosificación , Metiltransferasas/antagonistas & inhibidores , Dependencia de Morfina/psicología , Nalorfina/administración & dosificación , Narcóticos/administración & dosificación , Narcóticos/metabolismo , Pupila/efectos de los fármacos , Autoadministración , Especificidad de la Especie , Factores de TiempoRESUMEN
Effects of intravenous infusions of LSD (3.75, 7.5, 15 microgram/kg over 5 min; crossover N = 4) and tryptamine (0.04, 0.08, 0.12 mg/kg/min for 150 min; crossover N = 6) were compared to saline in intact cats through observation of five sleep/waking patterns. Electrocorticogram (ECoG) was analyzed for frequency band indices and mean amplitude and frequency. LSD increases wakefulness and drowsiness and decreases spindle sleep and rapid eye movement (REM) sleep during the first 75 min (period 1). The increase in active wakefulness and decrease in REM sleep persist during period 2, with an increase in spindle sleep thereafter. LSD increases delta index and ECoG amplitude, with a decrease in ECoG frequency; these effects peaked in period 2. Tryptamine increases wakefulness and drowsiness during period 1, with decreases in spindle sleep and REM sleep. The increase in quiet wakefulness and decrease in REM sleep persist during period 2, but no significant tryptamine effect is seen in sleep/waking patterns after infusion ceases. ECoG frequency increases during tryptamine infusion (periods 1 and 2), while ECoG amplitude increases during periods 2 and 3. Thus LSD and tryptamine both increase wakefulness, decrease spindle sleep, and decrease REM sleep.
Asunto(s)
Electroencefalografía , Dietilamida del Ácido Lisérgico/farmacología , Sueño/efectos de los fármacos , Triptaminas/farmacología , Vigilia/efectos de los fármacos , Animales , Gatos , Masculino , Sueño REM/efectos de los fármacos , Factores de TiempoRESUMEN
The sleep of 6 opiate addicts was studied for 11 nights during 3 phases of a chronic morphine cycle. The control phase consisted of 5 consecutive nights before morphine administration. The induction phase consisted of 1 night at 21-36 days after the onset of morphine administration, when the daily dose was 140-220 mg. The stable dose phase consisted of 5 consecutive nights after the subjects had received 240 mg of morphine daily for 8-19 weeks. No sleep could be studied during the withdrawal phase. Sleep was continuously monitored with EEG, EMG and EOG. Chronic morphine produces signs of a small but persistent sleep disturbance: delta sleep (early night) becomes less stable and shifts toward later in the night, waking state increases during the middle of the night, RME sleep (expecially its activated EEG without eye movements) decreases, the RMES cycle increases, and burst of delta activity (with mean duration of 5-6 sec) increase. Although this disturbance persists throughout the night, it is much less than that seen after single doses of morphine in a previous study. With chronic morphine, therefore, partial tolerance develops to the sleep disturbance produced by morphine. The small but persistent nocturnal arousal during chronic morphine contrasts with the sedation seen during chronic methadone. Both opioids produce an increase in delta bursts during chronic administration, which might be an EEG phenomenon specific to chronic opioid intake.
Asunto(s)
Dependencia de Morfina/fisiopatología , Morfina/farmacología , Sueño/efectos de los fármacos , Adulto , Ritmo alfa , Nivel de Alerta/efectos de los fármacos , Ritmo Delta , Tolerancia a Medicamentos , Humanos , Masculino , Metadona/farmacología , Morfina/administración & dosificación , Fases del Sueño/efectos de los fármacos , Sueño REM/efectos de los fármacos , Síndrome de Abstinencia a SustanciasRESUMEN
The effects of oral methadone on EEG and sleep were studied in 6 male postaddicts. Continuous nocturnal measurement of EEG, EMG and EOG was used to define sleep patterns. Period analysis and power spectral analysis were performed on each 8 min sample of daytime (eyes closed) EEG. Both sleep and EEG were studied during a predrug control period, during the methadone induction phase (45-60 mg/day), stabilization phase (100 mg/day), and then 6; 10, 13, 18 and 22 weeks after withdrawal. One subject did not complete the last two withdrawal sessions. While on methadone, subjects reported that they slept more and also showed an increase in slow wave activity and a decrease in fast wave activity of their EEG during this time. Nocturnal sleep was not markedly altered during the chronic administration of methadone. Subjects reported an increase in dreaming soon after withdrawal, and then 3-5 weeks of nocturnal isnomnia. At the 6th week after withdrawal, slow wave activity in the daytime EEG was decreased, fast wave activity was increased, and mean EEG frequency was increased. REM sleep and delta sleep were increased during withdrawal. These data provide further evidence that chronic administration of narcotic analgesics may induce persistent functional changes in the central nervous system.