Background: 2-chloroprocaine (2-CP) used for lumbar epidural anesthesia (LEA) reportedly decreases the efficacy of epidural morphine (EM) administered for post-cesarean section (CS) analgesia. The amount of supplemental i.v. morphine self-administered by the patient via the patient-controlled analgesia device (PCA) is used to study the interaction between EM and 2-CP. Methods: Forty-two patients scheduled for elective CS were randomly divided into 3 equal groups, and received 2-CP, 2-CP+epinephrine (Epi, 5 μg ml-1) or 2% lidocaine (Lido) with Epi for LEA. All patients received 5 mg EM and i.v. PCA morphine for postoperative pain. Cumulative amount of i.v. morphine used in the first 24 hours as well as the amount of the drug used during each 2-h period were noted. Nonparametric analysis of variance and Chi-squared analysis were used for statistical comparisons. Results: The mean cumulative 24-h i.v. PCA morphine requirement in the 2-CP, 2-CP+Epi and Lido+Epi groups respectively was 20.5±24, 33.1.5±27 and 4.07±6.3 (mean±SD). The Lido+Epi group used significantly less morphine ( P = 0.01) compared to either of the 2-CP groups with no significant difference between the 2-CP groups. The maximum i.v. PCA morphine use occurred in the first 4 hours following surgery in all three groups. Conclusion: Analgesic efficacy of EM is decreased when 2-CP is used for LEA compared to when Lido+Epi is used. 相似文献
Studies have shown that both food deprivation and response cost have important influences on the magnitude of self-administration of a wide variety of psychoactive drugs. In an attempt to extend these findings to the smoked route of drug self-administration, the effects of food allotment and fixed-ratio (FR) value were evaluated in four male rhesus monkeys trained to smoke cocaine base. In the first phase of the experiment, monkeys were trained to self-administer smoked cocaine base under a chained progressive-ratio (PR), fixed-ratio (FR) schedule during daily experimental sessions. Monkeys were required to make 20 lever-press responses and then five inhalations on a smoking spout to obtain the first smoke delivery. The lever ratio then increased to 60, 140, 300, 620, 1260, 2540, and 4940 for each successive smoke delivery. The initial lever ratio value was reset to 20 at the beginning of each daily session. The body weights of three monkeys were determined under free-feeding conditions. Monkeys were then restricted to 100 g food and, when body weights had stabilized, the daily food allotment was increased to 150 g, approximately 210 g, or greater than 400 g (satiation). As the daily food allotment and body weight increased, the mean number of smoke deliveries decreased in two of three monkeys. In the second phase of the experiment, three monkeys were maintained under either food-satiated or food-restricted conditions. Body weights were maintained at approximately 90% of their free-feeding weights under food-restricted conditions. The cost of the drug (lever FR value) was constant within each experimental session, but was increased after 3 consecutive days of stable responding. Fixed-ratio values were increased from 128 to 256, 512, 1024, and 2048. Monkeys were required to complete the lever FR value and then to make five inhalations on the smoking spout to gain access to 1.0 mg/kg per delivery cocaine base. The mean number of smoke deliveries increased at FR 256, 512, and 1024 when monkeys were food-restricted as opposed to food-satiated. Correspondingly, the mean number of responses increased under food-restricted conditions. Responding continued to increase over a wider range of FR values, and the peak number of responses was higher under food-restricted, as opposed to food-satiated conditions. These results, using the smoking route of administration, are consistent with the hypothesis that food deprivation increases the self-administration of reinforcing drugs. 相似文献
Recombinant human deoxyribonuclease I (rhDNase) is a new therapeutic agent developed to improve clearance of purulent sputum from the human airways. It is delivered by inhalation. Four jet nebulizers, T Up-Draft II (Hudson), Customized Respirgard II (Marquest), Acorn II (Marquest), and Airlife Misty (Baxter), were evaluated in vitro for their ability to deliver aerosols of rhDNase. The aerosols were generated from 2.5-mL aqueous solutions of rhDNase, at concentrations of either 1 or 4 mg/mL. In all experiments, the Pulmo-Aide Compressor (De Vilbiss) was used to supply the air to the nebulizers. Between 20 and 28% of the rhDNase dose initially placed in the nebulizers was delivered to the mouthpiece in the respirable range (1-6 µm). Evaluation of the rhDNase following nebulization in all four devices indicated that there was no loss in enzymatic activity and no increase in aggregation. Circular dichroism spectrophotometry indicated there was no change in either the secondary or the tertiary structure in rhDNase following nebulization. These results show that all four nebulizers are essentially equivalent in their ability to deliver respirable doses of rhDNase in an intact, fully active form. Changing the concentration of the solution in the nebulizer from 4 to 1 mg/mL rhDNase leads to a proportional reduction in the respirable dose delivered to the mouthpiece. 相似文献
1. The pharmacokinetics of Dalal-peptide T-NH2 (peptide T) was determined during phase I clinical trials in patients with acquired immunodeficiecy disease (AIDS) and AIDS related complex (ARC). Drug levels were determined by specific RIA, and in some cases with HPLC analysis, after intraveneous (i.v.) or intranasal (i.n.), via metered sprayer, administration.
2. The plasma kinetics appeared to be bi-phasic with a first compartment half-life of 30 to 60 minutes and a second plasma clearence rate of 4 to 6 hours, observed for both routes of administration. Peptide T, in one individual was confirmed to be present at 6 hrs in plasma, determined after HPLC isolation followed by specific RIA.
3. Bioavailabilty, determined for a 2 mg test dose in six individuals was 9.3 ± 6.9 nmol/L. Peak plasma levels of 41 ± 30 nmol/L after 10 mg i.n., 2.8 ± 5.9 nmol/L after 2mg i.n., and 0.13 ± 0.07 nmol/L after 0.4 mg i.n. were observed. In two individuals tested, peptide T was detected in CSF at levels 20% of the corresponding plasma level 90 and 145 minutes post i.v. administration. Peptide T was not detected in urine. I.N. administration was well tolerated for times up to 21 months. 相似文献