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At least 757 records · Page 42Linked to original sources
PubMed1986

Correlation between acetone-potentiated CCl4-induced liver injury and blood concentrations after inhalation or oral administration.

In studies of acetone-potentiated liver injury induced by haloalkanes, acetone is usually given by gavage, whereas industrial exposure to acetone normally occurs by inhalation. It was of interest to verify if the route of administration influences the potentiation. Male Sprague-Dawley rats were exposed for 4 hr to acetone vapors or treated orally with acetone; the minimal effective dose (MED) levels for potentiating CCl4-induced liver injury were estimated to be 2500 ppm and 0.25 ml/kg, respectively. Groups were treated with acetone using 0.4, 1, 2, 4, or 6 times the MED. Half of each group was killed at various time intervals after treatment for blood acetone measurements by gas chromatography; the other half was challenged with CCl4 (0.1 ml/kg, ip) 18 hr after acetone, and killed 24 hr later. Plasma alanine aminotransferase (ALT) activity and bilirubin concentrations were measured. Inhalation and oral administration of acetone both potentiated CCl4 toxicity. Rats exposed repetitively to acetone vapors (10 daily exposures) and subsequently challenged with CCl4 exhibited liver toxicity that was not significantly different from that of rats subjected to a single exposure. Correlations between ALT activities and maximal blood acetone concentrations were found to be linear (positive) and significant for both routes. For a given blood acetone concentration, however, toxicity was least severe following acetone exposure by inhalation. When the concept of threshold concentrations was applied to the data, the severity of the toxic response was dependent on the blood acetone concentration above the threshold, irrespective of the route of administration.

Acetone↗
PubMed1988

Chromosomal abnormalities and sister-chromatid exchange in bone marrow cells of mice and Chinese hamsters after inhalation and intraperitoneal administration. II. Cyclophosphamide.

The genotoxic effects of cyclophosphamide (CPP), a human and animal carcinogen requiring metabolic activation, were studied in bone marrow cells of mice and Chinese hamsters, analyzing chromosome abnormalities (CA) and sister-chromatid exchange (SCE) after a 2-h inhalation or a single intraperitoneal administration. In order to compare the genotoxicity after the different routes of administration in the dose range of 10-110 mg CPP/kg body weight, the systemic dose obtained by inhalation was calculated from blood concentrations and the inhalation duration after an analysis of the CPP blood kinetics. In NMRI mice the frequency of bone marrow cells with chromosome abnormalities was higher after aerosol exposure than after intraperitoneal administration of comparable CPP doses. In Chinese hamsters the CA frequency was similar with both exposure routes. Inhaled CPP was found to induce a higher frequency of CA and SCE in the bone marrow cells of mice compared to those of Chinese hamsters. The findings suggest that for genotoxins requiring metabolic activation species differences exist with respect to the influence of the route of entry and the sensitivity of bone marrow cells.

Aerosols↗
PubMed2004

Fatal intoxication as a consequence of intranasal administration (snorting) or pulmonary inhalation (smoking) of heroin.

In recent years we have noticed an increasing proportion of mortalities resulting from an overdose of heroin that involve routes of administration other than injection. Of 239 cases of fatal heroin intoxication examined at our department during the period 1997-2000, 18 deaths were associated with non-parental administration. Seven of these fatalities were experienced heroin users who had begun to use more sporadically, seven were recreational "party-users", while the remaining four persons had relapsed into heroin use following long periods of abstinence. The median blood morphine concentration of these non-injectors was 0.095 microg/g (range: 0.02-0.67 microg/g), significantly lower than that of the injectors. Concurrent use of alcohol, other illicit drugs and/or pharmaceutical preparations was observed in 17 of the 18 cases. However, there were no statistically significant differences between the victims of heroin intoxication by injection or by other routes with respect to the proportion who had simultaneously consumed alcohol or benzodiazepines. Pathological alterations like lung fibrosis, liver cirrhosis, endocarditis, etc. were not found to play a significant role in any of the 18 mortalities. We conclude that snorting or smoking heroin probably involves a reduced risk of obtaining high blood concentrations of morphine but still constitutes a considerable risk of lethal outcome due to high variability in blood concentrations. Furthermore, decreased tolerance resulting from periods of reduced or sporadic use appears to be an important risk factor in connection with heroin overdosing by snorting or smoking, which indicate that some heroin addicts may inaccurately assume that these routes of administration are safe when resuming their use of heroin after a period of abstinence.

Administration, Inhalation↗
PubMed2002

Two administration methods for inhaled salbutamol in intubated patients.

AIMS: To compare serum concentrations and effects on respiratory mechanics and haemodynamics of salbutamol administered by small volume nebuliser (SVN) and metered dose inhaler (MDI) plus spacer. METHODS: Blinded, randomised, crossover study in 12 intubated infants and children (mean age 17.8 months) receiving inhaled salbutamol therapy. Subjects received salbutamol as 0.15 mg/kg by SVN and four puffs (400 microg) by MDI plus spacer at a four hour interval in random order. Passive respiratory mechanics were measured by a single breath/single occlusion technique, and serum salbutamol concentrations by liquid chromatography-mass spectrometry at 30 minutes, 1, 2, and 4 hours after each dose. Haemodynamics (heart rate and blood pressure) were recorded at each measurement time. RESULTS: There was no difference in percentage change in respiratory mechanics or haemodynamics between the two methods of administration. Mean area under the curve (AUC(0-4)) was 5.86 for MDI plus spacer versus 4.93 ng/ml x h for SVN. CONCLUSIONS: Serum concentrations and effects on respiratory mechanics and haemodynamics of salbutamol were comparable with the two administration methods under the conditions studied. Future studies are needed to determine the most effective and safe combination of dose and administration method of inhaled salbutamol in mechanically ventilated infants and children.

Albuterol↗
PubMed1995

Comparison of two administration techniques of inhaled nitric oxide on nitrogen dioxide production.

The purpose of this study was to verify whether, compared with the introduction of the NO-N2 mixture at the air inlet of the ventilator (classical method), a direct injection of NO-N2 into the inspiratory line of the ventilator circuit with a new injection device (new method), would reduce NO2 formation by reducing contact time between O2 and NO. The effect of two FIO2(0.21 and 0.90) and NO concentrations on NO2 production was determined. In the classical method, NO and O2 were mixed with an air/oxygen blender before the gas mixture entered the ventilator. In the new method, NO was injected directly into the respiratory line with the injection system. Nitric oxide and nitrogen dioxide gases were measured using a chemiluminescence analyzer. For a FI02 of 0.90 and 90 ppm of NO2, the amount of NO2 produced was decreased from 8.9 +/- 0.8 ppm (mean +/- SD) with the classical injection system to 4.4 +/- 0.2 ppm with the new injection system (P = 0.0039, Mann-Whitney test), and NO2 production was decreased from 4.5 +/-0.2 ppm to 2.1 +/- 0.4 ppm (P = 0.02) at 60 ppm of NO. However, at a FIO2, no difference was found in the amount of NO2 produced. We conclude that, compared with the classical method of NO administration, the new NO injection system reduces considerably the concentration of inhaled NO2 when a high FIO2 and a high concentration of NO are used.

Administration, Inhalation↗
PubMed1977

Toluene concentrations in various tissues of rats after inhalation and oral administration.

The uptake, distribution, and elimination of 3H-toluene in various tissues of rats were studied after inhalation or after gastric intubation. The maximum radioactivity was measured 2--3 h after gastric intubation in tissues, except in white adipose tissue, where the peak radioactivity was reached at 5 h. After inhalation exposure, the uptake to various tissues was very rapid. The maximum radioactivity in most tissues was reached in 15--30 min. The accumulation was slowest in white adipose tissue, where it took 1--2 h. The radioactivity in tissues decreased after inhalation exposure more rapidly than after gastric intubation. Brown adipose tissue and white adipose tissue were different from other tissues in their ability to retain toluene. Twenty-four hours after exposures, only 1% or less of the initial radioactivity was found in tissues other than white adipose tissue, in which the corresponding value was 3.5--5%. The results show a very rapid absorption and distribution of toluene after inhalation and a retention of radioactivity in white adipose tissue. After oral ingestion the distribution showed a similar but much slower pattern.

Adipose Tissue↗
PubMed2006

Similar recovery from bispectral index-titrated isoflurane and sevoflurane anesthesia after outpatient gynecological surgery.

STUDY OBJECTIVE: To test the hypothesis that the recovery of gynecological day-case patients is equally fast after isoflurane and sevoflurane anesthesia, when administration of the inhaled agent is adjusted by monitoring the bispectral index (BIS). DESIGN: Prospective, randomized, controlled, single-blinded clinical study. SETTING: University-affiliated women's hospital. PATIENTS: 120 adult female patients, ASA physical status I or II, scheduled for ambulatory surgery under general anesthesia. INTERVENTIONS: Patients were randomized to receive either isoflurane or sevoflurane as the maintenance anesthetic. BIS values were titrated to remain between 50 and 60 during the maintenance of anesthesia by adjusting the inspired concentration of the inhaled agent. Administration of the inhaled agent was discontinued abruptly at the end of the procedure. MEASUREMENTS: The times to achieving several recovery end points were recorded. The main outcome parameter was the time to home-readiness. In the postoperative care unit, sedation was evaluated with the digit-symbol substitution test. The degree of pain and nausea was evaluated on the visual analog scale. MAIN RESULTS: There were no statistically significant differences in the times to home-readiness, or in any other parameters of early or intermediate recovery between the 2 groups. The degrees of sedation, pain, and nausea in the postoperative care unit were similar in the 2 groups. CONCLUSIONS: Isoflurane and sevoflurane are equally acceptable maintenance anesthetics in terms of the speed and quality of recovery in gynecological ambulatory surgery patients when the dose of the inhaled agent is adjusted to achieve a BIS between 50 and 60.

Adult↗
PubMed1985

Inhalation therapy. Oxygen administration, humidification, and aerosol therapy.

In addition to receiving treatment for the primary disease, patients with advanced respiratory disorders may benefit from other forms of respiratory support. This article discusses three techniques of inhalation therapy that will aid in maintaining an optimal pulmonary environment and in normalizing arterial oxygenation. The role of aerosol therapy in direct intrapulmonary administration of pharmaceuticals is also discussed.

Adrenal Cortex Hormones↗
PubMed2002

Safety, tolerability and acceptability of two dry powder inhalers in the administration of budesonide in steroid-treated asthmatic patients.

The purpose of this randomized, double-blind parallel group study was to compare the safety, tolerability and acceptability of Easyhaler and Turbuhaler dry powder inhalers for the delivery of budesonide 800 microg day(-1) in adult asthmatic patients who had already been treated with inhaled corticosteroids for at least 6 months prior to the study Additionally the efficacy of the products was evaluated. The main objective was to evaluate the systemic safety of budesonide inhaled from Easyhaler (Giona Easyhaler, Orion Pharma, Finland) as determined by serum and urine cortisol measurements. The secondary objective was to compare the tolerability acceptability and efficacy of the two devices in the administration of budesonide. After a 2-week run-in period (baseline), patients were randomized on a 2:1 basis to receive budesonide from Easyhaler (n = 103) or from Turbuhaler (Pulmicort Turbuhaler, AstraZeneca, Sweden) (n = 58) 200 g dose(-1), two inhalations twice daily for 12 weeks. There was no statistically significant change in morning serum cortisol values from baseline to the end of treatment in either group. Urine free cortisol and urine cortisol/ creatinine ratio increased from baseline in both groups. There were no significant differences between the groups in terms of morning serum cortisol, urine cortisol, adverse events or efficacy variables, but Easyhaler was generally considered more acceptable to the patients. In conclusion, at 800 microg day(-1), Giona Easyhaler is as safe and efficacious as Pulmicort Turbuhaler in adult asthmatic patients previously treated with corticosteroids, but more acceptable to patients.

Adult↗