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A comparison of the acute behavioral effects of inhaled amyl, ethyl, and butyl acetate in mice.

The acute neurobehavioral effects of three acetates (amyl, ethyl, and n-butyl acetate) were investigated after 20-min inhalation exposures in mice using locomotor activity and a functional observational battery (FOB). Ethyl and n-butyl acetate produced significant decreases in locomotor activity at the highest concentrations examined, while amyl acetate was without effect. Minimally effective concentrations for activity-decreasing effects were 2000 ppm for ethyl acetate and 8000 ppm for n-butyl acetate. The potency order was similar in the FOB where ethyl acetate was more potent in disrupting the neurobehavioral measures. The FOB profile of effects for all three acetates included changes in posture, decreased arousal, increased tonic/clonic movements, disturbances in gait, delayed righting reflexes, and increased sensorimotor reactivity. Furthermore, handling-induced convulsions were produced in some mice acutely exposed to each of these acetates. Recovery from the acute effects of these acetates was rapid and began within minutes of removal from the exposure chamber. The acetates produced a profile of neurobehavioral effects that were different from those reported for depressant solvents (i.e., toluene, 1,1,1-trichloroethane) that are subject to abuse. Evidence is emerging for qualitative differences in the acute neurobehavioral effects of various volatile chemicals.

Acetates↗

Halothane potentiates the effect of methamphetamine and nomifensine on extracellular dopamine levels in rat striatum: a microdialysis study.

Brain microdialysis was used to study the in vivo release and metabolism of dopamine (DA) in the rat striatum during halothane anaesthesia. Concentrations were measured in microdialysates collected every 20 min and applied directly to an on-line high-performance liquid chromatograph. Halothane was administered at concentrations of 0.5, 1.0, 1.5 and 2.0%. In another series of experiments, rats were treated intraperitoneally or locally with methamphetamine, a drug of abuse, or with nomifensine, a dopamine uptake blocker and antidepressant, in combination with 0.5 or 1.5% halothane. Halothane anaesthesia did not affect the dialysate (extracellular) concentration of DA at 2.0%. By contrast, the concentrations of DA metabolites [3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] increased during inhaled halothane anaesthesia in a dose-dependent manner and recovered after anaesthesia. Halothane potentiated the ability of methamphetamine to increase the extracellular concentration of DA when administered systemically, whereas only a small increase in DA accumulation was seen when methamphetamine was administered locally via the perfusate. Similarly, the increase in extracellular DA was accentuated by systemic nomifensine during halothane anaesthesia, but no obvious enhancement was observed when it was applied locally. It has been shown that the neurotoxic effect of methamphetamine is mediated by the suboxidation of DA released from the cytoplasm into the extracellular space and transformed into highly reactive free radicals. On the basis of our results, it is suggested that care should be exercised when halothane anaesthesia is used in patients abusing phenylethylamines (amphetamines) or being treated with DA uptake blockers (nomifensine).

Analysis of Variance↗

Pulmonary hypertension and foreign body granulomas in intravenous drug abusers. Documentation by cardiac catheterization and lung biopsy.

In this report we confirm the presence of pulmonary hypertension by cardiac catheterization in four intravenous drug abusers with biopsy-documented foreign body granulomas in the pulmonary vessels and interstitium. Each patient had a history of intravenous injections of alpha-sympathomimetic agents obtained from nasal inhalers. There agents may have contributed to the disease by constricting small vessels when simultaneously injected foreign bodies were passing through the vasculature of the lung. The severity of the pulmonary hypertension correlated well with the decrease in single breath diffusing capacity in each case. Pulmonary hypertension may contribute significantly to the increased morbidity and mortality observed in intravenous drug users.

Adult↗

Heroin smoking by "chasing the dragon" in young opiate users in Ireland: stability and associations with use to "come down" off "Ecstasy".

We explored the frequency of commencing opiate use by "chasing the dragon" to "come down" off Ecstasy and the stability of heroin smoking in young opiate takers by assessing 102 subjects in Dublin using a semistructured interview. Ninety-two subjects had used Ecstasy. Of these, 68 reported "chasing" to "come down" off Ecstasy at some point in their history and were found to have used Ecstasy more frequently and in larger amounts. Thirty-six reported that their first experience of using opiates was to "come down" off Ecstasy, 28 citing this as their main reason for commencement.Eighty-six of the 102 commenced opiates by "chasing" heroin, 61 of whom progressed to injecting after a mean of 2.9 years. This was associated with starting illicit drug use earlier, starting heroin earlier, and a history of using Ecstasy. Implications for service planners in developing responses to illicit drug use among adolescents are discussed.

Administration, Inhalation↗

Self-administration behavior is maintained by the psychoactive ingredient of marijuana in squirrel monkeys.

Many attempts to obtain reliable self-administration behavior by laboratory animals with delta-9-tetrahydrocannabinol (THC), the psychoactive ingredient in marijuana, have been unsuccessful. Because self-administration behavior has been demonstrated in laboratory animals for almost all other psychoactive drugs abused by humans, as well as for nicotine, the psychoactive ingredient in tobacco, these studies would seem to indicate that marijuana has less potential for abuse. Here we show persistent intravenous self-administration behavior by monkeys for doses of THC lower than doses used in previous studies, but comparable to doses in marijuana smoke inhaled by humans.

Animals↗

Psychological, social and health behaviour risk factors for deaths certified as asthma: a national case-control study.

BACKGROUND: Uncontrolled studies suggest that psychosocial factors and health behaviour may be important in asthma death. METHODS: A community based case-control study of 533 cases, comprising 78% of all asthma deaths under age 65 years and 533 hospital controls individually matched for age, district and asthma admission date corresponding to date of death was undertaken in seven regions of Britain (1994-98). Data were extracted blind from anonymised copies of primary care records for the previous 5 years and non-blind for the earlier period. RESULTS: 60% of cases and 63% of controls were female. The median age in both groups was 53. Cases had an earlier age of asthma onset, more chronic obstructive lung disease, and were more obese. 48% of cases and 42% of controls had a health behaviour problem; repeated non-attendance/poor inhaler technique was related to increased risk of death. Overall, 85% and 86%, respectively, had a psychosocial problem. Four psychosocial factors were associated with increased risk of death (psychosis, alcohol/drug abuse, financial/employment problems, learning difficulties) and two with reduced risk (anxiety/prescription of antidepressant drugs and sexual problems). While alcohol/drug abuse lost significance after adjustment for psychosis, other associations appeared independent of each other and of indicators of severity and co-morbidity. None of the remaining 13 factors including family problems, domestic abuse, bereavement, and social isolation were significantly related to risk of asthma death. CONCLUSION: There was an apparently high burden of psychosocial problems in both cases and controls. The associations between health behaviour, psychosocial factors, and asthma death are varied and complex with a limited number of factors showing positive relationships.

Adolescent↗

Alcohol, tobacco, and other drug use among rural/small town and urban youth: a secondary analysis of the monitoring the future data set.

OBJECTIVES: This study compared prevalence of substance use among high school seniors in rural and urban areas from 1976 through 1992. METHODS: We used data collected for these years from urban (n = 75,916) and rural (n = 51,182) high school seniors. Thirty-day prevalence for alcohol, cigarettes, marijuana, cocaine, LSD, and inhalant use, binge drinking, smoking a pack or more of cigarettes a day, and daily alcohol and marijuana use were evaluated. RESULTS: Substance use declined from 1976 through 1992. In 1976, urban students had greater prevalence for most substances, but by 1992, rural and urban students were similar, with rural students having higher prevalence for alcohol and cigarette use (particularly excessive use). Trends were similar for both sexes, though rural girls showed a later catch-up to use levels of urban girls. CONCLUSIONS: Rural students are currently at risk approximately equal to that of urban students. Other studies have demonstrated the association of substance use with increased morbidity and mortality. Policy alterations and health education programs should address this pattern in the nation's rural areas.

Administration, Inhalation↗

The continuing problem of youthful solvent abuse in New York State.

The major finding in the comparison of surveys of New York State secondary school students is the increasing use of solvents in this population over time. What in 1974-75 seemed to be limited use, by 1983 was found to be of widespread use. Very much like the survey of 1974-75 and the findings in the literature, age of first use together with the recentness of use appears to cluster in the preteens or the early teen years and tapers off during the teen years. Of interest is the fact that, along with the general upward rate of use over the surveys, those 18 years or older also show an upward trend. Some evidence in the recent literature indicates that adults, too, are found to have a problem with inhalants. Similar to the 1974-75 survey, but unlike findings in the literature, males and females continue to show similar rates of solvent use. Although males do generally surpass females in these use rates, the differences are usually not significant. In light of the literature on solvent abuse among Hispanic youth, the 1978 and 1983 surveys indicated mixed findings. Hispanic students in New York City consistently showed intermediate levels of solvent use; whereas, in 1983, Hispanic students residing in areas of the state outside of New York City showed excessive rates of solvent use. To the extent that the problem of acculturation among poor Hispanic youth may contribute to solvent abuse, an explanation may be found in the contrasts between living in New York City and living in the rest of the State. In New York City, which has an extremely large Hispanic population (about 20 percent of the population), feelings of isolation and cultural distance may not be so profound. In the rest of the state, where the proportion of Hispanics is quite small (about 2 percent of the population), these cultural problems may be more of a factor. Reasons, however, for the extraordinary increase in solvent use among those Hispanic youth, specifically between 1978 and 1983, are difficult to offer. Again, very similar to the 1974-75 findings, the 1978 and 1983 surveys found a strong relationship between solvent use and poor academic performance. Furthermore, the early findings relating to solvent use to a lack of family cohesion was supported by the 1978 survey where comparable information was gathered. The pattern of drug-using or polydrug use found among solvent users in the 1974-75 survey was underscored by the findings in the subsequent surveys.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation↗

Acute activation of circulating polymorphonuclear neutrophils following in vivo administration of cocaine. A potential etiology for pulmonary injury.

Crack cocaine has become a major drug of abuse in the United States and its use is associated with a broad spectrum of pulmonary complications. The present study was conducted to determine whether controlled in vivo administration of cocaine (inhaled or IV) alters the function of circulating inflammatory cells in a manner capable of contributing to acute lung injury. Subjects who regularly smoked crack cocaine were asked to abstain from illicit drug use for at least 8 h, and were then administered one of the following treatments on each of 4 study days: inhaled cocaine base (45 mg), inhaled placebo (4.5 mg cocaine base, a subphysiologic dose), IV cocaine HCl (0.35 to 0.50 mg/kg), or IV placebo (saline solution). Samples of blood were obtained from a peripheral venous catheter and blood cells were isolated before and 10 to 45 min after treatment. The administration of either cocaine base or cocaine HCl, but not their corresponding placebos, resulted in the activation of circulating polymorphonuclear neutrophils (PMNs). Exposure to cocaine in vivo enhanced the antibacterial activity of PMNs, as measured by their ability to kill Staphylococcus aureus. Antitumor activity, as measured in an antibody-dependent cell-mediated cytotoxicity assay, also increased following short-term administration of cocaine. Finally, short-term exposure to cocaine enhanced production of interleukin 8, a potent PMN chemoattractant and neutrophil-activating factor associated with both acute and chronic lung injury. These studies demonstrate that short-term in vivo exposure to cocaine activates the effector function and cytokine production of circulating PMNs. Therefore, it is possible that bursts of acute inflammatory activity resulting from crack use could contribute to lung injury.

Administration, Inhalation↗

[Heroin abuse among Danish prisoners on remand. I. Prevalence related to form of administration].

Two groups of Danish prisoners on remand (in solitary confinement and not in solitary confinement) were examined by interview on reception (n = 133 & n = 95) in order to evaluate the prevalence and form of administration of opioid abuse/dependence. About 50% had abused opioids during their lifetime; one third were dependent at the time of reception. Twenty percent of opioid dependent prisoners administered opioids by smoking. More intravenous users were treated with methadone before and during imprisonment than those who were dependent on smoking opioids. Few were objectively suffering from withdrawal symptoms. The psycho-social impact of dependence on smoking heroin and intravenous heroin one month prior to imprisonment was at the same level and substantial as measured by the Global Assessment Scale.

Administration, Inhalation↗

An unusual cause of chronic cough. Foreign body aspiration.

Foreign body aspiration (FBA) is a serious medical problem, causing thousands of deaths nationally each year. Clinical presentations range from acute suffocation and death to chronic and subtle respiratory symptoms. Although FBA is more common in children, adult patients are also at risk. We present a classic case of FBA in an adult male with a history of alcohol abuse and chronic cough.

Alcoholism↗

Dilated cardiomyopathy and cocaine abuse. Report of two cases.

Two young patients with dilated cardiomyopathies associated with long-term use of cocaine are described. A 42-year-old male cocaine abuser with normal coronary arteries experienced recurrent myocardial infarction, with development of a dilated, globally hypocontractile left ventricle. The second patient, a 28-year-old woman with a prominent history of inhaling vaporized cocaine ("free-basing"), presented with symptoms and signs of biventricular heart failure and was found to have a dilated cardiomyopathy. The clinical spectrum of cocaine cardiotoxicity is reviewed, and pathophysiologic mechanisms of cocaine-induced cardiomyopathy are discussed. Long-term cocaine use may cause dilated cardiomyopathy and recurrent myocardial infarction, even in the absence of atherosclerotic epicardial coronary artery disease.

Adult↗

Longitudinal surveys of prevalence rates and use patterns of illicit drugs at selected high-prevalence areas in China from 1993 to 2000.

AIMS: To identify the prevalence, patterns and trends of illicit drug use in the general population of selected high-prevalence areas in China between 1993 and 2000. DESIGN, SETTING AND PARTICIPANTS: Cluster sampling was employed and the Epidemiological Inventory for Illicit Drug Use (EIIDU) used as survey instrument. In 1993, 1996 and 2000, 56 792, 67 319 and 53 747 individuals aged 15 or above in community were interviewed, respectively, at the three time-points. MEASUREMENTS: Demographics and drug-related data were collected and the prevalence patterns of illicit drug are described. FINDINGS: The life-time prevalences of illicit drug use in the three consecutive surveys in 1993, 1996 and 2000 were 1.08, 1.60 and 1.52%, respectively, and the 1-year prevalence rates were 0.91, 1.17 and 1.17%, respectively. Heroin was the first choice for drug use (51.8% in 1993, 83.4% in 1993 and 95.9% in 2000). The two most frequent routes of drug administration were inhalation (89.2% in 1993, 60.1% in 1996 and 93.5% in 2000) and intravenous injection (27.2% in 1993, 31.0% in 1996 and 25.7% in 2000). CONCLUSION: At least for the time being, illicit drug use may have plateaued in these selected high-prevalence areas.

Administration, Inhalation↗

Propofol withdrawal syndrome in an adult patient with thermal injury.

A 48-year-old man with a history of ethanol abuse and bipolar disease fell asleep while smoking in an intoxicated state. The patient received a 30% total body surface area burn involving his face and upper torso that resulted in an inhalation injury. Several attempts at weaning from mechanical ventilation failed due to his extreme agitation, which was unresponsive to benzodiazepines, opiates, and antipsychotic agents. Propofol therapy was begun in combination with valproic acid, fluoxetine, and risperidone to assist in the treatment of his severe agitation associated with the bipolar disease, inhibiting ventilatory weaning. Repeated attempts to discontinue propofol were associated with withdrawal symptoms such as severe agitation, tremors, tachycardia, tachypnea, and hyperpyrexia. His symptoms resolved only after each time the propofol infusion was restarted. The patient received propofol for 95 days for management of his agitation before dying from refractory septic shock and multiple organ failure.

Bipolar Disorder↗

[Cocaine toxicity].

The paper presented the effects of cocaine on the human, particularly toxic effects induced by chronic use of cocaine. It was demonstrated that the toxic effects depend on the mode of administration (oral, nasal, intravenous, inhaled) of various forms of cocaine (cocaine hydrochloride and cocaine base, i.e. crack).

Administration, Inhalation↗

The association between sniffing inhalants and injecting drugs.

There is evidence that the use of inhalants might prove to be a modifiable risk factor for intravenous (IV) drug use, or possibly an important vulnerability marker. However, this evidence has come from studies using samples of convenience, such as a mixture of psychiatric patients, felons, and their relatives. If there is a link between these two different forms of drug-using behaviors, then a statistical association should be found in epidemiologic studies with rigorous sampling procedures--even after statistical adjustment for plausible confounding variables such as sex, age, socioeconomic status, and the use of drugs such as marijuana. To probe this suspected causal association, we analyzed epidemiologic data from the 1990 National Household Survey on Drug Abuse sponsored by the National Institute on Drug Abuse. The population for this survey consisted of all household residents aged 12 years and older in the conterminous United States, with respondents selected by probability sampling. A total of 9,259 respondents completed the confidential self-report interview conducted by trained interviewers; 192 persons reported a history of injecting drugs for nonmedical reasons (e.g., to get high), and 9,067 reported never injecting drugs. As hypothesized, inhalant use was found to be associated with injecting drugs (relative odds [RO] = 11.8). After adjustment for sex, age, race, socioeconomic status, and use of marijuana, inhalant users still were 5.35 times more likely than nonusers to have injected drugs (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗