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PubMed1994

T cell functions are impaired by inhaled isobutyl nitrite through a T-independent mechanism.

Isobutyl nitrite is representative of a group of inhalants abused by male homosexuals and adolescents. Inhalation exposure of mice to isobutyl nitrite at 900 ppm for 45 min per day for 14 days caused serious deficits in T cell-mediated immune responses. Cytotoxic T lymphocyte (CTL) activity was reduced by 36% following the exposure. T cell proliferative responses to mitogenic and allogeneic stimulation were reduced by 37% and 51%, respectively. The exposure did not directly alter the ability of cells to synthesize or respond to IL-2. Accessory cell function in facilitating T cell activation was inhibited by about 50% following exposure to the inhalant.

Administration, Inhalation↗
PubMed1999

Toluene inhalation induced epididymal sperm dysfunction in rats.

Toluene is a widely abused inhaled solvent. This study was designed to determine whether toluene abuse affects the reproductive functions or general health of males. Seven-week-old male Sprague-Dawley rats were exposed to toluene vapor inhalation (0, 4000, or 6000 ppm; 2 h/day) daily for 5 weeks. Exposure-related suppression of body weight gain and food consumption were observed. Salivation and lacrimation were observed during exposure periods and intensified with repeated exposure. Rats exposed to 6000 ppm toluene had decreased spleen and thymus weights, as well as suppressed lymphocyte counts. In 6000 ppm group, the epididymal sperm counts, sperm motility, sperm quality and in vitro penetrating ability to zona-free hamster eggs were significantly reduced, while no exposure-related changes in the testes weight or spermatogenesis within testes were detected. Tail-less sperm heads were seen within zona-free eggs incubated with sperm from rats exposed to 6000 ppm toluene, but not control rats. No significant changes were observed in serum luteinizing hormone, follicle-stimulating hormone, or testosterone levels following 1 month of exposure to 6000 ppm toluene. These results indicate that high concentrations of toluene may directly target sperm in the epididymis and disrupt sperm maturation.

Animals↗
PubMed2006

Abuse of proprietary (over-the-counter) drugs.

A predominantly overlooked type of substance abuse by adolescents and young adults in the United States and around the world is the abuse of medications and other products sold without a prescription, or over-the-counter (OTC), to the public. OTC substance abuse causes significant morbidity and mortality, and there are concerns that some types of OTC substance abuse are increasing. Regular office screening for inhalant abuse and other substance abuse and health risk behaviors must be part of standard pediatric care. This article discusses what is known about the extent and clinical impact of OTC substance abuse and reviews key points about recognition, detection, and management.

Humans↗
PubMed2006

Developmental toxicity of prenatal exposure to toluene.

Organic solvents have become ubiquitous in our environment and are essential for industry. Many women of reproductive age are increasingly exposed to solvents such as toluene in occupational settings (ie, long-term, low-concentration exposures) or through inhalant abuse (eg, episodic, binge exposures to high concentrations). The risk for teratogenic outcome is much less with low to moderate occupational solvent exposure compared with the greater potential for adverse pregnancy outcomes, developmental delays, and neurobehavioral problems in children born to women exposed to high concentrations of abused organic solvents such as toluene, 1,1,1-trichloroethane, xylenes, and nitrous oxide. Yet the teratogenic effects of abuse patterns of exposure to toluene and other inhalants remain understudied. We briefly review how animal models can aid substantially in clarifying the developmental risk of exposure to solvents for adverse biobehavioral outcomes following abuse patterns of use and in the absence of associated health problems and co-drug abuse (eg, alcohol). Our studies also begin to establish the importance of dose (concentration) and critical perinatal periods of exposure to specific outcomes. The present results with our clinically relevant animal model of repeated, brief, high-concentration binge prenatal toluene exposure demonstrate the dose-dependent effect of toluene on prenatal development, early postnatal maturation, spontaneous exploration, and amphetamine-induced locomotor activity. The results imply that abuse patterns of toluene exposure may be more deleterious than typical occupational exposure on fetal development and suggest that animal models are effective in studying the mechanisms and risk factors of organic solvent teratogenicity.

Animals↗
PubMedDate not supplied

MR imaging of "spray heads": toluene abuse via aerosol paint inhalation.

PURPOSE: Three male patients with a history of spray-paint inhalation are presented. METHODS: Spin-echo MR was used to evaluate the central nervous system changes secondary to toluene inhalation delivered via spray-paint fumes. RESULTS: The remarkable findings included the loss of cerebral and cerebellar gray-white matter discrimination, scattered multifocal deep white matter lesions, and gross generalized atrophy of the cerebrum, the cerebellum, and the corpus callosum. CONCLUSION: Although the observed changes are nonspecific, combined with a positive history the diagnosis of inhalation toluene abuse can be made on the basis of consistent MR findings.

Adult↗
PubMed1979

Inhalant, marijuana, and alcohol abuse among barrio children and adolescents.

Prevalence of inhalant, marijuana, and alcohol abuse was studied in a sample of 457 male and female Mexican-American children and adolescents between the ages of 9 and 17 years. Subjects interviewed resided in four housing projects located in East Los Angeles. All interviews were conducted by adolescents who resided in the same housing projects. Results indicated that compared to a national sample, Mexican-American adolescents were at least 14 times more likely to be currently abusing inhalants. The prevalence rate of marijuana was double the national rate, but the prevalence of alcohol was equal to that found nationally. Reasons for elevated substance abuse rates are explored.

Adolescent↗
PubMedDate not supplied

Social and legal factors related to drug abuse in the United States and Japan.

This article is an overview of social and legal differences in the United States and in Japan that are related to patterns of current drug abuse epidemics in these countries. These two nations have drug abuse problems with different histories and take different approaches currently to handling illicit drug marketing and use. Histories of opiate and cocaine abuse in the United States and of stimulant and inhalant abuse in Japan are discussed. The United States has experienced three heroin epidemics in the last three decades; cocaine addiction began to merit national concern by the end of the 1980s. In Japan, the first methamphetamine epidemic began after World War II; it was controlled in the 1950s. The current inhalant epidemic began in the late 1960s and was followed by the second methamphetamine epidemic that began in 1970; both are continuing to the present. The criminal justice system is always given first consideration when assessing societal measures employed to reduce drug use. Legal penalties for illicit drug offenses reflect the societal differences of these two nations with respect to the seriousness of particular types of crimes. Characteristics of the health care system of a nation may also influence patterns of drug abuse, particularly where functions of criminal justice and health care systems overlap. Health care systems in the United States and in Japan are based on different treatment philosophies and patients' expectations; these differences are discussed along with explanations of their potential influence on the epidemiology of drug abuse.

Attitude to Health↗
PubMed1999

Oral frostbite injury from intentional abuse of a fluorinated hydrocarbon.

BACKGROUND: A serious but rarely reported complication of halogenated hydrocarbon inhalation abuse is severe mucosal frostbite. CASE REPORT: A 16-year-old male attempted to "get high" by inhaling airbrush propellant which contained 1,1-difluoroethane (CAS #75-376). The patient lost consciousness and upon awakening his lips and tongue were frozen. He suffered first- and second-degree burns of the larynx with vocal cord involvement and first-degree burns of the trachea, main stem bronchi, and esophagus. The oral cavity had second- and third-degree burns which required debridement. CONCLUSION: This case demonstrates the unusual but severe damage that can occur with the abuse of fluorinated hydrocarbons.

Adolescent↗
PubMed2003

Inhaled drugs of abuse enhance serotonin-3 receptor function.

Despite the prevalence of their use, little is currently known of the molecular mechanisms of action of inhaled drugs of abuse. Recent studies have shown effects on NMDA, GABA(A) and glycine receptors in vitro, suggesting that inhalants may exert at least some of their pharmacological effects on ligand-gated ion channels. Enhancement of serotonin-3 receptor function has been shown to play a role in the reinforcing properties of drugs of abuse. We tested the hypothesis that the commonly abused inhaled agents 1,1,1-trichloroethane, trichloroethylene, and toluene enhance serotonin-3 receptor function. All three inhalants significantly and reversibly potentiated, in a dose-dependent manner, serotonin-activated currents mediated by mouse serotonin-3A receptors expressed in Xenopus oocytes. Our findings add the serotonin-3 receptor to the growing list of molecular targets commonly affected by both inhalants and classic CNS depressants such as ethanol and the volatile anesthetics.

Animals↗
PubMed1988

Calcium oxalate retinopathy associated with methoxyflurane abuse.

A 34-year-old woman developed a crystalline retinopathy after 2 years of inhalational abuse of methoxyflurane. After the woman developed renal failure, a renal biopsy showed multiple birefringent crystals in the renal tubular lumens, epithelial cells, and interstitium compatible with calcium oxalate. Multiple bright yellow-white crystals were deposited throughout the retina and at the level of the retinal pigment epithelium with a retinal arterial and periarterial predilection. This is the first reported case of methoxyflurane abuse with secondary hyperoxaluria in which there was a widespread retinal distribution of crystalline deposits, especially along the retinal arteries and arterioles.

Acute Kidney Injury↗
PubMed1993

Disorders of spinal cord, nerve, and muscle.

Substance abuse may lead to acute or chronic injuries to the spinal cord or PNS in addition to injuries caused by trauma and infection. The most widespread of these conditions are the chronic myopathy and chronic peripheral neuropathy of alcoholism. Less common, but more striking, illnesses attributed to substance abuse include ATM, a subacute myeloradiculoneuropathy resembling combined systems disease, Guillain-Barré syndrome, plexitis, fulminant axonal neuropathy, and acute myoglobinuria with or without severe weakness. If the cause of such syndromes is not otherwise evident, careful probing may reveal a possible causal substance abuse history. Publicity about an imputed association may sometimes (as in inhalant abuse) change the behavior of persons at risk and prevent more cases.

Central Nervous System Agents↗
PubMedDate not supplied

Neurobehavioral consequences of intermittent prenatal exposure to high concentrations of toluene.

The effects of several concentrations of toluene on physical and behavioral development were examined in CD-1 mice prenatally exposed during the last week of gestation. Pregnant mice were exposed to either 200, 400, or 2000 ppm toluene (TOL) for 60 min three times a day during gestational days 12-17. A sham group was exposed concurrently to filtered air. No group differences were observed in maternal weight gain or food consumption, common measures of maternal toxicity. Initial litter characteristics including gestation length, number of litters delivered, and litter size were also similar. At birth, mean initial individual pup weight from representative male and female 2000 TOL-exposed pups was less than sham-exposed pups; however, entire litter weight did not differ. Pups were evaluated on postnatal days 1-20. Pups exposed to 2000 TOL gained less weight and performed more poorly on the behavioral tests of the righting reflex, grip strength, and inverted screen. In contrast, pups exposed to either 200 or 400 TOL did not differ from sham-exposed pups on any of the measures of development or behavior. These data provide evidence for the neurobehavioral teratogenicity of prenatal exposure to high levels of toluene late in gestation. Because this exposure regimen of intermittent high-concentration exposure was designed to simulate human exposures that might occur with toluene abuse, these results are consistent with case reports of adverse consequences of inhalant abuse by pregnant women.

Animals↗
PubMed2002

Cytotoxicity by nitrite inhalants is not related to peroxynitrite formation.

Nitrite inhalant abuse has been correlated with HIV and Kaposi's sarcoma. Mouse models of inhalant exposure show immunosuppression and loss of immune cells. In the present study, isobutyl nitrite caused a dose-dependent loss of viability of a macrophage cell line. In the absence of cells, isobutyl nitrite reacted with hydrogen peroxide to form peroxynitrite. However, assays of mitochondrial respiration and nitration that detect peroxynitrite indicated that very little was present in cell cultures following exposure to the inhalants. Isobutyl, isoamyl, and butyl nitrites inhibited mitochondrial respiration, but only at high concentrations. Similarly, the nitrating activity of isobutyl nitrite occurred only at high concentrations and was not affected by the presence of hydrogen peroxide. Western blots showed that the inhalant did not increase nitrotyrosine formation in RAW cells or in peritoneal exudate macrophages (PEM) from exposed mice. Thus, the toxicity induced by isobutyl nitrite was probably not due to peroxynitrite formation.

Administration, Inhalation↗
PubMed2002

A survey of attitudes among drug user treatment providers toward the treatment of inhalant users.

This study assessed the attitudes of drug user treatment program directors towards the problem of inhalant "abuse." In 2000, surveys were mailed to directors asking about treatment success and prognosis for inhalant users, level of neurological damage incurred by users, availability of treatment resources, their program's policies toward admission of users, and staff training needs for inhalant use. Two open-ended questions queried their assessment of barriers to treatment and subjective feelings about the topic of inhalant use. Five hundred and fifty responses were received. Findings show that program directors perceive a great deal of neurological damage incurred through inhalant use and have a general pessimism about treatment effectiveness and recovery. The respondents also felt that there were insufficient resources for inhalant user treatment and that special staff training in the area was needed. The majority of the directors indicated that they have or would treat inhalant users. Implications for future research and policy change are discussed.

Administration, Inhalation↗
PubMed2004

The N-methyl-D-aspartate receptor inhibitory potencies of aromatic inhaled drugs of abuse: evidence for modulation by cation-pi interactions.

Benzene and several close structural analogs are inhaled drugs of abuse with general anesthetic activity. By virtue of their pi electron clouds, they may engage in attractive electrostatic interactions with cationic atomic charges on protein targets. In this study, we tested the hypothesis that inhaled drugs of abuse inhibit human N-methyl-D-aspartate (NMDA) receptors with potencies that correlate with their abilities to engage in cation-pi interactions. Electrophysiological techniques were used to define the NR1/NR2B NMDA receptor inhibitory concentrations of volatile benzene analogs, and computer modeling was used to quantify their abilities to engage in cation-pi interactions and their molecular volumes. In addition, each compound's octanol/gas partition coefficient (a measure of hydrophobicity) was quantified. All 18 compounds inhibited human NR1/NR2B NMDA receptors reversibly and in a concentration-dependent manner. NMDA receptor inhibitory potency correlated strongly with the ability to engage in cation-pi interactions, weakly with hydrophobicity, and was independent of molecular volume. This is consistent with the hypothesis that cation-pi interactions enhance the binding of inhaled drugs of abuse to the NMDA receptor and suggests that the receptor binding site(s) for these drugs possesses significant cationic character.

Animals↗
PubMed1988

Indian youth and inhalants: an update.

There is some basis for the perception that Indian youth are more susceptible to inhalant use than their non-Indian peers. Many Indian youth live in disadvantaged and often stressful environments that set the stage for turning to drugs for relief or to seek excitement. Inhalants are cheap and available even to very young children. While levels of inhalant use are comparatively high, the tendency to overrate this use and to label all Indian youth as inhalant abusers must be avoided. By the time Indian youth reach their senior year, only around 4 percent are using inhalants seriously enough to warrant concern. On the other hand, those 4 percent cannot be ignored and, for them, prevention efforts at earlier ages could avert a great deal of needless suffering. Furthermore, there are a significant number of school dropouts who are likely to be chronically inhalant involved. The age pattern of inhalant use indicates that such use by Indian youth begins when they are very young--the predisposing factors are well in place by the 4th and 5th grades. Prevention efforts may need to start very early if they are to succeed.

Administration, Inhalation↗
PubMed2006

Death associated with volatile substance inhalation--histologic, scanning electron microscopic and energy dispersive X-ray spectral analyses of lung tissue.

The investigation of deaths due to the inhalation of volatile substances may be complicated by a lack of scene and autopsy findings. Mechanisms of death may not be determinable at autopsy, and there may be very few markers of inhalant abuse. A 21-year-old man is reported who died from the combined effects of methadone toxicity and toluene inhalation. Histological examination of the lungs revealed congestion and edema, as well as particles of blue, pigmented material within the interstitium and in macrophages. Scanning electron microscopy was undertaken, revealing that the particles contained granules that measured 0.15-0.2microm in diameter, within the range of mean particle sizes for inorganic paint pigments. Energy dispersive X-ray spectral analysis of the granules demonstrated a significant percentage of titanium (12%) confirming their origin from paint. Ancillary investigations such as electron microscopy and X-ray spectral analysis in cases of possible lethal volatile inhalation may prove useful adjuncts in determining the type of substance inhaled and in providing evidence of previous non-lethal episodes.

Administration, Inhalation↗
PubMedDate not supplied

Developmental neurotoxicity of toluene: in vivo and in vitro effects on astroglial cells.

Toluene, an inexpensive and available industrial solvent, has become increasingly popular as a drug of abuse. Inhaling toluene leads to a feeling of euphoria and several reports have shown that children born to women who had abused toluene during pregnancy present a syndrome (toluene embryopathy or fetal solvent syndrome) that is characterized by CNS effects (e.g. microencephaly), growth retardation and facial dysmorphologies. The characteristics of the fetal solvent syndrome are very similar to those observed in the fetal alcohol syndrome. As exposure of rats to ethanol during the brain growth spurt has been shown to cause microencephaly and to affect glial cell proliferation and maturation, the present study examines the effects of toluene administration (250, 500 and 750 mg/kg) in neonatal rats from postnatal day 4 to 10. This treatment resulted in a significant decrease in both brain and body weights, and in a significant reduction of levels of glial fibrillary acidic protein, but not of neuron-specific enolase in rat brain. In vitro experiments demonstrate that pharmacologically relevant concentrations of toluene (250-1,000 microM) significantly inhibit proliferation of rat cortical astrocytes without causing overt cytotoxicity. These results indicate that toluene does not cause selective microencephaly; however, it affects brain weight, and appears to target developing astrocytes, possibly by inhibiting their proliferation.

Aging↗