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PubMedDate not supplied

Inhalants: the instant, but deadly high.

There is an alarming increase in the number of children and adolescents inhaling chemicals for euphoric purposes. This trend merits serious concern, as abuse of inhalants can cause cardiac arrest, asphyxiation, and accidents. Substances such as gas, butane, and lighter fluid are highly toxic and destroy organs, and in some cases, inhalants have caused death on the first use. Pediatric nurses are in a key position to identify abusers and educate parents and children about these potentially fatal chemicals.

Adolescent↗
PubMed2006

Concentration-dependent conditioned place preference to inhaled toluene vapors in rats.

OBJECTIVES: Toluene is present in many commercial products and is subject to abuse by inhalation. The goal of this study was to extend previous reports indicating that rats will exhibit a positive conditioned place preference to inhaled toluene vapors and to determine the dose-response relationship for inhaled toluene in terms of exposure concentration and number of exposures. For the conditioned place preference experiments rats were exposed to toluene vapors at concentrations of 800, 2000, 3000 or 5000 ppm in one compartment of a three-compartment box. RESULTS: Following six conditioning sessions with toluene, a significant place preference was obtained at 2000 and 3000 ppm, but not at 800 or 5000 ppm. Extending the number of toluene pairings at the 2000 and 3000 ppm concentration to 12 significantly enhanced the place preference compared to that at six pairings. CONCLUSIONS: These experiments extend our previous finding that rats will show a conditioned place preference to inhaled toluene, and indicate that a reinforcing "dose" of toluene depends on both the concentration and number of pairings.

Administration, Inhalation↗
PubMed2003

Toluene-induced locomotor activity is blocked by 6-hydroxydopamine lesions of the nucleus accumbens and the mGluR2/3 agonist LY379268.

The abuse of volatile inhalants remains a prominent, yet poorly understood, form of substance abuse among youth. Nevertheless, the identification of a mechanism underlying the reinforcing properties of inhalants has been hampered by the lack of a clearly identifiable neural substrate upon which these chemicals act. One ingredient that is common to many abused inhalants is toluene, an organic solvent that is self-administered by nonhuman primates and rodents. Most drugs of abuse have been found to elicit forward locomotion in rats, an effect owing to the activation of mesoaccumbal dopamine (DA) pathways. Thus, the present study was undertaken using two different approaches to determine whether toluene-induced locomotor hyperactivity is also ultimately dependent upon DA neurotransmission in the mesolimbic nucleus accumbens (NAC). Here we report on the effects of 6-hydroxydopamine (6-OHDA) lesions of the NAC or pretreatment with the metabotropic mGlu2/3 receptor agonist LY379268 on toluene-induced locomotor activity. Both procedures, which are known to alter neurotransmission within the NAC, significantly attenuated toluene's locomotor stimulatory effects. These results provide strong support for a central mechanism of action of inhalants, which in the past has been more typically attributed to general nonspecific mechanisms throughout the brain. Moreover, as with other drugs of abuse, the NAC may be the final common pathway subserving toluene's abuse liability.

Amino Acids↗
PubMed2001

Repeated exposure to inhaled toluene induces behavioral and neurochemical cross-sensitization to cocaine in rats.

RATIONALE: Toluene is a solvent found in many commercial products and is frequently abused by inhalation. Whether previous exposure to toluene alters subsequent responses to other drugs of abuse is not known. OBJECTIVES: This study determined the effects of repeated toluene exposure on the acute motor-stimulant response to cocaine and on cocaine-induced dopamine (DA) concentrations in the nucleus accumbens (NAc). METHODS: One week following bilateral cannulae implantation over the NAc, 27 adult, male Wistar rats began a daily 30-min exposure regimen to either toluene (8,000 ppm) or air for ten sessions. Approximately 24 h or 96 h after their last exposure, animals were injected with either saline or cocaine (15 mg/kg, i.p.) and locomotor activity and DA concentrations in the NAc were measured. RESULTS: Exposure to toluene rendered the rats immobile, and the time required for recovery of normal posture decreased across the ten sessions. In all animals tested, systemic cocaine administration enhanced both locomotor activity and DA concentrations in the NAc. These increases, however, were significantly greater in rats previously exposed to toluene. CONCLUSIONS: Overall, these findings show that repeated toluene exposure enhances behavioral and neurochemical responses to subsequent cocaine administration.

Administration, Inhalation↗
PubMed2001

Inflammatory macrophage nuclear factor-kappaB and proteasome activity are inhibited following exposure to inhaled isobutyl nitrite.

A history of abuse of nitrite inhalants has been correlated with HIV seropositivity and Kaposi's sarcoma. A series of 14 daily, 45-min exposures of mice to 900-ppm isobutyl nitrite in an inhalation chamber reduced the number of peritoneal exudate macrophages (PEM) by 35% and the number of resident peritoneal macrophages (RPM) by 18%. Although the tumoricidal activity of RPM was not affected by the inhalant, the cytotoxicity of PEM was reduced by 26%. The induction of nitric oxide (NO) and the inducible NO synthase (iNOS) protein in PEM were inhibited by the inhalant to a similar extent. Inhibition of NF-kappaB activation in PEM from mice exposed to the inhalant corresponded to reduced degradation of the NF-kappaB inhibitor, IkappaB alpha. Proteasome-associated, enzymatic activity was compromised in PEM from inhalant-exposed mice, suggesting that inhaled isobutyl nitrite compromised macrophage, tumoricidal activity by inhibiting proteasomal degradation of the NF-kappaB inhibitor, IkappaB alpha.

Administration, Inhalation↗
PubMed2006

Gestational toluene exposure effects on spontaneous and amphetamine-induced locomotor behavior in rats.

Gestational Toluene Exposure Effects on Spontaneous and Amphetamine-Induced Locomotor Behavior in Rats. Bowen, S.E., Mohammadi, M.H., Batis, J.C., and Hannigan, J.H. Neurotoxicology and Teratology, XX, 2006. The abuse of volatile organic solvents (inhalants) continues to be a major health concern throughout the world. Toluene, which is found in many products such as glues and household cleaners, is among the most commonly abused organic solvents. The neurobehavioral teratogenic sequelae of solvent abuse (i.e., repeated, brief inhalation exposures to very high concentrations of solvents) have not been examined thoroughly. In a preclinical model of inhalant abuse, timed-pregnant Sprague-Dawley rats were exposed to 0, 8000, or 12,000 parts per million (ppm) for 15 min twice daily from gestation day 8 (GD8) through GD20. In the first experiment, separate groups of offspring were observed individually in an open-field on postnatal day 22 (PN22), PN42 or PN63. In the second experiment, other offspring given identical prenatal toluene exposures were observed in an "open-field" following an acute i.p. injection of amphetamine (0, 0.56, 1.78 mg/kg) on PN28. Automated measurements of distance traveled and ambulatory time were recorded. Prenatal toluene exposure resulted in small alterations in spontaneous activity compared to non-exposed rats. Prenatal exposure to 12,000 ppm toluene resulted in significant hyposensitivity to the locomotor stimulatory effects of the amphetamine challenge in male but not female rats on PN28. The results demonstrate that prenatal exposure to abuse patterns of high concentrations of toluene through inhalation can alter spontaneous and amphetamine-induced locomotor behavior in rats. The expression of these effects also appears to depend upon the postnatal age of testing. These results imply that abuse of organic solvents during pregnancy in humans may also produce long-lasting effects on biobehavioral development.

Age Factors↗
PubMed2000

Effect of thinner inhalation on lipid peroxidation and some antioxidant enzymes of people working with paint thinner.

Paint thinner is a commonly used industrial solvent with considerable potential for abuse by inhalation. Paint thinner is taken into the body by inhalation or by contact with the skin. Paint thinner is oxidized gradually by cytochrome P450-dependent monooxygenase and consequently free radicals are produced. In the present study we measured plasma malondialdehyde (MDA, a product of lipid peroxidation) levels as an indicator of oxidative damage and activity levels of antioxidant enzymes gluthatione peroxidase (GSH-Px) and superoxide dismutase (SOD) in erythrocytes of a group of people (n = 18) working with paint thinner. The control group was composed of 18 healthy adults. There was a statistically significant (p < 0.001) increase in MDA (2.0+/-0.7 nmol ml(-1)) and GSH-Px (86.5+/-16.6 U g(-1) Hb) activity levels in people working with paint thinner compared with control subjects (MDA: 1.0+/-0.3 nmol ml(-1); GSH-Px: 53.9+/-14.5 U g(-1) Hb). Similarly, there was also an increase (p < 0.05) in the SOD levels (1079+/-214.6 U g(-1) Hb) of people working with paint thinner compared with controls (953.3+/-46.7 U g(-1) Hb). Based on our results, it can be concluded that paint thinner inhalation may increase lipid peroxidation and consequently induce antioxidant enzymes.

Adult↗
PubMed2000

[Multiple organ failure following inhalation of butane gas: a case report].

Most cases of acute poisoning by butane and other volatile compounds occur in young people as a consequence of substance abuse by inhalation. Clinical symptoms are caused by asphyxia and mainly affect the cardiovascular, respiratory and central nervous system. There are also reported deaths from intoxication of butane inhalation, mostly by cardiac arrhythmia. We report the case of a healthy 14 year-old boy who inhaled butane gas from an aerosol can for refilling cigarette lighters. Despite successful resuscitation and defibrillation, he died two days later from multiple organ failure involving the central nervous system, cardiovascular system, pulmonary system and the liver. Although such incidents are rare in middle European countries, emergency and intensive care medicine staff should be instructed on the consequences and management of butane gas poisoning.

Adolescent↗
PubMed1999

Phenomenology of gasoline intoxication and withdrawal symptoms among adolescents in India: a case series.

Inhalant withdrawal symptoms have previously been described but not well documented. This case-series describes the sociodemographic and clinical characteristics of nine children and adolescents with gasoline abuse. Gasoline inhalation was the drug of choice in our patients. The mean age was 13.6 years and all the subjects belonged to low socioeconomic status. Most of the subjects used daily and all subjects reported alcohol abuse in the father. All subjects reported a syndrome of intoxication as described in previous reports. All subjects also reported a withdrawal syndrome including irritability, psychomotor retardation, anhedonia, dry mouth, sleep disturbances, craving, and increased lacrimation.

Adolescent↗
PubMedDate not supplied

Tissue injuries associated with parenteral propylhexedrine abuse.

Propylhexedrine, the active ingredient in Benzedrex Inhalers, is extracted from the wicks of the inhalers by drug abusers for intravenous injection to provide a "desirable high." Six representative cases treated over a one-year period are presented to exemplify the potential for soft tissue injury. Because the actual constituents of the injected material prepared from the inhalers were not established, solutions were prepared from Benzedrex Inhalers according to the formula provided by one of the patients. The extract was then subjected to vigorous qualitative and quantitative analyses; the presence of essentially pure propylhexedrine hydrochloride was confirmed in varying concentrations. To examine the progression of injury following injection of the prepared extract, the ears of 12 New Zealand white rabbits were injected either intra-arterially or subcutaneously. The opposite ear of each rabbit served as a control. Both clinical and pathologic observations demonstrated injury consistent with intense local vasoconstriction. Injury did not appear to relate to impurities in the solution or other embolic phenomena. Finally, the laboratory findings are discussed with regard to the clinical examples. In sum, the insult to tissue from intravascular or local injection with propylhexedrine appears to respond, although poorly, to efforts to reverse the intense pharmacologic vasoconstriction.

Adult↗
PubMed2005

Neuroimaging in drug and substance abuse part II: opioids and solvents.

The central nervous system is one of the primary targets for the detrimental effects of drugs of abuse. Diagnostic imaging, especially MRI, plays an important role in the detection of complications associated with drug abuse. We present the imaging findings associated with the abuse of opioids and other morphine derivatives, as well, as solvents. Of the morphine derivatives, heroin is the most commonly abused. Several CNS pathologic effects have been described in association with its abuse. These include neurovascular complications such as microvascular ischemic changes or ischemic stroke. A rare form of leukoencephalopathy has been described in those abusers who inhale heroin vapors. Other neurologic complications include atrophy and various infectious processes. Solvent inhalation is a common practice among adolescents and young adults secondary to its ease of access and low cost. The most important component of industrial solvents is toluene. Complications of toluene abuse may be either acute, showing no neuroradiological changes, or chronic, characterized by cerebral and cerebellar demyelination as well as atrophy.

Administration, Inhalation↗
PubMedDate not supplied

Butane abuse associated Encephalopathy.

Butane contained in household products is easily available for abuse and is not subject to legal prosecution in Germany. The toxicological properties of butane mainly affect the heart and the CNS. A serious pathophysiological mechanism is asphyxia due to the replacement of oxygen by butane. We report an abusive butane inhalation in a 15-year old girl, resulting in cardiopulmonary resuscitation and subsequent development of severe brain damage. After reviewing the medical literature and questioning German toxicological information centres it became obvious, that abuse of butane is an increasing problem. We give an survey about the complications associated with butane intoxication.

Administration, Inhalation↗
PubMed2004

Assessment of heat production, heat loss, and core temperature during nitrous oxide exposure: a new paradigm for studying drug effects and opponent responses.

Studies using core temperature (T(c)) have contributed greatly to theoretical explanations of drug tolerance and its relationship to key features of addiction, including dependence, withdrawal, and relapse. Many theoretical accounts of tolerance propose that a given drug-induced psychobiological disturbance elicits opponent responses that contribute to tolerance development. This proposal and its theoretical extensions (e.g., conditioning as a mechanism of chronic tolerance) have been inferred from dependent variables, such as T(c), which represent the summation of multiple underlying determinants. Direct measurements of determinants could increase the understanding of opponent processes in tolerance, dependence, and withdrawal. The proximal determinants of T(c) are metabolic heat production (HP) and heat loss (HL). We developed a novel system for simultaneously quantifying HP (indirect calorimetry), HL (direct gradient layer calorimetry), and T(c) (telemetry) during steady-state administrations of nitrous oxide (N(2)O), an inhalant with abuse potential that has been previously used to study acute and chronic tolerance development to its hypothermia-inducing property. Rats were administered 60% N(2)O (n = 18) or placebo gas (n = 16) for 5 h after a 2-h placebo baseline exposure. On average, N(2)O rapidly but transiently lowered HP and increased HL, each by approximately 16% (P < 0.001). On average, rats reestablished and maintained thermal equilibrium (HP = HL) at a hypothermic T(c) (-1.6 degrees C). However, some rats entered positive heat balance (HP > HL) after becoming hypothermic such that acute tolerance developed, i.e., T(c) rose despite continued drug administration. This work is the first to directly quantify the thermal determinants of T(c) during administration of a drug of abuse and establishes a new paradigm for studying opponent processes involved in acute and chronic hypothermic tolerance development.

Administration, Inhalation↗
PubMed2004

Acute inhalant-induced neurotoxicity with delayed recovery.

OBJECTIVE: To report a case of neurotoxicity and subsequent hospitalization due to abuse of an ethyl chloride inhalant. CASE SUMMARY: A 41-year-old African American male presented to the emergency department due to mental status changes and an inability to walk. After the blood alcohol and urine drug screen returned negative, a family member revealed that the patient frequently abused an inhalant containing the volatile solvent ethyl chloride. DISCUSSION: Inhalant abuse is common and is facilitated by the widespread availability of volatile solvents that have legitimate commercial or household uses. Most inhalants are central nervous system depressants and are highly lipophilic. Maximum Impact, which contains ethyl chloride, is sold in stores and is readily available over the Internet. While the product has a legitimate use as a VCR head cleaner, it is often illicitly marketed over the Internet as a means of getting a "rush" or "high" and for enhancing sexual pleasure. Neurologic symptoms have been reported after deliberate inhalational exposure to ethyl chloride, and 2 deaths have been associated with its use. An objective causality assessment using the Naranjo probability scale revealed a probable adverse drug event. CONCLUSIONS: Inhalants should be included in the differential diagnosis of patients presenting with acute mental status changes and neurologic impairment that resolve over less than one week.

Adult↗
PubMed1982

Abuse of aerosol products by inhalation.

1 The nature of an aerosol and the techniques that have been used to obtain altered states of consciousness by deliberately inhaling the contents are described. 2 The development of the phenomenon, first in the USA, and subsequently in the UK is traced. 3 The consultation between Government Departments and the British Aerosol Manufacturers Association (BAMA) is outlined, and the decisions reached are detailed. 4 Reference is made to the ingredients contained in aerosols which when abused, cause altered states of consciousness and a brief review of their properties is included. 5 The mortality statistics in the UK collected by BAMA are described and analysed in detail and finally the approach of manufacturers to the problem is defined.

Aerosol Propellants↗
PubMedDate not supplied

Drug abuse in Asia.

The article focuses on countries and areas of South-East Asia, which are seriously affected by drug abuse and the problems associated with it. Opium has traditionally been used for treating illnesses and alleviating physical and mental stress, as well as for recreational and social purposes. The prohibition of the sale and use of opium in Burma, Hong Kong, Malaysia, Singapore and Thailand forced many habitual opium users to switch to heroin. Over the past two decades there has been an increasing trend towards drug use, often involving experimentation with more than one substance, among youth in and out of school. For example, a survey of students at teachers' colleges in northern Thailand showed that at some time in their lives 30-40 per cent of the male respondents and 3-6 per cent of the female respondents had used cannabis, and that 18-20 per cent of the males and 12-27 per cent of the females had sniffed volatile solvents. The same survey showed that 5-10 per cent of both the males and females had used stimulants and nearly 2 per cent had used heroin. During the 1970s the abuse of heroin and other opiates emerged as a serious problem of epidemic nature, predominantly affecting young people in many countries of South-East Asia. While opiates, including heroin, have been abused by inhaling and by smoking, there has recently been an increasing trend towards injecting heroin of high purity (80-90 per cent pure heroin). Heroin addiction spread first to the populations of capital cities and then to other cities and towns and even to the hill tribes, as studies in Thailand have revealed. Most recent studies have shown that heroin abuse has spread further in Asia, both socially and geographically, involving such countries as India and Sri Lanka, which had no previous experience with the problem. Studies have also shown that the abuse of manufactured psychotropic substances has been increasing and that heroin addicts resort to these substances when heroin is difficult to find. The article also briefly reviews the history of opium use in China and the history of drug abuse in Japan, particularly with regard to the problem of methamphetamine abuse, which has appeared in two epidemic-like waves. The first followed the end of the Second World War and disappeared at the end of the 1950s; the second reappeared in 1975 and since then has gradually been increasing in size.

Adolescent↗