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PubMed1995

Inhalants in Peru.

In Peru, the prevalence and consequences of inhalant abuse appear to be low in the general population and high among marginalized children. Inhalant use ranks third in lifetime prevalence after alcohol and tobacco. Most of the use appears to be infrequent. Among marginalized children, that is, children working in the streets but living at home or children living in the street, the problem of inhalant abuse is a serious problem. Among children working in the streets but living at home, the lifetime prevalence rate for inhalant abuse is high, ranging from 15 to 45 percent depending on the study being cited. For children living in the streets, the use of inhalant is even more severe. As mentioned earlier in this chapter, most of these street children use inhalants on a daily basis. The lack of research on the problem of inhalant abuse is a serious impediment to development of intervention programs and strategies to address this problem in Peru. Epidemiologic and ethnographic research on the nature and extent of inhalant abuse are obvious prerequisites to targeted treatment and preventive intervention programs. The urgent need for current and valid data is underscored by the unique vulnerability of the youthful population at risk and the undisputed harm that results from chronic abuse of inhalants. Nonetheless, it is important to mention several programs that work with street children. Some, such as the Information and Education Center for the Prevention of Drug Abuse, Generation, and Centro Integracion de Menores en Abandono have shelters where street children are offered transition to a less marginal lifestyle. Teams of street educators provide the children with practical solutions and gain their confidence, as well as offer them alternative socialization experiences to help them survive the streets and avoid the often repressive and counterproductive environments typical of many institutions. Most of the children who go through these programs tend to abandon inhalant use as they mature out of street life.

Adolescent↗
PubMed1989

Facial swelling secondary to inhaled bronchodilator abuse: catecholamine-induced sialadenosis.

A patient with asthma presented with a history of recurrent episodes of facial swelling. The swelling occurred in the preauricular area and extended to the angle of the jaw. The patient attributed these episodes to a "food allergy" as they occurred during or immediately following meals. The only medication the patient was using was inhaled epinephrine (Primatene MistR), two puffs, ten to twenty times a day. Subsequent evaluation revealed that the patient had sarcoidosis. Differential diagnosis of the facial swelling included food-related angioedema, sarcoid parotitis, or catecholamine-induced sialadenosis, which is a rare complication associated with excessive catecholamine administration. A gallium-67 citrate scan demonstrated abnormal pulmonary and hilar uptake of the radiotracer, but not lacrimal or parotid gland uptake, strongly arguing against sarcoidosis as the cause of the facial swelling. Episodes of swelling completely abated when the patient stopped using the epinephrine inhalers. At 5 months of follow-up she has had two recurrent episodes of facial swelling, each time associated with the use of inhaled epinephrine. Thus this patient's facial swelling most likely represents catecholamine-induced sialadenosis. This adverse drug reaction, associated with excessive use of inhaled catecholamines must be kept in mind in patients who abuse inhaled beta-adrenergic agonists and report parotid swelling.

Administration, Inhalation↗
PubMed1999

Chronic inhaled cocaine abuse may predispose to the development of pancreatic adenocarcinoma.

BACKGROUND: The acute and chronic effects of cocaine over various organ systems have been well documented. A more recent approach to the effects of this drug has focused on the immunological consequences of its exposure, with results that indicate a possible carcinogenic effect. METHODS: A chart review was made in order to search for young pancreatic adenocarcinoma patients (arbitrarily defined as younger than 40) who made use of inhaled cocaine. This age was chosen because of a higher probability of cocaine addiction than at older ages. RESULTS: Of the 198 patients with pancreatic adenocarcinoma, 13 were younger than 40 years (range 19 to 37) and 5 of these had abused inhaled cocaine for about a decade. One patient had abused marijuana, and there was no information on drug usage in the other 7 patient charts. CONCLUSION: Although this is a very small series, we believe there might be a possibility that chronic cocaine exposure predisposes to the development of pancreatic adenocarcinoma. Further studies are necessary.

Adenocarcinoma↗
PubMed2004

Poppers: epidemiology and clinical management of inhaled nitrite abuse.

Commonly referred to as "poppers," inhaled nitrites have a long history of abuse. Poppers are rapid-onset, short-acting potent vasodilators that produce a rush characterized by warm sensations and feelings of dizziness. Poppers sometimes are used to facilitate anal intercourse because of their actions on the anal sphincter. Epidemiologically, the frequent use of nitrites by men who have sex with men has led some experts to implicate these chemicals in the pathogenesis of Kaposi's sarcoma and acquired immunodeficiency syndrome. Controlled clinical trials to examine this potential correlation have not been conducted, and the use of nitrites simply may be a marker for other high-risk behaviors such as unprotected sex. Although regulated in the United States, many nitrite compounds and isomers are sold at various venues including bars, bookstores, and over the Internet. Adverse effects associated with these products vary from mild allergic reactions to life-threatening methemoglobinemia. The potential for drug-drug interactions and a propensity toward unsafe sex also exist. Clinicians should be familiar with the populations most likely to abuse these agents and with the clinical effects and management guidelines for acute ingestions.

Administration, Inhalation↗
PubMed2006

Solid-phase microextraction: investigation of the metabolism of substances that may be abused by inhalation.

Purified liquefied petroleum gas (LPG), a mixture of butane, isobutane, and propane, is commonly abused by inhalation. Little is known about the mammalian metabolism of these substances. Metabolism of other hydrocarbons, including n-hexane and cyclohexane, has been studied in vitro using a range of liver preparations, with metabolites analyzed by static headspace techniques. Solid-phase microextraction (SPME) for sampling metabolites in the headspace of incubates of volatile compounds with activated rat liver microsomes is investigated. Cyclohexanol and cyclohexanone were formed from cyclohexane and 1-, 2-, and 3-hexanol and 2-hexanone from n-hexane as predicted. Secondary alcohols are found for the other compounds studied, except for propene and isobutane, together with 2-propanone and 2-butanone from propane and n-butane, respectively. Samples from three individuals who died following LPG abuse contained a range of putative n-butane metabolites: n-butanol, 2-butanol, 2,3-butanediol, 3-hydroxy-2-butanone, and 2,3-butanedione. To our knowledge, the last three compounds have not been proposed as metabolites of n-butane in man. These might be produced through similar metabolic pathways to those of n-hexane and n-heptane. The findings indicate the value of SPME for investigating the metabolism of volatile substances and for detecting and monitoring exposure to these compounds.

Animals↗
PubMed2003

Single-voxel proton MR spectroscopy in toluene abuse.

Inhalation of toluene, which is an organic solvent, causes toxic encephalopathy characterized by cognitive impairment, cerebellar and extra-pyramidal symptoms. We studied cranial MR images and single-voxel MR spectroscopy of 22 toluene abusers and age-matched control subjects. The mean age of the abusers and mean duration of abuse were 18,1 years and 47 months, respectively. We got three MR spectra from the centrum semiovale, cerebellum and thalamus by using STEAM sequence with a TE value of 30 ms. N-acetyl aspartate (NAA)/Creatine (Cr), Choline (Cho)/Cr, myo-inositol (mI)/Cr peak integral ratios were calculated. NAA/Cr in the cerebellum and centrum semiovale of the abusers were significantly lower than those of the control subjects. mI/Cr in centrum semiovale and cerebellum were higher in toluene abusers. No significant difference was found in the metabolite ratios of the thalami. The association of NAA/Cr and mI/Cr ratios in cerebellum and centrum semiovale with the duration of abuse was significant. Normal level of NAA in thalamus, which was a neuron rich gray matter structure, might imply that toluene inhalation did not cause direct neuronal injury. Selective reduction of NAA and increased level of mI in white matter supported the theory of that axonopathy and gliosis were the main mechanisms of pathophysiology in chronic toluene encepholopathy. Insignificance of elevation of Cho/Cr ratios demonstrated that toluene inhalation did not cause active demyelination.

Adolescent↗
PubMed2001

Clinical review of inhalants.

While the rate of inhalant abuse continues to rise in this country, it remains one of the least studied or discussed groups of abused substances. This review focuses on the current knowledge of the epidemiology, pharmacology, and sequela of inhalant abuse. We will discuss three groups of inhalants: volatile solvents, nitrous oxide, and nitrites. We will then conclude by proposing means by which inhalant abuse may be prevented and treated.

Administration, Inhalation↗
PubMedDate not supplied

Abuse pattern of gestational toluene exposure and early postnatal development in rats.

Inhalant abuse in the United States trails only alcohol, marijuana and nicotine abuse. Toluene, found in glues and cleaners, is among the most commonly abused inhalants. While teratogenicity due to occupational exposure to organic solvents (i.e., relatively long-term exposure to lower concentrations) has been studied, the teratogenic potential of organic solvent abuse (i.e., brief inhalation exposures to very high concentrations) has not been thoroughly examined. In a preclinical model of abuse patterns of fetal solvent exposure, timed-pregnant rats were exposed to 8000 parts per million (ppm) or 12,000 ppm of toluene, or to air (0 ppm), for 15 min twice daily from gestation day 8 (GD8) through GD20. After parturition, pups were tested from postnatal day 4 (PN4) to PN21 in a developmental test battery including measures of growth (i.e., body weight), maturational milestones (i.e., pinnae unfolding, incisor eruption and eye opening) and biobehavioral development (e.g., negative geotaxis, surface righting and grip strength). Pups exposed in utero to 12,000 ppm toluene weighed significantly less than the control pups at all ages before PN16. There were significant toluene-induced increases in an index of poor perinatal outcome (i.e., a combination of malformations, "runting" and neonatal death) and deficits in negative geotaxis. There were no significant delays in reaching maturational milestones. The results demonstrate that brief, repeated, prenatal exposure to high concentrations of toluene can cause growth restriction, malformation and impairments of biobehavioral development in rats. A comparison of the present outcomes to previous studies of occupational exposure patterns suggests that for a given daily "dose" of toluene, a binge pattern of exposure may pose a greater risk for fetal development. Since the pattern of exposure in this experiment models binge exposure in human solvent abuse, the results imply that abuse of inhaled organic solvents, such as toluene, can cause similar teratogenic outcomes in humans.

Abnormalities, Drug-Induced↗
PubMed1988

[Substance abuse with inhalants].

In this article, Charles Vaille maintains that for the past two decades there has been a renewed outbreak of substance abuse with inhalants among youth throughout the world. He asserts that this phenomenon can no longer be considered as limited to a few isolated incidents. The volatile substances are common place, inexpensive, and unlike other drugs, legal; they are subject to neither international nor national controls. The specificity of addicts to inhalants renders prevention very difficult. Vaille discusses this point after describing the following two types of inhalant addiction: 1. Inhalation of gas fumes: two examples of youths inhaling fumes are cited followed by a description of ways in which inhaling or "sniffing" is performed. Vaille then presents the short-term effects of the "high", both psychological and physical. He then proceeds to disclose the harmful long-term effects concluding that addiction due to inhaling fumes seems to be developed throughout Europe. 2. Forced hyperventilation: a detailed description of how the "game" of forced hyperventilation is played is followed by a discussion of its effects on health. In discussing regulatory measures, Vaille maintains that a country's first effort at preventing substance abuse is to limit and modify the existence of such substances. After describing the various means attempted, he concludes that these effects will always result in an elusive prevention, due to the extraordinary number of inhalant substances as well as the enticing aspect of the "forbidden fruit". Regulatory measures offer an answer to those seeking a clear conscience rather than attempting to get at the root of the problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Sensory evoked potentials in inhalant (volatile solvent) abuse.

A study was made to determine whether children with a significant history of inhalant abuse but who lack clinical evidence of neurological abnormality have abnormal visual, auditory or somatosensory evoked potentials. Visual, auditory and somatosensory evoked potential studies were obtained from 15 such children aged 9-17 years. Eight of the children had abnormal visual or auditory evoked potentials. Somatosensory evoked potentials were normal in all. It was concluded that evoked potentials may serve as an objective marker of early neurological damage in children who abuse inhalants and demonstrate potential usefulness for counselling and intervention.

Administration, Inhalation↗
PubMed2005

Within-subject comparison of the subjective and psychomotor effects of a gaseous anesthetic and two volatile anesthetics in healthy volunteers.

Inhalant abuse is a serious public health problem throughout the world. The present study compared the states of intoxication produced by three inhaled anesthetics that represent two of the three major classes of abused inhalants, as classified by [Balster, R.L., 1998. Neural basis of inhalant abuse. Drug Alcohol Depend 51, 207-214.]. Isoflurane and sevoflurane represent the class of volatile substances, and nitrous oxide (N2O) comprises a class of its own. Fourteen healthy volunteers inhaled the vehicle (100% O2) and two concentrations each of isoflurane (0.1 and 0.2%), sevoflurane (0.2 and 0.4%), and N2O (15 and 30%) for 40 min each, across seven separate sessions. Drug concentrations were chosen to produce similar ratings of drug effect strength and similar impairment on a psychomotor test, the digit-symbol substitution test (DSST). Ratings of drug effect strength and performance on the DSST were similar across drugs; however, the volatile anesthetics produced greater sedation and greater impairment on three other psychomotor tests than N2O, whereas N2O produced a greater magnitude of putatively pleasant and psychedelic-like subjective effects. These results are consistent with the drugs' putative receptor mechanisms of action and confirm Balster's classification of the volatile anesthetics into a class distinct from N2O.

Adult↗
PubMedDate not supplied

Barotrauma related to inhalational drug abuse.

Three patients are described who developed either pneumomediastinum or "clicking pneumothorax" after abusing illicit drugs. In recent years, patients presenting with pneumomediastinum after abusing cocaine have been frequently reported; these patients are most commonly young males with pleuritic chest pain. Seventy-three percent have detectable subcutaneous emphysema and fifty percent have a Hamman's sign. The pathophysiology, presenting features, and treatment of patients with barotrauma related to inhalational drug abuse are reviewed.

Administration, Inhalation↗
PubMed1996

Cerebral venous thrombosis associated with inhalational drug abuse.

Cerebral venous thrombosis is a life-threatening disorder for which the management has been controversial. A 23-year-old critically-ill man with superior sagittal sinus thrombosis (SSST) and cavernous sinus thrombosis secondary to sinusitis following inhalational drug abuse was managed with full heparinization from the fourth day of presentation. He went on to make a full recovery. The association between this form of drug abuse, sinusitis and SSST is an important one, and warrants antibiotics and early aggressive anticoagulation therapy.

Adult↗
PubMed2004

Inhibition of gap junction currents by the abused solvent toluene.

Abused inhalants are a large class of compounds that are inhaled for their intoxicating and mood altering effects. They include chemicals with known therapeutic uses such as anesthetic gases as well as volatile organic solvents like toluene that are found in paint thinners and adhesives. Because of their widespread commercial use and availability, inhalants are often among the first drugs that children encounter and use of these compounds is often associated with adverse acute and long-term consequences. The cellular and molecular sites of action for abused inhalants is not well known although recent studies report that toluene and other organic solvents alter the activity of specific ligand- and voltage-gated ion channels that regulate cellular excitability. As part of an ongoing effort to define molecular sites of action for abused inhalants, this study examined the effect of toluene on the function of gap junction proteins endogenously expressed in human embryonic kidney (HEK 293) cells. Gap junctions allow cell-to-cell electrical communication as well as passage of small molecular weight substances and are critical for synchronizing cellular activity in certain tissues. Gap junction currents in HEK 293 cells were measured during brief voltage steps using patch-clamp electrophysiology and were blocked by known gap junction blockers confirming expression of connexin proteins in these cells. Toluene dose-dependently inhibited these conductances with threshold effects appearing at approximately 0.4 mM and near complete inhibition occurring at concentrations of 1 mM and higher. The estimated EC50 value for toluene inhibition of gap junction currents in HEK 293 cells was 0.57 mM. The results of these studies suggest that volatile solvents including toluene may produce some of their effects by disrupting inter-cellular communication mediated by gap junction proteins.

Cell Line↗
PubMed2003

Drug abuse with inhalated xylazine.

Given the difficulty of obtaining traditionally illicit drugs, consumption is turning towards less restricted products. We report the case of an 18-year-old man, who after inhaling xylazine (a non-narcotic sedative used in veterinary medicine for analgesia, hypnosis and muscle relaxation) presented with an episode of chills and dizziness followed by sweating, gait instability, palpitations and two episodes of syncope with bradycardia and hypotension. Ten cases of toxicity caused by xylazine consumption by oral and parenteral administration (intramuscular, subcutaneous, and intravenous) have been documented in humans. In these cases, consumption was either involuntary or for suicidal or homicidal purposes, or used as an agent of drug abuse, occasionally resulting in death. We present the second documented case of toxic effects of drug abuse with inhalated xylazine.

Adolescent↗
PubMed1994

Volatile substance abuse.

Volatile substance abuse (VSA) (glue sniffing, inhalant abuse, solvent abuse), the deliberate inhalation of volatile substances in order to achieve intoxication, has now been reported from most parts of the world, mainly among adolescents, individuals living in remote communities and those whose occupations give ready access to abusable substances. Solvents from contact adhesives, notably toluene, petrol (gasoline), halogenated solvents, volatile hydrocarbons such as those found in cigarette lighter refills, aerosol propellants, halocarbon fire extinguishers, and inhalational anaesthetics may be abused in this way. VSA gives rise to dose-related effects similar to those of other hypnosedatives. Small doses can rapidly lead to euphoria and other disturbances of behaviour similar to those caused by ethanol (alcohol), and may also induce delusions and hallucinations. Higher doses may produce life-threatening effects such as convulsions and coma. Death may ensue indirectly after, for example, inhalation of vomit, or from direct cardiac or central nervous system toxicity. Chronic abuse of toluene-containing products and of chlorinated solvents such as 1,1,1-trichloroethane, for example, can produce severe organ damage, especially in the liver, kidneys, and brain. Drunken behaviour, unexplained listlessness, anorexia and moodiness may result from VSA, especially in children and adolescents. The hair, breath and clothing may smell of solvent, and empty adhesive tubes or other containers, potato crisp bags, cigarette lighter refills, and aerosol spray cans are often found. Toxicological examination of blood and tissue specimens is especially important in confirming a diagnosis of sudden VSA-related death. The development and evaluation of strategies for the treatment of chronic abusers and for prevention are major challenges for the future.

Death, Sudden↗
PubMed2002

Study of brain uptake and biodistribution of [11C]toluene in non-human primates and mice.

Inhalant abuse is a rapidly growing health problem particularly among adolescents. Yet we know little about the neural mechanisms underlying the abuse liability of inhalants, particularly when compared to other addictive drugs. Specifically, our understanding of the relationship between the regional brain phamacokinetics and features classically associated with drug reinforcement is lacking. Under the hypothesis that the abuse liability of toluene can be related to its pharmacokinetic properties and the pattern of regional brain uptake, we developed the methodology for radiolabeling and purifying [11C]toluene for use in PET studies. Here we report the regional brain distribution and kinetics of the widely abused solvent toluene in non-human primates and the whole body biodistribution in mice. To our knowledge, this is the first reported study of the in vivo brain pharmacokinetics of labeled toluene in non-human primates. Rapid uptake of radioactivity into striatal and frontal regions was followed by rapid clearance from the brain. Concurrent findings in rodents indicate similar radio-tracer kinetics, with excretion through kidneys and liver. Taken together, our data provides insight into pharmacokinetic features possibly associated with the abuse liability of toluene.

Administration, Inhalation↗