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[Development of a drug information registry system in Mexico].

Mexico's need for uniform information about drug abuse led to the creation of an information collection system in 1986. This system, known as the System for Registry of Information on Drugs (SRID), currently covers the Mexico City metropolitan area; plans call for it to be expanded in two phases--so as to provide coverage first of the states near the US border and those with substantial tourism, and then to cover the nation as a whole. This article describes the data collection procedures used and the results of the four SRID assessments conducted in the Mexico City area from mid-1986 through mid-1988. These results indicate there were about nine male drug abusers in this period for every female; that drug use typically began young; that the drugs most commonly abused were marijuana, inhalants, alcohol, tobacco, and tranquilizers; that cocaine use was limited but apparently increasing; and that most of the drug abusers interviewed had not completed secondary school, were not in school at the time interviewed, and had relatively low socioeconomic status.

Adolescent↗

Tolerance and sensitization to inhaled 1,1,1-trichloroethane in mice: results from open-field behavior and a functional observational battery.

RATIONALE: 1,1,1-Trichloroethane (TCE), a representative abused solvent, has well described acute behavioral effects in animals. Much less is known about repeated high-concentration exposures as would be encountered in inhalant abusers. Tolerance has been demonstrated in some, but not all, studies with TCE while sensitization has also been seen with other abused solvents. OBJECTIVE: The present study was designed to further characterize changes in the effects of repeated exposure to TCE on a variety of mouse behaviors. METHODS: Mice were tested using locomotor activity as well as a functional observational battery (FOB) both before and after a regimen of daily exposures to various concentrations of TCE. RESULTS: The initial locomotor effects of acute 30-min exposures to TCE were biphasic with concentration-dependent increases in activity at lower concentrations and decreases observed at higher concentrations. The profile of acute effects as measured by the FOB included changes in posture, decreased arousal, disturbances in gait, delayed righting reflexes, and decreased sensorimotor reactivity. Animals were then divided into five groups and exposed 30 min/day to either air or one of four concentrations of TCE (2,000, 6,000, 10,000, or 13,300 ppm) for 15 consecutive days. The TCE concentration used primarily affected the magnitude of change, not whether tolerance or sensitization occurred. Tolerance developed on the measures of forelimb grip strength, inverted screen, and number of rears. Conversely, sensitization developed to measures of locomotor activity. CONCLUSION: Depending on the behavioral measure, both tolerance and sensitization can occur in mice with repeated exposure to TCE. Both of these phenomena are characteristic of drugs of abuse.

Administration, Inhalation↗

Nitrite inhalation in rats elevates tissue NOS III expression and alters tyrosine nitration and phosphorylation.

Organic nitrites are nitric oxide (NO) donors that are used predominantly as inhalant drugs of abuse and have been shown to have immunomodulating effects. NO donors can modulate NOS activity and expression, thus altering the level of endogenous NO production. NO can react with superoxide (O(*)(2)(-)) to form peroxynitrite (ONOO(-)), which can nitrate tyrosine residues in proteins and alter tyrosine phosphorylation. We investigated the effects of inhaled isobutyl nitrite (ISBN) on NOS expression, tyrosine nitration, and tyrosine phosphorylation in selected organs of rats. Following exposures of 109 and 1517 ppm ISBN for 4 h, the lung, spleen, liver, and kidney were removed and assayed by SDS-PAGE for NOS III (eNOS), NOS II (iNOS), nitrotyrosine (NT)- and phosphotyrosine (PT)-immunoreactive proteins using specific antibodies. ISBN at 1517 ppm, but not 109 ppm, caused an increase in NOS III expression in the liver and kidney, but not in the lung and spleen. No apparent effect on NOS II expression was observed in these organs. The expressions of NT and PT protein bands (30-200 kDa) were increased in the liver and kidney, but not in the lung and spleen. This increase in NT persisted for 24 h post-exposure. Increased NOS III expression in the liver and kidney may promote peroxynitrite formation and contribute to the increase in NT and PT immunoreactivity. ISBN inhalation may thus cause changes in cellular signaling involving tyrosine phosphorylation. These findings may suggest a mechanistic basis for the apparent immunotoxicity associated with nitrite abuse.

Animals↗

Volatile substances of abuse.

Substances that are inhaled for the purpose of recreational self-intoxication include aliphatic hydrocarbons, alkyl halides, alkyl nitrites, aromatic hydrocarbons, ethers, and ketones. All have the ability to cause asphyxia, arrhythmias, cardiovascular depression, neurologic dysfunction, and mucosal, pulmonary, and skin irritation following acute exposure and permanent neurologic damage with chronic exposure. The acute effects of alkyl halides and alkyl nitrites also include carbon monoxide poisoning and hepatorenal toxicity, and methemoglobinemia, respectively. Chronic exposure to aromatic hydrocarbons and ketones can result in liver, kidney, and bone marrow injury; myopathy, rhabdomyolysis, metabolic acidosis, and electrolyte abnormalities are further complications of chronic aromatic hydrocarbon inhalation.

Drug Overdose↗

Antagonism of inhalant and volatile anesthetic enhancement of glycine receptor function.

Recent studies suggest that alcohols, volatile anesthetics, and inhaled drugs of abuse, which enhance gamma-aminobutyric acid, type A, and glycine receptor-activated ion channel function, may share common or overlapping molecular sites of action on these receptors. To investigate this possibility, these compounds were applied singly and in combination to wild-type glycine alpha(1) receptors expressed in Xenopus laevis oocytes. Data obtained from concentration-response curves of the volatile anesthetic enflurane constructed in the presence and absence of ethanol, chloroform, or toluene were consistent with competition for a common binding pocket on these receptors. A mutant glycine receptor, insensitive to the enhancing effects of ethanol but not anesthetics or inhalants, demonstrated antagonism of anesthetic and inhalant effects on this receptor. Although ethanol (25-200 mm) had no effect on its own in this receptor, it was able to inhibit reversibly the enhancing effect of enflurane, toluene, and chloroform in a concentration-dependent manner. These data suggest the existence of overlapping molecular sites of action for ethanol, inhalants, and volatile anesthetics on glycine receptors and illustrate the feasibility of pharmacological antagonism of the effects of volatile anesthetics.

Anesthetics, Inhalation↗

Anesthetic and ethanol effects on spontaneously opening glycine receptor channels.

Strychnine-sensitive glycine receptors mediate inhibitory neurotransmission occurring in the brain stem and spinal cord. Alcohols, volatile anesthetics and inhaled drugs of abuse are positive allosteric modulators of glycine receptor function, normally enhancing function only in the presence of glycine. A complication in studying allosteric actions on ligand-gated ion channels is in the dissection of their effects on neurotransmitter binding from their effects on channel opening. Mutation of an aspartate residue at position 97 to arginine in the glycine receptor alpha1 subunit simulated the effects of glycine binding, producing receptors that exhibited tonic channel opening in the absence of neurotransmitter; i.e. these receptors demonstrated a dissociation of channel opening from neurotransmitter binding. In these receptors, ethanol, enflurane, chloroform, halothane, 1,1,1-trichloroethane and toluene elicited inward currents in the absence of glycine. We previously identified mutations on ligand-gated ion channels that eliminate ethanol, anesthetic and inhalant actions (such as S267I on alpha1 glycine receptors). The double mutant (D97R and S267I) receptors were both constitutively active and resistant to the enhancing effects of ethanol and enflurane. These data demonstrate that ethanol and volatile anesthetics can affect glycine receptor channel opening independently of their effects on enhancing neurotransmitter binding.

Allosteric Regulation↗

Frequency of burn-trauma patients in an urban setting.

BACKGROUND: Burn-trauma patient encounters constitute 5% of the emergency department population. HYPOTHESIS: A large urban hospital will treat twice as many (ie, 10%) burn-trauma patients. DESIGN: Retrospective 44-month study. SETTING: Metropolitan county hospital. PATIENTS: Population-based sample of burn-only (n = 1102), burn-trauma (n = 120), and assault burn-trauma (n = 43) patients. MAIN OUTCOME MEASURES: Frequency and demographics. RESULTS: Just under 10% (n = 120) of the burn population had burn-trauma injuries. The mean +/- SD Injury Severity Score was 12 +/- 12 in these burn-trauma patients: 4 +/- 2 in outpatients and 14 +/- 13 in inpatients. The burn-only and burn-trauma groups had similar age ranges, ethnic distribution, frequency of inhalation injury, substance abuse, malnutrition, sepsis, pneumonia, diabetes mellitus, percentage total burn surface area, number of procedures, grafted areas, and mortality. Forty-three burn-trauma patients (35.8%) sustained injuries due to assault, compared with 123 (11.2%) in the burn-only group (P<.001). Burn-trauma patients who were assaulted had a mean +/- SD Injury Severity Score of 11 +/- 10. There was a significantly increased male-female ratio among the assault burn-trauma patients (6:1) compared with the burn-trauma (3:1) and burn-only (2.3:1) groups (P<.04). Most of these injuries were caused by an unknown assailant, in connection with an automobile, a motorcycle, a bicycle, or pedestrians intentionally struck by moving vehicles, or by child abuse. The main mechanism of injury was contact in 57 burn-trauma patients (47.5%), compared with 127 (11.5%) in the burn-only group (P<.001). CONCLUSIONS: A large urban population will have an increased frequency (2-fold in our center) of burn-trauma injuries. Assault and child abuse are significant contributory factors to burn-trauma injuries in this population.

Adolescent↗

Mineral-associated hepatic injury: a report of seven cases with X-ray microanalysis.

The patterns of hepatic injury associated with various minerals were studied in seven patients. The subjects included one patient who was a sandblaster (silica by inhalation), one patient who was a dental laboratory technician (silica and chromium-cobalt alloy by inhalation), one patient with inhalational talcum powder abuse, and four chronic intravenous (IV) drug abusers (talc by IV injection). In all cases, the liver was examined by light and polarizing microscopy, and by scanning electron microscopy with energy-dispersive x-ray microanalysis. In the two patients with silica exposure, silica-containing sclerohyaline nodules were diffusely present in portal tracts and lobules. Both chromium-cobalt alloy and silica were present in the dental technician. In contrast, in all cases of talc exposure, aggregates of talc-laden macrophages were present in portal and centrilobular areas. Three IV drug abusers and the talcum powder abuser had histologic evidence of chronic hepatitis, most probably of viral etiology. We conclude that mineral type plays an important role in the pathogenesis and fibrogenesis of hepatic lesions. Compared with silica, talc primarily elicits a macrophage response without granuloma formation or fibrosis. Hepatic silicosis is a rare complication in dental laboratory technicians, and chromium-cobalt alloy may contribute to hepatic injury and fibrosis in this setting.

Adult↗

Cocaine-induced myocardial infarction: an analysis and review of the literature.

The objectives of this paper are to analyze the case reports of cocaine-induced myocardial infarction and to better define the clinical characteristics of this syndrome. An English language literature search was carried out using MEDLINE, and a bibliographic review of all identified articles and book chapters was conducted. Ninety-one cases of cocaine-induced myocardial infarction were identified. Intranasal, intravenous, and inhalational routes of abuse all resulted in myocardial infarction. Fourty-four percent of patients had previously noted chest pain. Eighty-seven percent of patients were cigarette smokers. Two-thirds of patients had their myocardial infarction within 3 hours of the use of cocaine (with a range of 1 minute to 4 days). Cardiac catheterizations were abnormal in 30 of 54 patients (55%). Of the 24 patients with reported follow-up, 14 (58%) had further ischemic events after discharge. In conclusion, cocaine-induced myocardial infarction identifies a group of young individuals who may be prone to recurrent complications after initial presentation.

Adolescent↗

Toluene alters appetite, NPY, and galanin immunostaining in the rat hypothalamus.

Toluene is a neurotoxic organic solvent widely used in industry and extensively inhaled by solvent abusers. Toluene, diluted 1:1 in olive oil, was administered intraperitoneally at a dose of 1.3 ml/kg/day for 4 days. Controls received the vehicle in the same dose and duration. Food intake and body weight were measured daily. A regional hypothalamic NPY and galanin immunocytochemical study was also performed. Acute toluene administration in rats generated a reduction in food intake and body weight gain. A significant decrease in NPY immunostaining in the paraventricular nucleus and an increase in arcuate nucleus without changes in other hypothalamic regions were observed. Also, acute toluene administration increased galanin immunostaining in paraventricular and arcuate nuclei. These results suggest that the hypothalamic NPY arcuate-paraventricular projection is involved in the anorectic effect of acute high-dose toluene administration. Changes in regional hypothalamic galanin expression could represent a compensatory mechanism against toluene-induced anorexia.

Animals↗

Adverse virus-drug interactions.

Over the last 3 decades, epidemiologists and clinicians have identified a few clinical entities that appear to result when a viral infection and a chemical exposure overlap and interact. Ampicillin rash during infectious mononucleosis, Reye's syndrome following salicylate ingestion and certain viral infections, and the association of AIDS-related Kaposi's sarcoma with abuse of nitrite inhalants and infection due to human immunodeficiency virus are examples of such phenomena. Preclinical research provides additional evidence that viruses and chemicals may interact and produce illnesses in animals. We hypothesize that other virus-drug interactions may exist. Identifying such interactions may lead to a better understanding of the pathogenesis of currently baffling illnesses and may provide insights into ways of preventing and/or treating diseases that appear uncontrollable now.

Acquired Immunodeficiency Syndrome↗

Borderline immunodeficiency in male homosexuals: is life-style contributory?

Results of our study suggest that white Southern male homosexuals without clinical evidence of AIDS who patronize "gay bars" may have significant zinc deficiency and moderately depressed T-helper/T-suppressor cell ratios. No single causative factor could be identified to explain the significantly low zinc and elevated copper levels measured in whole blood, as well as the depressed OKT4/OKT8 cell ratios. Seventy-four percent of the homosexual male subjects were "recreational" drug abusers, 81% used inhalant nitrites routinely, and 41% routinely treated themselves with antibiotics. Eighty-one percent practiced active and/or passive penile-oral insertion, and 55.5% practiced both active and passive anal intercourse. Of the latter, 19% reported anal bleeding. Clinically inapparent, though statistically significant, borderline immunodeficiency and aberrant zinc and copper levels may be a consequence of multiple factors comprising the gay bar life-style.

Acquired Immunodeficiency Syndrome↗

Electroconvulsive therapy in a middle-aged adult with cortical atrophy.

A 48-year-old male with treated hypothyroidism presented with a long-standing history of depression that had been refractory to treatment. A computed tomography scan of the brain revealed atrophy in the frontal regions. This finding is significant because the patient has no known history of traumatic brain injury, inhalant or alcohol abuse, or prolonged exposure to gasoline. On the basis of the results of the brain imaging in conjunction with the patient's clinical presentation and neuropsychological testing, frontotemporal dementia was considered in the diagnosis and was thought to explain his chronic symptoms of apathy, anhedonia, and suicidal ideation. Electroconvulsive therapy was implemented, with resolution of the patient's depressed mood and neurovegetative symptoms of depression as well as improvement in his Mini Mental Status Examination scores.

Atrophy↗

An emergency psychiatry update.

A review of trends in emergency psychiatry since 1981 indicates that the scope and complexity of the field have greatly increased. Clinicians have found it useful to identify patient groups with special assessment and treatment needs, including adolescents, the elderly, victims of rape and of domestic violence, and repeat visitors to the emergency service. The spread of AIDS requires greater medical attentiveness by psychiatric emergency clinicians, and two recreational substances of abuse, cocaine and inhalants, have become increasingly popular. The use of psychotropic drugs in the emergency room has received more attention, and new trends in rapid tranquilization are apparent. Also reviewed are current medicolegal controversies related to emergency room practice, findings on prediction and control of violence, and the use of the psychiatric emergency service as a training site.

Acquired Immunodeficiency Syndrome↗

An introduction to the clinical toxicology of volatile substances.

Acute poisoning with organic solvents and other volatile compounds now usually follows deliberate inhalation (volatile substance abuse) or ingestion of these compounds. Solvents from adhesives, typewriter correction and dry cleaning fluids, cigarette lighter refills (butane) and aerosol propellants are commonly abused. The major risk is that of sudden death. Arrhythmias leading to cardiac arrest are thought to cause most deaths, but anoxia, respiratory depression and vagal stimulation leading to cardiac arrest may also contribute, as may indirect causes such as aspiration of vomit or trauma. In the United Kingdom (UK), 3.5 to 10% of young people have at least experimented with volatile substance abuse and mortality is more than 100 per annum. The products abused are cheap and readily available despite legislation designed to limit supply. Volatile substance abuse is not illegal and only a minority of abusers are known to progress to heavy alcohol or illicit drug use. Prevention of abuse by education, not only of children but also of parents, teachers, retailers and health care workers, is important in limiting the problem. However, volatile substance abuse-related deaths are still increasing in the UK despite many measures aimed at prevention. Clinically, volatile substance abuse is characterised by a rapid onset of intoxication and rapid recovery. Euphoria and disinhibition may be followed by hallucinations, tinnitus, ataxia, confusion, nausea and vomiting. It is important not to further alarm the patient if signs of serious toxicity are present, since a cardiac arrest may be precipitated. Further exposure should be prevented and the patient resuscitated and given supplemental oxygen if necessary. Cardiac arrhythmias should be treated conventionally and respiratory failure managed supportively. Long term exposure to n-hexane is associated with the development of peripheral neuropathy, while prolonged abuse (notably of toluene or chlorinated solvents) can cause permanent damage to the central nervous system, heart, liver, kidney and lungs. Knowledge of the routes of absorption, distribution and excretion of volatile compounds, and of the rates governing these processes, is important in understanding the rate of onset, intensity and duration of intoxication, and rate of recovery after volatile substance abuse. In addition, such knowledge is helpful when the clinician is attempting to interpret the results of toxicological analyses performed on samples (blood, other tissues, urine) from such patients. Many volatile substances are partly metabolised, the metabolites being eliminated in exhaled air or in urine. Although metabolism normally results in detoxification, enhanced toxicity may also result as with carbon tetrachloride, chloroform, dichloromethane, n-hexane, trichloroethylene and possibly halothane.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗

Toluene, halothane, 1,1,1-trichloroethane and oxazepam produce ethanol-like discriminative stimulus effects in mice.

Drug discrimination procedures were used to compare the discriminative stimulus properties of ETOH and volatile inhalants. Mice were trained to discriminate between i.p. injections of ETOH (1 g/kg) and saline in a two-lever operant task. Stimulus generalization was examined after 20-min inhalation exposures to toluene (300-5400 ppm), halothane (500-8000 ppm) and 1,1,1,-trichloroethane (TCE; 125-14000 ppm). Oxazepam (10-30 mg/kg i.p.) also was tested. Concentration- or dose-related increases in ETOH-lever responding were observed with toluene, halothane, TCE and oxazepam. Shared discriminative stimulus properties among toluene, halothane, TCE and ETOH indicate that some volatile inhalants share pharmacological properties with ETOH. Previous research has shown that these inhalants also produce pentobarbital-like discriminative stimulus effects in mice. Thus, at least some inhaled anesthetics and abused solvents have behavioral effects in common with abused central nervous system depressant drugs such as ETOH and barbiturates.

Animals↗