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Methoxyflurane, a general anesthetic, is a known nephrotoxin. A case is presented that demonstrated diffuse, bilateral renal cortical calcification on CT secondary to repeated methoxyflurane inhalation.
The authors discuss in detail the pharmacology and toxicity of illicit drugs that pose a major threat to adolescent health, including marijuana, cocaine, hallucinogens, opiates, inhalants, and designer drugs. The discussion of each drug concludes with guidelines for clinical management of adolescent users.
Among the various syndromes caused by excess mineralocorticoids, the factitious syndrome produced by excessive 9-alpha-fluorprednisolone inhalations is more common than might be expected, especially in places where the drug is easily obtained without a doctor's prescription. A fairly typical case of addiction to a nasal spray containing ephedrine hydrochloride and an imidazoline compound as well as the steroid is described. The diagnosis of the case is analysed with details of certain differences from similar cases reported in the literature and the modifications to clinical and instrumental parameters achieved after over two months' treatment with spironolactone are described.
CASE REPORT: Acetylene is a commonly found industrial agent that, when mixed with oxygen, is used for welding. This report outlines circumstances surrounding the death of a 40-year-old male with presumptive evidence of abuse of the substance and subsequent death. The article covers the uses of acetylene, the toxic effects attributed to the gas, and the circumstances of the incident.
There are a several drugs that lead to the production of methamphetamine and/or amphetamine in the body which are subsequently excreted in the urine. These drugs raise obvious concerns when interpreting positive amphetamine drug testing results. Famprofazone is an analgesic found in a multi-ingredient medication (Gewodin) used for pain relief. Two Gewodin tablets (50 mg of famprofazone) were administered orally to healthy volunteers with no history of amphetamine, methamphetamine, or famprofazone use. Following administration, urine samples were collected ad lib for up to six days, and pH, specific gravity, and creatinine values were determined. In order to determine the quantitative excretion profile of amphetamine and methamphetamine, samples were extracted using liquid-liquid extraction, derivatized with heptafluorobutyric anhydride, and analyzed by gas chromatography-mass spectrometry (GC-MS). The ions monitored were 91, 118, 240 for amphetamine and 254, 210, 118 for methamphetamine. Amphetamine-d(6) and methamphetamine-d(11) were used as internal standards. Peak concentrations for amphetamine ranged from 148 to 2271 ng/mL and for methamphetamine 615 to 7361 ng/mL. Concentrations of both compounds peaked between 3 and 7 h post-dose. Amphetamine and methamphetamine could be detected (limit of detection = 5 ng/mL) at 121 and 143 h post-dose, respectively. Using a cutoff of 500 ng/mL, all subjects had individual urine samples that tested positive. One subject had 14 samples above the cutoff with the last positive being detected over 48 h post-dose. The profile of methamphetamine and amphetamine enantiomers was also determined using liquid-liquid extraction, derivatization with N-trifluoroacetyl-l-prolyl chloride and analysis by GC-MS. Data showed the famprofazone metabolites amphetamine and methamphetamine to be both d- and l-enantiomers. The proportion of l-methamphetamine exceeded that of its d-enantiomer from the first sample collected. Initially, the proportion was approximately 70% l-methamphetamine and this proportion increased over time. Amphetamine results showed l- and d-amphetamine were virtually the same in the early samples with the proportion of l-amphetamine increasing as time progressed. Forensic interpretation of drug testing results is a challenging critical part of forensic drug testing area because of the potential repercussions the results found may have on an individual's life. The finding of each enantiomers by itself differentiates famprofazone use from the most commonly abused form of methamphetamine and all medicinal methamphetamine available in the U.S., which is either d-methamphetamine (prescription medication) or l-methamphetamine (Vicks inhaler). Coupling this information with the concentrations of amphetamine and methamphetamine helps to determine the potential for use of this drug.
Current evidence suggests that the incidence of recreational nitrous oxide inhalation is on the rise. Due to the possibility of clinically significant myelopathy, as well as potential response to treatment, it is important to consider this diagnosis when appropriate. We present a case of acquired ataxia and myelopathy due to nitrous oxide abuse and discuss diagnosis, pathophysiology, and response to treatment.
A case of spongiform leucoencephalopathy in a known intravenous heroin abuser is presented. To our knowledge, this is the only case of heroin-related spongiform leucoencephalopathy reported in Australia. The relationship to intravenous rather than inhaled heroin is particularly unusual with only one other possible case documented in the literature. The imaging and histopathological findings are described.
The receptors for tetrahydrocannabinol, the active ingredient of marijuana, have been identified. A microsatellite polymorphism (AAT)n at the cannabinoid CB1 (brain) receptor gene (CNR1) consists of 9 alleles. Since the cannabinoid system is part of the reward pathway we examined the hypothesis that genetic variants of the CNR1 gene might be associated with susceptibility to alcohol or drug dependence. The study consisted of 92 subjects on an Addiction Treatment Unit (ATU) and 114 controls. All were non-Hispanic Caucasians. The ATU subjects were screened for all types of substance dependence using the Diagnostic Interview Schedule (DIS), and for a variety of substance abuse symptoms using the Addiction Severity Index (ASI). Since inspection of the distribution of alleles in controls vs i.v. drug use showed a decrease in the frequency of the 4 allele, and the < 4 alleles were rare, the alleles were divided into two groups, < 5 and < or = 5, and three genotypes < 5/< 5, heterozygotes, and > or =/> or = 5. When all variables were subjected to factor analysis, factor 1 showed a clustering of drug dependence variables and factor 2 of alcohol dependence variables. By ANOVA only factor 1 showed significant differences by genotype consistent with a model where homozygosity for the > or = 5 repeat alleles showed the greatest effect. The number of i.v. drugs used was significantly greater for those carrying the > or =/> or = 5 genotype than for other genotypes (P = 0.005). The association with specific types of drug dependence was greatest for cocaine, amphetamine, and cannabis dependence. The results are consistent with a role of cannabinoid receptors in the modulation of dopamine and cannabinoid reward pathways. Independent studies should be designed to further confirm the hypothesis that cannabinoid receptors may contribute to the susceptibility to drug abuse.
Patients with schizophrenia and related psychoses frequently use, abuse and become dependent on psychoactive substances. Local surveys indicate differences in both types and patterns of substances used. A cross-sectional survey was conducted to document abuse in 207 successive outpatients presenting to a psychiatric continuing care facility in a large Canadian city. Nicotine, alcohol and cannabis were the most frequently abused substances in the cohort. Excluding nicotine, 44.9% met criteria for lifetime and 14.0% for current abuse/dependence. Cocaine, heroin, hallucinogen, amphetamine, and inhalant use were rarely reported. Patients with current substance abuse/dependence and a psychotic disorder (dual diagnosis, DD) had significantly higher Positive and Negative Symptom Scale (PANSS) positive scores than lifetime-DD or those with a single diagnosis (SD). Significantly more current-DD (69.0%) patients were depressed (HAM-D score > or =12) compared to SD (45.6%). Furthermore, current-DD (27.6%) patients were more likely than SD (4.5%) to be medication non-compliant. Patients with current-DD were more likely to smoke cigarettes (88.9%) compared to those with SD (49.6%) and they had significantly longer histories of cigarette smoking (19.1 for DD vs. 11.5 years for SD). The smoking behavior of the DD population is discussed in terms of enhanced risk for alcohol abuse, as well as effects on antipsychotic blood levels and metabolism.
There is a vast array of abused drugs, and only a few of the more commonly used substances have been discussed. Patients with drug abuse frequently present with atypical syndromes and diseases. These individuals usually have less social, medical and economic support, making them more susceptible to the diseases that are associated with poverty, such as tuberculosis, and the complications of diseases such as hypertension, congestive heart disease and diabetes that require long-term care. Our strategy in the evaluation of these patients should consider all these aspects of medicine. A meticulous assessment and comprehensive care are necessary to render quality care for these complicated human and toxicological problems.
In response to public pressure to allow the medical use of marijuana, the Office of National Drug Control Policy, Washington, DC, funded a study by the Institute of Medicine evaluating the scientific evidence for benefits and risks of using marijuana as a medicine. The report used scientific reviews, public hearings, and reports from other agencies, and was evaluated by knowledgeable advisors and reviewers. It called for heavier investment in research on the biology of cannabinoid systems, careful clinical studies of cannabinoids in clinical syndromes, analysis of cannabinoids' psychological effects on symptoms, and evaluations of the health consequences of heavy marijuana use; recommends against the use of smoked marijuana in medicine and for the development of a medical cannabinoid inhaler; and recommends that compassionate use of marijuana be considered under carefully reviewed protocols. Finally, the report evaluates the abuse potential, tolerance, withdrawal, and gateway risks of medical use of cannabinoid drugs.
Six cases of cocaine-related deaths of infants have covered the spectrum of potentially devastating effects. They include an intrauterine death of a 35-week-old fetus following acute maternal cocaine abuse; anoxic encephalopathy at birth with 3 months' vegetative survival from a similar episode; traumatic compression asphyxia in a 4-month-old; infectious cardiomyopathy with heart failure in a twin at age 21 months following maternal cocaine abuse at birth; malnutrition and dehydration in a 7-week-old during continuing cocaine abuse by the parents; and a teenage sibling's cocaine lacing of a baby milk bottle ingested by his 6-week-old brother. All the cases had positive toxicological screening for cocaine or metabolites or both in the mother at delivery or in the infant at birth, or both. There were no instances of sudden infant death syndrome (SIDS, or "crib death"). Pathologic and toxicologic, as well as birth, developmental, and social data are presented. An integrated medical, public health, law enforcement, and educational policy to prevent or at least ameliorate these tragic cases, now approaching epidemic proportions, has yet to be developed. A careful obstetrical history and examination of the mother, indication on the birth certificate of maternal drug abuse, and notification of health authorities (by birth certificate checking, among other ways) may send an early warning message to providers for intercession. Active ingestion/injection and passive inhalation by older children and teenagers require more intensive monitoring and aggressive interaction by pediatricians, social workers, school authorities, and employers.(ABSTRACT TRUNCATED AT 250 WORDS)
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To develop drug abuse prevention for adolescents in Japan, the author reviewed concepts of "gateway drug" and "stepping-stone hypothesis". Firstly, results obtained from high school students in New York State (Kandel, D., 1975) were introduced as a standard model of "stepping-stone hypothesis". Secondly, results obtained from serious drug abusers in New York City (Golub, A. et al., 1994) were introduced as an example that shows the importance of defining clearly which cohort a study refers to when we use "gateway drug". Thirdly, results of a junior high school students survey in Japan were introduced and discussed to consider whether alcohol and cigarette for junior high school students in Japan are "gateway drugs" to solvent. The author concluded: 1) that cigarette smoking in junior high school students in Japan has a strong relationship with solvent inhalation, and 2) that drinking alcohol, however, depends on the presence of adults. Lastly, the author emphasized the need for doing more research on drug abuse in Japan.
RATIONALE: Data obtained in laboratory animals and humans suggest that dopamine D1 receptor antagonists decrease cocaine self-administration and block cocaine's discriminative stimulus and subjective effects. OBJECTIVES: This study investigates the effects of the selective dopamine D1 antagonist, ecopipam (SCH 39166), on the reinforcing, cardiovascular, and subjective effects of cocaine in humans. METHODS: Ten non-treatment-seeking cocaine smokers (two females, eight males), residing on an inpatient research unit, were maintained on placebo and ecopipam (100 mg p.o.) in random order using a within-subjects, cross-over design. Cocaine self-administration (0, 12, 25, and 50 mg) was tested beginning on the 5th day of each 8-day maintenance condition. A six-trial choice procedure (cocaine vs $5 merchandise vouchers) was utilized, with sessions consisting of one sample trial, when participants smoked the cocaine dose available that day, and five choice trials, when participants chose between smoking the available cocaine dose or receiving one merchandise voucher. RESULTS: In the presence of placebo cocaine, ecopipam significantly decreased cocaine craving while increasing alcohol and tobacco craving. In the presence of active cocaine, ecopipam increased cocaine self-administration (12 mg) and increased ratings of "good drug effect," "high," "stimulated," and dose quality (25 and 50 mg). Ecopipam produced small but significant increases in blood pressure, regardless of cocaine dose. CONCLUSIONS: Maintenance on the long-acting dopamine D1 antagonist, ecopipam, enhanced both cocaine self-administration as well as its subjective effects compared to maintenance on placebo. These data suggest that chronic antagonism of the dopamine D1 receptor may not be a useful approach for the treatment of cocaine abuse.
In recent decades the organic solvent toluene (methylbenzene) has emerged as one of the best-studied neurotoxins. Long-term and intense exposure to toluene vapors in humans who abuse spray paint and related substances has led to the recognition that toluene has a severe impact on central nervous system myelin. Chronic toluene abuse produces a devastating neurological disorder, of which dementia is the most disabling component. The clinical syndrome, toluene leukoencephalopathy, can be detected by a combination of characteristic symptoms and signs, detailed neurobehavioral evaluation, and brain magnetic resonance imaging. In this paper, we consider the impact of toluene abuse on our society, describe the specific neurobehavioral deficits in toluene leukoencephalopathy, review the spectrum of neuroimaging findings in patients with this disorder, summarize the teratogenic effects of toluene in both humans and animal models, and offer possible explanations for the range of neuropathological damage seen in brains of individuals who chronically abuse toluene.
Drug abuse is a growing problem in industrialized countries, opening the way to new diseases of the respiratory tract. It has been demonstrated that regular inhalation of cannabis has the same consequences as tobacco smoking. The same cannot be said for other drugs. Cocaine, amphetamines or crack expose the patient to particular toxic effects: in addition to barotrauma related to the administration route, syndromes of acute respiratory distress have been described. These result either from bronchial reactions, asthma exacerbation or eosinophil bronchopneumonia, or alveolar involvement: intra-alveolar bleeding, pulmonary edema or organized pneumonia. Respiratory complications induced by opiates, often used in injections, are related to central alveolar hypoventilation and/or the development of injury from pulmonary edema or pneumonia. The pathophysiology of these lesions is not perfectly understood. Besides these specific conditions, infection is a major problem in drug abusers, irrespective of the drug: bacterial pneumonia, tuberculosis, HIV infection are much more frequent in this high-risk group. Finally repeated intravenous injections of various drugs designed for oral intake can lead to severe complications such as pulmonary hypertension or toxic interstitial lung disease. Summarizing, respiratory diseases in drug abuses can take on a wide range of quite complex presentations. Occasional or regular use of illicit drugs can lead, not exceptionally, to severe respiratory complications requiring rapid management. Knowledge of the principal complications and the appropriate diagnostic procedures is indispensable.