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PubMedDate not supplied

Pharmacokinetics of methamphetamine self-administered to human subjects by smoking S-(+)-methamphetamine hydrochloride.

S-(+)-methamphetamine hydrochloride ("ice") is abused by smoking (inhaling the vapors of the material). Male human volunteers inhaled the drug from a pipe heated at 300 degrees-305 degrees C for an average inhaled dose of 21.8 +/- 0.3 (SE) mg. The same volunteers were given an intravenous injection of 15.5 mg of S-(+)-methamphetamine hydrochloride. Methamphetamine and its metabolite amphetamine were analyzed in plasma, saliva, and urine by gas chromatography. The bioavailability of smoked methamphetamine was 90.3 +/- 10.4%. (Oral bioavailability calculated from this study and a previous one was 67.2 +/- 3.1%). The geometric mean plasma half-life was 11.1 hr for smoked methamphetamine and 12.2 hr for the intravenous drug. These values agreed with urinary excretion rate data. The volume of distribution in the elimination phase was 3.24 +/- 0.36 liter/kg for the smoked dose and 3.73 +/- 0.59 liter/kg for the intravenous dose. The mean residence times were 11.5 +/- 0.5 hr and 11.3 +/- 1.74 hr for the two routes. Metabolic clearance represented 58 and 55%, respectively, of the total clearance. Significant amounts of the drug (37-45% of the nominal dose) were excreted in urine as methamphetamine and lesser amounts (7% of the nominal molar dose) as amphetamine. Renal clearance was equivalent for the two routes. Methamphetamine concentrations in plasma after inhalation showed a plateau. A model involving both a fast and a slow input function fit the data from 4 of the 6 subjects and indicated a terminal elimination rate that agreed with results from model-independent pharmacokinetic calculations. The drug caused significant subjective and cardiovascular effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed2002

Inhibition of neuronal nicotinic acetylcholine receptors by the abused solvent, toluene.

1 Toluene is a representative example of a class of industrial solvents that are voluntarily inhaled as drugs of abuse. Previous data from this lab and others has shown that toluene modulates the function of N-methyl-D-aspartate (NMDA), gamma-aminobutyric acid (GABA) and glycine receptors at concentrations that do not affect non-NMDA receptors. 2 We utilized two-electrode voltage-clamp and whole cell patch-clamp techniques to assess the effects of toluene on neuronal nicotinic acetylcholine receptors expressed in oocytes and cultured hippocampal neurons. Toluene (50 micro M to 10 mM) produced a reversible, concentration-dependent inhibition of acetylcholine-induced current in Xenopus oocytes expressing various nicotinic receptor subtypes. The alpha4beta2 and alpha3beta2 subunit combinations were significantly more sensitive to toluene inhibition than the alpha4beta4, alpha3beta4 and alpha7 receptors. 3 Receptors composed of alpha4 and beta2(V253F) subunits showed alpha4beta4-like toluene sensitivity while those containing alpha4 and beta4(F255V) subunits showed alpha4beta2-like sensitivity. 4 In hippocampal neurons, toluene (50 micro M to 10 mM) dose-dependently inhibited ACh-mediated responses with an IC(50) of 1.1 mM. 5 Taken together, these results suggest that nicotinic receptors, like NMDA receptors, show a subunit-dependent sensitivity to toluene and may represent an important site of action for some of the neurobehavioural effects of toluene.

Acetylcholine↗
PubMed2000

A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler.

RATIONALE: Nicotine replacement therapy (NRT) in varying forms is becoming widely used. Clinicians, therapists and regulatory authorities are interested in the abuse liability and dependence potential of the different forms. OBJECTIVES: To compare the abuse liability and dependence potential of nicotine gum, transdermal patch, spray and inhaler. METHODS: 504 male and female smokers seeking help with stopping smoking were randomly allocated to the four products. Measures were taken at the designated quit date, then 1 week, 4 weeks, 12 weeks and 15 weeks later. Smokers were advised to use the product for up to 12 weeks. Those still using the product at the 12-week visit were advised to cease use by week 14. Measures included: pleasantness and satisfaction ratings at weeks 1 and 4 (used as a marker of abuse liability); ratings of feeling dependent on NRT at weeks 1, 4, 12 and 15 (used as a marker of subjective dependence); mood and physical symptoms ratings at weeks 12 and 15 (the change being used to assess physical dependence on NRT), continued usage of NRT at week 15 (used as an marker of behavioural dependence). RESULTS: Average ratings of pleasantness were low. The nicotine patch was rated as less unpleasant to use than all other products. There were no significant differences between the products in terms of satisfaction or subjective dependence except at week 15 when no patch users rated themselves as dependent. Continued use of NRT at week 15 was related to rate of delivery of nicotine from the products - 2% for patch, 7% for gum and inhaler, 10% for spray (P<0.05 for linear association). Among those

Adult↗
PubMed1988

"Crack smoke" is a respirable aerosol of cocaine base.

The smoking of cocaine base [corrected] ("crack") has emerged as a significant substance abuse problem. A detailed characterization of cocaine smoke is a prerequisite for studies of its pharmacokinetics, abuse potential and toxicity. Model pipes were used to generate cocaine smoke analogous to that inhaled by human "crack" abusers. Using procedures to minimize pyrolysis, cocaine base smoke was determined to be 93.5% cocaine particles with the remainder being cocaine vapor. The average particle size generated from all model pipes was 2.3 mu which is small enough to ensure deposition into the alveolar region of the human lung. Although this particle size is eminently respirable [corrected] by primates, a much smaller fraction will reach the alveolar region of rodents. Special generating procedures would therefore be required to expose rodents to meaningful doses of airborne cocaine that mimic the rapid absorption achieved by "crack" smokers.

Aerosols↗
PubMed2003

Neuromotor effects of acute ethanol inhalation exposure in humans: a preliminary study.

Ethanol (ETOH) is added to unleaded gasoline to decrease environmental levels of carbon monoxide from automobiles emissions. Therefore, addition of ETOH in reformulated fuel will most likely increase and the involuntarily human exposure to this chemical will also increase. This preliminary study was undertaken to evaluate the possible neuromotor effects resulting from acute ETOH exposure by inhalation in humans. Five healthy non-smoking adult males, with no history of alcohol abuse, were exposed by inhalation, in a dynamic, controlled-environment exposure chamber, to various concentrations of ETOH (0, 250, 500 and 1,000 ppm in air) for six hours. Reaction time, body sway, hand tremor and rapid alternating movements were measured before and after each exposure session by using the CATSYS 7.0 system and a diadochokinesimeter. The concentrations of ETOH in blood and in alveolar air were also measured. ETOH was not detected in blood nor in alveolar air when volunteers were exposed to 250 and 500 ppm, but at the end of exposure to 1,000 ppm, blood and alveolar air concentrations were 0.443 mg/100ml and 253.1 ppm, respectively. The neuromotor tests did not show conclusively significant differences between the exposed and non-exposed conditions. In conclusion, this study suggests that acute exposure to ethanol at 1,000 ppm or lower or to concentrations that could be encountered upon refueling is not likely to cause any significant neuromotor alterations in healthy males.

Adult↗
PubMed1981

Development of an animal model of solvent abuse for use in evaluation of extreme trichloroethylene inhalation.

Self-intoxication by inhalation of vapors of trichloroethylene (TCE) and other solvents is widespread. In order to develop exposure protocols which typify episodes of TCE "sniffing", male Wistar-Munich rats were exposed to TCE vapor levels ranging from 9000 to 16 000 ppm. TCE in concentrations of 14 000 ppm and greater quickly produced loss of righting reflex. Recovery from the narcosis was very rapid. Central nervous system (CNS) depression was found to be cumulative in rats subjected for 5 h to alternating periods of 5 min of 15 000 ppm TCE and 15 min of fresh air. Ethanol markedly potentiated depression in these subjects. No evidence of liver or kidney damage was seen in rats subjected to the repetitive 5-h TCE inhalation regimen, nor in rats fasted for 16 h before the TCE-exposure session. Oral administration of 5 ml/kg body wt of ethanol 1 h, 16 h, or once daily for 3 days before the TCE-exposure regimen had little if any potentiating effect on hepatorenal toxicity potential. Animals that received ethanol and were fasted before TCE exposure exhibited slight elevations in SGOT and SGPT levels.

Animals↗
PubMed1987

Abuse of smoking methamphetamine mixed with tobacco: I. Inhalation efficiency and pyrolysis products of methamphetamine.

Experiments of smoking methamphetamine in tobacco have been investigated. Inhalation efficiencies of methamphetamine into tar were 6 to 17% according to the additive amounts, suction volume, and intervals of smoking. Major pyrolysis products of methamphetamine in tar were identified as methamphetamine, amphetamine, phenylacetone, dimethylamphetamine, N-formyl-, N-acetyl-, N-propionyl-, and N-cyanomethyl-methamphetamine by the spectral analysis of infrared spectra (IR), mass spectra (MS), and proton magnetic resonance spectra (PMR), and comparison with the samples synthesized from authentic samples by one step. The largest pyrolysis product was N-cyanomethylmethamphetamine which is a new compound and easily metabolized to methamphetamine in the body. Methamphetamine itself transferred into tar was not so large, but the total active compounds in tar which would be metabolized to methamphetamine in the body were considerably larger.

Administration, Inhalation↗
PubMed1996

Medical complications of glue sniffing.

Glue sniffing refers to the deliberate inhalation of volatile solvents, commonly found in adhesives, for the purpose of intoxication. The increasing prevalence of inhalant use suggests that many physicians will encounter a glue-sniffing patient at some time during their practice. Knowledge of the epidemiology, toxicology, and medical complications associated with glue sniffing is essential in obtaining an accurate history of substance abuse and in clinically managing these patients. This review of sources is intended to aid clinicians in the recognition of glue-sniffing patients and in the diagnosis of acute and chronic medical complications associated with the abuse of glues, solvents, and related substances. Glue sniffing has been linked to sudden death and chronic damage to the heart, lungs, kidneys, liver, peripheral nerves, and brain. Inhalant abuse in general is associated with mortality and morbidity, including social, educational, and economic deprivation in adolescents and young adults.

Acute Disease↗
PubMed2000

Site of nicotine absorption from a vapour inhaler--comparison with cigarette smoking.

OBJECTIVE: The aim of the study was to assess the site of nicotine absorption during and after use of a nicotine-vapour inhaler compared with that after cigarette smoking. METHODS: Using a catheterisation technique, the nicotine plasma concentration-time profiles in arterial and jugular venous blood after using a nicotine inhaler were compared with those achieved after cigarette smoking a in seven healthy habitual smokers. RESULTS: After use of the inhaler, arterial nicotine concentrations rose slowly to a maximum level of 5. 9 +/- 1.5 ng/ml at a mean time to reach peak concentration (t(max)) of 9.0 +/- 1.1 min, whereas jugular venous nicotine levels peaked at 25.4 +/- 5.4 ng/ml at 6.7 +/- 0.3 min. The concentration-time curves indicate that the absorption occurs mainly via the mucosa of the oral cavity and the pharynx, and that there is minimal absorption via the lungs. In contrast, after smoking a cigarette, arterial nicotine plasma concentrations rose quickly to a maximum level of 49. 2 +/- 9.7 ng/ml after 4.0 +/- 0.6 min, while the maximum concentration of nicotine in the jugular vein was 22.4 +/- 3.9 ng/ml after 6.4 +/- 0.4 min, indicating primarily pulmonary absorption of nicotine. CONCLUSION: Nicotine absorption after use of the vapour inhaler occurs primarily via the mucosa of the oral cavity; the absorption occurs slowly and the arterial nicotine concentration spike, typical of cigarette smoking, is avoided. Thus, the likelihood for abuse of the nicotine inhaler is probably small.

Absorption↗
PubMed1999

[Pulmonary hemorrhagic syndrome after inhalation of cocaine].

Frequency of recreational abuse of cocaine is increasing. We report the case of a patient who developed an acute anemia associated with an alveolar hemorrhage after repeated inhalation of cocaine. He presented with daily hemoptysis and dyspnea. Chest-X ray and CT scan showed bilateral micronodular opacities. The fibroscopic alveolar lavage fluid showed fresh blood. DLCO/VA was 117% predicted. With oxygen therapy and no blood transfusion the evolution was positive within 48 hours, without relapse. The occurrence of hemoptysis in subjects who inhale cocaine must lead to suspect cocaine induced-pulmonary hemorrhage.

Adolescent↗
PubMedDate not supplied

Recent developments in the abuse of cocaine.

Cocaine is a powerful euphoriant and it relieves, though only transiently, depression, dread and dysphoria. New patterns of cocaine abuse, such as the inhalation of vaporized cocaine base, the intravenous injection of cocaine hydrochloride and the smoking of coca paste, produce a brief elation that quickly gives way either to a return to the baseline mood or to displeasure, resulting in a strong desire to return to the momentary ecstatic experience, a cycle that leads to compulsive use. The enormous profits made from illicit traffic in cocaine lead to corruption, violence and political destabilization. The individual costs of cocaine abuse include loss of personal fortunes, jobs and families. The safety of cocaine use is a myth. There are a number of ways in which cocaine can be lethal. The high doses of cocaine abused today induce physical dependence, but this is less a contributory factor than the intense psychological craving to perpetuate cocaine use. There is no specific way to treat dysfunctional cocaine use; instead the treatment plan must deal with the individual's specific situation. Except for a reduction of cocaine supply at the source, preventive measures are only feasible in the context of abstinence from all abusable drugs.

Animals↗
PubMed2006

Inhalant use and disorders among adults in the United States.

OBJECTIVE: To examine the patterns of adult inhalant use and correlates of inhalant use disorder. METHOD: We drew study data from the 2002 and 2003 National Surveys on Drug Use and Health (NSDUH). We used logistic regression to identify the characteristics associated both with inhalant use and inhalant use disorder. RESULTS: One in 10 of all adults had used an inhalant at least once in their lives, and 0.5% used one in the past year. Among all past year inhalant users, 8% met the criteria for an inhalant use disorder (i.e., 6.6% for abuse and 1.1% for dependence) within that period. We found an increased prevalence of past year inhalant use among young adults aged 18-25 years, Asians, past year alcohol abusers and dependents, lifetime drug users, white women, and men reporting symptoms of serious mental illness. Inhalant-using adults who met the criteria for an inhalant use disorder were predominantly adults aged 35-49 years and were less educated, had received recent professional treatment for emotional or psychological problems, used inhalants weekly, and had a coexisting alcohol use disorder. CONCLUSION: The patterns and consequences of adult inhalant use differ from those of adolescents. Compared with adolescent inhalant users, adult users tend not to initiate inhalant use until adulthood, use inhalants less frequently, use fewer inhalants, and are less likely to engage in criminal activities.

Administration, Inhalation↗
PubMed2001

Airway effects of marijuana, cocaine, and other inhaled illicit agents.

Several substances besides tobacco are inhaled for recreational purposes, including marijuana, crack cocaine, amyl and butyl nitrites, heroin, methamphetamine, and phencyclidine. Abuse of most of these inhaled substances has risen in recent years, thereby increasing concern about potential pulmonary and other medical complications. Regular marijuana use can lead to extensive airway injury and alterations in the structure and function of alveolar macrophages, potentially predisposing to pulmonary infection and respiratory cancer. Crack cocaine use can lead to a variety of acute pulmonary complications, including severe exacerbations of asthma and an acute lung injury syndrome associated with a broad spectrum of histopathologic changes ("crack lung"). Habitual cocaine smoking may also produce more subtle long-term pulmonary consequences due to chronic alveolar epithelial and microvascular lung injury. Heroin inhalation can induce severe and even fatal exacerbations of asthma. Pulmonary consequences of inhaled amyl and butyl nitrites, crystalline methamphetamine (ice), and phencyclidine have been less well documented.

Animals↗
PubMed2000

Current status of burn resuscitation.

Rapid assessment and management of airway and breathing problems are required in the patient with severe burns complicated by significant facial burns and inhalation injury. A policy that results in intubation of all patients at potential risk for airway compromise can be both foolish and dangerous. At the same time, it is recognized that intubation of patients who are likely to develop unstable airways is necessary if transport times to burn centers are long and if i.v. resuscitation is initiated during transport. The ideal burn resuscitation formula does not exist. Whichever formula is used, patients must be monitored closely and the fluid resuscitation individualized according to their responses. Patients with delay in resuscitation, associated trauma, inhalation injury, or alcohol abuse may require fluid resuscitations greater than those predicted. The goal is to maintain urine outputs in the range of 0.5 to 1 mL/kg/hr for adults and 1 to 1.5 mL/kg/hr in children. In patients with fluid requirements greater than 150% of that predicted by formula, the addition of colloid at 12 hours can reduce total fluid requirements and burn edema. Early placement of pulmonary artery catheters can be useful in patients with known myocardial dysfunction, age greater than 65 years, severe inhalation injury, or fluid requirements greater than 150% of that predicted by formula.

Adult↗
PubMed1990

Passive inhalation of cocaine by infants.

Cocaine abuse has increased greatly in recent years, creating important medical, legal, and social problems. Urine drug testing is used to diagnose cocaine ingestion. The presence of the cocaine metabolite benzoylecgonine (BZ) is commonly believed to be proof of recent cocaine intoxication. However, oral ingestion of even a minute quantity of cocaine can result in a positive test result. BZ was detected in the urine of four nonbreast-fed infants aged 6 weeks to 14 months who were admitted with diagnoses unrelated to cocaine poisoning. These infants were exposed to cocaine by passive inhalation of vapors generated by adult caretakers smoking "crack" cocaine. Two of the infants were retested 12 hours later and had no detectable BZ, strongly suggesting ingestion of a subpharmacologic amount of cocaine. Because passive inhalation of cocaine can produce measurable urine BZ concentrations, a positive urine screen does not necessarily indicate poisoning or intentional administration of the substance and therefore is not proof of child abuse or neglect.

Cocaine↗
PubMed2000

Comparison of nonradioactive microtiter plate enzyme immunoassays for the sensitive detection of fentanyl.

Fentanyl is a very strong opioid with analgesic properties that are approximately 80 times stronger than those of morphine and therefore is used in major surgery and treatment of pain in tumor patients. Cases of fentanyl abuse by intravenous injection, inhalation, oral or nasal application have been reported especially in the USA. Therapeutic levels of fentanyl are as low as 1 ng/ml of serum and therefore a screening test must have a detection limit below that concentration. Recently three non-radioactive enzyme immunoassays (EIAs) have become commercially available from COZART, STC and DIAGNOSTIX, all of them supplied by MAHSAN Diagnostika for evaluation with serum samples from forensic and clinical cases. A calibration curve is obtained with samples that contain 0, 0.1, 0.5, 1 and 5 ng fentanyl per ml of negative serum. The calibration curve of COZART is especially in the low range, steeper than those of STC and DIAGNOSTIX. The cut-off for all these EIAs, however, can be set at 0.5 ng/ml. After the administration of therapeutic doses, fentanyl concentrations were between 3 and more than 5 ng/ml as determined with the EIAs. The presence of the typical drugs of abuse, e.g. heroin, methadone, cocaine, cannabinoids and amphetamines including the derivatives of methylenedioxyamphetamine, don't generate false-positive results. No cross-reactivity was also observed at toxic levels of benzodiazepines and paracetamol and therapeutic levels of barbiturates, phenothiazines, antidepressants and analgesics. The EIAs tested so far appear to be suitable for the detection of fentanyl at therapeutic levels. False-positive results or cross-reactivity towards other compounds have not been observed.

Analgesics, Opioid↗
PubMed1991

[A preliminary study on the behavior of 225 drug abusers and the risk factors of HIV infection in Ruili county Yunnan Province].

We carried out the investigation on 225 drug abusers in L village, Ruili county in March 1990, and tested blood specimens of intravenous users (IVDUs) for HIV infection. Of 225 drug abusers, 153 (68.0%) were by inhaling and 72 (32.0%) were by intravenous. In the recent two years, the proportion of IVDUs in drug abusers sharply increased from 13.5% in 1988 to 30.5% in 1989, and 32.0% in spring 1990. Blood specimen were collected from 64 out of 72 IVDUs, among them 51 (79.7%) were HIV-positive. The findings of relation between HIV infection and drug abuse suggested that the sharing common syringes with others and failure of their sterilization were independent risk factors.

Adolescent↗