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PubMed2004

A comparison of alcohol and drug disorders: is there evidence for a developmental sequence of drug abuse?

Whereas the model of Jellinek [Q. J. Stud. Alcohol 7 (1952) 673] of a predictable progression of alcoholism is generally supported, there have been few published studies regarding the natural history of illicit drug disorders. Identification of the development of drug abuse and/or dependence can inform clinicians and researchers on issues, such as diagnosis, prognosis, assessment, and prevention. This study employed a new measure adapted from the 46 events described in Jellinek's progression of alcoholism. Nine licit and illicit substances were also included within the cardsort. Fifty-two individuals motivated to enter drug treatment by a loved one were assessed pretreatment. The drug initiation sequence reported by this sample was as follows: alcohol, tobacco, inhalants, marijuana, and then other drugs. Spearman rank correlation coefficients were conducted between the drug sample and that of Jellinek yielding a modest correlation (r=.35, P=.019). These results suggest that Jellinek's model of progression of alcoholism may also apply to the development of drug disorders. However, important differences found between the alcohol and drug progressions are discussed.

Adolescent↗
PubMed1982

The relationship between alcohol use and other drug use among New York State college students.

A questionnaire dealing with alcohol and drug use was administered to a representative sample of 7723 New York State undergraduate students. Those students who were heavy drinkers were also more likely to use tobacco, marijuana, and other drugs. Factor analysis revealed patterns of use of four distinct types of drugs: "party" drugs, medical sedatives, inhalants, and psychedelic drugs. Users of party drugs were typically male, white and American-born. Sedative users were typically female, white and older students. Inhalant users were typically male, while psychedelic drug users tended to be white Americans of either sex.

Adolescent↗
PubMed2004

The measurement of nicotine in human plasma by high-performance liquid chromatography-electrospray-tandem mass spectrometry.

The authors describe a reverse-phase high-performance liquid chromatography-electrospray-tandem mass spectrometry method for the measurement of nicotine in human plasma. Samples (500 microL) with added deuterium-labeled d3-nicotine as an internal standard (IS) were treated with a 2-step process of ether extraction (6 mL) followed by back-extraction into 0.1% formic acid (50 microL). Chromatography was performed on a phenyl Novapak column with a mobile phase consisting of 50% 10 mM ammonium formate (pH 3.3) and acetonitrile (50:50, vol/vol). A flow rate of 0.2 mL/min resulted in a total analysis time of 5 minutes per sample. Mass spectrometric detection was by selected reactant monitoring (nicotine m/z 163.2 --> 130.2; IS m/z 166.2 --> 87.2). The assay was linear from 0.5 to 100 microg/L (r > 0.993, n = 9). The accuracy and imprecision of the method for quality control samples were 87.5% to 113% and <10.2%, respectively. Interday accuracy and imprecision at the limit of quantification (0.5 microg/L) was 113% and 7.2% (n = 4). The process efficiency for nicotine in plasma was >75%. The method described has good process efficiency, stabilized nicotine, avoided concentration steps, and most importantly minimized potential contamination. Further, we have established that water-based standards and controls are interchangeable with plasma-based samples. This method was used successfully to measure the pharmacokinetic profiles of subjects involved in the development of an aerosol inhalation drug delivery system.

Chromatography, High Pressure Liquid↗
PubMed1987

The epidemiology of illicit drug use in Spain.

On the basis of a review of the available information, this article summarizes the situation, patterns and trends in respect of the use of cannabis, heroin and other opiates, cocaine, amphetamines, hallucinogens and inhalants, as well as multiple drug use. The review clearly shows that since the early 1980s there has been an increasing trend in the use of drugs, particularly heroin and cannabis. Drug use predominantly affects young people. The use of two or more drugs simultaneously or successively, often involving alcohol, is reported as the most common pattern of drug use among youth. Drug use has become incorporated into the current youth culture, with all the individual, social and economic implications this engenders. The average age of users at first use of inhalants was 16.3 years, cannabis 17.5 years, hallucinogens 18.8 years, cocaine 20.6 years and amphetamines 23.5 years.

Adolescent↗
PubMed1990

[Anesthetic care of a patient intoxicated with thinner].

This is a report of a 28 year old male who underwent emergency laparotomy. He had a history of asthma and chronic abuse of thinner (toluene), and he stabbed himself after acute intoxication by the drug. Anesthesia was induced and maintained by halothane and oxygen. Vecuronium was used for muscle relaxation. Abnormal EKG was seen during perioperative period: A-V dissociation and incomplete RBBB. After emergence from anesthesia, so called "flash back" phenomenon was observed but this was controlled by diazepam. Since the chronic abuse of toluene causes organic changes in many vital organs, we must take special precautions when we anesthetize a patient with thinner intoxication: (1) toluene has a negative inotropic effect and also delays the S-A and A-V conduction rate, which may potentiate the cardiac effect of inhalation anesthetics; (2) toluene causes liver damages; and (3) the patient may experience "flash back" phenomenon.

Adult↗
PubMedDate not supplied

Informed consent and investigational new drug abuses in the U.S. military.

OBJECTIVE: The focal point of this investigation was to research the ethical issues surrounding the military's requests for informed consent waivers when using investigational drugs, and the recent debate surrounding the anthrax vaccine as an investigational new drug (IND). DESIGN: The military's management of the informed consent process was examined using documents obtained through the Freedom of Information Act, Institutional Review Board (IRB) minutes, legal pleadings, and protocols for specific investigational drugs. RESULTS: In December 1990, prior to Operation Desert Storm, the Federal Drug Administration (FDA) granted the Department of Defense (DoD) an unprecedented waiver to the federally mandated informed-consent requirement for the use of investigational drugs. However, the waiver approval was conditional, and the FDA insisted on several safeguards. Partially in response to the subsequent Gulf War Syndrome debate, the FDA recently evaluated the military's use of investigational drugs during the Gulf War. The FDA cited the military for significant deviations from the originally approved protocols. Most notably, the military was found to be abusing the IRB process by convening a second IRB when the first IRB concluded that waiving informed consent was unethical. In addition, there was a gross lack of documentation and no monitoring of adverse reactions. The DoD's plan to use the current anthrax vaccine on all 2.4 million troops against inhalation anthrax has kindled an additional investigational drug controversy. The safety and efficacy of the use of the anthrax vaccine as a prophylactic against inhalation anthrax have been questioned by both military and medical organizations. There have never been any published studies of human efficacy or long-term effects for the anthrax vaccine. In addition, the military is not using the vaccine for its intended purpose, and it is also not adhering to prescribed dosing schedules. There is clear evidence to support the claim that, in fact, the military's use of the anthrax vaccine should be considered unethical. CONCLUSIONS: I argue that in medical situations, the military is obligated to treat its troops as autonomous persons entitled to basic rights and protections. The DoD is currently using an approved drug, the anthrax vaccine, for an unapproved purpose and in an unapproved manner. In doing so, the DoD is not only violating the FDA's regulations against such practices, it is also violating an executive order which only allows the president to authorize the use of INDs on service members without their consent.

Anthrax↗
PubMed1989

Incidence and risk factors for human immunodeficiency virus seroconversion in a cohort of Sydney homosexual men.

By means of prospective cohort data from the Sydney AIDS Project, we report on 55 homosexual or bisexual men who have become infected with human immunodeficiency virus (HIV), as measured by the development of serum HIV antibodies (seroconversion). We have compared the sexual practices, recreational drug abuse, history of sexually-transmissible diseases, and antecedent immunological findings of the men who seroconverted with those of 588 subjects who persistently remained seronegative in the same time-period. The cumulative incidence rate of HIV infection over the three years of observation was 8.5%. The cumulative incidence rate ranged from less than 1% for the six months before August 1, 1984, to a peak of 5% in the six months before August 1, 1985. Of those subjects for whom we had data for the period of seroconversion, all but two of the subjects who seroconverted admitted to a recognized high-risk sexual practice in the six months before the first visit at which they were found to be seropositive. Univariate analysis found that men who seroconverted were significantly more likely to have had a greater number of recent sexual partners (relative risk per partner, 1.02; P less than 0.001), to have engaged in receptive anal intercourse (incidence rate ratio, 3.1; 95% confidence interval [CI], 1.3-7.6; P = 0.01) and to have used nitrite inhalant (incidence rate ratio, 2.6; 95% CI, 1.2-5.9; P = 0.02) and amphetamine (incidence rate ratio, 4.8; 95% CI, 2.2-10.5; P less than 0.001) drugs. The men who seroconverted were significantly (incidence rate ratio, 2.7; 95% CI, 1.2-6.1; P = 0.014) more likely to have antecedent T-suppressor-cell counts of greater than 800 cells/microL. Factors that retained significance in multivariate analysis were the number of recent sexual partners, recent amphetamine abuse and a T-suppressor-cell count of greater than 800 cells/microL.

Adolescent↗
PubMed1996

[Measurement of expired alcohol concentrations with a new electrochemical sensor. A model investigation to determine interference with volatile anesthetics and clinical application].

UNLABELLED: Absorption of irrigating fluid in transurethral prostatic resection (TURP) and percutaneous nephrolitholapaxy (PNL) into veins or delayed absorption due to fluid extravasation may result in a TURP syndrome. The measurement of end-tidal breath alcohol concentration (et AC) as a monitor of absorption of irrigating fluid labelled with 2% ethanol is limited by the disturbance of infrared sensors by volatile anaesthetics and nitrous oxide (N2O) (Fig. 2). An electrochemical sensor is acceptable for this method. The aim of the present study was the evaluation of breath alcohol measurements using an electrochemical sensor device (Alcomed 3010, Envitec). The stability of the sensor in the presence of volatile anaesthetics was examined using a lung model. In a clinical investigation, the device was then applied to spontaneously breathing or mechanically ventilated patients inhaling volatile anaesthetics during endoscopic urological surgery. METHOD: A two-chamber lung model filled with water for performing noninvasive measurements at the mouth of a patient has already been introduced by Brunner et al. (Fig. 1). With the addition of different amounts of ethanol to the temperature-controlled water, a constant ethanol concentration is achievable in the air above the water that is dependent on adjustments of the ventilator. Increasing concentrations of volatile anaesthetics (isoflurane, enflurane, halothane, and sevoflurane) were added to the fresh gas flow (2 l O2/3 l N2O) and etACs were measured using the manually triggered self-absorbent electrochemical sensor. First, regression equations were established between breath alcohol concentrations and increased volatile anaesthetic concentrations. Regression equations were then established between end-tidal anaesthetic gas concentrations and vaporizer adjustments in order to rule out an influence of ethanol on the anaesthetic gas monitor Ultima V (Datex). In the clinical investigation, 53 intubated and ventilated patients (33 undergoing PNL, 20 undergoing TURP) and 48 patients breathing spontaneously (32 with inhalation anaesthesia, 16 with spinal anaesthesia) were investigated. The etAC was measured with the Alcomed 3010 and compared with gas-chromatographically registered blood alcohol concentrations (BAC). The study had previously been approved by the Ethical Committee of the Medical University of Luebeck. Patients with liver disease and a history of toxic abuse were excluded. Only one value per patient (maximum BAC) was included in the statistics in order to avoid a cluster effect. RESULTS: The lung model experiments demonstrated that the measurement of etAC with an electrochemical sensor is free of interference by volatile anaesthetics (Table 1). The slope of the regression between the measured alcohol concentration and increased concentrations of anaesthetics did not differ significantly from baseline values. The measurement of end-tidal anaesthetic concentrations was not significantly different from vaporizer adjustments in the presence of increased alcohol concentrations (Table 2). During the clinical investigation, a regression between etAC and BAC was determined for both groups. For the group of patients breathing spontaneously, the correlation coefficient was 0.961 and the regression equation revealed etAC = 0.5677*BAC-0.1303 (Fig. 5). However, in the group of ventilated patients a biphasic course was shown that was dependent on BAC (Fig. 6). At BAC < 0.4%, a similar correlation (r = 0.856) to the spontaneously breathing group could be seen (regression equation: etAC = 0.617*BAC-0.020). Above 0.4% BAC there was no acceptable correlation (r = 0.444, regression equation: etAC = 0.202*BAC+0.104). CONCLUSIONS: The tested electrochemical sensor does not interfere with volatile anaesthetics and N2O as demonstrated by a lung model. There is a good correlation between etAC and BAC measurements in patients breathing spontaneously with special regard to the slope of the regression (s = 0.57).

Anesthetics↗
PubMed2003

Reasons for selecting an initial route of heroin administration and for subsequent transitions during a severe HIV epidemic.

AIM: To identify the most important reasons for selecting a particular route of heroin administration and for subsequent transitions during a period of epidemic HIV transmission. To study temporal trends in these reasons. DESIGN: Cross-sectional survey. PARTICIPANTS: Nine hundred heroin users in three Spanish cities: 305 in Seville, 297 in Madrid and 298 in Barcelona. MEASUREMENTS: A separate analysis was made of the reasons for five types of behaviour: (a) selecting injection as the initial usual route of heroin administration (URHA); (b) changing the URHA to injection; (c) never having injected drugs; (d) selecting the smoked or sniffed route as the initial URHA; and (e) changing the URHA to a non-injected route. Subjects were invited to evaluate the importance of each reason included in a closed list. Spontaneously self-perceived reasons were also explored in an open-ended question for each of the five types of behaviour studied. FINDINGS: The primary reason selected for each type of behaviour was: (a) pressure of the social environment; (b) belief that injection is a more efficient route than smoking or sniffing heroin; (c) concern about health consequences (especially fears of HIV and overdose), and fear of blood or of sticking a needle into one's veins; (d), pressure of the social environment and (e) concern about health consequences and vein problems. For women, having a sexual partner who injected heroin played a decisive role in initiating or changing to injection. Few people spontaneously mentioned market conditions for purchasing heroin as an important reason for any behaviour, nor did many mention risk of overdose as reasons for (c) or (d). CONCLUSIONS: These findings should be considered when designing interventions aimed at preventing initiation of injecting or facilitating the transition to non-injected routes.

Administration, Inhalation↗
PubMed2004

Heroin use among female adolescents: the role of partner influence in path of initiation and route of administration.

This study examined heroin initiation and route of administration among 16 female adolescents in the greater Baltimore Metropolitan area. Participants were more than twice as likely to be introduced to heroin by a male friend or boyfriend (IHM) than introduced to heroin by other means (IHO). The majority of IHM females were introduced by a male friend rather than a romantic partner. No relationship was found between path of initiation (IHM, IHO) and initial route of administration (inhalation, smoking, injecting) or history of injection (ever injected, never injected). The effect of opposite-gender peer influence in the initiation of female adolescent heroin use is discussed along with how the current findings may influence treatment and prevention efforts. A statistically significant relationship was found for initial route of administration and for history of injection. Ninety-four percent of participants reported initiation of heroin use by inhalation, while an alarming 75% of participants reported injecting heroin at some time during their history of use. Participants were no more likely to be introduced to injection by a boyfriend or male friend than by other means. The finding that the majority of females first try heroin through inhalation is consistent with an increased use of heroin by this method among young people in recent years. However, the majority of users in this study used heroin through injection at least once in their addict career, a route of administration associated with increased health and safety risks. Potential explanations for the progression from snorting to injection are presented as well as implications for the delivery of prevention and treatment services.

Administration, Inhalation↗
PubMed1989

Perinatal cocaine intoxication.

This report describes a case in which cocaine abuse during pregnancy was related temporally to abruptio placentae, preterm labour and to rapid delivery. The neonate developed respiratory distress with features of persistent pulmonary hypertension of the newborn and also signs of neurological dysfunction. He was managed by supportive therapy and has been followed-up to nine months of age. Perinatal cocaine intoxication, either directly or indirectly, is discussed as a cause of his cardiorespiratory and neurological maladaptation. As cocaine abuse appears to be an escalating problem in Australia, increased public awareness of the dangers of both acute and long-term abuse of the drug is seen as a priority in preventive care.

Adult↗
PubMed1988

New concepts in chronic asthma. What is the impact on therapy?

The following management guidelines, based on changing concepts in asthma pathogenesis and treatment, outline an approach aimed at reducing asthma morbidity and mortality. Use of these guidelines may help to reduce airway hyperreactivity and result in improved care for these patients. Maintain open lines of communication between patient and physician. Promote positive patient-physician interaction. Remain alert for signs of psychological problems. Use maintenance antiinflammatory medications and bronchodilators as needed. Discuss medication requirements and possible side effects. Caution against abuse of beta agonists. Monitor drug diaries and theophylline levels to assess medication requirements and compliance with treatment. Monitor daily peak expiratory flow rates in patients prone to severe attacks of asthma. Encourage patients to report progressive symptoms or peak expiratory flow rates less than 200 liters/min. For asthma uncontrolled by bronchodilators and inhaled antiinflammatory medications, treat promptly with systemic corticosteroids.

Allergens↗
PubMed2006

Variations in respiratory distress characterize the acute agonal period during heroin overdose death: relevance to postmortem mRNA studies.

AIMS: To determine whether there are factors during apparent rapid heroin overdose death that affect agonal state and thus brain pH (index of hypoxia) that can influence neurobiological systems linked to drug abuse. DESIGN AND METHODS: Brain specimens and autopsy/medical reports were investigated in subjects dying from heroin overdose (n=70) and compared to normal controls (n=45) as well as suicide victims (n=31) with a documented rapid cause of death. Detailed autopsy material was characterized as to positive and negative respiratory distress in relation to brain pH; drug toxicity and other demographic information was also evaluated. In situ hybridization histochemistry was used to study mRNA expression levels of dopamine (e.g., D2 receptor, dopamine transporter) and opioid (e.g., proenkephalin) related markers in various structures in relation to brain pH. FINDINGS: Brain pH was generally reduced in heroin overdose cases versus normal and suicide subjects. There was, however, significant variation in heroin overdose deaths related to differences in respiratory distress that differentially altered brain pH levels. Various factors such as vomit inhalation, resuscitation, pulmonary embolism and suffocation contributed to positive respiratory distress. Elevated brain pH was observed in heroin overdose with positive alcohol toxicity suggesting potentiated alcohol-induced rapidity of heroin deaths. mRNA expression levels of the dopamine-related genes and proenkephalin were positively correlated with brain pH. CONCLUSIONS: Respiratory distress contributes to variations in the acute agonal state during heroin overdose death that differentially alters brain pH levels and significantly impacts mRNA levels. Such findings should be considered for postmortem molecular/neurochemical neurobiological studies of opiate abusers.

Adolescent↗
PubMedDate not supplied

The heroin epidemic in New York City: current status and prognoses.

Since 1989, heroin production worldwide has risen; in New York City, as its purity rose and prices fell, street-level markets were restructured and offered heroin in addition to cocaine and crack (which had been popular during the 1980s). While officials estimate that there are between 500,000 and one million hard-core, chronic heroin users nationwide, evidence of supplemental users heralding another heroin era includes: more overdoses and overdose deaths, greater demand for treatment, larger seizures of heroin at all levels of distribution and related arrests, and broader media coverage. In this article, the authors describe the characteristics of populations in which there may have been a percentage increase of new users, such as young middle- or upper-class European-Americans, young Puerto Ricans and recent Haitian and Russian immigrants. The abstinence of young African-Americans is also noted. The article ends with a preliminary needs assessment of the new users in the areas of health (including AIDS), housing, employment, treatment, arrest and imprisonment.

Administration, Inhalation↗
PubMed1992

A regional poison center's experience with poisoning exposures occurring in schools.

The nature of and response to poisonings in the school setting has not been characterized. To define these problems a retrospective review of calls to a Regional Poison Information Center (RPIC) involving school exposures was done for the 1988-89 academic year. 362 cases were reported; 74% were reported by school nurses, 10% by other school employees, 10% by parents, 5% by health care facilities, and 1% by students themselves. Ingestions accounted for 45% of exposures, dermal 24%, ocular 19%, inhalation 7%, with the remainder being combinations of routes. Correct treatment prior to RPIC consultation occurred in only 40% of the cases. None developed major symptoms, 23% had minor and 10% had moderate symptoms. High school students accounted for the greatest number (20) of suicide gestures, while middle schools reported more cases of substance abuse. School nurses often were unaware of situations until several hours later. 61% of suicide gestures were referred to an HCF; 7 of these developed moderate symptoms. Exposures to chemicals in science or vo-tech classes accounted for 102 cases; 28% were referred to a HCF and 15% had moderate symptoms. There was often a delay in evaluation by the school nurse and initial decontamination was inadequate or absent. Parents were often instructed by school personnel to contact the RPIC for information and then relay it to the school. These delays could have resulted in greater toxicity. School nurses should be targeted for educational programs by poison centers, but teachers and other school employees must also be included since often they are the first at the scene. Students should be instructed to report exposures to a teacher immediately.

Accidents↗
PubMed2004

Occupational exposure and addictions for physicians: case studies and theoretical implications.

Risk of addiction through occupational exposure to drugs of abuse is an important but relatively neglected public health problem. Stress and access may have much less of a role in addiction among certain populations than originally was thought. Risk of addition may be increased dramatically by unintentional exposure in the workplace to potent substances that sensitize the brain. Everyone knows that second-hand inhalation of crack vapors is a very dangerous proposition, but rarely has alarm been raised about exposing anesthesiologists to second-hand fentanyl. Additional studies of the relationship between exposure in the workplace and addiction are necessary. These studies should include biological measures, such as blood levels in exposed workers, and sensitive assays that quantitatively assess levels of exposure in the workplace.

Behavior, Addictive↗
PubMed2000

Intratracheal clenbuterol in the horse: its pharmacological efficacy and analytical detection.

Clenbuterol, a beta2 agonist/antagonist, is the only bronchodilator approved by the US Food and Drug Administration for use in horses. The Association of Racing Commissioners International classifies clenbuterol as a class 3 agent, and, as such, its identification in post-race samples may lead to sanctions. Anecdotal reports suggest that clenbuterol may have been administered by intratracheal (IT) injection to obtain beneficial effects and avoid post-race detection. The objectives of this study were (1) to measure the pharmacological efficacy of IT dose of clenbuterol and (2) to determine the analytical findings in urine in the presence and absence of furosemide. When administered intratracheally (90 microg/horse) to horses suffering from chronic obstructive pulmonary disease (COPD), clenbuterol had effects that were not significantly different from those of saline. In parallel experiments using a behavior chamber, no significant effects of IT clenbuterol on heart rate or spontaneous locomotor activity were observed. Clenbuterol concentrations in the urine were also measured after IT dose in the presence and absence of furosemide. Four horses were administered i.v. furosemide (5 mg/kg), and four horses were administered saline (5 mL). Two hours later, all horses were administrated clenbuterol (IT, 90 microg), and the furosemide-treated horses received a second dose of furosemide (2.5 mg/kg, i.v.). Three hours after clenbuterol dose (1 h after hypothetical 'post-time'), the mean specific gravity of urine samples from furosemide-treated horses was 1.024, well above the 1.010 concentration at which furosemide is considered to interfere with drug detection. There was no interference by furosemide with 'enhanced' ELISA screening of clenbuterol equivalents in extracted and concentrated samples. Similarly, furosemide had no effect on mass spectral identification or quantification of clenbuterol in these samples. These results suggest that the IT dose of clenbuterol (90 microg) is, in pharmacological terms, indistinguishable from the dose of saline, and that, using extracted samples, clenbuterol dose is readily detectable at 3 h after dosing. Furthermore, concomitant dose of furosemide does not interfere with detection or confirmation of clenbuterol.

Administration, Inhalation↗