Correlation of saliva cocaine levels with plasma levels and with pharmacologic effects after intravenous cocaine administration in human subjects

The behavioral and physiologic effects of single, intravenous bolus doses of cocaine in 5 male human subjects were correlated with cocaine levels in saliva and blood. All measures were performed under double-blind conditions. Two test doses of cocaine (15 mg and 40 mg) and one placebo test dose were administered to each subject in a random, cross-over design. Each test day was separated by a minimum of 48 h. Cocaine levels in saliva and blood significantly (p less than or equal to 0.05) correlated with responses on self-rating scales for drug sensation (Feel Drug scale), psychotomimetic effects (LSD scale), and feelings of rush (Rush scale). Significant (p less than or equal to 0.01) correlations also were obtained with cocaine biofluid levels and pulse rate. The close relationship observed between cocaine saliva levels and cocaine-induced behavior and physiologic effects presents the opportunity for development of a new noninvasive method for detection of current cocaine use.     

Cardiopulmonary support in the intensive care unit.

The cardiopulmonary support system is an extracorporeal device that allows for rapid cardiopulmonary support of the critically ill patient in the intensive care unit. It provides immediate and complete support of cardiac and pulmonary functions to maintain perfusion to vital organs in patients who are severely physiologically compromised (eg, in cardiogenic shock, adult respiratory distress syndrome or pulmonary edema). Successful cardiopulmonary support requires systemic anticoagulation, percutaneous venous and arterial cannulation and careful monitoring by the critical care team to maintain adequate tissue perfusion and oxygenation. Although patient mortality can occur secondary to bleeding, embolism or sepsis, this technique provides life-sustaining circulatory and respiratory support until definitive treatment can be initiated.     

Testing human hair for drugs of abuse. III. Identification of heroin and 6-acetylmorphine as indicators of heroin use

Hair samples from 20 documented heroin users contained 6-acetylmorphine, a unique metabolite of heroin, in all samples. Heroin was identified in smaller amounts in seven of these samples. The identity of 6-acetylmorphine and heroin was established by comparison of full scan spectra of extracts to standard reference materials. The presence of 6-acetylmorphine generally predominated over heroin, morphine, and codeine. The mean concentrations of analytes were as follows: 6-acetylmorphine, 0.90 ng/mg, N = 20; heroin, 0.17 ng/mg, N = 7; morphine, 0.26 ng/mg, N = 20; codeine, 0.18 ng/mg, N = 15. Analysis of hair samples obtained from 10 drug-free control subjects were negative for 6-acetylmorphine, morphine, and codeine. However, a small interfering peak was observed at the retention time for heroin. Control samples soaked in aqueous solutions of heroin and 6-acetylmorphine were found to be contaminated, even though an initial wash step was included in the analysis. These data suggest that hair analysis for 6-acetylmorphine can be used to differentiate heroin users from other types of opiate exposure (e.g., poppy seed, licit morphine, and codeine); however, environmental contamination can potentially produce false positives during opiate testing.     

Acute effects of smoking marijuana on hormones, subjective effects and performance in male human subjects

Four healthy male subjects smoked two marijuana cigarettes or one marijuana cigarette and one placebo cigarette, or two placebo cigarettes on separate days in a random order crossover design. Each marijuana cigarette contained 2.8% delta-9-tetrahydrocannabinol (THC). Plasma hormones and THC were measured before and after each smoking session. Plasma LH was significantly depressed and cortisol was significantly elevated after smoking marijuana. Nonsignificant depressions of prolactin, FSH, testosterone and free testosterone and elevation of GH also occurred. Concurrent measures of subjective effects via subscales of the Addiction Research Center Inventory, Single Dose Questionnaire and a Visual Analog Scale were generally elevated. Significant impairment on a psychomotor performance task paralleled elevations in subjective effects, hormone effects and peak THC determinations. Although all the hormone effects were within normal basal ranges, interactions between these systems, and their effects on behavior cannot be discounted.     

The disposition of cocaine and opiate analytes in hair and fingernails of humans following cocaine and codeine administration

This study investigated the disposition patterns of cocaine and opiates into hair and fingernail specimens collected from 8 volunteers enrolled in a 10-week inpatient clinical study. All subjects were African-American males with a confirmed drug use history. Scalp hair and fingernail scrapings were collected weekly throughout the course of the study. Head hair was collected from the posterior vertex region, and fingernail scrapings were collected along the entire ventral surface of the nail plate. The specimens were introduced to successive decontamination washes including an isopropanol wash and three phosphate buffer washes. All decontamination washes were collected and analyzed. All specimens were enzymatically digested prior to being subjected to solid-phase extraction and derivatization. Analyses were performed using electron impact gas chromatography-mass spectrometry. Analytes investigated included eight cocaine analytes and five codeine analytes. The limit of quantitation for all analytes ranged from 0.1 to 0.5 ng/mg for both matrices. Cocaine was present at the highest concentrations of any analyte in both hair and nail. Benzoylecgonine and ecgonine methyl ester were the primary metabolites in both matrices and were typically less than 15% of cocaine concentrations. Codeine was the only opiate analyte identified in either hair or nail. Observed drug disposition profiles were different for hair and nails. A significant dose-response relationship was observed for hair specimens. The mean peak concentrations in hair after low dosing were half the concentration observed after high-dose administration. Generally, no clear relationship was evident between nail drug concentrations and dose. Decontamination washes removed less than 20% of the total drug present in hair, but removed most of the drug concentrations (60-100%) in nail. This investigation demonstrated that higher concentrations of drug were found in the subjects' hair than in their fingernails and that cocaine was found in both matrices at a greater concentration than codeine. Although both hair and nail have similar physical and chemical properties and may share common mechanisms of drug incorporation, this clinical study suggests that there are distinct differences in their disposition profiles.     

Urine drug testing of chronic pain patients. III. Normetabolites as biomarkers of synthetic opioid use

Opioids are important therapeutic agents available to patients with moderate to severe pain. The synthetic opioids, buprenorphine, fentanyl, meperidine, methadone, and propoxyphene have been utilized for decades as analgesics. One of the major biotransformation pathways of these drugs occurs through N-demethylation leading to the formation and excretion of normetabolites. Normetabolites generally exhibit longer half-lives than the parent drug leading to accumulation with prolonged use. As part of continuing research efforts to improve monitoring programs of chronic pain patients undergoing opioid treatment, we evaluated the prevalence and relative abundance of normetabolites of buprenorphine, fentanyl, meperidine, methadone, and propoxyphene in patients? urine specimens. Selected sets of specimens were analyzed without prior immunoassay screening by liquid chromatography-tandem mass spectrometry for buprenorphine, fentanyl, meperidine, methadone, propoxyphene, and their respective normetabolites. Limits of quantitation (LOQ) were as follows: buprenorphine, 1 ng/mL; fentanyl, 0.5 ng/mL; meperidine, 50 ng/mL; methadone, 50 ng/mL; and propoxyphene, 50 ng/mL. LOQs for normetabolites were equal to the parent drug with the exception of norbuprenorphine (2.5 ng/mL). The percentage of positive specimens that contained normetabolite (only) ranged from 8.0% for EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) to 53.1% for norpropoxyphene. Inclusion of the five normetabolites in the test panel produced an increase in detection rates for parent drug use as follows: buprenorphine, 10.0%; fentanyl, 42.1%; meperidine, 98.7%; methadone, 8.7%; and propoxyphene, 113.2%. The authors conclude that testing for synthetic opioid normetabolites enhances the effectiveness of monitoring programs for pain patients.     

Asthma diagnosed after 11 September 2001 among rescue and recovery workers: findings from the World Trade Center Health Registry

BACKGROUND: Studies have consistently documented declines in respiratory health after 11 September 2001 (9/11) among surviving first responders and other World Trade Center (WTC) rescue, recovery, and clean-up workers. OBJECTIVES: The goal of this study was to describe the risk of newly diagnosed asthma among WTC site workers and volunteers and to characterize its association with WTC site exposures. METHODS: We analyzed 2003-2004 interview data from the World Trade Center Health Registry for workers who did not have asthma before 9/11 (n = 25,748), estimating the risk of newly diagnosed asthma and its associations with WTC work history, including mask or respirator use. RESULTS: Newly diagnosed asthma was reported by 926 workers (3.6%). Earlier arrival and longer duration of work were significant risk factors, with independent dose responses (p < 0.001), as were exposure to the dust cloud and pile work. Among workers who arrived on 11 September, longer delays in the initial use of masks or respirators were associated with increased risk of asthma; adjusted odds ratios ranged from 1.63 [95% confidence interval (CI), 1.03-2.56) for 1 day of delay to 3.44 (95% CI, 1.43-8.25) for 16-40 weeks delay. CONCLUSIONS: The rate of self-reported newly diagnosed asthma was high in the study population and significantly associated with increased exposure to the WTC disaster site. Although we could not distinguish appropriate respiratory protection from inappropriate, we observed a moderate protective effect of mask or respirator use. The findings underscore the need for adequate and timely distribution of appropriate protective equipment and the enforcement of its use when other methods of controlling respiratory exposures are not feasible.     

Visual dysfunction among former microelectronics assembly workers.

Although known neurotoxins with potential ophthalmotoxic properties are commonly used in microelectronics assembly, there has been no systematic study of visual disturbances among past or present workers in this industry. The objective of the present study was to compare visual functions, using a matched-pair design, between former workers from a microelectronics plant and a local reference population. From an initial population of 180 former workers and 157 potential referents, 54 pairs were matched for age (+/- 3 y), education (+/- 2 y), sex, ethnic origin, and number of children. Near and far visual acuity, chromatic discrimination, and near contrast sensitivity were assessed monocularly. Paired comparisons (Signed-rank Wilcoxon test) revealed that the former microelectronics workers had significantly lower contrast sensitivity, particularly in the intermediate frequencies, independently of near visual acuity loss. There were no differences for far visual acuity in both eyes. Even though near visual acuity and color vision were compromised among the former workers, the differences were only significant for one eye, as was the prevalence of acquired dyschromatopsia (chi-square for matched pairs, p less than .001). These findings suggest a pattern of contrast sensitivity deficits consistent with impairment to foveal and/or neuro-optic pathways among these former microelectronics workers. Exposure to ophthalmotoxic chemicals is proposed as the most probable risk factor.     

Oxycodone involvement in drug abuse deaths: a DAWN-based classification scheme applied to an oxycodone postmortem database containing over 1000 cases

An oxycodone postmortem database was created from 1243 solicited cases from Medical Examiner and Coroner (ME/C) offices in 23 states in the United States over the period from August 27, 1999, through January 17, 2002. The request for cases was specific to only those cases in which the ME/C opined that the death involved oxycodone. Each case was evaluated to determine the role of oxycodone and the specific drug product OxyContin tablets in the death. Oxycodone identification was based on toxicology testing, and OxyContin identification was based on evidence found at the scene, credible witness reports, or identification of tablets in gastrointestinal contents. A system of case categorization was developed for this study based on the Drug Abuse Warning Network (DAWN) system for reporting drug abuse mortality data in the United States, using the same standardized, well-understood terminology. Of the 1243 cases, 79 cases were incomplete and could not be evaluated. There were an additional 150 cases submitted in which oxycodone was not identified by the originating ME/C. Of the remaining 1014 cases, 919 (90.6%) were related to drug abuse, whereas 95 (9.4%) cases were categorized as not involving drug abuse. Only 30 (3.3%) of the drug abuse cases involved oxycodone as the single reported chemical entity; of these, 12 cases had OxyContin identified as a source of oxycodone. Of the 919 drug abuse cases, the vast majority (N = 889, 96.7%) were multiple drug abuse deaths in which there was at least one other plausible contributory drug in addition to oxycodone. The most prevalent drug combinations were oxycodone in combination with benzodiazepines, alcohol, cocaine, other narcotics, marijuana, or antidepressants. Using the DAWN definitions, drug abuse cases were further categorized as drug-induced or drug-related. A total of 851 (92.6%) cases met the criteria for classification as being drug-induced, and the remaining 68 (7.4%) cases were categorized as drug-related. Cause of death (COD) statements from the originating ME/C indicated a general recognition of the role of abuse of multiple drugs in causing fatalities. Approximately 70% of the 889 cases in the multiple-drug-induced categories were listed in the COD or contributing COD statements as multiple-drug deaths. A variety of terms were employed in the COD statements to indicate multiple drug involvement such as "polydrug toxicity", "polypharmacy", "multiple drug poisoning", and "polypharmaceutical overdose". The system for death classification employed in this study recognizes the problems inherent in COD attribution when multiple drugs are involved. Use of this new system for reporting mortality data in future studies involving opioids is recommended.