Bryan S. Finkle

A national assessment of propoxyphene in postmortem medicolegal investigation, 1972-1975.

Eighteen medical examiners, coroners, and forensic science laboratories and offices, representing a total jurisdictional population of 52.6 million, were visited during November 1975, and more than 1200 cases occurring in the four years from 1972 through 31 July 1975 were evaluated for inclusion in the study. The sites were distributed across the United States and Ontario, Canada, and included urban and rural, states, city, and county jurisdictions. Scientific data and circumstantial information was gathered consistently for each case and site by means of five questionnaires. Finally, 1022 cases were compiled and examined, and the data were analyzed to form the body of data from which this report is written. The following conclusions may be drawn. 1. The number of deaths involving propoxyphene is increasing each year, and at a faster rate than total drug deaths. The absolute numbers and rate are different in urban and rural areas, but the frequency reached 6.0 deaths per million population in 1974. Deaths attributed to suicide as well as those determined to be accidental deaths and undetermined have increased. 2. Approximately 66% of all the cases studied had the word propoxyphene included in the cause of death statement on the death certificate. Approximately 46% of the cases were classified as suicide (64% of them female and 36% male), 26% as accidents, and 21% as undetermined. 3. The deceased were mainly middle-class, Caucasian, urban dwellers, with male and female evenly distributed. Their ages were from 20 to 50 years, with few outside this range. Female ages were uniformly distributed, but males in their early twenties were very prominent. This is different from the U.S. population age distribution, which is currently dominated by teenagers. Propoxyphene does not appear to be a pediatric problem, as seen in the study. 4. The deceased were not part of the illegal drug abuse population and had no particular propensity for the use of heroin or narcotics, but rather they were a particular medical population of those who misuse prescription drugs and alcohol. 5. The deceased did have a marked tendency to hypochondria, chronic minor illnesses and emotional problems. Some 43% had recent medical histories, and 82% had a documented psychiatric history which often included (51%) self-destructuve behavior such as suicide attempts. Almost all received a wide range of prescription drugs, particularly tranquilizers, which they often misused in the sense of self-medicating, multiple drug ingestion, and combining alcohol with their medication. Approximately 34% had a history of misusing some drug, and 20% could be defined as abusers in that they were prone to excessive use of their medications; 44% had diazepam available to them, and 17% were either problem drinkers or alcoholics.

The forensic toxicology of cocaine (1971-1976).

It is the general purpose of this study-report to assess the role of cocaine in postmortem, medieolegal investigation, and a primary, particular objective is to determine whether cocaine is significant as a causative agent in a growing number of sudden, unexplained deaths. The significance can be evaluated in terms of either the absolute number of deaths directly attributable to cocaine ingestion or relative to fatalities caused by other abused and misused drugs. A total of only 111 cases involving cocaine occurred at 27 study sites, encompassing a jurisdictional population of 79.2 million over a five- to six-year period ending in mid-1976. Further, of the total cases, only 26 involved cocaine alone.

Concentrations of Lidocaine and Monoethylglycylxylidide (MEGX) in Lidocaine Associated Deaths

Concentrations of lidocaine and MEGX were determined in a variety of tissues and other samples collected at autopsy. In 13 of the cases examined in which lidocaine was associated with death, tissue concentrations were greater than 15 mg/kg. Tissue concentrations in other patients treated with lidocaine were significantly lower.

Drugs and driving: a systematic analytical approach

To collect useful epidemiological data about drug involvement in highway safety, it is essential that sensitive and specific analytical procedures be used to establish the presence of and to determine the concentrations of drugs and metabolites in samples collected from drivers. This paper describes a comprehensive and systematic screening procedure requiring 6 mL of blood, which has been used for the analysis of samples collected from injured and fatally injured drivers. The procedure uses radioimmunoassay, gas chromatography with selective detectors, and high performance liquid chromatography. Drugs and metabolites presumptively identified are then confirmed primarily using gas chromatography--chemical ionization mass spectrometry.

Proficiency testing in forensic toxicology: a feasibility study.

This study has shown that a national proficiency testing program in forensic toxicology is feasible. Samples that resemble typical case specimens were prepared and shipped to approximately 100 laboratories. Participation varied between 61 and 73%. Tissue samples obtained from laboratory animals can be used to simulate those encountered by forensic toxicologists. This has been demonstrated using liver homogenates from animals administered pentobarbital and methaqualone and propoxyphene and acetaminophen. There was a large coefficient of variation however, for the quantitation of acetaminophen in liver. The qualitative data obtained during the course of this study showed a very low incidence of false positives. However, there was a disappointingly low percentage of positive responses for (a) low concentrations of secobarbital and (b) the opiate narcotics (morphine and codeine) in blood, despite the fact that sensitive immunoassay procedures are available for detecting these particular compounds in blood samples. The quantitative determination of drugs and metabolites, other than ethanol, shows wide interlaboratory variation. This variation is presumably not a result of the use of different analytical techniques, since gas liquid chromatography was used by the majority of participants to quantitate drugs and metabolites. Forensic toxicologists are willing to participate in a voluntary proficiency testing program conducted by an independent agency. The performance data developed in this study can serve as a baseline for current forensic toxicology laboratory functional capability in the assessment of future changes and improvements in analytical forensic toxicology.

Cumulation of active metabolites of levo-alpha-acetylmethadol in the rat fetus and neonate

Levo-alpha-acetylmethadol (LAAM, 0.2 or 2.0 mg/kg/day) was orally administered to female Sprague-Dawley rats for one month prior to and throughout pregnancy. The rats were killed on the 18th day of gestation along with a group of 18-day pregnant females given a single oral 2.0 mg/kg dose of LAAM 24 hours earlier. Although cumulation of LAAM or its active metabolites was not seen in plasma or brain of pregnant rats given drug chronically, significant cumulation was observed in whole fetus and in fetal brain. In addition, a 2-3 fold elevation in the concentrations, and an even greater elevation of total content, was noted in the newborn pup. These data suggest that opiate intoxication soon after birth may be a factor responsible for the increased morbidity and mortality of rat pups prenatally exposed to LAAM.

Review of Needle Sharing Among Intravenous Drug Abusers

There is much that is right and pertinent about this volume, which is the eightieth in the National Institute on Drug Abuse (NIDA) Research monograph series, but the title is misleading. The real story presented here is about how to prevent the spread of Human Immunodeficiency Virus (HIV) infection. Acquired Immunodeficiency Syndrome (AIDS). The title should be “The Relationship Between HIV Infection (AIDS) and Needle Sharing Practices Among Intravenous Drug Abusers.” This book is based upon papers and discussion from a technical review which took place in May 1987, sponsored by the Division of Clinical Research, NIDA, but it was not printed until a year later and became available in early 1989.

LAAM Induction: Behavioral Correlates

There has been great interest for the past few years in the development of 1-alpha-acetylmethadol (LAAM) as an alternative maintenance treatment agent for heroin addicts. This methadone derivative is capable of suppressing abstinence for up to 72 hours and this clinical effect is related to its biotransformation and accummulation of active metabolites, in particular noracetylmethadol (N-LAAM) and dinoracetylmethadol (DN-LAAM). As part of a cooperative pharmacokinetic study of LAAM between us and the University of Utah, we attempted to make certain observations on the patients’ cognitive functions and other behavioral parameters after each dosing, both during initial administration and after repeated dosing for several weeks, to see if these observations correlated with the level of active metabolites. This report deals with the correlation between the plasma level of the major metabolite N-LAAM and clinical observations including the results of several specific psychometric tests. It was anticipated that the results of these tests may reflect impairment or the lack thereof, in everyday functioning such as driving, operating equipment, ability to concentrate, memory, etc.