5. Pharmaceuticals and medicinal chemistry

2017 ◽  
pp. 71-89
Author(s):  
Graham Patrick
Keyword(s):  
Drug Testing ◽  
Medicinal Chemistry ◽  
Drugs Of Abuse ◽  
Rational Drug Design ◽  
Design And Synthesis ◽  
Regulatory Affairs ◽  
Preclinical Trials ◽  
The 1960S ◽  
Drug Optimization ◽  
Pharmaceutical Agents

One of the most important applications of organic chemistry involves the design and synthesis of pharmaceutical agents—a topic defined as medicinal chemistry. ‘Pharmaceuticals and medicinal chemistry’ describes the pathfinder years of the 19th and 20th centuries before considering the development of rational drug design from the 1960s. It explains the identification of a drug target; how drug testing and bioassays work; the identification of lead compounds, structure activity relationships, and pharmacopores; and drug optimization. It outlines the processes of drug development through preclinical trials, clinical trials, and regulatory affairs. Finally, it looks to the future and outlines some of the challenges ahead as well as considering veterinary drugs and drugs of abuse.

A Prediction Model for Positive Infant Meconium and Urine Drug Tests

2020 ◽  
Author(s):  
Elizabeth A. Simpson ◽  
David A. Skoglund ◽  
Sarah E. Stone ◽  
Ashley K. Sherman
Keyword(s):  
Prediction Model ◽  
Drug Testing ◽  
Clinical Decision Making ◽  
Drugs Of Abuse ◽  
Clinical Decision ◽  
P Value ◽  
Test Characteristics ◽  
Drug Test ◽  
Urine Drug ◽  
Urine Drug Test

Objective This study aimed to determine the factors associated with positive infant drug screen and create a shortened screen and a prediction model. Study Design This is a retrospective cohort study of all infants who were tested for drugs of abuse from May 2012 through May 2014. The primary outcome was positive infant urine or meconium drug test. Multivariable logistic regression was used to identify independent risk factors. A combined screen was created, and test characteristics were analyzed. Results Among the 3,861 live births, a total of 804 infants underwent drug tests. Variables associated with having a positive infant test were (1) positive maternal urine test, (2) substance use during pregnancy, (3) ≤ one prenatal visit, and (4) remote substance abuse; each p-value was less than 0.0001. A model with an indicator for having at least one of these four predictors had a sensitivity of 94% and a specificity of 69%. Application of this screen to our population would have decreased drug testing by 57%. No infants had a positive urine drug test when their mother's urine drug test was negative. Conclusion This simplified screen can guide clinical decision making for determining which infants should undergo drug testing. Infant urine drug tests may not be needed when a maternal drug test result is negative. Key Points

Interpretation and Utility of Drug of Abuse Immunoassays: Lessons From Laboratory Drug Testing Surveys

2010 ◽  
Vol 134 (5) ◽  
pp. 735-739 ◽  
Author(s):  
Stacy E. F. Melanson ◽  
Leland Baskin ◽  
Barbarajean Magnani ◽  
Tai C. Kwong ◽  
Annabel Dizon ◽  
...  
Keyword(s):  
Drug Testing ◽  
Drugs Of Abuse ◽  
False Negative ◽  
Cross Reactivity ◽  
Treatment Programs ◽  
Drug Of Abuse ◽  
Negative Results ◽  
Urine Drug ◽  
Clinically Significant ◽  
Pain Services

Abstract Context.—To assist with patient diagnosis and management, physicians from pain services, drug treatment programs, and the emergency department frequently request that urine be tested for drugs of abuse. However, urine immunoassays for drugs of abuse have limitations. Objective.—To use data from the College of American Pathologists Proficiency Testing Surveys to determine and summarize the characteristics, performance, and limitations of urine immunoassays for drugs of abuse. Design.—Six years of urine drug testing proficiency surveys were reviewed. Results.—Lysergic acid diethylamide and methaqualone are infrequently prescribed or abused and, therefore, testing may be unnecessary. However, implementation of more specific testing for methylenedioxymethamphetamine and oxycodone may be warranted. Each drug of abuse immunoassay exhibits a different cross-reactivity profile. Depending on the cross-reactivity profile, patients with clinically insignificant concentrations of drugs may have false-positive results, and patients with clinically significant concentrations of drugs may have false-negative results. Conclusions.—Laboratory directors should be aware of the characteristics of their laboratories' assays and should communicate these characteristics to physicians so that qualitative results can be interpreted more accurately. Furthermore, manufacturer's claims should be interpreted with caution and should be verified in each organization's patient population, if possible.

scholarly journals Adulteration of Urine by “Urine Luck”

1999 ◽  
Vol 45 (7) ◽  
pp. 1051-1057 ◽  
Author(s):  
Alan HB Wu ◽  
Ben Bristol ◽  
Karen Sexton ◽  
Gina Cassella-McLane ◽  
Verena Holtman ◽  
...  
Keyword(s):  
Drug Testing ◽  
Drugs Of Abuse ◽  
Spot Test ◽  
Gas Chromatography Mass Spectrometry ◽  
Pyridinium Chlorochromate ◽  
Urine Drug ◽  
Chain Of Custody ◽  
Drug Assays ◽  
Workplace Drug Testing

Abstract Background: In vitro adulterants are used to invalidate assays for urine drugs of abuse. The present study examined the effect of pyridinium chlorochromate (PCC) found in the product “Urine Luck”. Methods: PCC was prepared and added to positive urine controls at concentrations of 0, 10, 50, and 100 g/L. The controls were assayed for methamphetamine, benzoylecgonine (BE), codeine and morphine, tetrahydrocannabinol (THC), and phencyclidine (PCP) with the Emit II (Syva) and Abuscreen Online (Roche) immunoassays, and by gas chromatography/mass spectrometry (GC/MS). Two tests were also developed to detect PCC in urine: a spot test to detect chromate ions using 10 g/L 1,5-diphenylcarbazide as the indicator, and a GC/MS assay for pyridine. We tested 150 samples submitted for routine urinalysis, compliance, and workplace drug testing for PCC, using these assays. Results: Response rates decreased at 100 g/L PCC for all Emit II drug assays and for the Abuscreen morphine and THC assays. In contrast, the Abuscreen amphetamine assay produced apparently higher results, and no effect was seen on the results for BE or PCP. The PCC did not affect the GC/MS recovery of methamphetamine, BE, PCP, or their deuterated internal standards, but decreased GC/MS recovery of the opiates at both intermediate (50 g/L) and high (100 g/L) PCC concentrations and apparent concentrations of THC and THC-d3 at all PCC concentrations. Two of 50 samples submitted for workplace drug testing under chain-of-custody conditions were positive for PCC, whereas none of the remaining 100 specimens submitted for routine urinalysis or compliance drug testing were positive. Conclusions: PCC is an effective adulterant for urine drug testing of THC and opiates. Identification of PCC use can be accomplished with use of a spot test for the oxidant.

Financial viability of screening for drugs of abuse

1995 ◽  
Vol 41 (5) ◽  
pp. 805-808 ◽  
Author(s):  
M A Peat
Keyword(s):  
Drug Testing ◽  
Drugs Of Abuse ◽  
The United States ◽  
Economic Benefits ◽  
Postal Service ◽  
Test Results ◽  
United States Postal Service ◽  
Financial Benefits ◽  
Urine Drug Testing ◽  
Urine Drug

Abstract Urine drug testing is now a common practice in the American workplace; a recent survey indicated that > 90% of companies with > 5000 employees have some type of testing program. These programs have indeed reduced the rate of drug-positive test results; for example, recent data from the Federal Aviation Agency show that the rate for 1993 was 0.82% compared with 0.95% for 1992. Many corporations have stated that urine drug testing, as a component of a substance abuse policy, results in significant savings, e.g., from decreased absenteeism and turnover. The United States Postal Service recently completed a longitudinal study on the economic benefits and found that, over the average tenure of an annual intake of employees, there were savings of more than $100 million. Although this study clearly demonstrates the financial benefits of preemployment drug testing, the decision to test is not based solely on this but also on the regulatory environment and on the potential impact of a major accident attributable to the use of drugs or alcohol in the workplace.

Preliminary tests for drugs of abuse.

1988 ◽  
Vol 34 (2) ◽  
pp. 331-334 ◽  
Author(s):  
I Sunshine
Keyword(s):  
Thin Layer ◽  
Drug Testing ◽  
Drugs Of Abuse ◽  
Random Access ◽  
Turnaround Time ◽  
Test Procedures ◽  
Testing Program ◽  
Selection Of

Abstract A drug-testing program must be designed by the client in consultation with the laboratory. The test procedures selected for the analytes in question depend on the defined "cutoff" concentrations, equipment available, and turnaround time. Preliminary tests are needed to separate the large number of negatives from presumptive positives, which then have to be confirmed. Immunoassays done with random-access analyzers are the procedures of choice. In clinical situations, thin-layer chromatographic procedures may be favored. The attributes and liabilities of the various procedures are presented as guides to the selection of a suitable procedure for a particular client.

Hair as a Biological Indicator of Drug Use, Drug Abuse or Chronic Exposure to Environmental Toxicants

2006 ◽  
Vol 25 (3) ◽  
pp. 143-163 ◽  
Author(s):  
Vassiliki A. Boumba ◽  
Kallirroe S. Ziavrou ◽  
Theodore Vougiouklakis
Keyword(s):  
Drug Use ◽  
Chronic Exposure ◽  
Drug Testing ◽  
Drugs Of Abuse ◽  
Hair Analysis ◽  
Clinical Chemistry ◽  
Biological Indicator ◽  
Environmental Toxicants ◽  
Hair Samples ◽  
Hair Testing

In recent years hair has become a fundamental biological specimen, alternative to the usual samples blood and urine, for drug testing in the fields of forensic toxicology, clinical toxicology and clinical chemistry. Moreover, hair-testing is now extensively used in workplace testing, as well as, on legal cases, historical research etc. This article reviews methodological and practical issues related to the application of hair as a biological indicator of drug use/abuse or of chronic exposure to environmental toxicants. Hair structure and the mechanisms of drug incorporation into it are commented. The usual preparation and extraction methods as well as the analytical techniques of hair samples are presented and commented on. The outcomes of hair analysis have been reviewed for the following categories: drugs of abuse (opiates, cocaine and related, amphetamines, cannabinoids), benzodiazepines, prescribed drugs, pesticides and organic pollutants, doping agents and other drugs or substances. Finally, the specific purpose of the hair testing is discussed along with the interpretation of hair analysis results regarding the limitations of the applied procedures.

scholarly journals Drugged driving in South Africa: An urgent need for review and reform

2019 ◽  
pp. 7-18
Author(s):  
Jade Liebenberg ◽  
Lorraine Du Toit-Prinsloo ◽  
Gert Saayman ◽  
Vanessa Steenkamp
Keyword(s):  
South Africa ◽  
South African ◽  
Road Safety ◽  
Traffic Accident ◽  
Drug Testing ◽  
Drugs Of Abuse ◽  
Road Traffic ◽  
Driving Under The Influence ◽  
Drugged Driving ◽  
National Road

  Driving under the influence is a major threat to road safety in South Africa. Various psychoactive substances (both licit and illicit) have the potential to adversely affect driving performance and increase the probability of a road traffic accident. While it is common practice in South Africa to test drivers for alcohol levels, testing for additional impairing substances (including drugs of abuse) is rarely performed. In terms of current South African legislation, only driving under the influence of alcohol and a ‘drug having a “narcotic” effect’ is prohibited. This excludes several impairing psychoactive drugs which are not classified as narcotic substances. The aim of this article is to highlight issues and/or limitations surrounding drugged driving and to propose appropriate considerations for revision of the National Road Traffic Act. We also recommend revising existing legislation to include a comprehensive statutory definition and detailed provisions for drug testing to deter impaired driving.

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