[Thin layer chromatographic and spectrophotometric studies on the detection of a phenolic adulteration of neostigmine].
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Adulteration of samples is a serious problem in the analysis of drugs of abuse. One of the most frequent methods is substitution of urines by "clean" urines to gain false-negative results in laboratory tests for drugs of abuse. One way to approach this problem may be to label the patient's urine with marker substances which are given orally prior to the delivery of urine. This concept is based on methods for determining malabsorption in pediatric medicine. We report a protocol for evaluating low-molecular-mass polyethylene glycols as enteral labelling marker substances. For monitoring renal excretion of the ingested polyethylene glycols we have developed and optimised an isocratic reversed-phase high-performance liquid chromatographic method with automatic sample cleanup by column switching in the back-flush technique and with RI detection. The chromatographic procedure is simple, reliable and rapid, allowing a high sample throughput for routine screening.
Among alternative therapeutic approaches that have shown global popularity during the past decades, herbal medicine stands out as a major concern in the countries where allopathic medicine prevails. The sales of herbal products as health care adjuvants in these countries have increased exponentially. Lack of quality control, commercial profiteering and exploitation leading to adulterations, lack of proper knowledge about the herbs and their contents that may exhibit drug-drug interactions and other adverse side-effects, and inappropriate usage of the herbal products have become a cause for concern in the health care professions, particularly in the United States. This review provides an incisive description of the known chemical, pharmacological, clinical and toxicological profiles of four of the most widely used herbal products.
INTRODUCTION: Serious cutaneous adverse reactions to traditional medicines are not well described or reported in the literature, despite growing use of these medicines. METHODS: This is a case series of four patients who were found to have various serious cutaneous adverse reactions to the traditional Chinese medicines that they had taken. RESULTS: In this series, there was a patient with toxic epidermal necrolysis from traditional Chinese medicine, another with acute generalised exanthematous pustulosis from piroxicam and salicylate-contaminated traditional Chinese medicine, and two patients with drug hypersensitivity syndrome--one from traditional Chinese medicine and the other from phenylbutazone-adulterated traditional Chinese medicine. CONCLUSION: The series illustrates that serious cutaneous adverse reactions do occur with traditional medicines and emphasises the importance of being aware of such reactions.
A review of the history of the evolution of the science of toxicology from the original concepts of Paracelsus through the early development of analytical chemistry and its contributions to the detection of toxic substances in foods and drugs as these have led to modern regulatory rules for public protection is presented. The legal actions taken to protect against adulteration of food prior to the early steps by the U.S. Department of Agriculture that concluded with the passage of the 1906 Food and Drug Act are systematically documented. The history is reviewed of the Food and Drug Administration's role in the use of animal toxicity studies to develop reasonable criteria for safety of foods and drugs for man. Modern concepts of molecular distribution, metabolism, and excretion of substances in the animal body are discussed as these impinge on the so-called "protection index." The legal and often litigious controversies over the claimed carcinogenicity of chemical substances is documented with comments on the Delaney dilemma and the role of in vitro tests in toxicology. The review concludes with a discussion of the hazards of use of stochastic mathematical models to assess carcinogenicity and suggests that the criteria employed in the report of the Scientific Committee of the Food Safety Council are properly structured to give a contemporary evaluation of all the currently available data. References give documentation of events over the past 200 years that explain the present state of toxicology as a discipline.
Botanicals such as herbal products (HPs) and nutraceuticals (NCs) are often regarded as low risk because of their long history of human use. Anecdotal and literature reports of adverse drug events (ADEs) and clinical studies with HPs are increasing, but many of the reports are incomplete and contradictory. These reports need to identify confounding factors and explain contradictory findings if they are to help health care professionals or patients understand what risks are involved. HPs are complex botanicals, not single-active ingredient (SAI) products. Studies can be confounded by different manufacturing processes and formulations, including cosmetics and food supplements; environment; chemotypes; misidentification or adulteration; and factors associated with the patient or user population such as use, total drug load, and genetics. Future studies need to be conducted with characterized product that includes all commercially available related products. Clinical trials should be relevant to the user population and take into account the confounding factors that may influence the interpretation of the findings.
Drug abuse is a widespread problem across society, and its negative impact on performance and safety in the workplace cannot be overstated. Even as abuse of older, illicit drugs such as heroin, cocaine, marijuana, and amphetamines persists, new mind-altering chemicals continue to emerge, contributing to an ever-changing landscape of drug abuse and its physical and psychological consequences. Abuse of multiple drugs, and the combined use of alcohol and illicit and prescription drugs, have become increasingly common. The growing and continually evolving problem of drug abuse demands novel strategies for drug testing that reliably and reproducibly detect drugs of abuse, offer an effective solution to persistent problems related to test accuracy and the potential for sample adulteration and substitution, and speak to the growing concerns over issues of individual privacy. Oral fluid testing is a reliable, new technology that overcomes many of the problems of older methods for drug detection.
Controlled and uncontrolled fluid intake studies were conducted on series of volunteers over the 6 or 12 h of the study periods. Urine specimens were obtained from each subject randomly or at specified times relative to fluid ingestion. Creatinine analysis performed by a modification of the Abbott TDx procedure demonstrates that the values obtained from single collection specimens fall almost in the same range as the values from 24 h pooled collection specimens. The creatinine concentration can be used to indicate possible adulteration of urine specimens by dilution as a means of avoiding detection of use of drugs of abuse. Between 4 and 7 h are required for a decrease in creatinine concentration to about 100 mg/dL from an initial mean of about 170 mg/dL. A minimum of 6 h is needed for any creatinine value to fall to 50 mg/dL or less. Thus, it appears that creatinine output is sensitive to the amount of fluid ingested, but the relationship is neither linear nor immediate. The absence of a significant creatinine concentration in a specimen can be used as an indication of direct or indirect adulteration of the urine specimen by dilution or replacement with water. At NDSL-Great Lakes, a decline of the creatinine concentration to 30 mg/dL is used as a cutoff for differentiating between urine specimens that might have been tampered with to avoid detection of drug use and those specimens that are dilute for other reasons. Values at 10 mg/dL or less are suggestive of replacement by water. The information is provided to local commands for investigation prior to initiation of punitive action by the command.
Liquid injectable silicone is a unique soft tissue augmenting agent that may be effectively utilized for the correction of specific cutaneous and subcutaneous atrophies. Although historical complications have occurred, resulting likely from the presence of adulterants and impurities, modern purified silicone products approved by the Food and Drug Administration for injection into the human body may be employed with minimal complications when strict protocol is followed. In this article the present authors review the history and controversy regarding silicone as well as describe the appropriate indications, patient selection, instrumentation, treatment protocol, and anticipated complications involved with the use of liquid injectable silicone for soft tissue augmentation. Although its use is controversial, the present authors maintain that liquid injectable silicone is an important and effective augmenting agent for the long-term correction of scars and facial contour defects such as HIV facial lipoatrophy. Furthermore, it is a treatment modality deserving of continued investigation.
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In order to assess the effects of anorexigenic agents on appetitive and consummatory behavior, rats were given sweetened milk either in a bottle or by infusion through an intraoral cannula. In the first experiment, amphetamine (AMP; 0, 0.25, 0.5, and 1 mg/kg) had no effect on the intake of cannula-fed rats but suppressed the intake of bottle-fed rats at the highest two doses. Although increased activity was observed at the highest dose, bottle-fed rats drank less than cannula-fed rats at each dose of the drug. Fenfluramine (FEN; 0, 2.5, 5, and 10 mg/kg) produced a dose-dependent decrease in intake with both methods of feeding, but the effect was greater in bottle-fed rats. Although FEN had marked sedative effects at the highest two doses, bottle-fed rats drank less than cannula-fed rats at each dose of the drug. In a second experiment, cannula- and bottle-fed rats were given milk adulterated with various concentrations of quinine hydrochloride (QHCl; 0, 0.0025, 0.005, 0.01, and 0.02%). QHCl had no effect on the intake of cannula-fed rats but decreased the intake of bottle-fed rats at the highest two concentrations. In a final experiment, the effect of AMP (1 mg/kg) was assessed in a conditioned aversion paradigm. Rats were given four conditioning trials in which access to a 0.1% sodium saccharin solution was followed by an injection of AMP. Again, bottle-fed rats showed greater suppression of intake than cannula-fed rats. Taken together, these results demonstrate that anorexigenic drugs affect appetitive behavior more than consummatory behavior. The implications of these findings for understanding the mechanism of behavioral tolerance are discussed.
Stroke is a frequently reported, though uncommon, complication of drug abuse, primarily cocaine. The pathogenesis is uncertain, although such cerebrovascular events may result from sympathetically mediated vasoconstriction of cerebral vessels. Amphetamine, another sympathomimetic amine that is commonly abused, may also cause strokes by producing cerebral vasospasm and/or vasculitis. Amphetamine and its derivatives are frequent adulterants of illegally obtained cocaine and may also be used concurrently; the effect(s) of this combination of drugs upon the cerebral vasculature is not known. Our aim was to develop an animal model that would enable us to study the ability of these drugs to produce acute cerebral vasospasm and to observe the response to IV administration of amphetamine and cocaine, either alone or together. Magnified basilar artery arteriograms were obtained in 12 New Zealand white rabbits before and after IV administration of cocaine, methamphetamine, or both, at various dosages. Low doses produced mild vasodilatation. At higher doses, the animals who received cocaine and methamphetamine alone showed little or no basilar artery spasm, but coadministration produced definite basilar artery vasospasm, reflecting a synergistic vasoconstrictive effect. If a similar response exists in the human cerebral vasculature, then this could help explain the cause of strokes associated with drug abuse.
Cocaine abuse is a widespread problem in the USA. Illicit cocaine is usually never found in pure form but is adulterated with other agents, among which are the local anesthetics such as lidocaine. Adulteration of cocaine with another active agent allows the potential for various drug-drug interactions to occur. The presence of an additional active agent in illicit cocaine samples can complicate the pharmacological and toxicological responses elicited and possibly the mode of emergency medical care thereafter. When studying drug interactions, both the kinetic and dynamic aspects of each agent must be considered. This study investigated the plasma time course and tissue distribution of cocaine and lidocaine alone and in combination following a 5 mg kg(-1) intravenous injection in rats. The plasma time course of cocaine and lidocaine in combination did not differ from that seen when each drug was alone. Tissue contents were without change when administered alone or in combination at 5, 10 and 15 min following treatment. However, rats treated with cocaine and lidocaine in combination had significantly greater locomotor activity initially than animals treated with cocaine alone. The results suggest that cocaine and lidocaine interact on a pharmacodynamic basis without a change in the drug level of each agent.
Six cases of acute thrombocytopenic purpura occurred secondary to heroin abuse. Five of the six affected patients were seen over a six-month period between November 1977 and March 1978, and the last patient was seen in November 1978. The clinical manifestations were characteristic of drug-induced immune thrombocytopenia. We suspect this syndrome is related to a new adulterant added to local street heroin.
Plant extracts of the European mistletoe (MTE), Viscum album, the most widely used cancer treatment in Germany, have been used in European countries as sole intervention or as adjunct to conventional cancer therapies for more than 80 years. Preclinical data suggest immunostimulatory and cytotoxic effects of MTE. While the clinical efficacy of MTE in cancer is being investigated, toxicity and potential interactions of MTE with standard chemotherapeutic agents are unknown. Gemcitabine is an approved antimetabolite chemotherapeutic agent effective as single agent in patients with solid tumors (ST). The documented metabolism and pharmacokinetics of gemcitabine make this agent well suited for the study of botanical-chemotherapy drug interactions (BDIA) in cancer. Based on reports of altered drug metabolism associated with botanical preparations, research into BDIA has intensified. The phase I, 2-stage, dose-escalation study outlined here will test MTE with gemcitabine as a paradigm for the phase I investigation of botanical-drug combination treatments in patients with advanced ST. The protocol including the following components has been reviewed and approved by the National Cancer Institute Institutional Review Board (IRB), the National Naval Medical Center IRB, and the Navy Clinical Investigation Program (study 02-074): (1) use of a standardized MTE, approved by the Food and Drug Administration for investigational use; (2) independent verification of key MTE components considered biologically active; (3) identification of contaminants and adulterants; (4) pharmacokinetics of gemcitabine and its principal metabolites before and upon exposure to MTE; (5) safety and toxicity data collection; (6) assays of plasma ML antibody production in vivo; and (7) pharmacodynamic studies of the botanical-drug combination.
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