PubMed · 14409302
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H KIRCHMAIR. 1959-11-06. [Immunothrombopenia after codeine medication].. https://pubmed.ncbi.nlm.nih.gov/14409302/
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Opiate and cocaine addictions are major social and medical problems that impose a significant burden on society. Despite the size and scope of these problems, there are few effective treatments for these addictions. Methadone maintenance is an effective and most widely used treatment for opiate addiction, allowing normalization of many physiological abnormalities caused by chronic use of short-acting opiates. There are no pharmacological treatments for cocaine addiction. Epidemiological, linkage, and association studies have demonstrated a significant contribution of genetic factors to the addictive diseases. This article reviews the molecular genetics and pharmacogenetics of opiate and cocaine addictions, focusing primarily on genes of the opioid and monoaminergic systems that have been associated with or have evidence for linkage to opiate or cocaine addiction. This evidence has been marshalled either through identification of variant alleles that lead to functional alterations of gene products, altered gene expression, or findings of linkage or association studies. Studies of polymorphisms in the mu opioid receptor gene, which encodes the receptor target of some endogenous opioids, heroin, morphine, and synthetic opioids, have contributed substantially to knowledge of genetic influences on opiate and cocaine addiction. Other genes of the endogenous opioid and monoaminergic systems, particularly genes encoding dopamine beta-hydroxylase, and the dopamine, serotonin, and norepinephrine transporters have also been implicated. Variants in genes encoding proteins involved in metabolism or biotransformation of drugs of abuse and also of treatment agents are reviewed.
BACKGROUND: In clinical practice the major role of opioid drugs is the management of malignant and nonmalignant pain. The primary aim of this study is to evaluate the trend in sales of four opioid analgesic drugs (codeine, tramadol, morphine, fentanyl), from wholesalers to community pharmacies, as an indicator of opioid consumption in nine European countries in 2001, 2002 and 2003. Secondary aims are to compare: (a) the amount of each drug purchased by different countries in 2003; (b) the average price for each drug in the different countries in 2003; and (c) the total expenditure for each opioid from 2001 to 2003. METHODS: Data from the Statistical Report on drugs purchased by pharmacies was supplied by IMS Health, an internationally accepted information provider for the pharmaceutical and health care industries. FINDING: In the period 2001 2003, while the percentage increase of purchases of fentanyl and tramadol was considerable, that of morphine was the lowest in most of the nine countries. The largest consumer of codeine was the UK and of tramadol was Belgium. The consumption of morphine was the lowest reported in all the countries together and was three times lower than that of transdermal fentanyl. There was a high variability in the costs of the opioids among the different countries. In 2003, the total expenditure for fentanyl reached the highest total expenditure [corrected] followed by codeine. Morphine presents the lowest expenditure in all nine countries and over all three years. INTERPRETATION: These results open up many questions. What factors influence opioid purchasing and costs in these European countries? It would be interesting to have the answers from those people who know the actual situation in the individual countries.
Methods for separation and determination of multiple drugs of abuse in biological fluids using capillary electrophoresis (CE) with native fluorescence and laser-induced fluorescence (LIF) detection are described herein. Using native fluorescence, normorphine, morphine, 6-acetyl morphine (6-AM), and codeine were analyzed by CE without any derivatization procedure and detected at an excitation wavelength of 245 nm with a cut-off emission filter of 320 nm, providing a rapid and simple analysis. The detection limits were in the range of 200 ng/mL. For a highly sensitive analysis, LIF detection was also examined using a two-step precolumn derivatization procedure. In this case, drugs extracted from human urine were first subjected to an N-demethylation reaction involving the use of 1-chloroethyl chloroformate (ACE-Cl) and then derivatized using fluorescein isothiocyanate isomer I (FITC) and analyzed by CE coupled to a LIF detector. Variables affecting this derivatization: yield of demethylation reaction, FITC concentration, reaction time and temperature, were studied. The estimated instrumental detection limits of the FITC derivatives were in the range of 50-100 pg/mL, using LIF detection with excitation and emission wavelengths of 488 nm and 520 nm, respectively. The linearity, reproducibility and reliability of the methods were evaluated. In addition, a comparison of the characteristics for both native fluorescence and LIF detections was also discussed.