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Rise in use. Deaths caused by substance. Difficulty in detecting heroin overdose. Chemical reactions. Role of alcohol. Abstract. Table of Contents.... More...
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Rise in use. Deaths caused by substance. Difficulty in detecting heroin overdose. Chemical reactions. Role of alcohol. Abstract. Table of Contents.
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Thin Layer Chromatography tends to belabor intensive and results between laboratories can vary. Journal of Forensic Sciences. He went on to explain that these physiologiceffects are often referred to as the heroin overdose syndrome, which wasoriginally described in the 197 =s. Immunoassays, which work by taking advantage ofantigen-antibody interactions, can suffer from cross-reactions, or behampered by drug dilution problems. (1998) to be found deposited either via blood supply orsweat glands into the hair shaft and remain locked away for up to severalmonths. In an exampleof a long survival time a 33-year-old male was found in an icy canal andwas autopsied 23 hours later. The technique differentiates ionic properties bylooking at the drift velocities of ions through gas within an appliedelectric field. Alcohol and the role it plays Sporer (1999) reported on the use of multiple drugs as being commonamongst the victims of fatal heroin overdose. Studies haveshown that perhaps it is much more complicated as most situations turn outto be. Bennett and Plum. The method isused to analyze samples in the gaseous state and drug particles in contactwith the skin surface. The prisoner was found deadthe next day. This technique is very expensive and requiresmuch laboratory expertise. Beike, J., Kohler, H., Brinkmann, B., Blaschke, G. Since the breakdownof 6-acetylmorphine to morphine is prevented when levels of alcohol arehigh the metabolite continues to have a deleterious effect on therespiratory system. 92:29-38. As aconsequence of this rise there has been a parallel increase in the amountsof deaths related to this substance. In fact he went as far as tosay that 29-75% of these individuals had alcohol in their system while 5-12% had benzodiazepines.Many studies including one by Polettini et al. References Barrera, P.B., Naviero, O., Pi?iero, A., Barrera, A. 1996. (1995) have written aboutthe concomitant use of alcohol and other central nervous system depressantsamong habitual heroin users. Recent studies may change our outlook on the deadly heroinoverdose and on the way we evaluate it and the situations that lead up toit. All of these factors make the need forfurther study and development of more precise techniques extremelyvaluable. Even this proves not to be a hard rule. 1996. In onespecific case a 37-year-old victim had been injected by his friend becausehe was too drunk to do it himself. 4 which agreed with the histologicalfindings that showed that the man died from exposure and hypothermia. (1995) presented a paper to the Journal ofForensic Sciences in which his group made very important conclusionsincluding that the use of even small amounts of ethanol used in conjunctionwith heroin elevates the risk of death from heroin use. These final metabolites are also the most active units, which areable to bind several types of receptors and produce the analgesic effectsthey are known for. The role of ethanol inheroin deaths. 351(912 ):1923-1925. 1999.Immunoaffinity extraction of morphine, morpine-3-glucuronide and morphine-6-glucuronide from blood of heroin victims for simultaneous high-performanceliquid chromatographic determination. Levine, B., Green, D., Smialek, J.E. The increasing purity of theheroin that is available today, the lower price of heroin on the streets,its increasing availability, the typical described transition from cocaineto heroin and the popular adaptation of snorting and smoking the heroin toavoid the transmission of AIDS have all played a role in increasing itsuse. Among these are the delay in reportingthe overdose to authorities so that adequate testing is done prior to achange in body chemistry, the very short half-life of heroin and itsmetabolites, and the concomitant use of ethanol and other central nervoussystem depressants, which may chemically alter the constituents ultimatelyfound in the bodily fluids and organs. 1997. Accordingto Goldberger et al. 1996. Other studies asmentioned by the group have entertained the same idea. (1997) used antibodies to purify bloodsamples in order to simultaneously determine the presence of morphine andmorphine glucuronides by utilizing high performance liquid chromatography.Though interpretations of this study should be somewhat cautious due to thefact that they only elaborated on 7 participants in the entire study, thegroup claims to be able to calculate the time elapsed from the last intakeof heroin by calculating quotients for the concentrations of morphine-6-glucunoride/morphine. The role of AlcoholAbuse in the Etiology of Heroin-related deaths. Heroin=s detection When death does occur it has been common practice to utilize modernextraction techniques such as gas chromatography- mass spectroscopy, radioimmuno assay, and high performance liquid chromatography in order toofficially assign a cause of death. We would hope that theinformation attained from these studies would not only better categorizedeaths related to heroin intake but could guide us in our approach todealing with addiction itself and provide addicts with information tocurtail certain activities which have been found to complicate an alreadycomplex circumstance. The presence of these other substances may be involvedin certain chemical reactions, which complicate the assignment of anofficial cause of death. 23:57 -575. Ion mobility spectrometry is an exampleof advances, which are constantly made. Rop, P.P., Fornaris, M., Salmon, T., Burle, J., Bresson, M. B. This time factor issuebecomes extremely important and studies such as the one by Beike et al.(1999) in which they strive to develop a quantitative way to uncover thetime period of the last heroin intake prior to death. Levine et al. Kronstrand, R., Grundin, R., Jonsson, J. Polenttini went on to explain that ethanol has alreadybeen shown to alter the activity of other drugs by raising theirbioavailability through influencing gastric absorption or increasinggastrointestinal blood flow. Recent studies have shown thatdeaths caused by this opioid have increased as much as 17 % in certaincountries over the last decade (Zador et al., 1992). [pic] Figure I. 41(1):1 6-1 9. Acute Heroin Overdose. Toxicological analysis was undertaken and large amounts ofmorphine were found in his system (114 ng/ml) followed by lesser amounts of6-monoacetylmorphine (168ng/ml) and 1 9ng/ml of heroin. These catabolic reactions occur at a fast rate due tothe unstable nature of heroin and an inherently short half-life. The Lancet. Goldberger, B.A., Cone, E.J., Grant, T.M. A case study presented by Rop et al. Lippincott-Raven, Philadelphia. Prevalence and correlates of non-fatal overdose.Addiction. These findings have reinforced the procedure utilized bythem when assigning an official cause of death where any person who isfound to have an alcohol level of over .1 must have alcohol included as acause of death. Their results showed that a large majority of thedeaths from heroin were in addicts that had alcohol in their system at thetime of death. Though heroin=s pharmacological characteristics allow the drug torapidly penetrate the body=s natural barriers, it is broken down quicklyinto metabolites such as 6-acetylmorphine and morphine. Table of ContentsAbstract 3Introduction 4Heroin=s pharmacological characteristics 6Heroin=s detection 9Alcohol and the role it plays 14Conclusion 16References 17 Abstract Heroin use is on the rise both in the United States and abroad. 1994. Ling and Smialek(1995) concluded that recent increases in heroin mortality might be due toseveral factors rather than a lone cause. These ultimateproducts of catabolism are responsible for delivering in some cases thedeadly result (Mycek et al., 1997). The only reasonthat heroine was still identified was due to the extremely large amounts ofthe drug that were swallowed. These circumstances force theinvestigator to find ways to isolate these metabolites from different partsof the body and draw conclusions about the deadly overdose. 1999. Investigations into these deaths haveshown that more often than not there is concomitant use of other drugs oralcohol and that in some cases the official cause of death may actually notbe heroin overdose. When the molarratio of morphine/glucuronides in the blood is above 3, the survival timeis thought to be anywhere from 2-8 hours. Mycek, J.M., Harvey, R.A., Champe, P.C. Since heroin has a short half-lifeand is quickly taken into the central nervous system where it is bound toreceptors and therefore sequestered, the level of this chemical is almostnonexistent in the blood or bodily organs of overdose victims as reportedby Rop et al., (1996). Activemetabolites such as morphine and some of the conjugates are also reportedby Tagliaro et al. 1997.concentrations of Heroin, 6-Monoacetylmorphine, and Morphine in a Lethalcase Following an Oral Heroin Overdose. This method is very good but again is expensive andrequires much expertise. Alcohol levels above 1 mg/L were associated with low levels of morphinein the system while as expected high levels of morphine were found inindividuals that had ethanol levels below 1 mg/L. Goldberger et al.(1994) reports that the time factor may actually be one of the details thatcould explain why such fluctuations are seen in the levels of morphineextracted after death and adds that complications in assessment become evenmore confounded when the concentrations found in heroin-related deathsoverlap with levels of non-drug related ones. 1995. Beike et al. 3) correlated with a short survival time. Li, L., and Smialek, J.E. Incidence of opiates,and cocaine in hair and blood in fatal cases of heroin overdose. Darke, S., and Zador, D. Heroin-related deaths in NewSouth Wales, 1992: toxicological findings and circumstances. 1999.Experimental designs in the optimization of the ultrasonic bath-acid-leaching procedures for the determination of trace elements in human hairsamples by atomic absorption spectrometry. (1996) to theJournal of Analytical Toxicology involved a drug free prisoner who wassupplying heroin to others and was surprised by a random inspection duringwhich he swallowed a large amount of heroin. Antibody-mediated clean-upof blood for simultaneous HPLC determination of morphine and morphineglucuronides. Sporer, K.A. Techniques to isolate compounds from hair and other body partshave become established and continue to evolve in order to shed light onthe difficult task that investigators have. W. The influence onthese products of breakdown by substances such as alcohol only compoundsthe difficulty by perhaps entering into reactions with the heroin itself orby influencing its metabolism. Journal of Forensic Sciences. The autopsy, which was carried out 28hours later, was able to show sudden death and the ratio that was assignedto the victim ( . Tagliaro, F., De Battisti, Z., Smith, F., Marigo, M. Introduction Heroin is the man made product resulting from the manipulation ofmorphine and it is this chemical reaction that bestows upon it thecharacteristics sought out by so many of the world=s heroin addicts. Sporer (1999) reported in a paper to the Annals ofInternal Medicine that the stimulation of the : and * receptors, lead torespiratory depression, analgesia, delayed gastric motility, miotic pupils,and chemical dependence. The conclusion that heroin is the cause of death is not astraightforward one due difficulties with the methods of detection and thepharmacokinetics previously described. These same metabolites becomeimportant when entities work to uncover an official cause of death. 91(3):4 5-411. Journal of AnalyticalToxicology. Polettini, A., Groppi, A., Montagna, M. Another factor tokeep in mind is that there are numerous ways in which individualschemically alter their hair. Complications involved in the detection of heroin overdose that leadsto the death of an individual are numerous but it is this same challengewith prompts investigators to uncover new and efficient methods ofdetection. Their study lookedat 119 narcotic or alcohol and narcotic deaths in order to uncover the rolethat ethanol plays. Heroin was found in his system however theratio for this victim was > 8. These changes may cause the need to reassess the way deaths caused byheroin are viewed, investigated and finalized. The group reports thatin several cases strongly suspected to be caused by heroin overdose,morphine and 6-acetylmorphine were completely absent. The prolonged presence of this metabolite worksagainst the already taxed central nervous system and could push the usertowards death. There are numerous considerations thatare taken in determining what method is utilized to analyze samples takenfrom victims of suspected deadly heroin overdose. Saunders Company, Philadelphia. Journal of Analytical Toxicology.21:232-235. 1998. High pressure liquid chromatography is similarto Gas Chromatography except that a liquid is used to propel the substancethrough the column. 1994. (1997) described the process during whichmorphine is transferred to the liver and is metabolized into glucunorideconjugates. Mycek et al. The victim collapsed almost at once anda physician was immediately called. Other considerations mentioned werethe type of sample that is available, the condition that the sample is inand the phase of the sample (i.e., solid, liquid, or gas). The group describescertain problems such as toxic fumes from current methods used for theextraction of metals from human hair. Thegroup also showed that an inverse relationship is known to exist betweenthe blood alcohol level and the conversion of 6-acetylmorphine to morphine. 1999. Conclusion The evaluation of death in a person who is thought to have overdosedon heroin seems on the surface to be a very simple thing. Evidence forPharmacokinetic Interactions Between Heroin and Alcohol. As modern as themethods of detection available today tend to be, they have inherentproblems, which makes detection a complicated act. Certain inherent characteristics of heroin alsoplay a role in confounding the situation. Drug Abuse and Dependence. By its very nature heroin has been shown to be an intricatesubstance with even more intricate metabolites. Nanji (1991) lists someof these considerations, which include sensitivity, specificity,reproducibility, simplicity, and cost. These alterations could influence hairsinnate storage capabilities and possibly cross react with substances beingmeasured. The technique that they utilize inthis paper employ diluted acids that are found to yield the same results asthose uncovered by using the original acid digestion procedure withoutproducing dangerous fumes and at the same time lowering procedural costs.There is no doubt that techniques to take advantage of hair=s storagequalities will continue to be refined but in the meantime it is importantto consider that growth rates for hair can differ among individuals andthis would lead to differences in storage potential. Themetabolites that are sought accumulate in the blood, urine, hair, andbodily organs. The group concluded that the estimated survival timescorrelated with witness reports at the scene of the occurrence. Though several modern techniques have been developed toextract, isolate and quantify the metabolites of heroin from differingregions of the body, these attempts are met by difficulties, which at timesare beyond the examiners control. 1996. GasChromatography-mass spectroscopy is commonly used as a confirmation devicefor another method and analyzes gasses and liquid substances according totheir fragmentation pattern. The short half-lives ofthe substances involved and collection strategies to remove the substancesfrom their final resting place poses a true challenge. The group raised the question as has beendone by others regarding the possible chemical interaction that could alterthe metabolism of heroin or somehow have a harmful additive effect on therespiratory system. Hair has been shown, according to this study as one of the majorvehicles of excretion and substance levels are highly concentrated whencompared to those found in blood or urine samples. 18:22-27. 91(12):1765-1772. A ratio of less than 1 wouldtherefore be equivalent to a survival time of less than 3 minutes afterthe deadly ingestion of heroin. Darke, S., Ross, J., Hall, W. Heroin=s Pharmacological characteristics Heroin is also known as diacetylmorphine and has the distinct abilityto cross lipid barriers and make its way into the central nervous systemwithin 15 seconds after intravenous injection (Goldberger et al., 1994).This immediate rush produces the overwhelming euphoria associated with thedrug and described by users. Eventually small amounts of the conjugate and morphine can befound in the bile while the rest is excreted in the urine. In 2nd ed., Pharmacology. 726:111-119. Nanji (1991) developed this methodto properly detect a compound of interest in bodily fluids. 13 (7)584-59 . Heroin, which is able to bypassthe blood brain barrier, has a very short half-life and is rapidly brokendown into morphine and other conjugates. Int J Legal Med. 11 :226-229. ForensicScience International. Journal of Chromatography B. 4 (5):8 8-81 . (1999) utilizedultrasonic bath-acid-leaching for the determination of substances in humanhair. Levine also reached the conclusion that heroin deaths inwhich there was no free morphine in the blood (all morphine is either onreceptors or has been broken down) were not associated with ethanol intake. Death, he further clarified is mainlythe result of respiratory depression often amplified by the presence ofother drugs, an overload of heroin, or by the exaggerated reaction to asmall amount of heroin by a habitual user whose tolerance is down forwhatever reason. Zador, D., Sunjic, S., Darke, S. Metabolic pathway of heroin (Sporer, 1999) Heroin=s physiologic effects Heroin and the metabolites, which follow its break down, carry outtheir effects by acting as agonists on several receptors in the centralnervous system. Opioid Analgesics andAntagonists. Research.164:2 4-2 7. (1994) heroin remains intact for approximately 5minutes before it enters into reactions and starts to be broken down.Furthermore, the metabolite 6-monoacetylmorphine remains in the system fora substantially longer time (45 minutes) but is also quite unstable. These complications and difficulties in assessing the fatal heroinoverdose have stimulated new research and have the potential of redefiningwhat was considered in the past to be well delineated and understood. Lack of specificity can also be anadded worry when dealing with this technique. Thin LayerChromatography for example has been used for many years as a broad-spectrumscreen for abused substances. Beike, J., Kohler, H., Blaschke, G., 1997. This higher availability would prolong theeffects of heroin by increasing the chances of receptor stimulation. Forensic Science Internationnal.1 7:1 5-12 . Once located in the brain and spinal cord,heroin is just as rapidly hydrolyzed into 6-monoacetylmorphine followed byanother hydrolyzing conversion into morphine as depicted in Fig I (Darkeand Zador, 1996). Annals of InternalMedicine. Disposition of Heroinand its Metabolites in Heroin-Related Deaths. It is important to remember that even themost tolerant habitual users will not ingest nearly as much heroin as thisperson did. Overdose among heroin users inSydney, Australia: I. The method tends to be rather insensitive attimes and yields only qualitative results thus making it difficult todetect low-level substance abuse. Death fromHeroin overdose: findings from hair analysis. They go on to explain that metabolites of heroin,which have a longer half-life and are excreted mostly through the urinarysystem can be identified as long as the identification of these substancesbegins within a reasonable amount of time thus preventing their furtherbreakdown. 1998. In 2 th ed., Ceciltextbook of Medicine. Journal ofAnalytical Toxicology. Thesesame characteristics give heroin the potential to cause death especiallywhen accompanied by other popular abuse substances that can potentiateheroin=s already harmfull attributes. Attempts areconstantly being made to find better ways for the isolation, purificationand identification of the active substances. Observations on Drug Abuse Deaths inthe State of Maryland. Attempts at developing ways of detecting, separating, and using thoseresults to shed light on the details leading to the fatal heroin overdoseare constantly under development. Thefinal metabolites which are left over at the end of these rapid reactionsinclude morphine and morphine-3-monoglucuronide, which have been reportedto have a mechanism of action of approximately 4-6 hours and have beenfound in urine 12-48 hours after the ingestion of heroin (Bennet and plum,1996). Fatal heroin Aoverdose@: a review.Addiction. In the experiments carried out by thisgroup, blood samples of 23 heroin victims were tested by HPLC and ratioswere recorded. In a different study Barrera et al.
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