Forensic implications of cocaine

The Forensic Implications of Cocaine – Richard Jones

The Forensic Implications of Cocaine


Introduction

Cocaine use in the UK is on the increase, particularly in London and the South East, and ismirroring the situation in the US. Cocaine is often thought of as a ‘safe’ drug, but more andmore evidence is becoming available suggesting that this is not the case. This report aimsto consider the forensic aspects of cocaine abuse, from the point of view of the ForensicMedical Examiner (FME) in terms of clinical signs and symptoms; the Forensic Psychiatristin terms of the psychiatric effects of cocaine intoxication and chronic abuse (with adiscussion of the phenomenon of ‘excited delirium’) and the forensic pathologist in termsof investigating the death of a suspected cocaine abuser, including findings at the sceneof death and at autopsy. A description is also given of the basic pharmacology of cocaineand it’s most important metabolites (including cocaethylene), the analysis of samplestaken for forensic investigation and the epidemiology of cocaine abuse.

Cocaine and ‘Crack’ Cocaine

Cocaine (benzoylmethylecgonine, C17H21NO4) is an alkaloid prepared from the leaves of theErythroxylon coca plant, which grows mainly in South Africa, and to a lesser extent in Africa, theFar East and India.

For centuries, the large Indian population of Peru have chewed coca leaves, and they have beenfound in the tombs of their ancestors dating back to 600 AD.

Coca leaves were first used in medicine in 1596, but it was not until the mid 1800’s that cocainewas extracted. Freud reported the effects of cocaine in 1884, and it was subsequently utilised inophthalmology and dentistry as a local anaesthetic. (Cregler et al (1986) pp.1495-6).

Cocaine hydrochloride is prepared by dissolving the alkaloid in hydrochloric acid, forming a watersoluble salt. It is sold illicitly as a white powder, or as crystals or granules. (See fig 1. illustratingthe coca leaves and cocaine hydrochloride).

Fig 1. Coca Leaves and Cocaine Hydrochloride powder

Street names include ‘coke’, ‘charlie’, ‘nose-candy’, ‘snow’ and ‘wash’. This form of cocainecan be ‘freebased’, prior to smoking, in which it is dissolved in ether or ammonia. The ‘freebase’remains after the volatile substance has evaporated. Although this form of cocaine was popular inthe late 1970s, a further refinement of this process became more prominent in the US during the1980s, in which ‘crack’ cocaine was produced.

Crack cocaine is produced when cocaine hydrochloride is mixed with sodium bicarbonate (bakingsoda) and water, and then heated. On cooling, ‘rocks’ are precipitated, and these are smoked incrack pipes, or are heated on foil with the vapour inhaled. Crack is an extremely ‘pure’ form of analready ‘pure’ substance (in comparison with other drugs of abuse such as amphetamines). Fig 2.Illustrates ‘rocks’ of crack cocaine.


Fig. 2. ‘Rocks’ of Crack Cocaine

Cocaine can be administered as a drug of abuse in the following ways,

• Cocaine hydrochloride – snorting (intranasal), smoking, intravenous (including beingmixed with heroin (‘speedball’ or ‘snowball’)), ingestion, application to genitalia

• Crack cocaine – inhalation of vapour from heated foil or pipe• Coca leaves – chewed/ ingested

In the UK, cocaine is classified as a Class A controlled drug, by virtue of Schedule 2 of theMisuse of Drugs Act 1971 (as amended by the Misuse of Drugs Regulations 1985). It is acriminal offence to ‘unlawfully possess’ (with or without intent to supply), to import or export thedrug, or produce it, and the police have extensive ‘stop and search’ powers to enforce theseoffences.

Cocaine addicts are required to be notified by doctors to the Chief Medical Officer underRegulation 3 of the Misuse of Drugs (Notification of and supply to Addicts) Regulations1973, and Regulation 4 prevents doctors from prescribing cocaine unless they are licensed to doso by the Home Secretary. However, this does not apply to those treating organic disease orinjury.

EpidemiologyEpidemiological data of drug misuse in the UK is not freely available in the same way that it is inthe US because there is no ‘National Drugs Survey’ or ‘National Household Drugs Survey’.However, data have been collated by the Health Education Authority (1995), and as part of the 2yearly British Crime Survey (most recently in 1998). The Four Cities Study (1992), and the YouthLifestyle Survey (1993) also provided useful data on drug misuse in the populations covered bythe study. (BMA 1997 pp,13-27, Institute for the Study of Drug Dependence, British Crime Survey1998).

The following points of note can be extracted from the data,

• 32% of the adult population is thought to have used a drug at some point in their life (11%in the last year, 6% in the last month)

• 49% of under 30s report having used a drug (16% within the last month)• the highest adult prevalence is in the 16-19 year age group – 31% using drugs on a

regular basis• drug use peaks at the end of the teens• male users outstrip female users by 2:1• unskilled workers abuse drugs more than other social classes, and chose more

dangerous routes of administration


• the highest prevalence is found among the unemployed – 40% report drug use within thelast year

• ethnic differences in drug abuse were negligible overall, but the type of drug abusedvaried (e.g. whites were found to abuse amphetamines and LSD more than Afro-Caribbeans).

• Drug use amongst Indians, Pakistanis and Bangladeshis was appreciably lower• 48% of male prisoners use drugs whilst in prison

In terms of cocaine and crack use, the data is often grouped with heroin use, and is not alwayseasy to separate out,

• 1% of 20-50 year olds had used these drugs • 9% of 16-29 year olds had taken these drugs, with cocaine representing a large

proportion of this • cocaine use is on the increase among young people, particularly in the London area

(due to increased availability and reduced cost?)• cocaine use has increased to 3% of 16-44 year olds – London and the South East have

borne the brunt of this increase• a recent ‘Time Out’ readers poll found that 3% used cocaine regularly, with 45% having

taken it at least once (compared to 2% and 6% respectively for crack)• heavy cocaine users spent £100 per day to support their habit• regular crack cocaine users could spend over £1000 over a weekend on 10g of the

drug• cocaine related deaths are increasing – 38 in 1997 compared to 18 in 1996

American data indicate that 23.7 million people used cocaine between 1990-1, nearly 4 millionof which were using crack. (Cone 1993). Mortality from cocaine abuse has also risen, andcocaine accounts for the most frequent substance related deaths. (Karch 1991(a) p.126).

Pharmacology

Pharmacokinetics

Cocaine has a half life of 40-50 minutes, and it’s effects on the body are felt rapidly, peakingafter 15-20 minutes when ‘snorted’, and wearing off by 1.5 hours. When injected or ‘freebased’,or when crack is smoked, the effects are almost instantaneous, and last for only 15 minutes orso.

Cocaine is metabolised to nearly a dozen pharmacologically inactive metabolites, the mostimportant being benzoylecgonine and ecgonine methyl ester, primarily in the liver byspontaneous hydrolysis. (Casale et al 1994). Plasma cholinesterase also hydrolyses cocaine toecgonine, and approximately 20% of the drug is excreted untouched into the urine. Bothcocaine and its metabolites may be detected in urine up to 15 days after last administration by achronic user.

Cocaethylene is the ethylbenzoylecgonine form of cocaine produced in the presence ofethanol, resulting from transesterification by hepatic enzymes. (da Matta Chasin et al 2000 p.2).It is pharmacologically active, and it is formed at significantly lower concentrations than either ofits parent substances. See fig 3. below for examples of cocaine metabolites.


Fig 3. Chemical structures of cocaine, norcocaine and the important metabolites.

Mechanisms of Action

Cocaine is a central nervous system stimulant, which gives rise to feelings of euphoria,excitement, increased motor activity and a feeling of being energised.

Its principal mode of action is the blockade of the transporter protein that is responsible for thereuptake of monoamines (i.e. noradrenaline, serotonin and most importantly dopamine) intopresynaptic terminals of neurons releasing these neurotransmitters. The result is that increasedconcentrations of these monoamines are found in the synaptic space, and their effects arepotentiated.

Blockage of the dopamine-reuptake transporter protein gives rise to the characteristic ‘high’ ofcocaine. Knockout mice that do not have the gene encoding for this transporter protein areimmune to the effects of cocaine, and studies have attempted to identify the exact dopaminereceptor subtype on the post-synaptic neuron that is responsible for modulating the effects ofcocaine. It appears that the D2 subtype modulates cravings associated with cocainedependence and drug seeking behaviour, whilst the D1 subtype may modulate feelings ofsatiety, opening up possibilities for therapeutic targeting of these receptors to treat cocainedependence and abuse. (Leshner 1996 pp.128-9).

Dopamine hyperactivity as a result of cocaine administration is particularly important in thenigrostriatal dopaminergic system, which incorporates the limbic system of the brain – the‘pleasure centre’. The activation of the limbic system by the drug gives rise to the intenseeuphoria, but in the chronic user, monoamine neurotransmitters are depleted, triggering areactive lowering of mood or depression (serotonin depletion?), as well as disturbed sleep andeating cycles. Body temperature control is adversely affected, and depletion of dopamine hasbeen linked to the onset of schizophrenia in susceptible individuals. Fig 4 below illustrates themechanism of action of cocaine.


Fig 4. Mechanism of action of Cocaine (Leisner 1996 pp.128-9)

In high doses, cocaine can cause tremors and convulsions via its effects on the cortex andbrainstem, and can lead to respiratory and vasomotor depression. O’Dell et al (2000 p.677)speculate that cocaine activation of serotonin (2) receptors may be responsible for mediatingconvulsions. Chronic users can experience hallucinations, delusions and paranoia.

Peripherally, cocaine potentiates noradrenaline action, and produces the typical ‘fight or flight’sympathetic response of tachycardia, hypertension, pupillary dilatation and peripheralvasoconstriction. Table 1 below lists the effects of cocaine.


Table 1. Physical and Psychological Effects of Cocaine (Sources: Stark et al 1996, Stark1999, Wetli (1985))

Dose Physical Effects Psychological EffectsInitial Low Doses Tachycardia, tachypnoea,

hypertension,Dilated pupils (& flattened lenses),sweating, reduced appetite, reducedneed for sleep, reduced lungfunction, dry mouth, impaired motorcontrol & performance of delicateskills and driving

Euphoria, sense of well being,impaired reaction time and attentionspan, impaired learning of new skills

Increased doses Seizures, cardiac arrhythmias,myocardial infarction, stroke,respiratory arrest

Anxiety, irritability, insomnia,depression, paranoia,aggressiveness, impulsivity,delusions, agitated/ excited delirium,reduced psychomotor function

Chronic Use Erosions, necrosis and perforation ofnasal septum, anosmia, rhinorrhoeaand nasal eczema (snorting), chestpains, muscle spasms, sexualimpotence, weight loss, malnutrition,vascular disease

Dependence, disturbed eating andsleeping patterns

Therapeutic Uses of Cocaine

Cocaine is used as a surface local anaesthetic (it blocks Na+-K+ activated ATPase acrossadrenergic neuron cell membranes), particularly in Ear, Nose and Throat (ENT) surgery. It is alsosometimes used in palliative care of terminally ill patients.

Dependence and Tolerance

There is tolerance to the psychological effects of cocaine, but not generally to the cardiac effects.However, acute tolerance appears to occur after administration of the drug. This has been notedwhen studying the effects of cocaethylene, which is formed at a slow rate, and appears in theuser’s blood at a time when the effects of cocaine are declining. Cocaethylene is active in thebrain, and has a similar effect to cocaine, but the subjective perception of the cocaine ‘high’, andits heart effects are not increased – instead they decline in intensity.

Niesink et al (1999 p.49) describes the ‘super sensitivity’ phenomenon that follows chroniccocaine use, and represents a form of chronic tolerance. Chronic use depletes the amount ofmonoamine neurotransmitters in the pre-synaptic neuron, and thus the amount available in thesynaptic cleft. This is compensated for by an increase in post-synaptic receptors.

Cocaine causes both physical and psychological dependence, the severity of which depends onthe route of drug administration. It is more severe when the drug has been injected or smoked.Withdrawal leads to strong craving and drug seeking behaviour, followed by a withdrawalsyndrome.

The cocaine ‘crash’ is characterised by

• irritability• insomnia• depression• anxiety• muscle pains• tremor• hunger• fatigue• hypersomnic episodes


Sufferers are at an increased risk of harming themselves or committing suicide, and frequentlyfind themselves in police custody. Such individuals can be settled with haloperidol and diazepam,whilst their vital signs need close monitoring in a hospital setting where potential complicationsmay be anticipated.

Cocaethylene

When alcohol and cocaine are ingested together, the liver produces the active metabolitecocaethylene. It is produced as a result of the transesterification of cocaine by the same non-specific carboxylesterases that normally convert cocaine to benzoylecgonine, for example, in theabsence of ethanol.

Cocaethylene is a non-polar structure, and can cross the blood brain barrier, where it blocks thedopamine-reuptake transporter protein in the same way that cocaine does.

The clinical importance of this metabolite has not been fully determined, but it has a longer half-life than cocaine (2.5 hours), and it is possible that it may prolong the cocaine ‘high’. (Cone et al1993). However, Perez-Reyes et al (1992 pp. 561-2 and 1994 pp.541-550) have found thatcocaethylene appearance in the blood of a cocaine/ ethanol user does nothing to alter subjectivecocaine ‘highs’ or increased heart rate etc. Indeed, it appears that the interaction betweencocaine and ethanol is ‘order-of-administration’ dependant. Ethanol only appears to enhance theeffects of cocaine if it is ingested prior to cocaine.

The issue of cocaine/ ethanol interaction is controversial. Karch et al (1999 pp.19-23) suggestthat cocaine toxicity is not enhanced by ethanol-cocaine interactions, when low concentrations ofethanol are ingested. They concede, however, that further research is required to determine theinteractions of higher concentrations of ethanol with cocaine.

The US Drug Abuse Warning System (DAWN) has identified cocaine/ethanol abuse as a majorcause of emergency medical admissions, and considers the concurrent use of these drugs to bethe cause of increases in cocaine related morbidity and mortality, as well as giving rise to anincreased risk of dual dependency and worsening of the ‘crash’ associated with chronic use. (LeeHearn et al 1991 p.698 and da Matta Chasin et al 2000 p.2).

Epidemiological evidence of the combined abuse of cocaine and ethanol in the US estimates that5 million people had used this combination within 1 month of the National Household DrugSurvey (1985), and that 12 million had done so within the preceding year. Despite a generaldecline in the prevalence of cocaine use reported by the 1990 Survey, the proportion combiningboth substances had increased. (Perez-Reyes and Jeffcoat 1992 p.553). Data are unavailable forcombined use in the UK, but it is conceivable that the increase in cocaine use in the UK will bemirrored with an increase in the combined abuse of cocaine and ethanol.

Analysis of Clinical and Forensic Specimens forCocaine and MetabolitesThe identification of cocaine or its metabolites in clinical specimens assists patient managementin clinical forensic medicine, and assists the pathologist in ascertaining cause of death.

Urine is convenient and easy to collect, and represents a longer chronological picture of drug usethan does the analysis of blood or saliva. The half-life of cocaine is short, and cocaine and itsmetabolites remain in the urine for up to 14 days in a chronic user (Karch 1991(a) p.126). Falsenegatives may result from bleach and salt added to specimens surreptitiously, and thoseindividuals with cholinesterase deficiencies continue to have detectable levels for a long time.

Recent advances have been made in the analysis of hair for toxicological purposes, and Cone etal (1993 pp.55-68) describe the results of analyses of head and arm hair for cocaine and it’smetabolites. Concerns have been raised, however, about the issue of external contamination ofhair shafts by smoke and sweat containing cocaine, and the implications for interpretation ofpositive analyses. Various pre-wash techniques have been described (Kintz et al 1995 pp.3-11and Blank et al 1993 pp.145-156), but the matter is far from being resolved.


Analysis of samples

Specimens need to be collected and preserved in sodium fluoride (or anotherpseudocholinesterase inhibitor), and refrigerated. Storage in a buffer at pH 5 can also preventcocaine metabolism prior to analysis. (Karch 1991(a)). Cocaine levels need to be interpreted withextreme care, because it is rapidly metabolised in blood, and continues to be broken down inpost-mortem blood if incorrectly stored for analysis. (Wetli 1987p.2).

Commercially available test kits are available (e.g. EMIT d.a.u. – an enzyme based immunoassaykit) for screening urine for cocaine metabolites, and positive samples are confirmed using the‘gold standard’ analytical techniques – gas chromatography/ mass spectrometry (GC/MS). (Coneet al 1990). GC/MS has a lower limit of detectability for cocaine in the blood of <0.5 mcg/L (or 0.5mg/ml), whereas the therapeutic blood cocaine level is in the region of 3 mcg/L (or 3 mg/ml).(Corburt et al 1993 pp.136-149). Typical blood cocaine levels are found in Table 2. below.

Blood levels do not correlate well with psychological and physiological effects, unlike bloodalcohol levels, as the measurement could represent a rising level associated with euphoria, or afalling level associated with dysphoria. A chronic user will also have built up tolerance to theeffects of cocaine, and so a high blood concentration may not be interpreted as having anyspecific effect on his/her mental state at the time the sample was taken. Benzoylecgonine is notfreely permeable across the blood brain barrier, and its presence at high levels in the brain mayindicate cocaine metabolism in the brain, suggesting that the individual is a chronic abuser(Karch 2000 p.431).

Table 2. Typical Blood Levels (Sources: adapted from Karch 1991(a) p.127 and Karch 1991(b) p.1)

Description ofAdministration

Blood Cocaine Levels(mg/ml)

Therapeutic dose 3Typical intranasal snort (of100mg)

1*10-4

Excited Delirium 6Fatal / seizure or respiratorydepression inducing dose

600

An interesting development in the analysis of specimens for the presence of cocaine is the reportby Nolte et al (1992 pp.1179-1185) of the use of the larvae of the blue bottle fly, Calliphora vicinaas a ‘toxicological specimen’, after being found on a decomposed body. Cocaine was found inthe larvae, and it is hoped that in the future, the pupal cases will also be capable of being utilisedin the same way that hair is currently being examined.

Psychiatric Implications of Cocaine Use

Substance Induced Psychosis

The abuse of hallucinogenic drugs (e.g. LSD) and stimulants (including cocaine) can give rise topsychological effects listed in Table 1 above. Although the threshold at which an individual mightsuffer psychotic effects differs, the prolonged use of large quantities may result in a paranoidpsychosis, which closely resembles paranoid schizophrenia. The individual may have thefollowing features,

• persecutory delusions• auditory and visual hallucinations• aggressive behaviour

This condition subsides within 1 or 2 weeks of the last administration of the drug, but may last formonths.


A detailed history of any drug use will assist in the differentiation between substance inducedpsychosis and an underlying psychotic disorder that has been precipitated by use of the drug,which is more likely to have been associated with prodromal symptoms and a decline in personalfunctioning predating the use of the drug. The period of psychosis may be shortened by ‘urineacidification’ procedures, which hasten drug elimination. (Collier et al 1999p.354, Gelder et al1994 p.288, Bloye et al 1999 p.56 and Gunn et al 1995).

Delirium and Excited Delirium

Delirium is an acute organic mental disorder characterised by an impairment of consciousness,disturbed attention, perception and thinking. Individuals are disorientated and may suffer fromvisual hallucinations or illusions.

Cocaine intoxication has been associated with ‘excited delirium’, which is a syndrome uniquelyassociated with chronic stimulant abuse, and is a medical emergency. It has the features listedbelow, and has been described as a ‘state of mental and physiological arousal, agitation,hyperpyrexia with euphoria and hostility’. (Farnham et al 1997 pp.1107-8). Karch (2000 p.431)describes the syndrome as having 4 sequential stages – hyperthermia, agitated delirium,respiratory arrest and death over a time course of approximately 4-6 hours.

The following features may be present during the early stages of the disorder,

• fear• panic• shouting / bizarre behaviour• physical violence• hyperactivity• thrashing about (especially after restraints have been applied)• unexplained strength / endurance• hyperthermia• mydriasis• extreme sweating

Deaths from excited delirium cluster in the late summer months, and are more common amongstblack males who are more likely to be cocaine injectors, and are younger than those who die ofcocaine overdoses. (Karch 2000 p.431).

Blood cocaine concentrations are generally in the range of 6 mg/ml, which is twice thetherapeutic dose, but are still well below those levels found in fatal cocaine intoxications. Themechanism behind the cause of death in these individuals is not well understood, but couldinvolve autonomic reflexes, arrhythmias or stress during restraint. Exhaustion and posturalasphyxia are probably not causal mechanisms because of the lack of overt asphyxial changesseen at autopsy, such as petechial haemorrhages etc.

High levels of circulating catecholamines could cause ventricular tacchyarrhythmias, coupled withcocaine induced myocardial hypertrophy in chronic users, and the effects of stress on levels ofhydration and the onset of lactic acidosis could all be contributory factors.

Treatment in the emergency setting may include the use of neuroleptics for sedation. However, itshould be noted that ‘neuroleptic malignant syndrome’ patients may present in a similar manner,and the use of these drugs would clearly worsen their symptoms. Some commentators believethat neuroleptic malignant syndrome is actually a variant of excited delirium (Karch 2000 p.431).

The management of excited delirium consists of careful restraint, seclusion and medication,although the use of electro-convulsive therapy (ECT) has also been found to be safe andeffective. (Farnham et al 1997 pp.1107-8).

An individual acting in a violent and erratic or bizarre manner usually attracts the attention of thepolice, and a struggle often ensues. After being restrained (often forcibly), the individual may


collapse and die, bringing the police actions into question. Excited delirium and it’s relationshipwith deaths in custody is thus an increasingly important area of research.

Forensic Pathology of Cocaine Abuse

The Scene of Death

An examination of the scene of death is useful in suspected cocaine related deaths, so thatautopsy findings can be interpreted in context. For example, wet towels at the scene may indicatethat the deceased was suffering from terminal hyperthermia, or a barricaded room may support ahypothesis that the deceased was suffering from a psychotic episode in the context of exciteddelirium etc.

Examination of the Body

External Findings

Table 3. below illustrates some external findings that may give rise to the suspicion that thedeceased was abusing cocaine or crack. Relatives or friends may remove physical evidence ofdrug use from the vicinity of a body, and in the absence of such paraphernalia, physical signs onthe body are important circumstantial evidence.

Table 3. External findings giving rise to a suspicion of cocaine abuse (Sources: Wetli1987 p.1, Karch 1991(a))

Signs suggestive of intravenous use Fresh needle tracks,Fresh injection sites (ecchymotic (bruised) areas with aclear central zone around the needle puncture),Shallow cutaneous ulcers with a clean base and pearlymargins (toxic effect of cocaine on capillaries), orround/oval scars

Signs suggestive of crack use ‘Crack callus’ (on the ulnar aspect of the thumb) fromrepeated activation of a flint-lighter

Signs suggestive of intranasal use Perforation of the nasal septum or collapse (‘saddle nose’deformity),Enamel erosions of the front teeth (from wiping thecocaine residue across the teeth)Positive nasal swab

Internal Findings

General Findings

• visceral congestion• pulmonary oedema• serosal petechiae• signs of terminal convulsions (bite marks on the tongue, cheeks and lower lip)

Cardiovascular System

Although the following pathological changes can be diagnostic of cocaine abuse or intoxication,their presence is inconsistent.

• Endocarditis• Eosinophilic myocarditis • Previous myocardial infarction (Fig. 5)• Contraction band necrosis (Fig. 6) suggesting coronary artery spasm (The aetiology of

which has been attributed to myocardial injury caused by increased levels of


catecholamines, or to a decreased perfusion through the coronary arteries resulting frombrief vasospastic episodes of occlusion followed by vasodilatation and reperfusion.(Zugibe et al 1998 p.142). Myocyte injury and necrosis may alternatively be due tococaine’s effects on calcium influx into blood vessels. The severity of contraction bandnecrosis correlates well with post mortem blood cocaine levels. Cellular infiltrationindicates a sub-acute process, and the presence of myocardial fibrosis as well gives anindication of a history of abuse).

Fig. 5. Previous Myocardial Infarction

Fig. 6. Contraction Band Necrosis.


Acute Cardiovascular Pathology

Cocaine is directly toxic to cardiac myocytes, and this cardiotoxic effect does not depend on theroute of administration, and may not necessarily have to occur at large doses. Neither does itappear that pre-existing cardiovascular pathology is a pre-requisite for cocaine toxicity, althoughthere is some suggestion that a genetic factor may be involved, giving rise to an increasedsusceptibility to the cardiotoxic effect of cocaine in some individuals. (Isner et al 1986 p.1438).The increased levels of circulating catecholamines associated with cocaine use also appear todamage the heart and great vessels. (Karch 2000 p.430).

Acute Myocardial Infarction

The mechanism of cocaine related myocardial infarction is likely to be multifactorial in nature,and could be related to focal vasoconstriction of coronary arteries, or spasm of these arteries.Cocaine acts both directly and indirectly on vascular smooth muscle, via -adrenergicstimulation (noradrenaline) and an independent, dose-related effect. Cocaine also increasescoronary vascular resistance at a time when it is increasing heart rate and myocardial oxygendemand. (Isner et al 1989 pp.1604-1606). Coronary artery spasm may not be severe enough toinduce ischaemia in fit individuals, but in the context of pre-existing coronary artery diseasefurther reductions in flow are catastrophic. Where there is thrombotic occlusion of coronaryarteries, there appears to be no association with atherosclerotic plaque rupture or haemorrhage,as is the case with non-cocaine-related coronary artery thrombosis. (Zugibe et al 1998 p.140).

It has also been noted that cocaine depletes protein C and Antithrombin III, giving rise to aprocoagulant effect, and increasing the risk of thrombus formation in vasoconstricted coronaryarteries. However, other studies have disputed this increased tendency for thrombosis. (Karch2000 p.430).

Anyone with pre-existing cardiac disease, such as coronary artery atherosclerosis will be at anincreased risk of developing acute ischaemia because of the predictable effects of cocaine onmyocardial oxygen demand etc. (Cregler et al 1986 p.1496).

A similar vasoconstriction mechanism has been hypothesised as being responsible for othercocaine related cardiovascular pathology, including,

• Cocaine related haemorrhagic stroke (see Figs. 7 & 8 below). The mechanism ofcocaine-related cerebrovascular accidents probably being related to adrenergicstimulation, cerebral vasoconstriction and a sudden surge in blood pressure. (Cregler etal 1986 p.1497 and Levine et al 1990 pp.702-3).

• Ischaemic stroke and infarction at all levels of the central neuraxis (including spinalcord and retina). This may be due to vasoconstriction, emboli secondary to cardiacarrhythmias or reperfusion injury following momentary ischaemia.

• Intracranial haemorrhage due to ruptured berry aneurysm or arteriovenousmalformation

• Rupture of aortic aneurysm• Rhabdomyolysis• Pulmonary haemorrhage, and• Peripartum foetal distress and abruption placentae (placental vasoconstriction

following cocaine administration, leading to decreased blood flow to the foetus, and theonset of labour)


Fig. 7. Cerebral haemorrhage.

Fig.8. Cerebral infarction

Cardiac Arrhythmias

Cocaine is a Class II antiarrhythmic agent, and exerts its actions by blocking sodium channels.In large doses it is arrhythmogenic, possibly due to it’s effects on catecholamines rather than anydirect effect, (Cregler et al 1986 p.1497) or due to secondary arrhythmias following cardiacischaemia due to prolonged coronary artery vasoconstriction. A cocaine-induced rise inintracellular calcium may also be responsible (Zugibe et al 1998 p.144) and a possible source ofthe re-entry arrhythmias may be the patchy fibrosis caused by chronic cocaine abuse (Karch2000 p.431). Cocaine abuse has been linked to the following arrhythmias,

• Sinus tachycardia• Ventricular premature contractions• Ventricular tachycardia and fibrillation• Asystole• Post infarction arrhythmias• Arrhythmias due to a hyperpyrexic state


Rupture of the Ascending Aorta

Cregler et al (1986 p.1497) have reported an acute aortic rupture in a cocaine ‘freebaser’, andhypothesised that the underlying mechanism was a massive increase in systolic blood pressurefollowing an overdose of the drug, in conjunction with the deceased individual’s pre-existingchronic systemic hypertension.

Chronic Cocaine Abuse Related Vascular Pathology

The following pathology has been associated with chronic cocaine abuse,

• Myocardial hypertrophy – long term and excessive catecholamine stimulation causingthe heart to work harder, coupled with increased systemic vascular resistance(afterload) caused by high levels of circulating noradrenaline. Cocaine also increasesplasma atrial natriuretic peptide, indicative of circulatory overload and pump failure, anda genetic component is also suspected. (Karch 2000 p.430). An enlarged heart,sometimes with patchy fibrosis (see Fig. 9) may be the only abnormality found at theautopsy of a cocaine abuser, and it should be noted that an enlarged left ventricle is anestablished risk factor in sudden death even in the absence of cocaine use.

• Cocaine-induced cardiomyopathy (resembling viral myocarditis) – this condition issuspected, and has been reported by several sources (Wetli 1987 p.2 and Zugibe et al1998 p.140)

• The promotion of coronary artery disease (atherosclerotic and coronary occlusivedisease) due to coronary artery sclerosis/ intimal hyperplasia (of smooth muscle) with orwithout collagen or elastin. Fig. 10 illustrates coronary artery sclerosis). Possibleaetiologies include prolonged vasoconstriction, or stimulation of smooth muscle growthfactor, endothelial disruption or injury; the action of nor-adrenaline or platelet derivedgrowth factor (PDGF). (Zugibe et al 1998 p.142-4)

A summary of the cardiotoxic effects of cocaine is shown in Fig. 11 below.

Fig. 9. Patchy myocardial fibrosis.


Fig. 10. Coronary artery sclerosis.

Fig. 11 Cardiotoxic Effects of Cocaine – Summary (Source: Zugibe et al 1998 p.143)


Respiratory System

Non-specific findings at autopsy include pulmonary oedema and congestion, possible due toexcess catecholamine release. Specifically, cocaine use has been associated with,

• granulomas in the lungs, and this may represent either impurities in the drug, or morelikely polydrug abuse

• spontaneous pneumothorax, and• spontaneous pneumopericardium (both in freebasing cocaine)

Forrester et al (1990 pp.462-467) report that crack abuse has been associated with,

• Haemoptysis (with haemosiderin-laden macrophages in the sputum and alveoli)• Pulmonary hypertension (hypertrophy and hyperplasia of medium sized pulmonary

arteries)• Diffuse alveolar haemorrhages• Intra-alveolar inflammatory infiltrates and prominent eosinophilia (with IgE deposition

seen in lymphocytes, and alveolar macrophages)• Bronchiolitis obliterans• Thermal injury to the airway

Gastrointestinal Tract

The pathological findings in the gastrointestinal tract of a cocaine abuser are similar to thosefound in experimental animals treated with high levels of catecholamines, i.e.

• Ulceration and perforation• Ischaemic colitis• Severe bowel ischaemia and gangrene (vasoconstriction of mesenteric vasculature)• Peptic ulcer perforation (due to a disruption of the internal elastic lamina of the small

vessels supplying the ulcerated areas).

The ischaemia is reported to be segmental in distribution (Garfia et al 1990 p.740), with therebeing no mesenteric vessel thrombus involved. Instead, an increase in intestinal vascularresistance is suspected, due to cocaine’s action on -adrenergic receptors (via noradrenaline).Vasoconstriction leads to a reduction and blood flow, and thus ischaemia.

Urinary System

Cocaine use is known to have caused,

• Renal infarction• Renal thrombosis• Haemolytic uraemic syndrome• Rhabdomyolysis with myoglobinuric renal failure

Mechanisms of rhabdomyolysis include a pressure-related injury, vasospasm and myocytenecrosis, hypovolaemia, renal artery vasoconstriction and myoglobinuria.

A histological picture similar to acute tubular necrosis has also been reported (vacuolation,fragmentation and desquamation of proximal tubular epithelial cells, with pigmented casts in somedistal tubules), and cocaine use may be a risk factor for the development of glomerulosclerosis.(Karch 2000 pp.434-435).


Central Nervous System (Non-vascular)

Due to cocaine’s ability to produce hyperpyrexia, combined with it’s effects on neurotransmitters,the drug may contribute to seizure formation as well as hyperthermia. Seizures may be ‘primary’,due to cocaine lowering the seizure threshold, or ‘secondary’ to cardiac effects such as ventriculartachycardia and fibrillation. (Cregler et al 1986 p.1497).

Excited Delirium

• Elevated core temperature• Abrasions and contusions from struggling against restraints, and fighting with police etc• Pulmonary congestion and oedema• Cerebral oedema• Non-lethal self-inflicted injuries (need to exclude a carotid ‘sleeper hold’)• Contraction band necrosis (chronic cocaine use)• Slightly enlarged heart• Patchy myocardial fibrosis

There is often no anatomically obvious cause of death (Farnham et al 1997 pp.1107-8), but it isnecessary to exclude myofibrillar degeneration, as this is a morphological hallmark of stresscardiomyopathy associated with sudden death (Wetli 1985 pp.873-80)

A neurochemical explanation for excited delirium has been put forward by several researchers(reported by Karch 2000 p.432), and involves differences in the distribution of dopamine D1 and D2

receptors and a failure of those who die of excited delirium to compensate for chronically highlevels of dopamine in the brain by increasing the amount of cocaine recognition sites. Chroniccocaine users will usually have a striking increase of striatal D1 receptors, with no change in D2

receptors. In those with excited delirium, hypothalamic D2 receptors are depleted, and thesereceptors are known to regulate temperature control. Excessive 2 opiate receptors in theamygdala, nucleus acumbens (and other parts of the limbic system) have also been reported inpsychotic cocaine users, and the amygdala is thought to be involved in the integration ofemotional responses and autonomic functions. Loss of control of emotional interaction is a classicfeature of excited delirium. (Karch 2000 p.432). As neurochemical tests increase in sophisticationand accuracy, the differences between non-psychotic chronic abusers and those with exciteddelirium will be elucidated more effectively.

These deaths commonly occur at the time of or shortly after being taken into police custody, andso care must be taken to look for signs of suffocation or asphyxia related to choke holds etc, andwhether any police-inflicted injuries were lethal. However, it is important to note that those withexcited delirium die whether or not they are restrained, and ascribing the cause of death to‘positional asphyxia’ (a type of mechanical asphyxia seen in those whose cough reflexes aresuppressed by intoxication, or where postural splinting (especially in obese people) prevents chestexpansion and complete respiration) is not accurate. (Karch 2000 p.433).

Cocaine Abuse and Cause of Death

Karch et al (1991(b) p.1) highlight the implications of ascribing cause of death to cocaine abuse ortoxicity, particularly the difficulties interpreting blood cocaine levels and non-specific pathologicalfindings. In the US, cocaine related deaths are considered to be ‘accidental’, and insurers areobjecting to this because it means that they are liable to pay out despite their policies excludingpayment where death is due to the self-administration of drugs.

Persons with plasma pseudocholinesterase deficiency are at risk of sudden death when abusingcocaine, due to their inability to effectively metabolise the drug.

In determining whether cocaine abuse is causal, the pathologist should consider all strands ofevidence, from the scene of death, the presence of cocaine (at whatever level) in the blood ortissues etc in conjunction with autopsy and histopathological findings. Taken as a whole, thispattern of findings may be enough to ascribe causality. A strong history of cocaine abuse together


with typical myocardial pathology is sufficient evidence in Karch’s view (1991(b) p.2), that cocaineinduced sudden death can be ascribed even where toxicology is negative. Sudden death in youngpeople should begin with a consideration of the possible role of cocaine. Fig. 12 below illustratesan algorithm for determining whether cocaine is the cause of sudden death or not.

Fig. 12. Algorithm for Cocaine-related Sudden Death (Karch 1991(b) p.1)

Toxicology Results

+VE (with only trace or therapeutic levels of other agents)

-VE

+VE history of cocaine use

-VE history of cocaine use

Autopsy

No pathological find-ings identified

Diagnosis—cocaine or catechol toxicity (rule out phaeochromocytoma)

Diagnosis is not cocaine

Diagnosis is microfocal fibrosis (not otherwise

Summary

This report has outlined the forensic aspects of cocaine abuse, which is on the increase in the UK,particularly in London and the South East. Cocaine has wide ranging effects on the body, andcocaine intoxication as well as chronic cocaine use can give rise to serious and life threateningpathologies.


Cocaine related sudden death represents a particular challenge to the forensic pathologist interms of interpretation, because often a range of evidence has to be taken into account before acause of death can be ascribed to cocaine with the required degree of certainty. This is ofparticular importance when the death has occurred in police custody – a highly politically chargedsituation. Enormous advances have been made over the last decade in the understanding of thepathology associated with cocaine abuse, and as the prevalence of cocaine use spreads, it islikely that cocaine is going to exert it’s influence on substance-related deaths in the UK, and thusbecome an issue of increasing importance to professionals working in forensic science andmedicine.


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Documents

Forensic implications of cocaine