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Poisoning with illicit drugs
SYMPOSIUM: ACCIDENTS AND POISONING
Poisoning with illicit drugs
4000 years, and the oldest known reference to cannabis use is thought to be from the court of the Chinese Emperor Shen Nung in 2727 BC. It was not until the 19th century that the use of these drugs began to be widely considered illicit. The formal prohibition process began, perhaps, in 1805 with Napoleon’s ban on cannabis use for his troops occupying Egypt. This did not stop them from subsequently bringing it back to France. The foundation of the International Opium Commission in 1909 led to the first international drug control treaty, signed by thirteen nations in 1912. The US Harrison narcotic act in 1914 regulated and taxed opiate and cocaine importation, production and distribution. However, it was not until the UK Dangerous Drugs Act was enacted in 1920 that formal drug prohibition legislation began. This act prohibited the use of cocaine, in addition to opium, following stories of “crazed soldiers” in the First World War. The act was later extended to included cannabis in 1928. These early legislative efforts paved the way for much more coherent international efforts to enforce prohibition in many countries in the 1960s, although regulation of the different types of drugs used recreationally varies significantly between countries. Advances in drug design and laboratory chemistry has led to a significant expansion in the number of potential drugs for recreational use through the twentieth century, and into the twenty-first (Figure 1). Recreational drug development has more recently been driven by a desire to escape the illicit label. The most prominent recent examples of this process are the novel psychoactive substances, often incorrectly termed “legal highs” for this very reason. Manufacturers made minor modifications to the pharmacological structure of existing illicit compounds to create a novel “legal” substance. In the UK, the 2016 Psychoactive Substances Bill prohibited supply, but not possession, of all current and future novel psychoactive substances in order to try and counter the rise in production of these compounds.
Mark Anderson
Abstract It is estimated that approximately one quarter of adults in the European Union will have used illicit drugs at some point in their lifetime for recreational purposes. Cannabis is the most commonly used drugs by a significant margin. Illicit drug use in younger teenagers appears to have fallen in the UK over the last 10 years. However the level of use in 16e19 year olds remains one of the highest compared with other age groups, with hospital admission due to poisoning also common in this group. Assessment and management of the young person with evidence of toxicity due to illicit drugs is based upon meticulous attention to resuscitation and supportive care, combined with risk assessment dependent upon the suspected causative drug. Good knowledge of the pharmacology of the implicated drug allows early identification and avoidance of complications.
Keywords drug abuse; pharmacology; toxicology
Introduction Recreational use of illicit drugs is most prevalent in young adults in their twenties. However, use is not uncommonly initiated in adolescence as an outworking of the exploratory and risk-taking behaviour that typically characterizes this age group. This review seeks to outline the trends in illicit drug use, primarily in the UK, in young people and to summarize the recommended approach to management for acute poisoning with each of the most commonly used classes of illicit drugs, which will include a review of their pharmacology. A brief summary of a range of interventions that attempt to reduce the harm from illicit drug use will also be presented. For the purposes of this review, drugs will be considered illicit if they are prohibited by law in the UK or if they are licensed drugs with illicit use potential.
Epidemiology Surveys of young people in Europe consistently demonstrate lower prevalence of cannabis and other illicit drug use when compared with young people in the US. The overall prevalence of drug use in the UK amongst 11e15 year olds has fallen consistently over the last 15 years. In 2001, 30% of young people admitted to having ever taken drugs; by 2014 this had fallen to 15%. Those who admitted to regular use (within the last month) had also fallen, from 12% to 6% over the same time period. As might be expected, the prevalence of drug use increases with age. Above this age, approximately 1 in 5 young adults aged 16e24 years in the UK admit to having used an illicit drug within the last year. The most common illicit drug used by young people in the UK is cannabis by a significant margin. This situation is mirrored across other European countries, with lifetime prevalence among 15 and 16 year olds in 2007 ranging widely between under 10 and 45%. By comparison, ecstasy (MDMA) and amphetamine use in the same age group ranged between 1 and 7% and cocaine use between 1 and 5%. The prevalence of heroin use was less than 1%. Little comparative data are available in relation to acute morbidity and mortality in relation to illicit drug use in younger
History of illicit drug development The use of drugs for recreational purposes is not new. According to cuneiform script on clay tablets, the Sumerians in 3000 BC appear to have cultivated the opium poppy, calling it the “plant of joy”. This nomenclature would suggest its recreational use to induce euphoria. By 1000 AD, there is evidence of widespread use of opium in China and the Far East, 500 years before its introduction into the practice of medicine by Paracelsus as laudanum. Similarly, the leaves of the coca plant, Erythroxylon coca, have been used as a medicine and stimulant in South America for over
Mark Anderson BSc BMedSci BM BS MRCPCH is Consultant Paediatrician & Paediatric Adviser to the National Poisons Information Service (UK), Great North Children’s Hospital, Newcastle Upon Tyne, UK. Conflict of interest: none declared.
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Crown Copyright Ó 2017 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Anderson M, Poisoning with illicit drugs, Paediatrics and Child Health (2017), http://dx.doi.org/10.1016/ j.paed.2017.05.006
SYMPOSIUM: ACCIDENTS AND POISONING
1859 Cocaine isolated from coca leaves
1914 1961 2010 Harrison Narcotics UN Convention on Narcotic Drugs urges Widespread Act (US) regulates action against opiates and cocaine use and opium and coca development 1912 1971 trade of novel 1920 International Opium UN Convention on psychoactive Convention – first Psychotropic Mephedrone first substances international drug Substances urges (NPS) reported synthesised in control treaty action on Germany amphetamines and LSD
1800 Napoleon’s ban on cannabis usage for army in Egypt
1805 Morphine isolated from opium
1912 MDMA synthesised by Merck 1889 Amphetamine synthesised in Germany
1938 LSD synthesised by Albert Hofman
1920 Dangerous Drugs Act (UK) bans opium and cocaine
1978 MDMA recreational use begins to spread widely
1967 US makes LSD illegal
2016 Psychoactive Substances Bill (UK) prohibits supply of all current and future NPS
Figure 1 Timeline of selected events in illicit drug use.
people. However, data from all illicit drug users of all ages would suggest that use of heroin and related opiates carries the highest mortality, in spite of the relatively low prevalence rates. The high risk of death associated with heroin use is supported by experience from the opiate-abuse epidemic in the United States, where death rates have soared over the last 10 years. Amphetamine use is also associated with significant toxicity leading to mortality and although death due to cannabis overdose is unusual, it has a high rate of associated hospitalization. The mechanism of harm or death may be due to direct toxicity (common with opiates) but also indirectly; for example, due to impulsive or careless behaviour associated with the dissociative hallucinogens (for example, ketamine or phencyclidine).
Resuscitation • Airway • Breathing • Circulation • Blood glucose
Examples of street names of common illicit drugs Drug name
Street names
Cannabis
Marijuana, pot, weed, dope, ganja, grass, herb, bud, green, trees, skunk Brown sugar, smack, horse, dope, H or Big H, junk, skag, skunk, white horse or China white Candy, snow, rock, flake, blow and toot Drone, M-CAT, white magic, meow meow, meth, drone, bubbles
Heroin Cocaine Mephedrone
Table 1
History • Drug(s) identity, if possible • Dose(s) • Route • Timing • Other agents (alcohol, prescribed medication)
Examination • Top-to-toe assessment including evidence of injury • Vital Signs • Neurological assessment including GCS
Investigations • ECG • Blood gas • Urine toxicology
Figure 2 Clinical assessment of suspected poisoning.
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PAEDIATRICS AND CHILD HEALTH --:-
“Desired” effect
Illicit drug(s)
Pharmacology
Toxic symptoms
Complications
Management
Depressant
Euphoria
Opioids e.g. Heroin (diamorphine) Fentanyl Oxycodone
Bind presynaptic mopioid receptors inducing euphoric and toxic effects
Drowsiness Coma Miosis Respiratory depression Shock
Respiratory failure Pulmonary oedema Hypotension Hypothermia
Benzodiazepines e.g. Diazepam Diclazepam (NPS)
Flubromazepam (NPS) Potentiate inhibitory neuronal effect of gaminobutyric acid (GABA) through allosteric modulation of GABAA receptor Drowsiness Agonist at GHB and GABAB receptors
Coma Nystagmus Ataxia
Slurred speech Respiratory depression Hypotension
Respiratory support with measurement of pCO2 (arterial or end-tidal) Naloxone IV boluses titrated to clinical effect e beware inducing acute withdrawal May need naloxone infusion for long acting opioid Respiratory failure Respiratory and circulatory support Use of flumazenil should be avoided due to risk of seizures due to benzodiazepine dependence or co-ingestion of a proconvulsant drug
Rapid onset of coma and associated bradycardia and respiratory depression followed by abrupt resolution
Respiratory failure
Supportive care
Partial or complete agonists at cannabinoid receptors SCRAs lack cannabidiol (naturally found in cannabis) which has a protective anxiolytic effect Increase synaptic concentrations of serotonin, dopamine and noradrenaline
Ataxia Incoordination Anxiety CNS depression Prolonged (up to 36 hours) coma in children Orthostatic hypotension & syncope Sympathomimetic toxidrome: CNS e agitation, psychosis, tremor Autonomic e hyperthermia, diaphoresis CVS e tachycardia, arrhythmia GI e nausea, vomiting, diarrhoea
Agitation Psychosis and paranoia Hyperemesis
Agitation and psychosis: benzodiazepines and antipsychotics if necessary Vomiting: IV hydration and anti-emetics
Hypertension Seizures Acute coronary syndrome Stroke Shock Hyperthermia Serotonin toxicity (MDMA especially)
Agitation and seizures: benzodiazepines Hypertension: benzodiazepines and nitrates if necessary Acute coronary syndrome: aspirin, nitrates, & benzodiazepines Arrhythmia: sodium bicarbonate Hyperthermia: Active cooling e may need intubation, ventilation and paralysis
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Cannabinoid
Pleasant state of relaxation and feeling “stoned”
Stimulant
Increased empathy Euphoria Heightened sensation
g-Hydroxybutyric acid (GHB) e a CNS depressant but with similar desired effects to MDMA Cannabis Synthetic cannabinoid receptor agonists (SCRAs) (NPS)
Cocaine Amphetamine MDMA Mephedrone (NPS)
(continued on next page)
SYMPOSIUM: ACCIDENTS AND POISONING
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Please cite this article in press as: Anderson M, Poisoning with illicit drugs, Paediatrics and Child Health (2017), http://dx.doi.org/10.1016/ j.paed.2017.05.006
Clinical presentations and managements of illicit drugs
SYMPOSIUM: ACCIDENTS AND POISONING
Benzodiazepines for agitation and anxiety
The initial assessment of the young person with suspected drug overdose is outlined in Figure 2. Resuscitation, with concomitant risk assessment, is the first priority. This will involve a focused history and examination. The prime determinant of risk is the identity of the causative drug. While this may be apparent from report by the poisoned individual or those accompanying them, for illicit drug use it can be more difficult to ascertain this information. The individual may be unaccompanied and unable to give the information either due to the degree of poisoning or because the exact substance was not identified to them. In addition, confusion may be added by the nomenclature of illicit drugs employed by their users e street drug names are fluid and change with both time and geographical location. Some street names may refer to multiple compounds, for example ecstasy may refer to MDMA, ghydroxybutyrate or piperazines. Table 1 gives some examples of the multiple street names for commonly used illicit drugs. Those accompanying the poisoned patient may not wish to divulge information for fear of getting into trouble. It is also important to recognise that the poisoned patient may have ingested multiple illicit drugs, or co-ingested licit substances such as alcohol or over the counter or herbal preparations. These other substances may be responsible for the toxic effects, rather than the illicit drug. While there is no agreed way to categorise the illicit drugs they can broadly be classed by desired effect into four, albeit overlapping, groups: depressant, cannabinoid, stimulant and hallucinogenic. Table 2 outlines the main illicit drugs and their related compounds within these categories in relation to pharmacology, toxic effects and acute treatment strategies. The young person acutely poisoned by illicit drugs typically will present in one of three ways: The deeply sedated or unconscious patient may have been using one of the central nervous system depressants such as opiates, benzodiazepines or GHB. The presence of agitation, tachycardia and autonomic features may suggest toxicity from a stimulant such as cocaine, MDMA or mephedrone and its associated compounds. Acute psychosis in a young person known to use illicit drugs may indicate cannabinoid or stimulant use, or perhaps an atypical reaction to one of the psychedelic drugs. Although this review has concentrated primarily on the use and effects of illicit drugs in teenagers and young people, it is important to acknowledge that younger children can also be poisoned by them due to exploratory ingestion, often with tragic results. It is vital that clinicians consider drug toxicity (illicit or otherwise) as a cause for unusual presentations (e.g. acute behavioural changes in toddlers) in this age group, in tandem with investigating for other aetiologies. It is also important that safeguarding investigations are undertaken and followed up, whenever illicit drug poisoning is suspected or proven in this age group.
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Use of specific antidotes Table 2
NPS e novel psychoactive substance.
Panic attacks and extreme anxiety (“bad trip”) Some NPS compounds also have stimulant properties 5-HT2A receptor agonists Lysergic acid diethylamide (LSD) Psilocybin NBOMe-mescaline (NPS)
Agitation
Supportive care Catatonic state Harm due to impulsive, uninhibited behaviour Profound dissociation Aggression Psychosis NMDA receptor antagonists
Dissociation: Perception of disconnection from the physical Psychedelia: Perceptual alterations e not true hallucinations Hallucinogen
Ketamine Phencyclidine (PCP) Methoxetamine (NPS)
“Desired” effect Category
Table 2 (continued )
Illicit drug(s)
Pharmacology
Toxic symptoms
Complications
Management
The approach to acute drug overdose
Naloxone is a complete competitive antagonist of the opioid receptors. It reverses all opioid effects including sedation and
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Please cite this article in press as: Anderson M, Poisoning with illicit drugs, Paediatrics and Child Health (2017), http://dx.doi.org/10.1016/ j.paed.2017.05.006
SYMPOSIUM: ACCIDENTS AND POISONING
It is self-evident, however, that reducing harm from recreational drugs would be best achieved by preventing the use of the drugs in the first place. Schools seem an ideal environment to reach young people to educate them and conduct interventions to prevent drug use. Evidence from randomised controlled trials of various drug education programmes demonstrates some benefit, but the effects are small and inconsistent. Analysis of the available data would suggest that social influence and peer-led programmes show the most promise. Media campaigns have been a well-used device to inform young people about the potential harms of illicit drug use. The “Just Say No” campaign of the 1980s was used on both sides of the Atlantic to alert children and young people to the risks associated with drug use e in the UK this was particularly memorable for its linking with a story line in Grange Hill, a popular school-based drama of the time. More recently in UK, the FRANK advertising campaign has aimed to increase the information available to young people. Despite their popularity, there has been little rigorous study of the efficacy of these campaigns, and information from the US has suggested that they have no effect on changing behaviours or attitudes once young people have started using drugs.
respiratory depression. It can be administered intravenously, intramuscularly or via endotracheal tube. It is indicated as an empirical treatment for coma or respiratory depression, which may be due to opioid toxicity. The dose of naloxone needed to reverse opioid effects is very variable. Non-opioid-dependent individuals can be treated with a large dose without risk of significant side effects. Such as dose is indicated, for example, in toddlers who may have been accidentally poisoned by an exploratory ingestion of opiates. In opioid-dependent individuals however, much more care is needed as large doses can produce agitation and aggression as part of a withdrawal syndrome. In these cases, small doses (100 mg IV) should be given and titrated against clinical effect. The therapeutic endpoint is the achievement of a safe airway and adequate respiratory rate to maintain a normal pCO2. If repeated doses of naloxone do not have any clinical effect, a further search for the cause of the coma and respiratory depression should be undertaken while supporting the patient’s airway, breathing and circulation. Flumazenil is a competitive GABAA receptor antagonist at the benzodiazepine binding site. It reverses the effects of benzodiazepines. Significant care is needed in its use in the acutely poisoned patient. It may precipitate a withdrawal syndrome in individuals dependent on benzodiazepines, manifesting as agitation and seizures. It may also precipitate seizures in cases where another proconvulsant drug has been ingested. As a result it should be reserved for use in cases of accidental poisoning of children where it is known the symptoms are solely due to benzodiazepine toxicity, or in the rare occurrence where personnel and equipment are not available to provide supportive care. It is worth noting that isolated benzodiazepine overdose very rarely causes sufficient CNS depression to need reversal. As a result, in cases of deep coma or sedation where benzodiazepines are known to have been taken, another CNS depressant drug may have been co-ingested.
Summary The prevalence of illicit drug use in young people in the UK appears to have reduced over the last 10 years. In spite of this, use of these drugs is associated with the potential for significant harm, especially in relation to the opioids. There are significant lessons to be learned from the opiate-abuse epidemic that has swept through the US in recent years. Advances in synthetic chemistry have made an increasing number of compounds available, presenting a challenge for legislators as well as clinicians. Effective management of acute poisoning requires appropriate acute risk assessment and primarily the provision of highly effective supportive care while monitoring for adverse effects based on sound pharmacological knowledge. A
Prevention of harm Drug overdose is the most frequent cause of death in people who use illicit drugs for recreational purposes, though these deaths most commonly occur in people aged 30e39 years. Worldwide, government strategies to reduce drug-related deaths have failed to meet their targets. The UK government set a target in 1999 to reduce mortality due to drugs by 20% by 2004 and fell significantly short. Interest in providing “take home” naloxone for administration by intravenous drug users and their families has been growing since the 1990s, alongside training the same people in resuscitation in order to try and reduce mortality. Uncontrolled studies show that the training works and naloxone is administered but there is yet to be any concrete evidence of efficacy.
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FURTHER READING Fletcher A, Calafat A, Pirona A, Olszewski D. Young people, recreational drug use and harm reduction. Addiction 2011; 106(suppl 1): 37e46. Murray L, Little M, Pascu O, Hoggett KA. Toxicology handbook. 3rd edn. Australia: Churchill Livingstone, 2015. Quinones S. Dreamland: the true tale of America’s opiate epidemic. New York, NY: Bloomsbury Press, 2015. The Poison Review www.thepoisonreview.com. Toxbase www.toxbase.org (requires a password). Winters KC, Botzet AM, Fahnhorst T. Advances in adolescent substance abuse treatment. Curr Psychiatry Rep 2011; 13: 416e21.
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Poisoning with illicit drugs
4000 years, and the oldest known reference to cannabis use is thought to be from the court of the Chinese Emperor Shen Nung in 2727 BC. It was not until the 19th century that the use of these drugs began to be widely considered illicit. The formal prohibition process began, perhaps, in 1805 with Napoleon’s ban on cannabis use for his troops occupying Egypt. This did not stop them from subsequently bringing it back to France. The foundation of the International Opium Commission in 1909 led to the first international drug control treaty, signed by thirteen nations in 1912. The US Harrison narcotic act in 1914 regulated and taxed opiate and cocaine importation, production and distribution. However, it was not until the UK Dangerous Drugs Act was enacted in 1920 that formal drug prohibition legislation began. This act prohibited the use of cocaine, in addition to opium, following stories of “crazed soldiers” in the First World War. The act was later extended to included cannabis in 1928. These early legislative efforts paved the way for much more coherent international efforts to enforce prohibition in many countries in the 1960s, although regulation of the different types of drugs used recreationally varies significantly between countries. Advances in drug design and laboratory chemistry has led to a significant expansion in the number of potential drugs for recreational use through the twentieth century, and into the twenty-first (Figure 1). Recreational drug development has more recently been driven by a desire to escape the illicit label. The most prominent recent examples of this process are the novel psychoactive substances, often incorrectly termed “legal highs” for this very reason. Manufacturers made minor modifications to the pharmacological structure of existing illicit compounds to create a novel “legal” substance. In the UK, the 2016 Psychoactive Substances Bill prohibited supply, but not possession, of all current and future novel psychoactive substances in order to try and counter the rise in production of these compounds.
Mark Anderson
Abstract It is estimated that approximately one quarter of adults in the European Union will have used illicit drugs at some point in their lifetime for recreational purposes. Cannabis is the most commonly used drugs by a significant margin. Illicit drug use in younger teenagers appears to have fallen in the UK over the last 10 years. However the level of use in 16e19 year olds remains one of the highest compared with other age groups, with hospital admission due to poisoning also common in this group. Assessment and management of the young person with evidence of toxicity due to illicit drugs is based upon meticulous attention to resuscitation and supportive care, combined with risk assessment dependent upon the suspected causative drug. Good knowledge of the pharmacology of the implicated drug allows early identification and avoidance of complications.
Keywords drug abuse; pharmacology; toxicology
Introduction Recreational use of illicit drugs is most prevalent in young adults in their twenties. However, use is not uncommonly initiated in adolescence as an outworking of the exploratory and risk-taking behaviour that typically characterizes this age group. This review seeks to outline the trends in illicit drug use, primarily in the UK, in young people and to summarize the recommended approach to management for acute poisoning with each of the most commonly used classes of illicit drugs, which will include a review of their pharmacology. A brief summary of a range of interventions that attempt to reduce the harm from illicit drug use will also be presented. For the purposes of this review, drugs will be considered illicit if they are prohibited by law in the UK or if they are licensed drugs with illicit use potential.
Epidemiology Surveys of young people in Europe consistently demonstrate lower prevalence of cannabis and other illicit drug use when compared with young people in the US. The overall prevalence of drug use in the UK amongst 11e15 year olds has fallen consistently over the last 15 years. In 2001, 30% of young people admitted to having ever taken drugs; by 2014 this had fallen to 15%. Those who admitted to regular use (within the last month) had also fallen, from 12% to 6% over the same time period. As might be expected, the prevalence of drug use increases with age. Above this age, approximately 1 in 5 young adults aged 16e24 years in the UK admit to having used an illicit drug within the last year. The most common illicit drug used by young people in the UK is cannabis by a significant margin. This situation is mirrored across other European countries, with lifetime prevalence among 15 and 16 year olds in 2007 ranging widely between under 10 and 45%. By comparison, ecstasy (MDMA) and amphetamine use in the same age group ranged between 1 and 7% and cocaine use between 1 and 5%. The prevalence of heroin use was less than 1%. Little comparative data are available in relation to acute morbidity and mortality in relation to illicit drug use in younger
History of illicit drug development The use of drugs for recreational purposes is not new. According to cuneiform script on clay tablets, the Sumerians in 3000 BC appear to have cultivated the opium poppy, calling it the “plant of joy”. This nomenclature would suggest its recreational use to induce euphoria. By 1000 AD, there is evidence of widespread use of opium in China and the Far East, 500 years before its introduction into the practice of medicine by Paracelsus as laudanum. Similarly, the leaves of the coca plant, Erythroxylon coca, have been used as a medicine and stimulant in South America for over
Mark Anderson BSc BMedSci BM BS MRCPCH is Consultant Paediatrician & Paediatric Adviser to the National Poisons Information Service (UK), Great North Children’s Hospital, Newcastle Upon Tyne, UK. Conflict of interest: none declared.
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Crown Copyright Ó 2017 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Anderson M, Poisoning with illicit drugs, Paediatrics and Child Health (2017), http://dx.doi.org/10.1016/ j.paed.2017.05.006
SYMPOSIUM: ACCIDENTS AND POISONING
1859 Cocaine isolated from coca leaves
1914 1961 2010 Harrison Narcotics UN Convention on Narcotic Drugs urges Widespread Act (US) regulates action against opiates and cocaine use and opium and coca development 1912 1971 trade of novel 1920 International Opium UN Convention on psychoactive Convention – first Psychotropic Mephedrone first substances international drug Substances urges (NPS) reported synthesised in control treaty action on Germany amphetamines and LSD
1800 Napoleon’s ban on cannabis usage for army in Egypt
1805 Morphine isolated from opium
1912 MDMA synthesised by Merck 1889 Amphetamine synthesised in Germany
1938 LSD synthesised by Albert Hofman
1920 Dangerous Drugs Act (UK) bans opium and cocaine
1978 MDMA recreational use begins to spread widely
1967 US makes LSD illegal
2016 Psychoactive Substances Bill (UK) prohibits supply of all current and future NPS
Figure 1 Timeline of selected events in illicit drug use.
people. However, data from all illicit drug users of all ages would suggest that use of heroin and related opiates carries the highest mortality, in spite of the relatively low prevalence rates. The high risk of death associated with heroin use is supported by experience from the opiate-abuse epidemic in the United States, where death rates have soared over the last 10 years. Amphetamine use is also associated with significant toxicity leading to mortality and although death due to cannabis overdose is unusual, it has a high rate of associated hospitalization. The mechanism of harm or death may be due to direct toxicity (common with opiates) but also indirectly; for example, due to impulsive or careless behaviour associated with the dissociative hallucinogens (for example, ketamine or phencyclidine).
Resuscitation • Airway • Breathing • Circulation • Blood glucose
Examples of street names of common illicit drugs Drug name
Street names
Cannabis
Marijuana, pot, weed, dope, ganja, grass, herb, bud, green, trees, skunk Brown sugar, smack, horse, dope, H or Big H, junk, skag, skunk, white horse or China white Candy, snow, rock, flake, blow and toot Drone, M-CAT, white magic, meow meow, meth, drone, bubbles
Heroin Cocaine Mephedrone
Table 1
History • Drug(s) identity, if possible • Dose(s) • Route • Timing • Other agents (alcohol, prescribed medication)
Examination • Top-to-toe assessment including evidence of injury • Vital Signs • Neurological assessment including GCS
Investigations • ECG • Blood gas • Urine toxicology
Figure 2 Clinical assessment of suspected poisoning.
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“Desired” effect
Illicit drug(s)
Pharmacology
Toxic symptoms
Complications
Management
Depressant
Euphoria
Opioids e.g. Heroin (diamorphine) Fentanyl Oxycodone
Bind presynaptic mopioid receptors inducing euphoric and toxic effects
Drowsiness Coma Miosis Respiratory depression Shock
Respiratory failure Pulmonary oedema Hypotension Hypothermia
Benzodiazepines e.g. Diazepam Diclazepam (NPS)
Flubromazepam (NPS) Potentiate inhibitory neuronal effect of gaminobutyric acid (GABA) through allosteric modulation of GABAA receptor Drowsiness Agonist at GHB and GABAB receptors
Coma Nystagmus Ataxia
Slurred speech Respiratory depression Hypotension
Respiratory support with measurement of pCO2 (arterial or end-tidal) Naloxone IV boluses titrated to clinical effect e beware inducing acute withdrawal May need naloxone infusion for long acting opioid Respiratory failure Respiratory and circulatory support Use of flumazenil should be avoided due to risk of seizures due to benzodiazepine dependence or co-ingestion of a proconvulsant drug
Rapid onset of coma and associated bradycardia and respiratory depression followed by abrupt resolution
Respiratory failure
Supportive care
Partial or complete agonists at cannabinoid receptors SCRAs lack cannabidiol (naturally found in cannabis) which has a protective anxiolytic effect Increase synaptic concentrations of serotonin, dopamine and noradrenaline
Ataxia Incoordination Anxiety CNS depression Prolonged (up to 36 hours) coma in children Orthostatic hypotension & syncope Sympathomimetic toxidrome: CNS e agitation, psychosis, tremor Autonomic e hyperthermia, diaphoresis CVS e tachycardia, arrhythmia GI e nausea, vomiting, diarrhoea
Agitation Psychosis and paranoia Hyperemesis
Agitation and psychosis: benzodiazepines and antipsychotics if necessary Vomiting: IV hydration and anti-emetics
Hypertension Seizures Acute coronary syndrome Stroke Shock Hyperthermia Serotonin toxicity (MDMA especially)
Agitation and seizures: benzodiazepines Hypertension: benzodiazepines and nitrates if necessary Acute coronary syndrome: aspirin, nitrates, & benzodiazepines Arrhythmia: sodium bicarbonate Hyperthermia: Active cooling e may need intubation, ventilation and paralysis
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Cannabinoid
Pleasant state of relaxation and feeling “stoned”
Stimulant
Increased empathy Euphoria Heightened sensation
g-Hydroxybutyric acid (GHB) e a CNS depressant but with similar desired effects to MDMA Cannabis Synthetic cannabinoid receptor agonists (SCRAs) (NPS)
Cocaine Amphetamine MDMA Mephedrone (NPS)
(continued on next page)
SYMPOSIUM: ACCIDENTS AND POISONING
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Please cite this article in press as: Anderson M, Poisoning with illicit drugs, Paediatrics and Child Health (2017), http://dx.doi.org/10.1016/ j.paed.2017.05.006
Clinical presentations and managements of illicit drugs
SYMPOSIUM: ACCIDENTS AND POISONING
Benzodiazepines for agitation and anxiety
The initial assessment of the young person with suspected drug overdose is outlined in Figure 2. Resuscitation, with concomitant risk assessment, is the first priority. This will involve a focused history and examination. The prime determinant of risk is the identity of the causative drug. While this may be apparent from report by the poisoned individual or those accompanying them, for illicit drug use it can be more difficult to ascertain this information. The individual may be unaccompanied and unable to give the information either due to the degree of poisoning or because the exact substance was not identified to them. In addition, confusion may be added by the nomenclature of illicit drugs employed by their users e street drug names are fluid and change with both time and geographical location. Some street names may refer to multiple compounds, for example ecstasy may refer to MDMA, ghydroxybutyrate or piperazines. Table 1 gives some examples of the multiple street names for commonly used illicit drugs. Those accompanying the poisoned patient may not wish to divulge information for fear of getting into trouble. It is also important to recognise that the poisoned patient may have ingested multiple illicit drugs, or co-ingested licit substances such as alcohol or over the counter or herbal preparations. These other substances may be responsible for the toxic effects, rather than the illicit drug. While there is no agreed way to categorise the illicit drugs they can broadly be classed by desired effect into four, albeit overlapping, groups: depressant, cannabinoid, stimulant and hallucinogenic. Table 2 outlines the main illicit drugs and their related compounds within these categories in relation to pharmacology, toxic effects and acute treatment strategies. The young person acutely poisoned by illicit drugs typically will present in one of three ways: The deeply sedated or unconscious patient may have been using one of the central nervous system depressants such as opiates, benzodiazepines or GHB. The presence of agitation, tachycardia and autonomic features may suggest toxicity from a stimulant such as cocaine, MDMA or mephedrone and its associated compounds. Acute psychosis in a young person known to use illicit drugs may indicate cannabinoid or stimulant use, or perhaps an atypical reaction to one of the psychedelic drugs. Although this review has concentrated primarily on the use and effects of illicit drugs in teenagers and young people, it is important to acknowledge that younger children can also be poisoned by them due to exploratory ingestion, often with tragic results. It is vital that clinicians consider drug toxicity (illicit or otherwise) as a cause for unusual presentations (e.g. acute behavioural changes in toddlers) in this age group, in tandem with investigating for other aetiologies. It is also important that safeguarding investigations are undertaken and followed up, whenever illicit drug poisoning is suspected or proven in this age group.
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Use of specific antidotes Table 2
NPS e novel psychoactive substance.
Panic attacks and extreme anxiety (“bad trip”) Some NPS compounds also have stimulant properties 5-HT2A receptor agonists Lysergic acid diethylamide (LSD) Psilocybin NBOMe-mescaline (NPS)
Agitation
Supportive care Catatonic state Harm due to impulsive, uninhibited behaviour Profound dissociation Aggression Psychosis NMDA receptor antagonists
Dissociation: Perception of disconnection from the physical Psychedelia: Perceptual alterations e not true hallucinations Hallucinogen
Ketamine Phencyclidine (PCP) Methoxetamine (NPS)
“Desired” effect Category
Table 2 (continued )
Illicit drug(s)
Pharmacology
Toxic symptoms
Complications
Management
The approach to acute drug overdose
Naloxone is a complete competitive antagonist of the opioid receptors. It reverses all opioid effects including sedation and
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Please cite this article in press as: Anderson M, Poisoning with illicit drugs, Paediatrics and Child Health (2017), http://dx.doi.org/10.1016/ j.paed.2017.05.006
SYMPOSIUM: ACCIDENTS AND POISONING
It is self-evident, however, that reducing harm from recreational drugs would be best achieved by preventing the use of the drugs in the first place. Schools seem an ideal environment to reach young people to educate them and conduct interventions to prevent drug use. Evidence from randomised controlled trials of various drug education programmes demonstrates some benefit, but the effects are small and inconsistent. Analysis of the available data would suggest that social influence and peer-led programmes show the most promise. Media campaigns have been a well-used device to inform young people about the potential harms of illicit drug use. The “Just Say No” campaign of the 1980s was used on both sides of the Atlantic to alert children and young people to the risks associated with drug use e in the UK this was particularly memorable for its linking with a story line in Grange Hill, a popular school-based drama of the time. More recently in UK, the FRANK advertising campaign has aimed to increase the information available to young people. Despite their popularity, there has been little rigorous study of the efficacy of these campaigns, and information from the US has suggested that they have no effect on changing behaviours or attitudes once young people have started using drugs.
respiratory depression. It can be administered intravenously, intramuscularly or via endotracheal tube. It is indicated as an empirical treatment for coma or respiratory depression, which may be due to opioid toxicity. The dose of naloxone needed to reverse opioid effects is very variable. Non-opioid-dependent individuals can be treated with a large dose without risk of significant side effects. Such as dose is indicated, for example, in toddlers who may have been accidentally poisoned by an exploratory ingestion of opiates. In opioid-dependent individuals however, much more care is needed as large doses can produce agitation and aggression as part of a withdrawal syndrome. In these cases, small doses (100 mg IV) should be given and titrated against clinical effect. The therapeutic endpoint is the achievement of a safe airway and adequate respiratory rate to maintain a normal pCO2. If repeated doses of naloxone do not have any clinical effect, a further search for the cause of the coma and respiratory depression should be undertaken while supporting the patient’s airway, breathing and circulation. Flumazenil is a competitive GABAA receptor antagonist at the benzodiazepine binding site. It reverses the effects of benzodiazepines. Significant care is needed in its use in the acutely poisoned patient. It may precipitate a withdrawal syndrome in individuals dependent on benzodiazepines, manifesting as agitation and seizures. It may also precipitate seizures in cases where another proconvulsant drug has been ingested. As a result it should be reserved for use in cases of accidental poisoning of children where it is known the symptoms are solely due to benzodiazepine toxicity, or in the rare occurrence where personnel and equipment are not available to provide supportive care. It is worth noting that isolated benzodiazepine overdose very rarely causes sufficient CNS depression to need reversal. As a result, in cases of deep coma or sedation where benzodiazepines are known to have been taken, another CNS depressant drug may have been co-ingested.
Summary The prevalence of illicit drug use in young people in the UK appears to have reduced over the last 10 years. In spite of this, use of these drugs is associated with the potential for significant harm, especially in relation to the opioids. There are significant lessons to be learned from the opiate-abuse epidemic that has swept through the US in recent years. Advances in synthetic chemistry have made an increasing number of compounds available, presenting a challenge for legislators as well as clinicians. Effective management of acute poisoning requires appropriate acute risk assessment and primarily the provision of highly effective supportive care while monitoring for adverse effects based on sound pharmacological knowledge. A
Prevention of harm Drug overdose is the most frequent cause of death in people who use illicit drugs for recreational purposes, though these deaths most commonly occur in people aged 30e39 years. Worldwide, government strategies to reduce drug-related deaths have failed to meet their targets. The UK government set a target in 1999 to reduce mortality due to drugs by 20% by 2004 and fell significantly short. Interest in providing “take home” naloxone for administration by intravenous drug users and their families has been growing since the 1990s, alongside training the same people in resuscitation in order to try and reduce mortality. Uncontrolled studies show that the training works and naloxone is administered but there is yet to be any concrete evidence of efficacy.
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FURTHER READING Fletcher A, Calafat A, Pirona A, Olszewski D. Young people, recreational drug use and harm reduction. Addiction 2011; 106(suppl 1): 37e46. Murray L, Little M, Pascu O, Hoggett KA. Toxicology handbook. 3rd edn. Australia: Churchill Livingstone, 2015. Quinones S. Dreamland: the true tale of America’s opiate epidemic. New York, NY: Bloomsbury Press, 2015. The Poison Review www.thepoisonreview.com. Toxbase www.toxbase.org (requires a password). Winters KC, Botzet AM, Fahnhorst T. Advances in adolescent substance abuse treatment. Curr Psychiatry Rep 2011; 13: 416e21.
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Crown Copyright Ó 2017 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Anderson M, Poisoning with illicit drugs, Paediatrics and Child Health (2017), http://dx.doi.org/10.1016/ j.paed.2017.05.006