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Curr Top Med Chem. Subst Use Misuse. Clin Toxicol Phila. Drug Alcohol Depend. An emerging drug of abuse. Ann N Y Acad Sci. J Addict Dis. Am J Addict. Boyer EW Dextromethorphan abuse. Pediatr Emerg Care. Br J Clin Pharmacol. Med J Aust. Eur J Clin Pharmacol. Chittrakarn S, Keawpradub N, Sawangjaroen K The neuromuscular blockade produced by pure alkaloid, mitragynine and methanol extract of Kratom leaves Mitragyna speciosa Korth. J Ethnopharmacol. Chopra A, Morrison L Resolution of caffeine-induced complex dysrrythmia with procainamide therapy. J Emerg Med. Am J Emerg Med. Mix Mag. J Anal Toxicol. Salvia divinorum. Lancet Oncol. Clinical Toxicology. Hammersley R Dangers of banning spice and the synthetic cannabinoid agonists. Emerg Med J. J Psychoactive Drugs. Military Med. Kelly BC Legally tripping: a qualitative profile of Salvia divinorum use among young adults. J Psychoact Drug. Am J Psychiatry. The Intern J Drug Policy. Addict Biol. Moritz ML, Ayus JC New aspects in the pathogenesis, prevention, and treatment of hyponatremic encephalopathy in children. Pediatr Nephrol.. Schizophrenia Research. J Med Toxicol. New York: McGraw Hill; Eur J Pharmacol. Roche K Kratom: a case of a legal high.. Clin Toxicol. J Am Pharm Assoc. Sarnaik AP, Meert K, Hackbarth R Management of hyponatremic seizures in children with hypertonic saline: a safe and effective strategy. Crit Care Med. Forensic Science International. Abuse of pentazocine and tripelennamine. Vet Hum Toxicol. Siebert DJ Salvia divinorum and salvinorin A: new pharmacologic findings. Staack RF Piperazine designer drugs of abuse. Legal highs on the internet. Substance Use and Misuse. J Psychopharmacol. Forensic Sci Int. Addict Behav. Ped Emerg Care. Int J Drug Policy. Adolesc Med Clin. Am J Med. Savithiri Ratnapalan. The explosive proliferation and widespread availability of these legal highs combined with the ease of purchase from the internet and other sources makes it easy for consumers to obtain them and difficult for health professionals to keep up with the knowledge of newer drugs, and management of intoxicated individuals. This review will describe non-prescription drugs of abuse and other the different groups of legal highs and discuss management options. The initial high is followed by other effects such as feelings of power, self confidence, increased energy, and relaxation, out of body experience, increased sensations or altered perception, based on the substance or substances used. Using psychoactive substances is perceived as a recreation activity and most substance users and abusers believe that they can control their substance use but drug abuse can become habitual leading to addiction. Any psychoactive drug can alter cognitive process resulting in significant cost to the individual and society. Furthermore, most of these drugs also have physiological effects that can lead to morbidity and mortality. Due to the potential negative effects associated with most psychoactive substances used for non medical purposes, they are classified as scheduled prohibited or illegal drugs. These classification may vary in different countries and there have been calls to readdress the classification system in UK Nutt et al, Some substances with abuse potential are prescription drugs such as opioids, ketamine and benzodiazepines; non prescription drugs of abuse such as antihistamines and dextromethorphan, legal substances of abuse such as cigarettes and alcohol; and the large array of illegal drugs of abuse. Most prescription drugs with abuse potential are controlled drugs, and possession of the drug without a prescription and sale of the drug by unauthorised individuals are considered criminal offences. Some of the illegal drugs such as marijuana or cannabis are used for medicinal purposes too, where it is prescribed for relieving nausea and pain management in cancer patients Furlow, Different countries and jurisdiction deem which substances will be classified as illegal substances with regards to possession and use. For example possession and use of marijuana in UK whereas the Canadian government and several states in US restrict it but have regulations for medical use of marijuana Health Canada, Almost all substances of abuse have psychoactive effects such as stimulant, sedative, hallucinogenic or a combination of them. The effects of the drug after the initial high vary. Stimulants give a sense of power and energy where as sedatives provide relaxation and calmness Gibbons, Stimulants can be either anticholinergic or sympathomimetic. These are also marketed as herbal supplements, herbal highs, party pills and legal club drugs. Hillebrand et al, Salvia divinorum salivinorin A , kratom mitragynine , hawaiian baby wood rose seeds lysergic acid amide , fly agaric mushroom that contains ibotenic acid and muscimol and genie synthetic cannbinoids JWH, CP were the top five products. Schmidt et al, The drug-related information is also provided on the internet by several sites such as the Lycaeum www. Gibbons, This review will describe the different groups of legal highs, their known and potential effects and discuss management option. A summary of non prescription drugs of abuse and other newer substances of abuse that are legal or were legal until recently are provided in Table 1. Stimulants such as caffeine, dextromethorphan in cough remedies, cough and cold remedies containing stimulants or antihistamines are misused and abused for improving performance and for their hallucinogenic properties by many young adults Williams and Kokotailo, ; Conca and Worthen, Wiegand et al, Sympathomimetics may be ingested orally or applied topically as in ocular and nasal drops and nasal sprays and gels. Non-prescription sympathomimetics and natural sources of Ephedra and its derivatives are found in plant-derived tinctures, teas, extracts and nutritional supplements Sloan and Kittner et al, ; Peterson and Stoebner et al, Sympathomimetics produce tachycardia, hypertension, hyperthermia, dilated pupils, diaphoresis and central nervous system effects such as psychosis, paranoia, nervousness, and irritability. Peterson and Stoebner et al, Sympathomimetic abuse has been associated with ischemic and hemorrhagic strokes Sloan et al. Topical products are generally considered safe by the lay public, however, sympathomimetics in nasal vasoconstrictors have been associated with severe adverse events, including cerebrovascular stroke. Costantino et al, The effects of sympathomimetics can be catastrophic when combined with other drugs as shown by a case of hypertensive crisis, accompanied by hypertensive encephalopathy and seizures, after the ingestion of plant-derived products containing both ephedrine alkaloids and caffeine Berman et al, Due to availability of a large variety of non-prescription sympathomimetics, their abuse and dependence may persist for several years and medical attention may be needed for withdrawal effects. Emergency medical services may be called in for cardiac events, strokes, seizures, decreased level of consciousness or abnormal behaviour in patients who have abused sympathomimetics, see Table 2 for general symptomatic management that are applicable to most intoxications. Management of acute intoxications of sympathomimetic agents consists of supportive care, aggressive sedation with benzodiazepines as needed for agitation, seizure, tachycardia, or hypertension and passive or active cooling measures to combat hyperthermia. Beta blockers should not be used for tachycardia as unopposed alpha action can lead to severe hypertension Olson, Please see other detail on management of sympathomimetic toxicity under cathinones. Antihistamines have anticholinergic properties such as tachycardia, hypertension, hyperthermia, dilated pupils, dry skin and mucus membranes and produce euphoria, detachment and hallucinations, and potentiate the effects of other psychoactive substances. Malcolm and Miller, ; Orzechowski et al. Tripelennamine and other antihistamines are often taken in combination with opiates and opiate-like drugs, including heroin and pentazocine to potentiate opiate effects and reduces histamine mediated itching and rhinitis associated with opiate use. Showalter, Antihistamine intoxication can result in a variety of serious central nervous system and cardiovascular effects, including delirium, psychosis, agitation or sedation, delayed cardiac conduction as manifested by prolonged QRS interval, which may lead to dangerous and lethal cardiac arrhythmias, wide fluctuations in blood pressure, and generalised seizures. Buckley et al, Antihistamine withdrawal can present with cholinergic symptoms such as rhinorhea, wheezing nausea and vomiting Thomas and Nallur et al, Management of acute intoxications of anticholinergic agents also consists of supportive care, aggressive sedation with benzodiazepines as needed for agitation, seizure, tachycardia, or hypertension and passive or active cooling measures to combat hyperthermia Table 2. Antihistamines can cause QT widening and arrhythmias. Sodium bicarbonate has been used with success in wide complex tachycardia caused by antihistamines. Cole and Stellpflug et al, The specific antidote physostigmine has not been used in pre-hospital settings. Some of the reasons for this may be; the need for full toxicology screen to exclude tricyclic ingestions, electrocardiograms to measure conduction delays, cardiovascular monitoring, qualified personnel for patient monitoring during administration of physostigmine and atropine for rescue has to available before using physostigmine. Physostigmine also has a very short half-life and several repeated doses may be necessary every 10—15 minutes Olson, Supportive care and atropine may be needed for severe anticholinergic withdrawal symptoms. Caffeine abuse and overdose can present with gastrointestinal symptoms such as nausea, vomiting, abdominal pain, diarrhea, tachyarrhythmia, headache, insomnia, agitation, tremor, hyper tonicity, tinnitus, and delirium Caffeine may induce cardiac arrhythmias, and precipitate seizures Chopra and Morrison ; Shum et al, ; Kendler and Prescott, Although caffeine abuse was not commonly associated with mortality, deaths due to caffeine overdose attributed to non prescription product abuse, with abrupt onset of intractable seizures and electroconvulsive activity, have been reported both in the literature and lay press Shum et al, ; Reuters News, Caffeine and taurine found in energy drinks can increase blood pressure and platelet aggregation and reduce endothelial function Worthley et al. The management of acute caffeine intoxication is similar to management of sympathomimetics as described above. Dextromethorphan, a cough suppressant structurally related to codeine and used in many cough and cold preparations acts as a dissociative hallucinogen in high doses and causes changes in sensations, perception Miller , Vahid et al, Dextromethorphan overdose or abuse can cause nausea, vomiting, somnolence, nystagmus, ataxia, hallucinations, hypertension, and breathing difficulties. Deaths have been reported with intentional dextromethorphan abuse. Logan et al, Serotonin syndrome, a potentially lethal condition with a variety of symptoms such as tremors, myoclonus, hyperreflexia, dilated pupils, hypertension, hyperthermia, diaphoresis, impaired coordination, hallucinations and coma, has been associated with dextromethorphan ingestion Boyer, ; Banken and Foster, ; Romanelli and Smith, The management of acute dextromethorphan intoxication is similar to management of sympathomimetics as described above Boyer, ; Romanelli and Smith, They are incorporated into herbal smoking mixtures and are widely available as incense or potpourri and have been sold virtually everywhere. As such, these products are not only found in head shops selling substances that can be smoked and smoking equipment such as pipes and bongs and tobacco shops but also in gas stations, convenience stores, and grocery stores. There is no international control by the United Nations UN drug control conventions for any of the synthetic cannabinoids, but several of them scheduled drugs in several countries including UK. However, more and more new versions are created to avoid legislature and synthetic cannabinoids use and abuse continues. However, completely opposite effects of anxiety, tachycardia, and nausea are in many first time users. Many of the synthetic cannabinoids produce elevated heart rate, elevated blood pressure, palpitations, diaphoresis, tremulousness, anxiety, and agitation Vearrierand and Osterhoudt, ; Schneir et al. Most of these effects appear within 30 minutes, last for within 3—4 hours, and resolve within 6 hours Quan et al, Acutely, management of synthetic cannabinoid toxicity is supportive care and benzodiazepines for calming agitation and anxiety. There is a case report of a young man who required intubation but was discharged in 24 hours Simmons et al. Patients should be observed until the resolution of vital sign abnormalities, vomiting, and psychiatric derangements. Opioid antagonist naloxone has been shown to reduce THC effects in animals and may be a consideration for the future Justinova et al. A single dose of naloxone does not produce significant side effects and should be considered for patients with suspected cannabinoid toxicity in the pre-hospital settings. The effects of salvia are due to salvinorin A, and it has more in common with hallucinogens such as lysergic acid diethylamide LSD and mescaline rather than those of marijuana Johnson et al. Salvia can be chewed though ingestion is ineffective or inhaled to produce hallucinations, which occur within seconds with both buccal exposure and inhalation, and last for about an hour after buccal exposure and 20—30 minutes after inhalation Siebert , Babu et al, Baggott et al. Headaches and drowsiness can last for several hours after use and persistent psychosis in a previously well patient has been reported Przekop and Lee, Clinically significant adverse effects are rarely reported with salvia which could be due to several reasons such as a lack of reporting by the patients or recognition by emergency care providers, or masking of symptoms due to coingestions. However, several media reports of salvia associated suicides has implication for monitoring and control of salvia USA Today, Acute salvia intoxications may present with normal vital signs or tachycardia and hypertension. It is more likely that patient presenting to medical care with cardiovascular effects or neuropsychiatric toxicity have used Salvia with other substances or alcohol Vohr et al, ; Rosenbaum et al, There is no antidote for salvia divinorum intoxication and supportive care and the use of benzodiazepines sedation for severe agitation should be provided. The long term effects of chronic salvia use may need both medical and psychiatric care. Multiple routes of exposure have been reported. Based on user reports, typical doses of mephedrone and methylone are — mg orally, with onset of effects around 30—45 min and duration of 2—5 hours Erowid Vaults , Rosenbaum et al, Cathionones are reported to produce of euphoria, heightened alertness, increased energy, talkativeness, and increased sexual arousal and many re-dose repeatedly to prolong the effects Winstock et al, ; Erowid Vaults, Snorting bath salts have led to be severely aggressive and psychotic behaviour American Association of Poison Control Centers, Self-mutilation, suicide attempts, and persistent paranoid psychosis are also reported. Cathinone intoxication also produces sympathomimetic toxicity with hypertension, tachycardia, hyperthermia, dehydration, and psychomotor agitation with trismus, bruxism, tremors, insomnia, and paranoia. James et al, ; Rosenbaum, et al, There have been case reports of myocardial infarction and mephedrone-related myocarditis. Nicholson, et al Multiple deaths have occurred in the setting of bath salt use, with mephedrone and MDPV identified during post-mortem Torrance. Synthetic cathinones are not detected by common drug tests; however, the cathinone derivates may cause a false positive methamphetamine screen Torrance and Cooper, Some commercially available kits can detect some of them. Attention should be paid to ensuring the safety of the first responders and patients may have to be physically or chemically restrained to provide care. Physical restraints can precipitate arrhythmias and should be avoided or should be kept to the minimum time period to allow sedation with benzodiazepines. Management of acute intoxications is similar to other sympathomimetic agents with supportive care and aggressive sedation with benzodiazepines as needed for agitation, seizure, tachycardia, or hypertension. There is no specific antidote. Persistent hypertension can be treated with vasodilators nitro-glycerine or sodium nitroprusside. Beta blockers should not be used as they may exacerbate of hypertension due to unopposed alpha-adrenergic stimulation. Cold packs, ice and cool saline should be available in ambulances. All symptomatic patients should have an electrocardiogram, be placed on a cardiac monitor, receive serial temperature and monitored until vital signs are normal and symptoms have resolved. Kratom, mitragyna speciosa korth , is a tropical tree found in many parts of South East Asia and its leaves have been chewed by natives to provide energy and relieve muscle pain. Kratom is an illegal substance in Thailand and Malaysia but is a legal substance in almost all other countries including UK Jansen and Prast ; Assanangkornchai and Muekthong et al, ; US Department of justice, Kratom products are available as powder, leaves, and gum and the drug is typically, chewed, smoked or brewed into tea Rosenbaum and Carreiro et al, Mitragynine, the most abundant chemical in Kratom, is 13 times more potent than morphine and responsible for its opium-like properties but also has the unusual dual properties that result in both stimulation and analgesia Vicknasingam et al. Kratom has been used for centuries as a substitute for opium and to treat opiod withdrawal and is freely available via the internet Boyer et al. Kratom also causes neuromuscular blockade, which may contribute to the relief of myalgia Chittrakarn et al. Kratom is also called herbal speedball and is advertised as an effective agent to relieve muscle pain, and prolong sexual intercourse. Some of the attributed medicinal effects include analgesic, anti-inflammatory, antipyretic, antitussive, antihypertensive, local anaesthetic, hypoglycaemic, anti- diarrheal, and anti-malarial effects. Suwanlert, ; Jansen and Prast, ; Vicknasingam et al. A cocaine-like stimulant effect is seen at low doses, and opiod effects at higher doses Babu et al. There are case reports of intractable seizures needing intubation with Kratom use Roche, ; Nelsen et al. A withdrawal syndrome consisting of symptoms of hostility, aggression, emotional lability, rhinorhea, diarrhea, achy muscles and bones, and jerky movement of the limbs has been observed. Several cases of kratom psychosis were observed where kratom addicts exhibited psychotic symptoms that included hallucinations, delusion and confusion Suwanlert, ; McWhirter and Morris, Kratom and its metabolites can be identified in urine, and several tests have been developed to identify Kratom in plant products Rosenbaum et al, Any patient with kratom intoxication should be given prompt medical attention due to the high potency of kratom and the high mortality associated with krypton. Patients intoxicated with Kratom should be treated like other opiod intoxications with parenteral naloxone, airway management and supportive care. Synthetic opioids such as tramadol may produce seizures which would need airway protection and benzodiazepines Rosenbaum et al, Patients with Kratom withdrawal may need medical attention and treatement with opiod replacements. Supportive care to reduce anxiety with benzodiazepines or clonidine, anti emetics and intravenous fluids should be administered as needed. Monitoring Centre for Drugs and Addiction, Methoxetamine can be ingested orally, inserted rectally, insufflated nasally, or injected intramuscularly. Typical doses range from 10—15 mg, with effects beginning in 10 minutes and lasting 1—2 hours. Compulsive re-dosing to prolong effects have also been described. Erowid vaults, Hypertension, laryngospasm, and pulmonary associated with ketamine have not been reported with methoxetamine. Intoxication can also result in severe nausea, vomiting, diarrhoea, paranoia, and anxiety Rosenbaum et al, There are no drug tests to detect methoxetamine and diagnosis of methoxetamine intoxication is based on patient history and presentation. No specific antidote is available and management is similar to those patients with ketamine or phencyclidine exposure with supportive care, aggressive sedation with benzodiazepines, anti-emetics, intravenous fluids, and respiratory support as needed. The other piperazine derivatives are still legal to possess and use. The piperazine derivatives frequently contain blends of two to four chemicals Staack, A typical dose of BZP is 75— mg, and the resultant effect lasts from 6—8 hours. The onset of BZP effect may take more than two hours after ingestion and users can take multiple doses before the onset of effect which can lead to significant toxicity Bye et al. The effects of the piperazine derivatives may be indistinguishable from those of the amphetamines, with BZP exhibits one-tenth the potency of dextroamphetamine clinically. In low doses, piperazine derivatives cause stimulant effects, while hallucinogenic effects predominate at higher doses Bye et al. In a prospective evaluation of 80 emergency department patient encounters involving piperazine derivatives, the most commonly reported symptoms were palpitations, anxiety, headache, and vomiting. Seizures occurred in 14 patients, with a range of 30 minutes to 8 hours after exposure. The exact incidence of hyponatraemia with abuse of ecstasy or its legal alternatives such as piperazine derivatives is unknown. However, severe hyponatraemia induced seizures is a potential cause of death and should be considered in patients with severe amphetamine toxicity. BZP and other legal highs derived from piperazines are not included in routine drug screen but can be detected from urine in amphetamines screens Elliott and Smith, Piperazine derivates give rise to sympathomimetics toxicity and management is similar to those described for cathiones with sedating using benzodiazepines, intravenous fluids, and aggressive cooling measures may be required. Intoxicated patients may have consumed large amounts of water as they do with ecstasy abuse, which can lead to significant hyponatraemia and seizures. As such, checking electrolytes early in addition to glucose is important in all intoxicated patients. Many emergency departments are using handheld point of care gas and electrolyte testing devices to manage patients and pre-hospital point of care testing of serum sodium should be a feasible solution in the near future. However, there may be concerns about rapid correction of serum sodium and adverse neurological outcomes when administering hypertonic saline without checking serum sodium levels. This strategy may be considered in intractable seizures when serum sodium concentrations are unknown as prompt management of hyponatremic encephalopathy or seizures is important as they can lead to death or permanent neurological damage. Policies and procedures for managing intractable seizures in suspected intoxication in pre-hospital settings should consider hypertonic saline for controlling hyponatremic seizures. Benzodiazepines are used for seizures and agitation and prolonged observation is necessary as seizures can occur up to eight hours after use Wood and Dargan et al, As QT prolongation is possible cardiac monitoring and serial electrocardiograms are necessary. Traditional drug regulatory mechanisms are outmatched by the rapidly expanding universal market of legal and herbal highs. New legal alternatives are replacing scheduled products and the legal system is unsure of how to respond to this explosive market. Blanket banning of all new drugs is not a feasible solution and some herbal drugs such as Krotam and synthetic drugs such as cannabinoids may have medicinal uses in the future Hammersley, Legal highs are affordable, freely available online and in-stores and are being used by all age groups. Many healthcare providers are often unaware of the potential toxicity of these drugs, and clinical management of intoxicated patients is complicated by lack of screening tests and standardised management guidelines. Furthermore, patients needing medical care with cardiovascular or neuropsychiatric toxicity may have ingested more than one substance including alcohol and may not have typical clinical features. Drug abuse with alcohol use may be more common with salvia, synthetic cannabinoids and other legal alternatives to popular party drugs in the local area. This should be taken into consideration in the pre-hospital management of semiconscious or unconscious patients with alcohol intoxication so that cardiac and neurological complications are identified and addressed in a timely manner. Emergency management depends on presenting signs and symptoms Table 2 and may be guided by the drug history, if available. Some of the changes that could be incorporated into paramedical practice in managing drug intoxications include, the use of naloxone for cannabinoid intoxications, intranasal administration of benzodiazepines such as midazolam using mucosal atomizer devices, provision of handheld devices for point of care testing of serum electrolytes, the use of hypertonic saline to control intractable seizures due to hyponatraemia and provision of drug testing kits that use saliva or sweat to screen for drugs. Healthcare providers should familiarise themselves with what is available in their area and popular online products of abuse. Drug histories including herbal supplemental use should be obtained in all patients. All suspected intoxications need clear descriptions of clinical presentations, toxicological testing and treatment provided. Regular audits and reporting of cases and case series should be undertaken to disseminate information on emerging drugs of abuse. Educating the public about the potential short term and long term consequences of legal highs should also be undertaken at local and national levels. Legal substances and their abuse: Legal highs. ISSN print : ISSN online : Download File. Table 1: Legal Highs Physical Effects Psychoactive effects Management Sympathomimetic ephedrine, oral and nasal decongestants, weight loss pills Increase in heart rate, blood pressure and temperature, sweating, dilated pupils. Agitation, nervousness, irritability psychosis, paranoia. Supportive care. Sedation with benzodiazepine, Passiveand active cooling, IV hydrationIf severe hypertension treat with vasodilators and titrate. Antihistamines, diphenhydramine Anti-cholinergic effects Increase in heart rate, blood pressure and temperature, dry skin and mucus membranes and dilated pupils. Delirium, psychosis, agitation or sedation. Supportive care, aggressive sedation with benzodiazepines as needed for agitation, seizure, tachycardia, or hypertension cooling measures to combat hyperthermia. Caffeine, energy drinks Nausea, vomiting, abdominal pain, diarrhoea, tachycardia, tachyarrhythmia, and seizures. Headache, insomnia, agitation, tremor, hyper tonicity, tinnitus, and delirium. Symptomatic treatment. Treat as for sympathomimetic intoxication. Dextrometaphan, cough syrups Nausea, nystagmus, ataxia, vomiting, hypertension, and breathing difficulties Serotonin syndrome: tremor and myoclonus, hyperreflexia, dilated pupils, hypertension, hyperthermia, diaphoresis, impaired coordination, hallucinations, coma. Somnolence or agitation and hallucinations. Treat as for sympathomimetic intoxication Nalaxone may be beneficial. Synthetic cannabinoids, spice gold, spice silver, genie, K2 Sympathomimetic toxicity with elevated heart rate, elevated blood pressure, palpitations, diaphoresis, seizures, arrhythmias. Supportive care and benzodiazepines for calming agitation and anxiety. May consider Nalaxone. Hallucinations of distortions of visual, body image, or environmental perception; accentuation of actual sensations, out of body experiences. Supportive care for the clinical presentation. Benzodiazepines sedation for severe agitation. Synthetic cathinones, bath salts, bubbles, meow meow, MCAT explosion, impact energy-1, NRG-1, ivory wave, vanilla sky, hurricane Charlie Sympathomimetic toxicity with hypertension, tachycardia, hyperthermia, dehydration, trismus, bruxism. Psychomotor agitation with tremors, insomnia, and paranoia. Similar to other sympathomimetic agents with supportive care and aggressive sedation with benzodiazepines as needed for agitation, seizure, tachycardia, or hypertension. Severe hypertension treated with vasodilators i. Beta blockers should not be used alone. Hyperthermia requires passive or active cooling if not resolved. Kratom, thang, kakuam, thom, ketum, biak Cocaine like stimulant effect at low doses, tachycardia hypertension ventricular dysrhythmias hyperthermia seizures, dilated pupils, chest pain with angina or myocardial infarction. Opiod effects at higher doses, respiratory depression, hypoventilation, bradycardia, hypotension. Psychomotor agitation, tremors, paranoia, hallucination, seizures and coma. Sedation, coma. Treated like other opiod intoxications with parenteralnalaxone, airway management and supportive care. Benzodiazepines for seizures. Aggressive cooling for hyperthermiaAlways combine with a vasodilator such as phentolamineif using esmolol for tachycardia. Wide QRs complex: treat with sodium bicarbonate bolus. Angina and myocardial infarction: as per life supportprotocol. Methoxetamine, MXE Ketamine like effects, nystagmus Increased heart rate, blood pressure severe nausea, vomiting, diarrhoea, Hypoventilation at high doses Anxiety, paranoia, hallucinations, altered perceptions Supportive care, aggressive sedation withbenzodiazepines. Anti-emetics, intravenous fluids, and respiratory supportas needed. Sinus tachycardia and QT prolongation, seizures Agitation, aggression, paranoia, hallucinations Similar to other sympathomimetic agents with supportivecare and aggressive sedation with benzodiazepinesas needed for agitation, seizure, tachycardia, orhypertension. Sodium bicarbonate bolus for QT prolongation. Table 2. Emergency care for intoxicated individuals Death: Death due to drug abuse is usually caused by cardiac arrhythmias, myocardial infarction, status epilepticus, intracranial haemorrhage or severe hyperthermia. As such full vital signs should be obtained as soon as possible and any of these conditions should be treated aggressively. Unconscious: If the victim is unconscious, check pulse and if absent start cardiopulmonary resuscitation, while your partner gets the AED ready. Agitation: Agitated and combative patients need to be sedated, with benzodiazepines lorazepaim IV or IM, Midazolam IV, IM or intransal and keep patient cool as increasing temperature will lead to clinical deterioration. Depressed level of consciousness: Depressed level of consciousness need air way protection. Use nalaxone to reverse opiod effects. ECG: Obtain electrocardiograms early. Sodium bicarbonate boluses should be given for wide complex tachycardia. Treat myocardial infarctions and other arrhythmias as per protocol. Pulse and blood pressure: Tachycardia can usually be reduced with sedation. If severe and associated with hypertension may need treatment for both. Beta blockers alone should be avoided. A combination of esmolol and nitroprusside may be used. Temperature: Hyperthermia is associated with many drugs and is worsened by agitation and seizures. Uncontrolled hyperthermia rapidly leads to rhabdomyolysis, renal failure, coagulopathy and death due to multi-organ failure. Sedate agitated patients, check the temperature early and institute passive and active cooling measures early. Hydration with 0. Seizures: Seizure may be due to the drug or secondary effects such as low Na, or glucose and point of care testing for both glucose and electrolytes should be done. Manage seizures as usual with benzodiazepines and get patient to a hospital. Phenytoin or dilantine sodium should be avoided in drug induced seizures. Phenobarbital may be used to control prolonged seizures. Example case: A 13 year old girl who was shopping with friends in a mall, starts assaulting the sales lady during a minor argument and the mall security is called in. As the security holds her down she loses consciousness and starts shaking her arms and legs. An ambulance is called in and you arrive and take care of the seizing child. Download jpar. Sympathomimetic ephedrine, oral and nasal decongestants, weight loss pills. Increase in heart rate, blood pressure and temperature, sweating, dilated pupils. Anti-cholinergic effects Increase in heart rate, blood pressure and temperature, dry skin and mucus membranes and dilated pupils. Nausea, vomiting, abdominal pain, diarrhoea, tachycardia, tachyarrhythmia, and seizures. Nausea, nystagmus, ataxia, vomiting, hypertension, and breathing difficulties Serotonin syndrome: tremor and myoclonus, hyperreflexia, dilated pupils, hypertension, hyperthermia, diaphoresis, impaired coordination, hallucinations, coma. Synthetic cannabinoids, spice gold, spice silver, genie, K2. Sympathomimetic toxicity with elevated heart rate, elevated blood pressure, palpitations, diaphoresis, seizures, arrhythmias. Sympathomimetic toxicity with hypertension, tachycardia, hyperthermia, dehydration, trismus, bruxism. Kratom, thang, kakuam, thom, ketum, biak. Cocaine like stimulant effect at low doses, tachycardia hypertension ventricular dysrhythmias hyperthermia seizures, dilated pupils, chest pain with angina or myocardial infarction. Ketamine like effects, nystagmus Increased heart rate, blood pressure severe nausea, vomiting, diarrhoea, Hypoventilation at high doses. Supportive care, aggressive sedation withbenzodiazepines. Sympathomimetic effects similar to ecstasy with palpitations, anxiety, headache, and vomiting. Sinus tachycardia and QT prolongation, seizures. Similar to other sympathomimetic agents with supportivecare and aggressive sedation with benzodiazepinesas needed for agitation, seizure, tachycardia, orhypertension. Death: Death due to drug abuse is usually caused by cardiac arrhythmias, myocardial infarction, status epilepticus, intracranial haemorrhage or severe hyperthermia.

When good times go bad: managing ‘legal high’ complications in the emergency department

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Official websites use. Share sensitive information only on official, secure websites. Ontario St. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Patients may misunderstand the substance they have been exposed to, there are rarely any readily available laboratory confirmatory tests for these substances, and the exact substances being abused may change on a near-daily basis. This review will attempt to group legal agents into expected toxidromes and discuss associated common clinical manifestations and management. A focus on aggressive symptom-based supportive care as well as management of end-organ dysfunction is the mainstay of treatment for these patients in the emergency department. Keywords: legal highs, novel psychoactive substances, toxicology, opioid toxidrome, anticho-linergic toxidrome, sympathomimetic toxidrome, hallucinogens, inhalants. After the Geneva Opium Convention attempted to establish international control over morphine, drug manufacturers started flooding the market with uncontrolled morphine chemical derivatives. Patients may misunderstand what the substance is they have been exposed to, there are rarely any readily available laboratory confirmatory tests for these substances, and the exact substances being abused may change on a near-daily basis. Recognizing these challenges we will attempt to group legal agents into expected toxidromes and discuss associated common clinical manifestations and management. Producing the toxidrome of tachycardia, mydriasis, urinary retention, dry mucosal membranes, skin flushing, and hypo-active bowel sounds, anticholinergic agents have long been abused for their hallucinogenic, euphoric, and stimulant effects. The belladonna alkaloids are atropine, hyoscyamine, and scopolamine, which are found in large concentrations in plants such as deadly nightshade Atropa belladonna , Jimson weed Datura stramonium , and moonflower Datura inoxia. Belladonna alkaloid overdoses manifest as anticholinergic toxicity. An analysis of cases reported to American poison centers revealed no attributable fatalities. In addition to supportive care, management of belladonna alkaloid plant toxicity centers around treating agitation as well as reversing severe anticholinergic effects if needed. Decontamination with activated charcoal is controversial, as most patients will present for medical care when clinically intoxicated and agitated. The classic signs of diphenhydramine overdose are an anticholinergic toxidrome combined with profound sedation and at times marked agitation. Management of diphenhydramine toxicity centers around control of agitation and hyperthermia, as well as treating rhabdomyolysis, potential tachyarrhythmias, and seizures. Widely available, nutmeg is known to provoke hallucinogenic effects in high dosages. According to available case reports, nutmeg reached a peak of abuse in the s and s. Nutmeg produces a biological effect similar to an anticholinergic toxidrome, with altered mental status, skin flushing, dry mucus membranes, tachycardia, and hypertension. The clinical toxidrome of fly agaric has been said to mimic that of an anticholinergic toxidrome, with flushing, fever, and pupillary dilation. Treatment is supportive, with consideration of GI decontamination with charcoal. As the USA grapples with unprecedented levels of opioid abuse, there has been an increased push among prescribers and regulatory bodies to curb long-term prescribing of these medications. Management of loperamide toxicity includes extended consideration of decontamination, treatment of respiratory depression, and monitoring and treatment of potential cardiotoxicity. Although opium and the poppy plant itself are controlled in the USA, poppy seeds are completely unregulated and can be bought in bulk. Although they do not contain any psychoactive opiates, poppy seeds have been shown to have trace amounts of opium latex containing morphine and codeine on their surface. Although official case reports of fatalities are sparse, scattered fatalities in the popular media have been reported among young people using PST. Kratom is the common name for the plant Mitragyna speciosa , a large leafy tree which is indigenous to Southeast Asia, containing psychoactive alkaloids with dose-dependent stimulatory and opioid-like effects. The safety profile of kratom has not been fully evaluated. Well-controlled data on the toxic effects of kratom on human subjects are lacking, and case reports of toxicity are relatively rare. There have been scattered case reports of intractable seizures that are refractory to benzodiazepines in patients with acute kratom ingestions, although many cases are associated with co-ingestion of other prescription and illicit drugs. However, it would be reasonable to give naloxone in the setting of a kratom ingestion with respiratory depression. Kratom has been frequently adulterated with other opioid receptor agonists such as O -desmethyltramadol, resulting in 9 deaths in 1 case series. In an effort to stem the flood of these agents, the DEA has continuously added synthetic opioids to Schedule I, including U, AH, and many fentanyl analogs. Still unscheduled, an opioid known as MT, a piperazine derivative, has found abuse as a legally available opioid. A more substantial public health threat than MT is the re-emergence of fentanyl and a wide range of fentanyl analogs to the illicit drug market. Many of them are abused by those seeking similar effects as the classic illicit psychostimulants such as cocaine, methamphetamine, and 3,4-methylenedioxy-N-methylamphetamine MDMA. Others are abused for their serotonin-mediated hallucinogenic effects, but are notable for producing sympathomimetic toxicity. Many of these agents will share similarities in their treatment approach, which entails benzodiazepines, active cooling for hyperthermia, and specific management of end-organ complications related to hypertension and vasoconstrictive effects. A Schedule I substance, cathinone is a monoamine amphetamine analog with stimulatory properties found in the shrub Catha edulis , commonly known as khat. Synthetic cathinones reached a peak of reports in , declining to in , 58 likely due to federal and state efforts at scheduling and regulating these psychoactive substances. Chemical similarity of amphetamine, cathinone, and mephedrone; note the addition of the ketone functional group to the latter two compounds. The toxicologic effects of synthetic cathinones mimic those of the amphetamines as well as MDMA, and treatment is primarily supportive around managing the agitation, fever, hyponatremia, and end-organ complications that can sometimes occur with these agents. The subjective effects of benzofurans have been described as much like MDMA, but with more adverse effects in the form of nausea, dry mouth, dry eyes, insomnia, diarrhea, palpitations, headache, and various adverse psychological symptoms, including visual and auditory hallucinations. Like many of the NPS, detailed toxicological information on the benzofurans are lacking, and acute ingestions are often concurrent with other intoxicants. The benzodifurans, commonly known as the Bromo-dragonFLY compounds, refer to a relatively novel group of hallucinogenic drugs that saw escalating amounts of abuse as legally available research chemicals over the past decade. Case reports indicate that Bromo-dragonFLY compounds have potent sympathomimetic and vasoconstrictive toxicity. Bromo-dragonFLY overdose treatment is supportive. The single chemical difference between propylhexedrine top and methamphetamine bottom is the aromatic ring. Toxicity of propylhexedrine mimics that of the amphetamines, but with seemingly more profound end-organ complications from its relatively higher hypertensive and vasoconstrictive effects, especially with intravenous injection. Clinical toxicity presents with a sympathomimetic-like toxidrome but with profound tachycardia and hypertension. Mescaline is a serotonergic phenethylamine hallucinogen most famously found in peyote, a small spineless cactus found in the deserts between the USA and Mexico that has been traditionally consumed by Native American tribes. Mescaline is chemically related to amphetamines, and cases of toxicity produce a sympathomimetic-like toxidrome. N-methyl-D-aspartate NMDA receptor antagonists such as phencyclidine PCP and ketamine are abused in recreational settings for their dissociative effects. Ketamine was officially scheduled in , 78 and in the decade to follow the recreational drug market saw the synthesis and emergence of legal ketamine analogs such as methoxetamine and others. Furthermore, the over-the-counter cough remedy DXM has long been abused for its dissociative effects. Methoxetamine, an analog of ketamine that has NMDA antagonist activity, has been marketed via the internet as a legal high, and oftentimes as a safer alternative to ketamine abuse. Much of the morbidity of methoxetamine and other novel dissociative psychoactive substances seem to be centered around their neurocognitive effects as well as sympathomimetic qualities and propensity to be taken with other stimulatory psychoactive substances. The subjective effects of DXM abuse have been noted to entail 3 dose-dependent plateaus, with low doses producing mild stimulant and euphoric effects, middle doses producing an effect like concurrent alcohol and marijuana intoxication, and large doses producing a dissociative effect like ketamine or PCP intoxication. The major toxic effects of DXM are managed with supportive care, and are centered around benzodiazepines for acute agitation, management of toxicity from coformulatory agents, as well as possible serotonin syndrome. A major concern with DXM ingestion, even at therapeutic dosages in concert with certain other serotonin-affective drugs, is the risk of serotonin syndrome. There have been cases of serotonin syndrome when DXM was taken at antitussive therapeutic dosages in patients on therapeutic MAOIs such as phenelzine, as well as selective serotonin reuptake inhibitors such as fluoxetine. As DXM is commonly found in bromide salt, there have been theoretical concerns that massive ingestions will result in bromide toxicity as well as false elevations of chloride and even negative anion gaps due to misidentification of bromide for chloride by laboratory autoanalyzers. However, the only available evidence of bromism in the form of elevated chloride and a low or negative anion gap in the context of DXM use comes from a single case report. There are many legal hallucinogenic compounds that lack a discrete toxidrome. Many do increase serotonergic transmission resulting in stimulatory effects, including tachycardia and hypertension. Agitation and neuropsychiatric symptoms predominate with these agents. Native to Oaxaca, Mexico, Salvia divinorum is a leafy plant of the mint family that has been long recognized for its psychoactive properties when inhaled or sublingually absorbed. There is a lack of reports of salvia intoxication resulting in any serious physiologic toxicity. Although seeds are often treated with an emetic by seed producers in order to discourage abuse, morning glory and woodrose seeds have been long abused as a legally available LSD substitute. Major side effects include nausea, vomiting, and abdominal discomfort, which are thought to limit the abuse potential of LSA-containing seeds. SCs are chemically heterogeneous but what they have in common is their affinity for cannabinoid receptors. Unlike marijuana, which contains over 50 known psychoactive chemicals, many of which have attenuating effects on THC, which is itself a partial agonist of cannabinoid receptors, many of the SCs are full agonists that demonstrate a much stronger affinity for these target receptors. Physical examination findings of those using SCs have been found to be similar to those with cannabis intoxication, with delayed pupillary light reactions, slurred speech, and retarded sequence of movements. Cases of rhabdomyolysis, acute kidney injury, and even myocardial infarction have been reported. Ayahuasca, also known as hoasca, yage, and natema, is a hallucinogenic tea brewed traditionally among Amazonian tribes for religious purposes from the jungle vine Banisteriopsis caapi together with the leaves of the Psychotria viridis plant. The most common clinical manifestations of ayahuasca intoxication as reported to poison centers were hallucinations, tachycardia, agitation, hypertension, mydriasis, and vomiting. Kava refers to a traditional beverage prepared from the tropical shrub plant Piper methysticum , native to the South Pacific. Used for centuries for its euphoric and anxiolytic effects, kava has seen increased use in the USA, where it is considered a health supplement. Reports of acute kava toxicity resulting in adverse events requiring medical care are rare, accounting for 20 cases reported nationally in Patients abusing inhalants may present with a wide variety of subjective complaints, including dyspnea, palpitations, lightheadedness, sneezing and coughing, as well as GI complaints, including nausea and vomiting. The inhalational hydrocarbons of abuse have numerous toxic effects on the body, with cardiotoxic, neurotoxic, hepatotoxic, and nephrotoxic effects having been reported. Nitrous oxide inactivates vitamin B12, decreasing conversion of homocysteine to methionine, ultimately resulting in demyelination within the central and peripheral nervous systems. However, a focus on aggressive symptom-based supportive care is the mainstay of treatment for these patients in the ED. As a library, NLM provides access to scientific literature. Open Access Emerg Med. Find articles by Charles R Caffrey. Find articles by Patrick M Lank. Collection date This work is published and licensed by Dove Medical Press Limited. Open in a new tab. Disclosure The authors report no conflicts of interest in this work. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel.

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