INTRODUCTION — This topic will discuss the basic pharmacology, clinical presentation, and management of acute intoxication with traditional amphetamines (eg, ephedrine, ma-huang, khat, propylhexedrine) and synthetic cathinones. Intoxication with other stimulants, such as methamphetamine, cocaine, and methylenedioxymethamphetamine, is reviewed separately. (See "Methamphetamine: Acute intoxication" and "Cocaine: Acute intoxication" and "MDMA (ecstasy) intoxication" and "General approach to drug poisoning in adults".)
BACKGROUND — Amphetamines first appeared as a nasal decongestant in the form of a Benzedrine inhaler and were then used by the military as agents to promote alertness in battle-fatigued troops. In the 1950s, they gained popularity as weight-loss drugs and shortly thereafter became popular substances of abuse. Amphetamine sulfate and other stimulants like ephedra have a long history of abuse in the United States. Cathinones are beta-ketone amphetamine analogs. Abuse of the new synthetic cathinones (bath salts) emerged in Europe in 2009 and spread to the United States in 2010 [1,2]; these drugs were initially marketed in the United States as "bath salts" or "plant food" to avoid restrictions under the United States Controlled Substances Act.
PHARMACOLOGY AND CELLULAR TOXICOLOGY — Phenethylamines, including traditional amphetamines and the newer synthetic compounds, share multiple pharmacodynamic properties. Stimulation of alpha and beta adrenergic receptors is primarily responsible for the acute effects of amphetamines, which include hyper-alertness, hypertension, tachycardia, mydriasis, and diaphoresis. Together, these symptoms are part of the sympathomimetic toxic syndrome (or toxidrome) (table 1). Adrenergic receptors are reviewed separately. (See "Use of vasopressors and inotropes", section on 'Physiologic mechanisms of vasoconstriction'.)
Phenylethylamines cause the release of neurotransmitters, such as dopamine, serotonin, and norepinephrine and may also inhibit their reuptake. Some cause the release of serotonin from central axons, and some are serotonin receptor agonists [1,3].
Psychotic symptoms in overdose occur from excess dopamine and serotonin. Ring substitutions and other "designer" modifications have produced various psychoactive properties. Hallucinogenic properties appear to be enhanced by greater 5HT-2a receptor agonism.
Our understanding of the mechanism of action for many of the synthetic cathinones is limited but specific actions are known for a few: methylone and pyrovalerone inhibit reuptake of norepinephrine and dopamine with few serotonin effects; mephedrone favors dopamine reuptake inhibition . Cytotoxicity of hepatocytes has been reported with some of these compounds.
The synthetic cathinones are analogs of a naturally occurring substance found in the leaves of Catha edulis (Khat). Another synthetic cathinone, methcathinone, was widely abused in the former Soviet Union, Eastern Europe, and the United States in the 1990s, and was banned worldwide . The most common cathinones identified in outbreaks of abuse include eutylone [1-(1,3-benzodioxol-5-yl)-2-(ethylamino)butan-1-one], mephedrone (4-methylenemethcathinone), MDPV (methylenedioxypyrovalerone), methedrone (4-methoxymthcathinone), methylone (3,4-methelenedioxy-n-methcathinone) and flephedrone (4-fluoromethcathinone) [1,2,5]. In the United Kingdom, analysis of 24 "legal high" products found 4-fluoromethcathinone, 3,4-methylenedioxypyrovalerone (MDPV), and 1-(3,4-methylenedioxyphenyl)-2-(methylamino)pentan-1-one (pentylone,2), 3,4-methylenedioxy-alpha-pyrrolidinobutyrophenone (MDPBP).
KINETICS — Our understanding of many of the synthetic cathinones is limited, but characteristics similar to other amphetamines would be expected based upon their structural similarities . Amphetamines are lipophilic compounds that readily cross the blood-brain barrier . This property results in rapid onset of effects when injected, inhaled, or insufflated. Oral ingestion yields peak concentrations in about two hours. Cathinone peaks after oral ingestion in about one hour. Amphetamines have large volumes of distribution (approximately 3 to 6 L/kg). Half-lives vary widely by drug, ranging from 3 to 24 hours, but may extend beyond 30 hours, as urinary elimination is extremely pH dependent.
The metabolism of amphetamines occurs by several hepatic pathways and elimination is primarily renal . Metabolism of cathinones generally occurs by demethylation followed by glucuronidation and sulfation, with metabolites eliminated primarily in the urine and bile . The relatively alkaline nature of amphetamines favors excretion in an acidic urine medium, but artificial measures to further acidify the urine entail unacceptable risks and are not recommended.
HISTORY — Although a history may be difficult to obtain or unreliable in the setting of acute intoxication, it is important to try to determine what drugs were taken and how much. History in the setting of drug poisoning is reviewed in greater detail separately. (See "General approach to drug poisoning in adults", section on 'History'.)
Patients suspected of amphetamine use may be poisoned with other substances as well. As an example, the results of a survey of 947 reported mephedrone users suggests that over 80 percent abuse other substances, including alcohol, cannabis, ecstasy (MDMA), and cocaine, both simultaneously and on separate occasions . (See "Ethanol intoxication in adults" and "MDMA (ecstasy) intoxication" and "Cocaine: Acute intoxication" and "Cannabis use and disorder: Epidemiology, pharmacology, comorbidities, and adverse effects".)
CLINICAL FEATURES OF OVERDOSE
Overview — Signs of sympathetic excess or agitated delirium are the clinical features most closely associated with amphetamine and synthetic cathinone intoxication [2,7,9,10]. These signs include tachycardia, hypertension, hyperthermia, diaphoresis, and mydriasis. Alterations in mental status can include anxiety, agitation, violent behavior, and seizures. Secondary complications can involve the kidneys, skeletal muscles, and gastrointestinal system. The most common causes of death related to amphetamine toxicity are arrhythmia, hyperthermia, and intracerebral hemorrhage .
Inexperienced users of amphetamine may develop toxicity at a dose of 1 mg/kg, but chronic abusers may tolerate much higher doses. A methamphetamine dose of 1.3 mg/kg has been fatal . Toxic doses for the newer synthetic cathinones have not yet been established.
Vital signs — Intoxication with amphetamines or synthetic cathinones causes tachycardia and hypertension. Hyperthermia can develop due to agitation.
Cardiovascular system — Amphetamine and synthetic cathinone intoxication can cause chest pain and palpitations, in addition to tachycardia and hypertension. A retrospective case series of 236 patients with exposure to cathinones reported tachycardia in 56 percent of patients (n = 132), hypertension in 17 percent (n = 41), and chest pain in 17 percent (n = 40) . Others report similar results . However, synthetic cathinones do not appear to be directly proarrhythmic . Increases in heart rate, contractility, and afterload may produce symptoms and signs of cardiac ischemia or dysfunction . Myocarditis has been reported.
Central and peripheral nervous system — Intoxication with synthetic cathinones produces a prominent neuropsychiatric syndrome whose symptoms and signs can include agitation (approximately 82 percent according to observational data), combativeness (approximately 57 percent), hallucinations (approximately 40 percent), paranoia (approximately 36 percent), confusion (approximately 34 percent), myoclonus (approximately 19 percent), and in rare cases seizures [2,9,14-16]. Self-inflicted injuries (including violent suicide) and violence against others may occur while patients are delusional. Neuropsychiatric findings may be prolonged; intoxication with MDPV (methylenedioxypyrovalerone) causes central nervous system (CNS) stimulation for approximately 48 hours.
Intoxication with typical amphetamines may produce similar effects on the CNS, but extreme neuropsychiatric symptoms and signs, which can occur following a single dosing of a synthetic cathinone, generally occur only following binge use of typical amphetamines.
Profound hyponatremia causing altered mental status, elevated intracranial pressure, and cerebral edema has been reported following abuse of mephedrone [14,17]. The mechanism remains unclear but may be similar to that proposed for MDMA (ie, ecstasy). (See "Causes of hypotonic hyponatremia in adults".)
Amphetamine intoxication often causes hyperreflexia.
Musculoskeletal system — Overdose with any amphetamine can produce persistent myoclonus and tremors, which can contribute to rhabdomyolysis [1,2,18].
Skin — Injection of amphetamines has been associated with extensive cellulitis, abscess formation, and necrotizing fasciitis leading to amputation [19,20].
Renal and hepatic systems — Acute renal injury with evidence of acute tubular necrosis has been reported after abuse of synthetic cathinones . Injury may be related to renal vasospasm producing renal ischemia. Renal injury can be complicated by rhabdomyolysis, which may be seen with any amphetamine intoxication.
Electrolyte disturbances and other effects — Hypokalemia, hyponatremia, hypermagnesemia, and elevated anion gap acidosis may occur following amphetamine intoxication [1,2,18]. Hyponatremia may produce profound CNS disturbances. (See 'Central and peripheral nervous system' above.)
General testing — Routine laboratory evaluation of the poisoned patient should include the following:
●Fingerstick glucose, to rule out hypoglycemia as the cause of any alteration in mental status.
●Acetaminophen and salicylate levels, to rule out these common coingestions.
●Electrocardiogram (ECG), to rule out conduction system poisoning by drugs that affect the QRS or QTc intervals. The ECG may also reveal signs of cardiac ischemia in patients with amphetamine intoxication.
●Pregnancy test in women of childbearing age.
Significant toxicity, which should be suspected in all patents with agitated delirium, is often associated with rhabdomyolysis, hyperthermia, acidosis, and hypovolemia. For such patients, the clinician should also obtain the following studies:
●Basic serum electrolytes; if hyponatremia is present, a serum osmolality is recommended
●Creatine kinase and urine myoglobin, to evaluate for rhabdomyolysis (see "Rhabdomyolysis: Clinical manifestations and diagnosis")
●Serum creatinine, to assess for renal injury
●Serum aminotransferase concentrations, to assess for hepatic injury
●Coagulation studies (ie, aPTT, PT, INR, platelet count, d-dimer), to assess for disseminated intravascular coagulation (see "Evaluation and management of disseminated intravascular coagulation (DIC) in adults")
Additional testing may be needed depending upon clinical circumstances. As an example, a head CT should be obtained for patients with prolonged seizures, refractory delirium, focal neurologic findings, or signs of head trauma.
Specific testing — Although routine urine drug screens may implicate a particular drug class in an overdose, clinicians should not rely upon such testing to make a diagnosis. Many amphetamines give positive results on routine urine drug assays, but a number of substances give false positive results, including cold preparations containing pseudoephedrine, the anti-Parkinsons agent selegiline, and the antidepressant bupropion .
Most of the newer synthetic cathinone and similar "legal high" compounds (eg, synthetic cannabinoids K2 and Spice) are not detected by routine urine drug testing. Selected laboratories have successfully identified the synthetic cathinone compounds using gas chromatography and mass spectrometry, but such testing is not routinely available, and is generally of no help with the acute management of intoxicated patients. Thus, such testing is usually not obtained unless needed for medico-legal reasons. (See "Synthetic cannabinoids: Acute intoxication", section on 'Testing for synthetic cannabinoids'.)
DIAGNOSIS — Amphetamine and synthetic cathinone toxicity is a clinical diagnosis. Serum drug concentrations are rarely available in a timely manner and therefore of limited clinical usefulness. The diagnosis is usually made on the basis of a history of abuse and clinical features consistent with an overdose of these substances, primarily symptoms and signs of a sympathomimetic syndrome (table 1). Intoxication with amphetamines or a synthetic cathinone should be considered in any case of agitated delirium of unclear etiology.
The newer synthetic cathinones differ from traditional amphetamines in that symptoms and signs often persist for many hours to several days in some cases. In severe cases, psychiatric findings and movement disorders have persisted for days to weeks [3,22].
DIFFERENTIAL DIAGNOSIS — Amphetamines and the newer synthetic cathinones cause a sympathomimetic syndrome with features that range from pure adrenergic stimulation to a mixed picture of stimulant and hallucinogenic effects (table 1). The most distinguishing feature of overdose with a synthetic cathinone is the prolonged duration of effect . Many reports of "bath salt" cases describe agitated delirium and psychotic features lasting for days to even weeks. These compounds should be considered a possible cause in any case with such prolonged symptoms. While psychosis is a common finding in amphetamine abuse, seizures and chest pain are more commonly seen with pure stimulants, such as cocaine .
Pure hallucinogens, such as lysergic acid diethylamide (LSD) or psilocybin, generally do not cause adrenergic stimulation, and thus signs such as tachycardia, hypertension, hyperthermia, and diaphoresis are not prominent findings. (See "Phencyclidine (PCP) intoxication in adults" and "Intoxication from LSD and other common hallucinogens".)
Anticholinergic poisoning has some features that are similar to amphetamine intoxication (eg, hyperthermia, tachycardia, agitation), but the absence of diaphoresis, dilated pupils, and flushed skin helps to distinguish this syndrome. (See "Anticholinergic poisoning".)
Withdrawal, particularly from sedative hypnotics, ethanol, and benzodiazepines, can mimic amphetamine and synthetic cathinone toxicity. Withdrawal is a difficult diagnosis that requires obtaining a history of prolonged abuse followed by cessation. Giving appropriate treatment (such as a benzodiazepine) generally causes withdrawal symptoms to improve or resolve. (See "Management of moderate and severe alcohol withdrawal syndromes", section on 'Management' and "Benzodiazepine poisoning and withdrawal", section on 'Benzodiazepine Withdrawal'.)
Thyrotoxicosis, pheochromocytoma, heat stroke, and paranoid schizophrenia are nontoxicologic conditions that can mimic aspects of acute amphetamine and synthetic cathinone intoxication (eg, hyperthermia, tachycardia, diaphoresis, agitation), but each manifests findings that may help to distinguish them. Patients with thyrotoxicosis often demonstrate eyelid retraction and lag, proximal muscle weakness, and a palpable goiter. Pheochromocytoma often causes intermittent hypertension, headache, and diaphoresis. Heat stroke normally develops in a hot, humid environment, either following exertion or in patients with compromised thermoregulation due to disability, old age, or medication (eg, diuretics, anticholinergics, antipsychotics). Patients with paranoid schizophrenia often have a history of prior psychosis and response to treatment. (See "Diagnosis of hyperthyroidism" and "Severe nonexertional hyperthermia (classic heat stroke) in adults" and "Exertional heat illness in adolescents and adults: Epidemiology, thermoregulation, risk factors, and diagnosis" and "Clinical presentation and diagnosis of pheochromocytoma" and "Schizophrenia in adults: Clinical features, assessment, and diagnosis".)
General approach — Control of agitation and other signs of sympathetic excess are the major problems confronting clinicians who manage patients with amphetamine or synthetic cathinone intoxication. Clinicians should also assess the hydration and nutritional status of patients presenting with acute intoxication from these agents. Many patients will have a long history of abuse and are at risk for acute decompensation if not given adequate hydration and proper nutritional support early in their course.
Airway management — Patients with agitated delirium from amphetamine or synthetic cathinone intoxication require aggressive management, which may entail protecting the patient's airway. This need may arise in patients with refractory agitation or loss of protective airway reflexes. Airway management in adults is reviewed separately. (See "Rapid sequence intubation in adults for emergency medicine and critical care" and "Overview of advanced airway management in adults for emergency medicine and critical care" and "Basic airway management in adults".)
When performing rapid sequence intubation in patients with agitated delirium from amphetamine intoxication, it is generally best to avoid ketamine as an induction agent due to its dissociative effects. Propofol, midazolam, and etomidate are all reasonable agents for induction. (See "Induction agents for rapid sequence intubation in adults for emergency medicine and critical care".)
Gastrointestinal decontamination — The effectiveness of gastrointestinal decontamination is related to the timing and route of administration. Activated charcoal (AC) and gastric lavage are generally of little value unless large doses of amphetamines have been ingested orally and the patient presents for medical care within one hour of the ingestion.
From a practical standpoint, we reserve GI decontamination with AC or lavage for the rare instance of a massive ingestion, such as might occur with a body-stuffer or body-packer who arrives before significant absorption has occurred. In such cases, the potential benefits of decontamination outweigh the risks. (See "Internal concealment of drugs of abuse (body packing)" and "Acute ingestion of illicit drugs (body stuffing)".)
Psychomotor agitation — Patients who are agitated or violent due to amphetamine intoxication pose a risk to themselves and healthcare personnel. Acute decompensation can occur if immediate measures are not taken to control the patient. Efforts to control agitated behavior should not be delayed while awaiting laboratory or other confirmation of drug exposure.
First line therapy for treating psychomotor agitation consists of IV benzodiazepines. Lorazepam 2 mg IV or diazepam 10 mg IV are reasonable starting doses for patients with significant agitation. The same or half the initial dose may be repeated every three to five minutes until agitation is controlled. Large cumulative doses of benzodiazepines (hundreds of milligrams) may be required and should be administered before abandoning this therapy. Monitor patients for respiratory depression and hypotension. Intramuscular lorazepam can be used if IV access is unavailable, but its peak effect is typically delayed (10 to 20 minutes). This approach is similar to that used to manage a pure stimulant overdose, such as cocaine or methamphetamine.
The response to the agitated patient should reflect the severity of the presentation, but a combination of physical control and chemical sedation are often necessary initially to manage severely agitated patients. To avoid complications from hyperthermia and overexertion, physical restraints should be removed as soon as chemical sedation is achieved. (See "Assessment and emergency management of the acutely agitated or violent adult", section on 'Management'.)
Hypovolemia is frequently associated with agitated delirium so fluid resuscitation with boluses of IV isotonic crystalloid should be given to patients with signs of volume depletion.
Although butyrophenones (eg, haloperidol) and second generation antipsychotics (eg, ziprasidone) have been suggested for use in sympathomimetic ingestions, there are no controlled studies evaluating their safety and efficacy in synthetic cathinone intoxications. Since these agents interfere with heat dissipation, lower the seizure threshold, and may prolong the QTc interval, we suggest they not be used as first-line therapy for psychomotor agitation in the setting of amphetamine or synthetic cathinone intoxication. These medications may have a role in the unusual circumstance of a patient with severe, acute intoxication whose psychomotor agitation fails to improve with large cumulative doses of benzodiazepines .
Hyperthermia — Uncontrolled agitation and excessive muscle activity generate heat and cause hyperthermia (temperature ≥41.1°C). Aggressive sedation with benzodiazepines and possibly neuromuscular paralysis may be required in the agitated hyperthermic patient. The approach used is identical to that used for patients with hyperthermia following methamphetamine intoxication and is described separately (see "Methamphetamine: Acute intoxication", section on 'Hyperthermia'). Supplemental measures, such as ice packs and evaporative cooling, may be necessary to prevent the mortality associated with severe hyperthermia. (See "Severe nonexertional hyperthermia (classic heat stroke) in adults".)
Hypertension — Hypertension from amphetamine intoxication is generally well controlled with the benzodiazepines used to manage psychomotor agitation. We believe that optimal therapy for patients experiencing cardiovascular complications from acute sympathomimetic poisoning begins with reduction in central nervous system catecholamine release rather than peripheral antagonism of released catecholamines, and that benzodiazepines have a proven role in this regard. (See "Cocaine: Acute intoxication".)
Hypertension that is refractory to aggressive treatment with sedatives, may require treatment with intravenous antihypertensive drugs, such as nitroprusside or phentolamine. (See "Drugs used for the treatment of hypertensive emergencies".)
Poisoning with sympathomimetic agents, such as amphetamines or methamphetamine, can produce a hyperadrenergic state associated with an increase in both alpha- and beta-adrenergic tone. Administration of beta blockers to patients with sympathomimetic drug toxicity raises the concern of exacerbating hypertension due to unopposed alpha-adrenergic vasoconstriction. Should beta blockade be performed in this setting, it should be reserved for patients with persistent hypertension despite appropriate treatment with benzodiazepines and done cautiously, ideally in combination with an alpha antagonist or some other vasodilator without beta blocking effects (eg, nitroglycerin or nitroprusside). These patients warrant under close observation, including frequent measurements of vital signs and serial ECGs. Most of the published experience concerning risk of beta blocker therapy in patients with sympathomimetic poisoning is specific to cocaine and is discussed separately. (See "Cocaine: Acute intoxication", section on 'Use of beta adrenergic antagonists (beta blockers)'.)
Seizure — Prevention and control of seizures is a priority in patients with amphetamine or synthetic cathinone intoxication . Serum electrolytes (particularly sodium) and glucose should be monitored and supplemented where necessary. Isolated seizures are treated in standard fashion. Benzodiazepines are the initial medication of choice (eg, lorazepam 1 mg IV or diazepam 5 mg IV). Multiple seizures or prolonged seizure activity should prompt a search for a cause other than amphetamine intoxication (eg, intracranial hemorrhage, hyponatremia, hypoglycemia) (table 2).
Disposition — All patients exhibiting agitated delirium from amphetamines or synthetic cathinones should be observed until no longer symptomatic and rhabdomyolysis has been ruled out. Hospital admission is needed for patients with persistent psychosis or other concerning clinical findings (eg, signs of cardiac ischemia).
PEDIATRIC CONSIDERATIONS — Young children that are around adults who abuse amphetamine and synthetic cathinone may present with symptoms and signs of intoxication following of such agents. These drugs are often sold in packages with misleading labels, such as plant food, lady bubbles, potpourri or aroma therapy, that may be confusing or attractive to children, . Small children may present with crying, tachycardia, agitation, abnormal eye movements, vomiting, ataxia, or seizures. A high index of suspicion should be maintained when evaluating children from home situations known or suspected to be involved in drug use.
The treatment of children with amphetamine intoxication is similar to that of adults, but special consideration should be directed toward aggressive cooling measures and close monitoring of vital signs and urine output. Hydration should be sufficient to maintain urine output at 2 mL/minute to prevent renal injury from myoglobin deposition. Appropriate social and child protective services should be enlisted in all cases prior to releasing the child from the hospital.
COMPLICATIONS — Both acute and chronic use of amphetamines and synthetic cathinones produce a wide range of potential complications involving nearly every organ system [7,18,25-27]. Common and important complications are described here.
●Rhabdomyolysis is a complication often encountered with use of these products particularly in situations of agitated delirium. Fluid and electrolyte abnormalities, metabolic acidosis, acute kidney injury, compartment syndrome, and disseminated intravascular coagulation may result from rhabdomyolysis. (See "Rhabdomyolysis: Clinical manifestations and diagnosis" and "Prevention and treatment of heme pigment-induced acute kidney injury (including rhabdomyolysis)" and "Assessment and emergency management of the acutely agitated or violent adult".)
●Cardiomyopathy is well described among chronic amphetamine abusers . The pathophysiology involves repetitive sympathetic stimulation and may be analogous to the cardiomyopathy seen in pheochromocytoma. (See "Clinical presentation and diagnosis of pheochromocytoma".)
●Valvular heart disease is a common complication of amphetamine abuse. Valvular dysfunction may be related to the direct serotonergic effects of these drugs, as was postulated in cases related to appetite-suppressants during the late 1990s. Valvular dysfunction from aortic rupture or dissection is likely due to vasospastic and hypertensive effects. The possibility of endocarditis is always a concern with injection drug use. (See "Valvular heart disease induced by drugs", section on 'Anorectic drugs' and "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis".)
●Cardiac arrhythmias may result directly from the stimulant effects of amphetamines or indirectly as a result of dehydration, electrolyte abnormalities, or acid-base disturbances associated with their use.
●Pulmonary hypertension is a rare but potentially fatal disease that has been linked to chronic amphetamine and methamphetamine abuse . (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults".)
●Aortic dissection has been associated with amphetamine and cocaine abuse . Like cocaine, amphetamines modulate norepinephrine and dopamine in the brain, causing increases in blood pressure and heart rate. (See "Clinical features and diagnosis of acute aortic dissection" and "Management of acute type B aortic dissection".)
●Amphetamines are associated with stroke. The use of illicit drugs should be explored in patients who experience ischemic stroke. The pathogenesis of amphetamine induced ischemic stroke includes vasospasm and vasculitis . Intracerebral hemorrhage is a rare but often devastating complication of amphetamine abuse. (See "Overview of the evaluation of stroke".)
●Acute tubular necrosis is a known complication of amphetamine toxicity. Case reports describe acute kidney injury from abuse of "bath salt" products containing synthetic stimulants like MDPV and mephedrone. Sympathetic hyperactivity may result in renal vasoconstriction and hypoperfusion . (See "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults".)
●An abstinence syndrome (ie, withdrawal) can develop following cessation of amphetamine abuse . Reports to date indicate that with frequent use tolerance for the effects of these drugs develops and dependence is a likely outcome. Users report strong psychological dependence with cravings, anxiety, and depression sometimes lasting several weeks after they stop . There is little evidence to guide the treatment of amphetamine withdrawal, but treatments have included benzodiazepines, antipsychotics, and antidepressants .
Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)
Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General measures for acute poisoning treatment" and "Society guideline links: Treatment of acute poisoning caused by recreational drug or alcohol use".)
SUMMARY AND RECOMMENDATIONS
●Clinical features of intoxication – Signs of sympathetic excess and agitated delirium are the clinical features most closely associated with traditional amphetamine and synthetic cathinone intoxication. These signs include tachycardia, hypertension, hyperthermia, diaphoresis, and mydriasis. Alterations in mental status can include anxiety, agitation, violent behavior, and seizures. Traditional amphetamines include ephedrine, ma-huang, khat, and propylhexedrine. (See 'Clinical features of overdose' above.)
The most distinguishing feature of overdose with a synthetic cathinone is the prolonged duration of effect. Intoxication produces a prominent neuropsychiatric syndrome whose symptoms and signs can include agitation, combativeness, hallucinations, paranoia, confusion, myoclonus, and in rare cases seizures. A similar syndrome can develop in patients who binge on traditional amphetamines.
●Laboratory testing – Many amphetamines give positive results on routine urine drug assays, but a number of substances give false positive results, including cold preparations containing pseudoephedrine. Newer synthetic cathinone are not detected by routine urine drug testing. Our suggested approach to laboratory testing is described in the text. (See 'Laboratory evaluation' above.)
●Diagnosis – Amphetamine and synthetic cathinone toxicity is a clinical diagnosis. Serum drug concentrations are of limited clinical usefulness. Diagnosis is usually made on the basis of a history of abuse and clinical features consistent with an overdose, primarily symptoms and signs of a sympathomimetic syndrome (table 1). Intoxication with amphetamines or a synthetic cathinone should be considered in any case of agitated delirium of unclear etiology. (See 'Diagnosis' above.)
●Differential diagnosis – The differential diagnosis for amphetamine and synthetic cathinone intoxication includes intoxication with other stimulants (eg, cocaine, methamphetamine), hallucinogens (eg, LSD), and anticholinergic drugs, withdrawal from sedative hypnotics, ethanol, or benzodiazepines, and a number of medical conditions that can cause agitated delirium, such as thyrotoxicosis and heat stroke. (See 'Differential diagnosis' above.)
●Management – Control of agitation and other signs of sympathetic excess are the major management problems in patients with amphetamine or synthetic cathinone intoxication. We suggest that benzodiazepines be used as first line therapy for treating psychomotor agitation due to traditional amphetamine or synthetic cathinone intoxication (Grade 2C). Lorazepam 2 mg IV or diazepam 10 mg IV are reasonable starting doses for patients with significant agitation. The same or half the initial dose may be repeated every three to five minutes until agitation is controlled. Large cumulative doses of benzodiazepines (hundreds of milligrams) may be required. It is important to address possible hydration and nutritional needs of patients presenting with acute psychomotor agitation. (See 'Psychomotor agitation' above.)
●Additional complications – Other potential complications that may require therapeutic intervention include electrolyte abnormalities (eg hyponatremia), hyperthermia, hypertension, rhabdomyolysis, acute kidney injury, seizure, stroke, and intracerebral hemorrhage. (See 'Complications' above and 'Management' above.)
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