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The dextroamphetamine-amphetamine combination is a central nervous system stimulant classified as a Schedule II drug by the Drug Enforcement Administration (DEA) and the US Food and Drug Administration (FDA) due to its high potential for abuse. Both immediate-release and sustained-release amphetamine medications are FDA-approved for treating attention-deficit hyperactivity disorder (ADHD) and narcolepsy in adult and pediatric populations. The drug works by increasing dopamine and norepinephrine levels through catecholamine release and reuptake inhibition. Off-label uses of dextroamphetamine-amphetamine include the management of cerebrovascular accidents. This activity reviews the indications, mechanism of action, adverse event profile, administration, pharmacokinetics, and clinical monitoring of dextroamphetamine-amphetamine. This activity provides healthcare professionals with essential knowledge and tools to effectively tailor treatments to individual patient needs. In addition, this activity emphasizes the importance of collaboration among the interprofessional healthcare team in delivering evidence-based care to optimize patient outcomes in dextroamphetamine-amphetamine therapy. Objectives: Identify the indications, contraindications, and potential adverse effects of dextroamphetamine-amphetamine, including risks for misuse and abuse. Implement precise dosing strategies and monitoring protocols to optimize therapeutic outcomes and minimize adverse effects. Select appropriate pharmacological interventions for managing adverse effects, including hypertension, tachycardia, and anxiety. Collaborate with the interprofessional healthcare team to tailor dextroamphetamine-amphetamine treatment to individual patient needs. Access free multiple choice questions on this topic.

Signs and Symptoms of Overdose Methamphetamine abuse has become an epidemic in recent years, raising significant concerns. Increased rates of depression, suicidal ideation, and suicide attempts are more commonly observed in adolescents abusing methamphetamine. The reported lethal dose for the adult population is 20 to 25 mg/kg, although the dose-response varies among individuals. Chronic amphetamine abusers may develop a tolerance to doses as high as 15,000 mg/d without experiencing lethal effects.[41][42][43] The mechanism of toxicity is primarily due to excessive extracellular dopamine, norepinephrine, and serotonin. The primary clinical manifestations involve prominent neurological and cardiovascular effects, while secondary complications may include renal, muscular, pulmonary, and gastrointestinal issues. Case reports have highlighted Takotsubo cardiomyopathy (TTC), also known as stress-induced cardiomyopathy, as a potential consequence of amphetamine overdose. In one case, a patient arrived at the emergency department after ingesting 30 amphetamine salt tablets, exhibiting symptoms of chest pain and shortness of breath. Upon initial examination, the patient had elevated cardiac enzymes, an unremarkable ECG, and an ejection fraction of 25% to 30% with severe hypokinesis. However, 24 hours later, the symptoms had resolved, and a repeat echocardiogram performed 3 days later revealed an ejection fraction of 60% with no regional wall motion abnormalities. Hyperactivity, hyperthermia, tachycardia, tachypnea, mydriasis, tremors, seizures, and altered mental status are among the most common signs and symptoms of amphetamine intoxication.[44] Diagnosis can be confirmed by detecting amphetamines in stomach contents or vomitus or through a positive urine toxicology screen for illicit drugs. False-positive amphetamine screens may occur following the intake of medications such as trazodone or bupropion.[26][45] Management of Overdose No antidote exists for amphetamine toxicity; however, activated charcoal can serve as an emergency treatment. In patients who can safely ingest, it is recommended to administer activated charcoal, 1 to 2 g/kg up to 100 g by mouth, if ingestion occurs within the past hour.

Hyperactivity, hyperthermia, tachycardia, tachypnea, mydriasis, tremors, seizures, and altered mental status are among the most common signs and symptoms of amphetamine intoxication.[44] Diagnosis can be confirmed by detecting amphetamines in stomach contents or vomitus or through a positive urine toxicology screen for illicit drugs. False-positive amphetamine screens may occur following the intake of medications such as trazodone or bupropion.[26][45] Management of Overdose No antidote exists for amphetamine toxicity; however, activated charcoal can serve as an emergency treatment. In patients who can safely ingest, it is recommended to administer activated charcoal, 1 to 2 g/kg up to 100 g by mouth, if ingestion occurs within the past hour. Amphetamine-related toxicity requires management by addressing life-threatening CNS and cardiovascular symptoms in a controlled, quiet environment. Supportive care in the hospital includes monitoring the airway, breathing, and circulation. Agitation and seizures can be controlled with benzodiazepines, phenothiazines, pentobarbital, or propofol. A beta-blocker, such as propranolol, may be used to manage cardiac tachyarrhythmias. Intravenous nitroprusside (starting at 0.5-1 mcg/kg/min, titrated as needed) should be considered for severe hypertension. Intravenous fluids are essential for countering hyperthermia, maintaining renal function, and promoting the elimination of amphetamine and its analogs. In cases of severe agitation, clinicians should consider aggressive treatment to prevent complications such as malignant hypertension, rhabdomyolysis, hyperthermia, and seizures. Evidence supports the use of large doses of benzodiazepines to manage amphetamine overdose-related psychosis and agitation. When agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies may include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol. In severe cases, neuromuscular paralysis, intubation, and active cooling measures may be necessary.

In cases of severe agitation, clinicians should consider aggressive treatment to prevent complications such as malignant hypertension, rhabdomyolysis, hyperthermia, and seizures. Evidence supports the use of large doses of benzodiazepines to manage amphetamine overdose-related psychosis and agitation. When agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies may include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol. In severe cases, neuromuscular paralysis, intubation, and active cooling measures may be necessary. Physicians should order an ECG and consider telemetry monitoring in patients with tachycardia. Intravenous fluids and sedation should be used to control cardiac symptoms. For severe hypertension, intravenous nitroprusside may be considered. The management of rhabdomyolysis includes initiating 0.9% normal saline for aggressive hydration and monitoring creatine kinase, electrolytes, and creatinine levels.[46] A systematic review indicates that the management of amphetamine-related derivatives and analogs (ARDA) overdose centers on treating agitation, psychosis, and hyperadrenergic symptoms. Effective pharmacologic treatments include antipsychotics, benzodiazepines, beta-blockers, dexmedetomidine, and alpha-blockers.[47]

All interprofessional healthcare team members should be aware of the potential complications associated with amphetamine-like agents. This healthcare team includes clinicians, specialists, advanced practice providers, nurses, and pharmacists. These medications should not be prescribed indiscriminately, and patients require close monitoring to prevent misuse. Psychiatrists prescribe stimulant medications such as amphetamines for ADHD while monitoring for potential misuse. Addiction medicine specialists address amphetamine use disorder through behavioral therapy and pharmacotherapy to manage cravings and withdrawal. Neurologists and sleep medicine specialists prescribe amphetamines for narcolepsy in appropriate clinical settings. Emergency medicine physicians manage acute amphetamine toxicity, addressing symptoms such as agitation, hyperthermia, and cardiovascular instability. A comprehensive history, physical examination, and cardiovascular evaluation should be conducted before initiating stimulant medication, as serious cardiac conditions can increase the risk of sudden death. The risk of abuse and dependence should be evaluated and monitored both before prescribing amphetamines and during therapy. Physicians should avoid prescribing the immediate-release (short-acting) form if there is a suspicion of potential misuse by the patient or their parents. The prescribing physician should advise the patient to report any symptoms of tachycardia, hypertension, angina, peripheral vasculopathy, or Raynaud phenomenon.[37][38] Patients should also receive education on the most common adverse effects of the medication. Most cases of amphetamine-related toxicity can be safely managed with supportive care, including monitoring the airway, breathing, and circulation, as well as controlling agitation with benzodiazepines. Effective interprofessional care coordination among clinicians, pharmacists, and nurses plays a crucial role in improving patient outcomes and reducing the risk of misuse associated with amphetamine-like agents.