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Methamphetamine Toxicity

  • Author: John R Richards, MD, FAAEM; Chief Editor: Asim Tarabar, MD  more...
 
Updated: Sep 11, 2015
 

Background

Methamphetamine is a highly addictive psychostimulant drug that is chemically related to amphetamine. Methamphetamine can produce euphoria and stimulant effects like those from other stimulants such as cocaine. In addition, methamphetamine is easily synthesized from inexpensive and readily obtainable chemicals. Those qualities have led to the widespread and rampant abuse of this dangerous drug.

Methamphetamine use has increased rapidly throughout the world, with more than 30 million users worldwide.[1] Over the past decade, all regions of the United States experienced a significant increase in the number of persons using the drug, and a corresponding increase in the number of patients with medical complications seen in emergency departments (EDs). Fortunately, this trend seems to have reached a plateau in most areas.[1, 2]

Methamphetamine may be taken orally or intravenously, or be snorted or smoked. The smokable form of methamphetamine (“ice”) produces an immediate euphoria similar to that of crack cocaine, but the effects may last much longer.[3, 4]

Inadvertent absorption of methamphetamine may occur in “body packers”, who swallow packages of the drug for transportation purposes, or “body stuffers”, who insert bags of methamphetamine rectally or vaginally in an attempt to elude drug enforcement. There are also users who indulge in "parachuting", in which the drug is loosely wrapped to delay absorption and prolong effect. These persons, and body stuffers, are at high risk for toxicity as the drug wrapping may be compromised and allow complete drug absorption.[5]

North American methamphetamine abusers are predominantly white males in their 30s and 40s.[6, 7] Recently, epidemic abuse has been described in adolescents; they cite availability, low cost, and a longer duration of action than cocaine as reasons for their drug preference.[8]

The medical history of amphetamine-like compounds extends back nearly 100 years.[3, 4] A Japanese pharmacologist first synthesized methamphetamine in 1919. A more detailed analysis of the pharmacology of amphetamine derived from the basic phenylethylamine structure was reported in 1930. In the 1930s, amphetamine was introduced in the form of inhalers for rhinitis and asthma treatment. The stimulant, euphoric, and anorectic effects of amphetamine were quickly recognized, leading to its abuse.

In 1937, a report that amphetamine enhanced intellectual performance and wakefulness further contributed to its popularity. Amphetamines were used extensively by Allied and Axis armed forces during World War II and during the recent Iraq and Afghanistan conflicts to increase wakefulness and attention.[3, 9]

In the late 1950s, initial federal controls were enacted; however, in spite of additional regulation and increased enforcement, amphetamines continued to be used by students, athletes, shift workers, long haul drivers, and for weight loss.[3, 4] The Controlled Substance Act of 1970 stringently regulated the manufacture of amphetamine.

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Pathophysiology

Amphetamines stimulate the central nervous system (CNS), which results in several clinical effects such as inducing euphoria, intensifying emotions, altering self-esteem, and increasing alertness, aggression, and sexual appetite.[3, 10] In the CNS, amphetamines block presynaptic reuptake of catecholamines (ie, dopamine, norepinephrine), causing hyperstimulation at selected postsynaptic neuron receptors. Indirect sympathomimetic effects result from blockade of presynaptic vesicular storage and by reduction in cytoplasmic destruction of catecholamines by inhibition of mitochondrial monoamine oxidase.[11, 12]

Indirectly, these hyperstimulated neurons can stimulate various other noncatecholaminergic central and peripheral nervous pathways. Changes in mood, excitation, motor movements, sensory perception, and appetite appear to be mediated more directly by CNS dopaminergic alterations. It has been postulated that serotonin alterations also contribute to mood changes, psychotic behavior, and aggressiveness.[13]

In humans, the half-life of methamphetamine ranges from 10-20 hours, depending on the urine pH, history of recent use, and dosage.[11] Metabolism occurs faster in acidic urine. Methamphetamine has greater CNS effects compared with D-amphetamine of equal milligram quantity. The majority of methamphetamine is metabolized to amphetamine, which provides further CNS stimulation.

Methamphetamine is absorbed readily from the gut, airway, nasopharynx, muscle, placenta, and vagina.[14, 15] Peak plasma levels are observed approximately 30 minutes after intravenous or intramuscular routes and 2-3 hours after ingestion.[12] Rapid tissue redistribution occurs with steady-state cerebrospinal fluid levels at 80% of plasma levels. Hepatic conjugation pathways with glucuronide and glycine addition result in inactivation and urinary excretion of metabolites.

When methamphetamine is used with ethanol, increased psychological and cardiac effects are observed.[16] This is presumed to be the result of pharmacodynamic rather than pharmacokinetic interactions. Similarly, the increased toxicity of concomitant opioids and amphetamines ("speedballing"), appear to result from pharmacodynamic interactions.

The euphoric effects produced by methamphetamine, cocaine, and various designer amphetamines are similar and may be difficult to clinically differentiate.[4] A distinguishing clinical feature is the longer pharmacokinetic and pharmacodynamic half-life of methamphetamine, which may be as much as 10 times longer than that of cocaine. Because of the variability in quality and concentration of illicitly purchased methamphetamines, the clinical observation of toxic effects is more relevant than estimated total ingested dose.[17]

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Epidemiology

Frequency

United States

Methamphetamine use is widespread in the United States but varies regionally, with higher use in Hawaii, the West, and parts of the Midwest.[18] The Drug Abuse Warning Network estimates that methamphetamine was involved in 102,961 emergency department visits in 2011.[2]

According to the 2012 National Survey on Drug Use and Health (NSDUH), approximately 1.2 million people (0.4% of the US population) reported using methamphetamine in the past year, and 440,000 (0.2%) reported using it in the past month; this represents a decrease from previous years. The NSDUH found that in 2013 the lifetime prevalence of methamphetamine use was 0.5% in those 12 to 17 years of age, 3.0% in those 1 to 25 years old, and 5.5% in those 26 years and older; those percentages had not changed significantly since 2011.[19]

International

Methamphetamine use is widespread, predominantly in North America, Eastern Europe, and Southeast Asia. The United Nations Office on Drugs and Crime estimates that worldwide in 2013 there were 33.9 million users of amphetamine-type stimulants, which includes methamphetamine.[1]

Mortality/Morbidity

Acute methamphetamine overdose may result in sympathetic overdrive, cardiovascular collapse, rhabdomyolysis, ventricular tachyarrhythmia, and death. Injuries from blunt and penetrating trauma are common.[3, 10, 20]

Long-term methamphetamine use may result in the following[21] :

Race-, Sex-, and Age-related Demographics

Demographic variations include the following[6, 7] :

  • In North America, methamphetamine use is predominantly by Caucasians
  • Males are more likely to abuse methamphetamine than females
  • Peak methamphetamine use is observed in the 20- to 40-year-old range
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Contributor Information and Disclosures
Author

John R Richards, MD, FAAEM Professor, Department of Emergency Medicine, University of California, Davis, Medical Center

John R Richards, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Robert W Derlet, MD Professor of Emergency Medicine, University of California at Davis School of Medicine; Chief Emeritus, Emergency Department, University of California at Davis Health System

Robert W Derlet, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Association for the Advancement of Science, Infectious Diseases Society of America, Society for Academic Emergency Medicine, Wilderness Medical Society

Disclosure: Nothing to disclose.

Timothy E Albertson, MD, MPH, PhD Professor of Pharmacology and Toxicology, Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Chair, Department of Internal Medicine, University of California, Davis, School of Medicine; Professor of Anesthesiology, Professor of Emergency Medicine and Clinical Toxicology, Davis Medical Center; Chief of Pulmonary and Critical Care, Veterans Affairs, Northern California Health Care System; Medical Director of Poison Control System, University of California, San Francisco, School of Pharmacy

Timothy E Albertson, MD, MPH, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Fred Harchelroad, MD, FACMT, FAAEM, FACEP Attending Physician in Emergency Medicine, Excela Health System

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Additional Contributors

Edward A Michelson, MD Associate Professor, Program Director, Department of Emergency Medicine, University Hospital Health Systems of Cleveland

Edward A Michelson, MD is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

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