Methamphetamine Toxicity 

  • Author: John R Richards, MD, FAAEM; Chief Editor: Asim Tarabar, MD   more...
 
Updated: Aug 18, 2011
 

Background

Over the past 25 years, methamphetamine use has increased rapidly throughout the world. In the United States, all regions have experienced a significant increase in the number of persons using the drug as well as medical complications seen in emergency departments (EDs).[1] Methamphetamine and related compounds can produce euphoria and stimulant effects and share many of the same toxic clinical effects seen with other stimulants such as cocaine. The ease of synthesis from inexpensive and readily obtainable chemicals has led to the widespread and rampant abuse of this dangerous drug.

The euphoria produced by methamphetamine is similar to that produced by cocaine. Methamphetamine may be taken orally, intravenously, snorted, or smoked. Patients who inhale the smokable form of methamphetamine (ie, ice) experience an immediate euphoria similar to that of crack cocaine, but the effects may last much longer.[2, 3, 4] North American methamphetamine abusers are predominantly Caucasian males in their 30s and 40s.[5, 6] 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.[7]

The medical history of amphetamine-like compounds extends back nearly 100 years.[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 Operation Desert Storm to increase wakefulness and attention.[8, 3]

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.[4] The Controlled Substance Act of 1970 stringently regulated the manufacture of amphetamine. Despite attempts to decrease production, illicit methamphetamine use continues to increase.[3, 9]

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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, presynaptic reuptake of catecholamines (ie, dopamine, norepinephrine) is blocked, causing hyperstimulation at selected postsynaptic neuron receptors. Indirect sympathomimetic effects of amphetamines are also caused by blocking presynaptic vesicular storage and by reducing cytoplasmic destruction of catecholamines by inhibiting 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.

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.[13, 14] 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 urine excretion of metabolites.

When methamphetamine is used with ethanol, increased psychological and cardiac effects are observed.[15] This is presumed to be the result of pharmacodynamic rather than pharmacokinetic interactions. Similarly, the increased toxicity of concomitant opioids and amphetamines (ie, 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 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.[16]

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Epidemiology

Frequency

United States

Methamphetamine use is widespread, predominantly in Midwest, Southwest, Northwest, and Western States.[9]

International

Methamphetamine use is widespread, predominantly in North America, Eastern Europe, and Southeast Asia.[17]

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.[18, 19]

Chronic methamphetamine use may result in atherosclerosis, hypertension, myocardial infarction, congestive heart failure, soft tissue infection, periodontal disease, sepsis, changes in cognitive CNS function, and personality disorders.

Race

In North America, methamphetamine use is predominantly by Caucasians.[9, 5, 6]

Sex

Males are more likely to abuse methamphetamine than females.[9, 5, 6]

Age

Peak methamphetamine use is observed in the 20- to 40-year-old range.[9, 5]

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Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

John R Richards, MD, FAAEM  Professor of Emergency Medicine, University of California at Davis School of Medicine

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

Disclosure: Nothing to disclose.

Timothy E Albertson, MD, MPH, PhD  Professor of Pharmacology and Toxicology, Division Chief and Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Vice-Chair, Department of Internal Medicine, University of California, Davis, School of Medicine; Professor of Anesthesiology, Associate Dean, Academic Clinical Programs, University of California, Davis Health System; 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 at San Francisco, School of Pharmacy.

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

Disclosure: Nothing to disclose.

Specialty Editor Board

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, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

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  Director of Medical Toxicology, Allegheny General Hospital

Disclosure: Nothing to disclose.

John D Halamka, MD, MS  Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center

John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine

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.

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