Methamphetamine Toxicity


Article Author:
John Richards
Abdul Waheed


Article Editor:
Erik Laurin


Editors In Chief:
Rodrigo Kuljis
Oleg Chernyshev
Aninda Acharya


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
6/21/2019 3:12:41 AM

Introduction

Methamphetamine is a highly addictive psychostimulant drug that is a derivative of 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. These characteristics have led to widespread and rampant abuse worldwide, currently estimated at 33 million users based on the 2016 United Nations Office on Drugs and Crime World Drug Report. In the United States, there were greater than 150,000 emergency department visits for toxicity from methamphetamine in 2011 based on data from the Substance Abuse and Mental Health Services Administration. The Drug Enforcement Agency estimated there were 439,000 past-month methamphetamine users in 2011.[1][2][3]

Etiology

Methamphetamine is a Schedule II stimulant under the Controlled Substances Act, which means that it has a high potential for abuse and limited medical use. Methamphetamine hydrochloride is FDA-approved for long-term treatment of attention-deficit hyperactivity disorder (ADHD) with and short-term treatment of exogenous obesity. With regard to prescribed methamphetamine, in 2011 6.4 (11%) of children 4–17 years old had at some point in their lives been diagnosed with attention deficit hyperactivity disorder (ADHD), and 3.5 million were taking an ADHD medication. Illicit use of these prescribed medications among young adults without ADHD is an increasing problem. Methamphetamine used illegally may be snorted, ingested, injected, or smoked. A dangerous form of methamphetamine ingestion, “parachuting,” in which drugs are wrapped in toilet paper or plastic wrap to delay absorption, is becoming more commonplace.[4]

Epidemiology

Methamphetamine was initially synthesized in the early 1900s and used unregulated as a nasal decongestant, to enhance alertness, and for weight loss. It was used extensively by myriad armed forces in World War II, the Korean War, and Vietnam War. Initially Japan experienced a high prevalence of abuse in the 1950s, followed by the United States in the 1960s. The street name “crank” refers to biker gangs’ transport of methamphetamine hidden in their motorcycle crankcase. The southwestern and west coast states (including Hawaii) reported the highest prevalence of abuse from the 1970s to 1990s. Over the past decade, all regions of the United States have experienced a significant increase in the number of persons using the drug and emergency department visits. In the USA, methamphetamine abusers are predominantly white males in their 30s and 40s. More recently, epidemic abuse has been described in adolescents. Methamphetamine abusers tend to be mendacious and mistrustful of health care professionals when describing their drug history.[4][5][6]

Pathophysiology

Methamphetamine promotes the release of monoamine neurotransmitters dopamine, serotonin, and norepinephrine within central (CNS) and peripheral nerve endings. It also blocks re-uptake of dopamine similar to cocaine, and it may act as a false transmitter. This explains its euphoric effects in the CNS and sympathomimetic effects such as tachycardia and hypertension.[7]

Toxicokinetics

For oral administration, peak methamphetamine concentrations are seen in 2-4 hours; snorting, smoking, and injecting peak concentrations occur within minutes. Elimination half-life ranges from 6-15 hours. Methamphetamine is metabolized via the cytochrome P450 complex to active amphetamine, and p-OH-amphetamine and norephedrine, which are both inactive. The rate of excretion into the urine is enhanced as pH falls. Urine toxicology screening may be positive up to 4 days after use. 

History and Physical

Acute and long-term methamphetamine use may lead to abnormal findings on examination of the following systems: cardiovascular, CNS, gastrointestinal, renal, skin, and dental. Tachycardia and hypertension are frequently observed, and atrial and ventricular dysrhythmias may occur. Chest pain from cardiac ischemia and infarction, acute aortic dissection or an aneurysm has been associated with methamphetamine abuse. Hypotension may be observed with methamphetamine overdose with profound depletion of catecholamines. Acute and chronic cardiomyopathy results directly from methamphetamine cardiac toxicity and indirectly from chronic hypertension and ischemia; intravenous use may result in endocarditis; patients may present with dyspnea, edema, and other signs of acute congestive heart failure (CHF) exacerbation. [8]  Acute noncardiogenic pulmonary edema and pulmonary hypertension may result from acute and chronic use, as well as from adulterants introduced during intravenous use such as talc or cornstarch.

Severe abdominal pain may result from acute mesenteric vasoconstriction; methamphetamine has also been associated with the formation of ulcers and ischemic colitis. Renal failure may occur from rhabdomyolysis, necrotizing angiitis, acute interstitial nephritis or tubular necrosis.  

Skin findings include delusions of parasitosis, and chronic skin-picking may result in neurotic excoriations and prurigo nodularis ("speed bumps"). Injectors frequently present with abscess and cellulitis, which they often blame on a "spider bite." Dental examination usually reveals severe caries, especially of the maxillary teeth "meth mouth.” This results from maxillary artery vasoconstriction, xerostomia, and poor hygiene. Methamphetamine use during pregnancy can be fatal to the mother and fetus from placental vasoconstriction resulting in spontaneous abortion. Methamphetamine is secreted in breast milk. 

Evaluation

An electrocardiogram should be performed to assess for myocardial ischemia and tachydysrhythmia. Complete blood count, comprehensive chemistry panel, troponin, B-type natriuretic peptide (BNP), creatine kinase (CK), and urinalysis are helpful tests to obtain for patients presenting with acute methamphetamine toxicity. Methamphetamine users are rarely forthcoming about their most recent drug use, and a urine toxicology screen is extremely helpful, as the differential diagnoses for sympathomimetic signs and symptoms is quite wide. Computed tomography of the head for acute headache or altered mental status may be necessary to rule our hemorrhage. A chest radiograph is essential for those patients presenting with chest pain or dyspnea.[9][10]

Treatment / Management

Benzodiazepines represent first-line treatment for methamphetamine toxicity but frequently require repeated and escalated dosing to achieve the effect. Methamphetamine users may be resistant to benzodiazepine treatment. Antipsychotics, such as haloperidol and olanzapine, are also useful in the management of agitation. Combination treatment with benzodiazepines and antipsychotics has been shown to be more efficacious than monotherapy. [11] Diphenhydramine is often added to enhance sedation and as prophylaxis against dystonia and akathisia. A common example of this is the “B-52” with its combination of haloperidol (5 mg), diphenhydramine (50 mg), and lorazepam (2 mg).[3][9]

For concomitant tachycardia and hypertension that does not respond to sedation, the combined beta/alpha-blocker labetalol is preferred based on a systematic review from 2015. [12] For tachycardia without hypertension, the beta 1-blocker metoprolol is preferred. Both labetalol and metoprolol have the added advantage of being lipophilic, with CNS penetration and antagonism of excess monoamines causing agitation. Despite the unfortunate persistence of dogma carried over from a small number (n=7) of cocaine cases, there have been no cases of “unopposed alpha stimulation” reported with beta-blocker use and treatment of methamphetamine toxicity. For severe hypertension without tachycardia, nitroprusside is recommended as it is easily titrated to effect and has a half-life of minutes. Administration of copious intravenous crystalloid is also recommended to enhance urinary elimination and prevent acute renal failure. Calcium channel blockers may be used but do not directly treat the hyperadrenergic state induced by methamphetamine, and their reduction of tachycardia and blood pressure is much less predictable than beta-blockers.    

Differential Diagnosis

  • Acute MI
  • Hypertensive crisis
  • Hallucinogen toxicity
  • Hyperthyroidism, Thyroid storm
  • Cocaine toxicity
  • Seizures
  • Subarachnoid hemorrhage
  • Ischemic stroke

Complications

  • Hypertension
  • Intracranial hemorrhage
  • Seizures
  • Ischemic stroke
  • Coma
  • Hyperthermia
  • Heart failure
  • Arrhythmias

Enhancing Healthcare Team Outcomes

Methamphetamine toxicity is best managed by a team of healthcare professionals that include a social worker, addiction nurse, cardiologist, internist, and a mental health counselor. Once a diagnosis of methamphetamine toxicity is made, the patient should be referred to a psychiatrist or a drug addiction center. Patients need to be educated about the potentially life-threatening adverse effects of this illicit agent. Unfortunately, addiction to methamphetamine is one of the most difficult to cure as there is no agent that can prevent abstinence. The majority of patients continue to abuse the drug until they run afoul of the legal system.[13][14](Level V)

Outcomes

Methamphetamine toxicity is a real serious social problem. The addiction is very difficult to stop, and as yet there is no pharmacological agent that can help patients abstain from this illicit agent. Despite referral to addiction clinics, relapses into addiction are common. When the drug is forcibly withdrawn while the individual is incarcerated or in hospital, withdrawal reactions are very common and often require sedatives or anti-anxiety agents. Deaths from methamphetamine toxicity are common and include arrhythmias, intracranial hemorrhage, and cardiogenic shock. Use of methamphetamine during pregnancy has also been linked to preterm birth and intrauterine growth restriction. The majority of patients come from a subculture that is involved in the manufacture of the drug, and until that environment is changed, the cycle of addiction will continue. [15][16][17](Level V)


  • Image 1577 Not availableImage 1577 Not available
    Contributed by Wikimedia Commons (Public Domain)
Attributed To: Contributed by Wikimedia Commons (Public Domain)

Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Methamphetamine Toxicity - Questions

Take a quiz of the questions on this article.

Take Quiz
A 58-year-old male presents with chest pain. His electrocardiogram shows sinus tachycardia with a rate of 160 beats/min and no ST-segment elevation. His blood pressure is normal. His initial troponin is elevated four times greater than the upper limit of normal and his urine toxicology screen is positive for methamphetamine. Several doses of benzodiazepines and nitroglycerin improve his chest pain but not the tachycardia. What drug should be used next?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 51-year-old male presents to the emergency department with agitation, choreiform movements, paranoid behavior, and pressured speech. On admission, his vital signs are within the normal range. The detailed patient history revealed that he is a long-time drug user of a specific agent, but he consistently refused to disclose the name of the drug. Based on the history and physical examination, the chronic use of which of the following agent is the most likely cause of the patient's symptoms?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 45-year-old male is brought to the emergency department by the police. He is being physically restrained by the officers and is screaming. The officers tell you that a friend told them that the patient was smoking something from a pipe earlier in the day. He is extremely agitated, paranoid, and appears very confused. A cursory exam reveals dyspnea, wheezing, and severe dental caries. What is the first line of treatment for chemical restraint?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 17-year-old patient admits to abusing methamphetamine. Which of the following are potential long-term consequences of her drug abuse? Select all that apply.

(Move Mouse on Image to Enlarge)
  • Image 1577 Not availableImage 1577 Not available
    Contributed by Wikimedia Commons (Public Domain)
Attributed To: Contributed by Wikimedia Commons (Public Domain)



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which characteristic regarding methamphetamine-associated cardiomyopathy is incorrect?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 34-year-old male who regularly snorts methamphetamine is concerned about multiple dental caries and loss of his upper front teeth. He visits his primary care physician and expresses his concerns about his health. During his interaction with the physician, he asks the physician about the "Meth mouth." This condition is a result of which of the following in chronic methamphetamine users?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Methamphetamine Toxicity - References

References

Maranella E,Mareri A,Nardi V,Di Natale C,Di Luca L,Conte E,Pannone V,Catalucci A,Di Fabio S, Severe neurologic and hepatic toxicity in a newborn prenatally exposed to methamphetamine. A case report. Brain     [PubMed]
Limanaqi F,Gambardella S,Biagioni F,Busceti CL,Fornai F, Epigenetic Effects Induced by Methamphetamine and Methamphetamine-Dependent Oxidative Stress. Oxidative medicine and cellular longevity. 2018     [PubMed]
Yang X,Wang Y,Li Q,Zhong Y,Chen L,Du Y,He J,Liao L,Xiong K,Yi CX,Yan J, The Main Molecular Mechanisms Underlying Methamphetamine- Induced Neurotoxicity and Implications for Pharmacological Treatment. Frontiers in molecular neuroscience. 2018     [PubMed]
Turner C,Chandrakumar D,Rowe C,Santos GM,Riley ED,Coffin PO, Cross-sectional cause of death comparisons for stimulant and opioid mortality in San Francisco, 2005-2015. Drug and alcohol dependence. 2018 Apr 1     [PubMed]
Liakoni E,Dolder PC,Rentsch K,Liechti ME, Acute health problems due to recreational drug use in patients presenting to an urban emergency department in Switzerland. Swiss medical weekly. 2015     [PubMed]
Karila L,Megarbane B,Cottencin O,Lejoyeux M, Synthetic cathinones: a new public health problem. Current neuropharmacology. 2015 Jan     [PubMed]
Schuring CA,Dodge DL,Whitcomb TJ,Wall GC,Smith HL,Hicklin GA, Overdoses and Substance Toxicity in Patients Admitted to Intensive Care Units in a Midwestern U.S. City. Journal of trauma nursing : the official journal of the Society of Trauma Nurses. 2018 Mar/Apr     [PubMed]
Richards JR,Hawkins JA,Acevedo EW,Laurin EG, The care of patients using methamphetamine in the emergency department: Perception of nurses, residents, and faculty. Substance abuse. 2018 Mar 29     [PubMed]
Carfora A,Cassandro P,Feola A,La Sala F,Petrella R,Borriello R, Ethical Implications in Vaccine Pharmacotherapy for Treatment and Prevention of Drug of Abuse Dependence. Journal of bioethical inquiry. 2018 Mar     [PubMed]
Matsumoto RR,Seminerio MJ,Turner RC,Robson MJ,Nguyen L,Miller DB,O'Callaghan JP, Methamphetamine-induced toxicity: an updated review on issues related to hyperthermia. Pharmacology     [PubMed]
Lappin JM,Darke S,Farrell M, Stroke and methamphetamine use in young adults: a review. Journal of neurology, neurosurgery, and psychiatry. 2017 Dec     [PubMed]
Roohbakhsh A,Shirani K,Karimi G, Methamphetamine-induced toxicity: The role of autophagy? Chemico-biological interactions. 2016 Dec 25     [PubMed]
Uhlmann S,DeBeck K,Simo A,Kerr T,Montaner JS,Wood E, Health and social harms associated with crystal methamphetamine use among street-involved youth in a Canadian setting. The American journal on addictions. 2014 Jul-Aug     [PubMed]
Fleckenstein AE,Volz TJ,Riddle EL,Gibb JW,Hanson GR, New insights into the mechanism of action of amphetamines. Annual review of pharmacology and toxicology. 2007;     [PubMed]
Richards JR,Harms BN,Kelly A,Turnipseed SD, Methamphetamine use and heart failure: Prevalence, risk factors, and predictors. The American journal of emergency medicine. 2018 Aug;     [PubMed]
Zun LS, Evidence-Based Review of Pharmacotherapy for Acute Agitation. Part 1: Onset of Efficacy. The Journal of emergency medicine. 2018 Mar;     [PubMed]
Richards JR,Albertson TE,Derlet RW,Lange RA,Olson KR,Horowitz BZ, Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review. Drug and alcohol dependence. 2015 May 1;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Neurology. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Neurology, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Neurology, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Neurology. When it is time for the Neurology board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Neurology.