{{Infobox medical condition (new) | name = Cocaine intoxication | synonyms = Cocaine toxicity, Cocaine poisoning, Cocaine overdose | image = Kokain - Cocaine.svg | caption = [[Cocaine]] | pronounce = | field = [[Toxicology]] | symptoms = | complications = | onset = | duration = | types = | causes = | risks = | diagnosis = | differential = | prevention = | treatment = | medication = | prognosis = | frequency = | deaths = }} '''Cocaine intoxication''' refers to the [[Subjective experience|subjective]], desired and adverse effects of [[cocaine]] on the mind and behavior of users. Both self-induced and involuntary cocaine intoxication have medical and legal implications (even in absence of relevant adverse effects).
Adverse effects can develop over time due to repeated use and so become chronic conditions. However, even a one-time intake of the substance can result in severe acute intoxication.
Recurrent cocaine use and dependence to the drug inevitably leads to the reduction of the desired effects perceived by the users, while the occurrence of adverse effects of intoxication increase. The last can sometimes be completely reversed without bearing consequences but they can also potentially kill the users (e.g., in cases of untreated or non-manageable overdoses).
==Signs and symptoms== Cocaine increases alertness, feelings of well-being, euphoria, energy, sociability, and sexuality. The former are some of the [[Cocaine#Recreational|desired effects]] of cocaine intoxication. Mild [[adverse effect]]s include anxiety, increased temperature, paranoia, restlessness, and teeth grinding. With prolonged use, the drug can cause chronic complications like [[insomnia]], [[weight loss]], [[Anorexia (symptom)|anorexia]], persistent [[tachycardia]], [[heart failure]], [[kidney failure]], [[hallucination]]s, and [[paranoid delusions]].<ref>{{Cite journal|last1=Glauser|first1=Jonathan|last2=Queen|first2=John R.|date=2007-02-01|title=An overview of non-cardiac cocaine toxicity|journal=The Journal of Emergency Medicine|volume=32|issue=2|pages=181–186|doi=10.1016/j.jemermed.2006.05.044|issn=0736-4679|pmid=17307630}}</ref>
Depression with [[suicidal ideation]] may develop in heavy users.<ref>{{Cite journal|last1=Narvaez|first1=Joana C. M.|last2=Jansen|first2=Karen|last3=Pinheiro|first3=Ricardo T.|last4=Kapczinski|first4=Flávio|last5=Silva|first5=Ricardo A.|last6=Pechansky|first6=Flávio|last7=Magalhães|first7=Pedro V.|date=2014-08-01|title=Psychiatric and substance-use comorbidities associated with lifetime crack cocaine use in young adults in the general population|journal=Comprehensive Psychiatry|volume=55|issue=6|pages=1369–1376|doi=10.1016/j.comppsych.2014.04.021|issn=1532-8384|pmid=24933652}}</ref> Finally, a loss of vesicular monoamine transporters, neurofilament proteins, and other morphological changes appear to indicate a long-term damage to dopamine neurons.<ref>{{Cite journal|last1=Little|first1=Karley Y.|last2=Ramssen|first2=Eric|last3=Welchko|first3=Ryan|last4=Volberg|first4=Vitaly|last5=Roland|first5=Courtney J.|last6=Cassin|first6=Bader|date=2009-08-15|title=Decreased brain dopamine cell numbers in human cocaine users|journal=Psychiatry Research|volume=168|issue=3|pages=173–180|doi=10.1016/j.psychres.2008.10.034|issn=0165-1781|pmid=19233481|s2cid=27618292}}</ref> Chronic intranasal usage can degrade the cartilage separating the nostrils (the [[nasal septum]]), which can eventually lead to its complete disappearance, a condition known as [[Cocaine-Induced Midline Destructive Lesions|Cocaine-Induced Midline Destructive Lesions (CIMDL)]].<ref>{{Cite journal|last1=Trimarchi|first1=M.|last2=Bussi|first2=M.|last3=Sinico|first3=R. A.|last4=Meroni|first4=Pierluigi|last5=Specks|first5=U.|date=2013-02-01|title=Cocaine-induced midline destructive lesions - an autoimmune disease?|journal=Autoimmunity Reviews|volume=12|issue=4|pages=496–500|doi=10.1016/j.autrev.2012.08.009|issn=1873-0183|pmid=22940554}}</ref>
Studies have shown that [[Prenatal cocaine exposure|cocaine usage during pregnancy]] triggers [[premature labor]]<ref>{{Cite journal|last1=Cain|first1=Mary A.|last2=Bornick|first2=Patricia|last3=Whiteman|first3=Valerie|date=2013-03-01|title=The maternal, fetal, and neonatal effects of cocaine exposure in pregnancy|journal=Clinical Obstetrics and Gynecology|volume=56|issue=1|pages=124–132|doi=10.1097/GRF.0b013e31827ae167|issn=1532-5520|pmid=23314714}}</ref> and may lead to [[placental abruption]].<ref>{{Cite journal|last1=Flowers|first1=D.|last2=Clark|first2=J. F.|last3=Westney|first3=L. S.|date=1991-03-01|title=Cocaine intoxication associated with abruptio placentae.|journal=Journal of the National Medical Association|volume=83|issue=3|pages=230–232|issn=0027-9684|pmc=2627035|pmid=2038082}}</ref>
In cases of severe acute intoxication, potentially lethal adverse effects include prolonged episodes of [[arrhythmia]] (i.e., a group of abnormal heart rhythms that also include tachycardia), heavy [[hypoglycemia]], [[tremor]]s, [[convulsion]]s, [[hyperthermia]] (i.e., markedly increased core temperature), untreated [[uremia]], [[myocardial infarction]], [[stroke]], and [[Cardiac arrest|sudden cardiac arrest]].<ref>{{Cite journal|last=Zimmerman|first=Janice L.|date=2012-10-01|title=Cocaine intoxication|journal=Critical Care Clinics|volume=28|issue=4|pages=517–526|doi=10.1016/j.ccc.2012.07.003|issn=1557-8232|pmid=22998988}}</ref>
===Overdose=== [[File:US timeline. Cocaine deaths.svg|thumb|upright=1.3|US yearly overdose deaths involving cocaine.<ref name=NIDA-deaths>[http://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates Overdose Death Rates]. By [[National Institute on Drug Abuse]] (NIDA).</ref>]] [[File:US timeline. Opioid involvement in cocaine overdose.jpg|thumb|upright=1.3|US. Opioid involvement in cocaine overdose deaths. Green line is cocaine and any opioid. Gray line is cocaine without any opioids. Yellow line is cocaine and other [[:Category:Synthetic opioids|synthetic opioids]].<ref name=NIDA-deaths/>]]
Cocaine can be snorted, swallowed, injected, or smoked. Most deaths due to cocaine are accidental but may also be the result of [[Mule (smuggling)|body packing or stuffing]] with rupture in the gastrointestinal tract. Use of cocaine causes [[cardiac arrhythmia|abnormally fast heart rhythms]] and a marked elevation of blood pressure ([[hypertension]]), which can be life-threatening. This can lead to death from acute [[myocardial infarction]], acute [[respiratory failure]] (i.e., [[hypoxemia]], with or without [[hypercapnia]]), [[stroke]], [[cerebral hemorrhage]], and [[Cardiac arrest|sudden cardiac arrest]].<ref>{{Cite journal|last1=O'Leary|first1=Michael E|last2=Hancox|first2=Jules C|date=2010|title=Role of voltage-gated sodium, potassium and calcium channels in the development of cocaine-associated cardiac arrhythmias|journal=British Journal of Clinical Pharmacology|volume=69|issue=5|pages=427–442|doi=10.1111/j.1365-2125.2010.03629.x|issn=0306-5251|pmc=2856043|pmid=20573078}}</ref> Cocaine overdose may result in [[hyperthermia]] as stimulation and increased muscular activity cause greater heat production. Heat loss is also inhibited by the cocaine-induced [[vasoconstriction]]. Cocaine and/or associated hyperthermia may cause muscle cell destruction ([[rhabdomyolysis]]) and [[myoglobinuria]] resulting in [[kidney failure]]. Individuals with cocaine overdose should be transported immediately to the nearest emergency department, preferably by ambulance in case cardiac arrest occurs en route. According to the [[National Institute on Drug Abuse]], approximately 14,600 deaths occurred in the US in 2017 due to an overdose where cocaine was somehow involved in any capacity, defined or undefined.<ref name=NIDA-deaths/> Because of the increase in heart rate, cocaine users can be prone to elevated body temperatures, tremors, chest pains, and subject to nausea and vomiting. Some psychological symptoms due to an overdose include paranoia, delirium, anxiety as well as panicked feelings. Some signs of an overdose of cocaine are difficulty breathing, loss of urine control, bluish color of the skin, loss of awareness or surroundings, and high blood pressure. Death can also be caused from an over intoxication of cocaine, especially if high doses are taken.<ref>{{Cite web|url=https://medlineplus.gov/ency/article/000946.htm|title=Cocaine intoxication: MedlinePlus Medical Encyclopedia|website=medlineplus.gov|language=en|access-date=2019-10-21}}</ref> Most severe overdoses occur when users combine cocaine with other substances like [[alcohol (drug)|alcohol]] or heroin, which increase the effects and heighten the chances of having a dangerous overdose. Treating an overdose can be done by bringing back blood flow to the heart, and restoring the body with oxygen rich blood, especially for the brain to reduce the risk of stroke.<ref>{{Cite web|url=https://www.drugabuse.gov/publications/drugfacts/cocaine|title=Cocaine|last=Abuse|first=National Institute on Drug|website=www.drugabuse.gov|language=en|access-date=2019-10-21}}</ref> Cocaine overdoses have fluctuated over the years. From 2006 to 2010 there has been a decline in the number of reported cases. Though, from 2010 to 2015 there has been an increase in the reported cases involving over cocaine intoxication. Males appear to have a much higher chance of overdosing than females. The ratio of male to female cocaine overdoses is 3:1. ===Withdrawal=== Cocaine withdrawal is not as severe as the withdrawal from other substances. For example, substances like heroin, alcohol and benzodiazepines can involve severe physical withdrawal symptoms while cocaine results in mostly psychological symptoms. Physiological changes caused by cocaine withdrawal include vivid and unpleasant dreams, insomnia, hypersomnia, anger, increased appetite, weight gain, psychomotor retardation, agitation, depression, and anxiety. According to a study done by Gawin and Kleber in 1986, there are three phases in the withdrawal process. They observed the behavior of 30 cocaine-dependent individuals. Phase one, the crash, is characterized by acute dysphoria, irritability and anxiety, increased desire for sleep, exhaustion, increased appetite, decreased craving to use. Phase two, withdrawal, is characterized by increasing craving to use, poor concentration, some irritability and some lethargy, which persisted for up to 10 weeks. Lastly, phase three is characterized by the intermittent craving to use in the context of external cues.<ref>{{Cite web|url=https://www1.health.gov.au/internet/publications/publishing.nsf/Content/drugtreat-pubs-modpsy-toc~drugtreat-pubs-modpsy-3~drugtreat-pubs-modpsy-3-7~drugtreat-pubs-modpsy-3-7-cws|title=Department of Health {{!}} The cocaine withdrawal syndrome|website=www1.health.gov.au|access-date=2019-10-29|archive-date=2020-12-03|archive-url=https://web.archive.org/web/20201203132056/https://www1.health.gov.au/internet/publications/publishing.nsf/Content/drugtreat-pubs-modpsy-toc~drugtreat-pubs-modpsy-3~drugtreat-pubs-modpsy-3-7~drugtreat-pubs-modpsy-3-7-cws|url-status=dead}}</ref> Cocaine and its metabolites are eliminated from the body by 3 days.<ref name=":0">{{Cite journal|last1=Jufer|first1=R. A.|last2=Wstadik|first2=A.|last3=Walsh|first3=S. L.|last4=Levine|first4=B. S.|last5=Cone|first5=E. J.|date=2000-10-01|title=Elimination of cocaine and metabolites in plasma, saliva, and urine following repeated oral administration to human volunteers|journal=Journal of Analytical Toxicology|volume=24|issue=7|pages=467–477|issn=0146-4760|pmid=11043648|doi=10.1093/jat/24.7.467|doi-access=free}}</ref> There are not any FDA-approved medications that specifically help treat cocaine withdrawal, however, there are some useful medications that could possibly help individuals overcome their addiction. One example is propranolol. Propranolol is a beta blocker that has been approved to treat hypertension, angina, anxiety, and other related psychological problems. Buprenorphine and naltrexone are two substances that act as an effective treatment in the earlier stages of withdrawal.
==Pathophysiology== Cocaine [[pharmacodynamics]] involve multiple complex mechanisms. Although it has a short half-life (~ 1 hour),<ref name=":0" /> cocaine metabolites, which rise in concentrations several hours after cocaine ingestion, persist in circulation for up to 24 hours, and may cause delayed or recurrent coronary vasoconstriction.<ref>{{Cite journal|last1=Brogan|first1=Walter C.|last2=Lange|first2=Richard A.|last3=Kim|first3=Anatole S.|last4=Moliterno|first4=David J.|last5=Hillis|first5=L. David|date=1991-08-01|title=Alleviation of cocaine-induced coronary vasoconstriction by nitroglycerin|journal=Journal of the American College of Cardiology|series=22nd Bethesda Conference: Congenital heart disease after childhood: An edpanding patient population|language=en|volume=18|issue=2|pages=581–586|doi=10.1016/0735-1097(91)90617-I|pmid=1906905|issn=0735-1097|doi-access=}}</ref> This drug binds and blocks [[Monoamine neurotransmitter|monoamine]] (dopamine, epinephrine, norepinephrine, and serotonin) re-uptake transporters with equal affinity. Monoamines accumulate in the [[Chemical synapse|synaptic cleft]] resulting in enhanced and prolonged sympathetic effects. Cocaine's acute effect in the [[central nervous system]] is to raise the amount of dopamine and serotonin in the [[nucleus accumbens]] (the pleasure center in the brain). When this effect ceases due to metabolism of cocaine, depletion of associated neurotransmitters, and receptor down-regulation ([[tachyphylaxis]]), the cocaine user may experience [[dysphoria]], or a "[[Drug withdrawal|crash]]" after the initial high. The principal actions of cocaine on the cardiovascular system are from alpha- and beta-1-[[adrenoceptor]] stimulation resulting in increased heart rate, systemic arterial pressure, and myocardial contractility, which are major determinants of myocardial oxygen demand. Cocaine and its metabolites may cause arterial vasoconstriction hours after use. Epicardial [[Coronary circulation|coronary arteries]] are especially vulnerable to these effects, leading to decreased myocardial oxygen supply. Cocaine-induced platelet activation and thrombus formation is another deleterious effect, caused by alpha-adrenergic- and adenosine diphosphate-mediated increase in platelet aggregation.<ref>{{Cite journal|last1=Heesch|first1=C. M.|last2=Wilhelm|first2=C. R.|last3=Ristich|first3=J.|last4=Adnane|first4=J.|last5=Bontempo|first5=F. A.|last6=Wagner|first6=W. R.|date=2000-06-01|title=Cocaine activates platelets and increases the formation of circulating platelet containing microaggregates in humans|journal=Heart|volume=83|issue=6|pages=688–695|issn=1468-201X|pmc=1760877|pmid=10814631|doi=10.1136/heart.83.6.688}}</ref> Plasminogen activator inhibitor is also increased following cocaine use, thereby promoting thrombosis. Cocaine acts like a class I antiarrhythmic agent by blocking sodium and potassium channels, in a similar way of local anesthetics such as [[lidocaine]] and interferes with action potential propagation.<ref>{{Cite journal|last1=Hariman|first1=Robert J.|last2=Liu|first2=Dong|last3=Loeb|first3=Henry S.|last4=McKieman|first4=Thomas L.|last5=Scanlon|first5=Patrick J.|last6=Bauman|first6=Jerry L.|date=1996-02-01|title=Competitive binding between cocaine and lidocaine|journal=Journal of the American College of Cardiology|volume=27|issue=2|pages=80|doi=10.1016/S0735-1097(96)80520-1|doi-access=free}}</ref><ref name=":3">{{Cite journal|last1=Schwartz Bryan G.|last2=Rezkalla Shereif|last3=Kloner Robert A.|date=2010-12-14|title=Cardiovascular Effects of Cocaine|journal=Circulation|volume=122|issue=24|pages=2558–2569|doi=10.1161/CIRCULATIONAHA.110.940569|pmid=21156654|doi-access=free}}</ref> This [[Vaughn-williams classification of antidysrhythmic drugs|Vaughn-Williams class IC]] effect increases the risk of conduction disturbance and tachyarrhythmias. Adding to its complex toxicity, cocaine targets [[Muscarinic acetylcholine receptor|muscarinic acetylcholine]], N-methyl-D-aspartate ([[N-Methyl-D-aspartic acid|NMDA]]), sigma, and kappa-[[Opioid receptor|opioid]] receptors.<ref>{{Cite journal|last1=Williams|first1=Mark J.|last2=Adinoff|first2=Bryon|date=2008-07-01|title=The role of acetylcholine in cocaine addiction|journal=Neuropsychopharmacology|volume=33|issue=8|pages=1779–1797|doi=10.1038/sj.npp.1301585|issn=0893-133X|pmc=2667818|pmid=17928814}}</ref><ref>{{Cite journal|last1=Haile|first1=Colin N.|last2=Mahoney|first2=James J.|last3=Newton|first3=Thomas F.|last4=De La Garza|first4=Richard|date=2012-05-01|title=Pharmacotherapeutics directed at deficiencies associated with cocaine dependence: focus on dopamine, norepinephrine and glutamate|journal=Pharmacology & Therapeutics|volume=134|issue=2|pages=260–277|doi=10.1016/j.pharmthera.2012.01.010|issn=1879-016X|pmc=3341931|pmid=22327234}}</ref><ref>{{Cite journal|last1=Narayanan|first1=Sanju|last2=Mesangeau|first2=Christophe|last3=Poupaert|first3=Jacques H.|last4=McCurdy|first4=Christopher R.|date=2011-01-01|title=Sigma receptors and cocaine abuse|journal=Current Topics in Medicinal Chemistry|volume=11|issue=9|pages=1128–1150|issn=1873-4294|pmid=21050176|doi=10.2174/156802611795371323}}</ref><ref>{{Cite book|last1=Kivell|first1=Bronwyn M.|last2=Ewald|first2=Amy W. M.|last3=Prisinzano|first3=Thomas E.|date=2014-01-01|title=Salvinorin A analogs and other κ-opioid receptor compounds as treatments for cocaine abuse|series=Advances in Pharmacology|volume=69|pages=481–511|doi=10.1016/B978-0-12-420118-7.00012-3|issn=1557-8925|pmc=4128345|pmid=24484985|isbn=9780124201187}}</ref>
==Management== [[File:Cocaïne alert Amsterdam.JPG|thumb|upright=1.3|A "cocaine alert" sign posted by GGD Amsterdam: the sign reminds people to "Call [[112 (emergency telephone number)|112]] for an ambulance."]]
There is no specific [[antidote]] for cocaine. Emergency treatment of cocaine-associated high body temperature consists of giving a [[benzodiazepine]] and physical cooling. Immediate administration of [[aspirin]] is required for patients reporting cocaine-associated chest pain.<ref name=":3" /><ref>{{Cite journal|date=2021-01-01|title=The current practice for cocaine-associated chest pain in the Netherlands|url=|journal=Toxicology Reports|language=en|volume=8|pages=23–27|doi=10.1016/j.toxrep.2020.12.011|issn=2214-7500|pmc=7770504|pmid=33384944|last1=Gresnigt|first1=Femke M.J.|last2=Gubbels|first2=Nanda P.|last3=Riezebos|first3=Robert K.}}</ref><ref name=":4" /> Cooling is best accomplished with tepid water misting and cooling with a fan.<ref>{{Cite journal|last1=Smith|first1=Caroline J.|last2=Johnson|first2=John M.|date=2016-04-01|title=Responses to hyperthermia. Optimizing heat dissipation by convection and evaporation: Neural control of skin blood flow and sweating in humans|journal=Autonomic Neuroscience: Basic & Clinical|volume=196|pages=25–36|doi=10.1016/j.autneu.2016.01.002|issn=1872-7484|pmid=26830064|s2cid=3790152}}</ref><ref>{{Cite journal|last1=Richards|first1=John R.|last2=Colby|first2=Daniel K.|date=2016-01-01|title=Stimulant-induced hyperthermia and ice-water submersion: Practical considerations|journal=Clinical Toxicology|volume=54|issue=1|pages=69–70|doi=10.3109/15563650.2015.1104536|issn=1556-9519|pmid=26515112|s2cid=207553540}}</ref> [[Antipyretic]]s (e.g., paracetamol) have no effect in lowering high temperature because cocaine is an [[muscarinic receptor agonist]].
The chest pain, high blood pressure, and increased heart rate caused by cocaine may be also treated with benzodiazepines.<ref name="McC2008">{{cite journal|last=McCord|first=J|date=Apr 8, 2008|title=Management of cocaine-associated chest pain and myocardial infarction: a scientific statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology.|journal=Circulation|volume=117|issue=14|pages=1897–907|doi=10.1161/CIRCULATIONAHA.107.188950|pmid=18347214|author2=Jneid, H|author3=Hollander, JE|author4=de Lemos, JA|author5=Cercek, B|author6=Hsue, P|author7=Gibler, WB|author8=Ohman, EM|author9=Drew, B|author10=Philippides, G|author11=Newby, LK|author12=American Heart Association Acute Cardiac Care Committee of the Council on Clinical, Cardiology|doi-access=free}}</ref> Multiple and escalating dose of benzodiazepines may be necessary to achieve effect, which increases risk of over-sedation and respiratory depression. A review of cocaine cardiovascular toxicity found benzodiazepines may not always reliably lower heart rate and blood pressure.<ref name=":1">{{Cite journal|last1=Richards|first1=John R.|last2=Garber|first2=Dariush|last3=Laurin|first3=Erik G.|last4=Albertson|first4=Timothy E.|last5=Derlet|first5=Robert W.|last6=Amsterdam|first6=Ezra A.|last7=Olson|first7=Kent R.|last8=Ramoska|first8=Edward A.|last9=Lange|first9=Richard A.|date=2016-06-01|title=Treatment of cocaine cardiovascular toxicity: a systematic review|journal=Clinical Toxicology|volume=54|issue=5|pages=345–364|doi=10.3109/15563650.2016.1142090|issn=1556-9519|pmid=26919414|s2cid=5165666}}</ref> Lidocaine and [[Lipid emulsion|intravenous lipid emulsion]] have been successfully used for serious ventricular tachyarrhythmias in several case reports.
People who are agitated are best treated with benzodiazepines, though [[antipsychotic]]s such as [[haloperidol]] and [[olanzapine]] may also be useful.<ref name=":1" /> The alpha-2 agonist [[dexmedetomidine]] may also be useful for agitation, but effects on heart rate and blood pressure are variable based on several studies and case reports.<ref name=":1" />
=== Vasodilators === [[Nitric oxide|Nitric-oxide]] mediated [[Nitrovasodilator|vasodilators]], such as [[nitroglycerin]] and [[Sodium nitroprusside|nitroprusside]], are effective at lowering blood pressure and reversing coronary arterial vasoconstriction, but not heart rate.<ref name=":1" /> Nitroglycerin is useful for cocaine-induced chest pain, but the possibility of reflex tachycardia must be considered.<ref>{{Cite journal|last1=Ma|first1=Sheng-xing|last2=Schmid|first2=Phillip G.|last3=Long|first3=John P.|date=1994-01-01|title=Noradrenergic mechanisms and the cardiovascular actions of nitroglycerin|journal=Life Sciences|volume=55|issue=21|pages=1595–1603|doi=10.1016/0024-3205(94)00325-4|pmid=7968233}}</ref>
=== Alpha blockers === [[Alpha blocker|Alpha-blockers]] such as [[phentolamine]] have been recommended<ref name="McC2008" /> and may be used to treat cocaine-induced hypertension and coronary arterial vasoconstriction, but these agents do not reduce heart rate.<ref name=":1" /><ref>{{Cite journal|last1=Lange|first1=Richard A.|last2=Cigarroa|first2=Ricardo G.|last3=Yancy|first3=Clyde W. Jr.|last4=Willard|first4=John E.|last5=Popma|first5=Jeffrey J.|last6=Sills|first6=Michael N.|last7=McBride|first7=Wade|last8=Kim|first8=Anatole S.|last9=Hillis|first9=L. David|date=1989-12-07|title=Cocaine-Induced Coronary-Artery Vasoconstriction|journal=New England Journal of Medicine|volume=321|issue=23|pages=1557–1562|doi=10.1056/NEJM198912073212301|issn=0028-4793|pmid=2573838}}</ref> Furthermore, phentolamine is rarely used, not readily available in many emergency departments, and many present-day clinicians are unfamiliar with its use.
===Beta blockers=== Although the use of [[beta blocker]]s is still controversial, notwithstanding decades of practice, despite research papers and systematic reviews on this subject<ref>{{Cite journal|last1=Shin|first1=Doosup|last2=Lee|first2=Eun Sun|last3=Bohra|first3=Chandrashekar|last4=Kongpakpaisarn|first4=Kullatham|date=2019|title=In-Hospital and Long-Term Outcomes of Beta-Blocker Treatment in Cocaine Users: A Systematic Review and Meta-analysis|journal=Cardiology Research|volume=10|issue=1|pages=40–47|doi=10.14740/cr831|issn=1923-2829|pmc=6396807|pmid=30834058}}</ref> (more details are in the next section), the intravenous racemic mixture<ref name="Robertson2012">Robertson D, Biaggioni, I. Adrenoceptor Antagonist Drugs. In: Katzung BG, Masters SB, Trevor AJ, eds. Basic & Clinical Pharmacology. 12th ed. San Francisco, CA: McGraw Hill Lange Medical; 2012: 151-168. {{ISBN|978-0-07-176401-8}}.</ref> of [[labetalol]], a non-selective β blocker and selective [[alpha 1 receptor|α<sub>1</sub>]] blocker is recommended for treating concomitant hypertension and tachycardia.<ref name=":1" /><ref>{{Cite journal|last1=Boehrer|first1=James D.|last2=Moliterno|first2=David J.|last3=Willard|first3=John E.|last4=Hillis|first4=L.David|last5=Lange|first5=Richard A.|date=1993-06-01|title=Influence of labetalol on cocaine-induced coronary vasoconstriction in humans|journal=The American Journal of Medicine|volume=94|issue=6|pages=608–610|doi=10.1016/0002-9343(93)90212-8|pmid=8506886|issn=0002-9343}}</ref><ref>{{Cite journal|last1=Richards|first1=John R.|last2=Lange|first2=Richard A.|date=2016-02-01|title=Labetalol and cardiovascular consequences of cocaine use|journal=Trends in Cardiovascular Medicine|volume=26|issue=2|pages=202–203|doi=10.1016/j.tcm.2015.05.002|issn=1873-2615|pmid=26116092}}</ref> Furthermore, the use of labetalol is approved by a [[American Heart Association|AHA]]/[[American College of Cardiology|ACC]] guideline for people who have used cocaine and methamphetamine with unstable angina/non-STEMI.<ref name=":4">{{Cite journal|last1=Anderson|first1=Jeffrey L.|last2=Adams|first2=Cynthia D.|last3=Antman|first3=Elliott M.|last4=Bridges|first4=Charles R.|last5=Califf|first5=Robert M.|last6=Casey|first6=Donald E.|last7=Chavey|first7=William E.|last8=Fesmire|first8=Francis M.|last9=Hochman|first9=Judith S.|date=2013-06-11|title=2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines|journal=Journal of the American College of Cardiology|volume=61|issue=23|pages=e179–347|doi=10.1016/j.jacc.2013.01.014|issn=1558-3597|pmid=23639841|doi-access=}}</ref>
A relative contraindication to the use of beta-blockers is still evident in some guidelines for the treatment of cocaine toxicity despite limited evidence. The phenomenon of "unopposed alpha-stimulation," in which blood pressure increases or coronary artery vasoconstriction worsens after blockade of beta-2 vasodilation in people using cocaine, is controversial.<ref>{{Cite journal|last1=Schurr|first1=James W.|last2=Gitman|first2=Brenda|last3=Belchikov|first3=Yuly|date=2014-12-01|title=Controversial therapeutics: the β-adrenergic antagonist and cocaine-associated cardiovascular complications dilemma|journal=Pharmacotherapy|volume=34|issue=12|pages=1269–1281|doi=10.1002/phar.1486|issn=1875-9114|pmid=25224512|s2cid=5282953}}</ref><ref>{{Cite journal|last1=Freeman|first1=Kalev|last2=Feldman|first2=James A.|date=2008-02-01|title=Cocaine, myocardial infarction, and beta-blockers: time to rethink the equation?|journal=Annals of Emergency Medicine|volume=51|issue=2|pages=130–134|doi=10.1016/j.annemergmed.2007.08.020|issn=1097-6760|pmid=17933425}}</ref> This rarely-encountered and unpredictable adverse effect has resulted in some clinicians advocating for an absolute contraindication of all beta-blockers, including specific, non-specific, and mixed.<ref name=":2">{{Cite journal|last1=Gupta|first1=Amit K.|last2=Greller|first2=Howard A.|last3=Hoffman|first3=Robert Steven|date=2010-11-08|title=Beta-blockers and cocaine: still a bad idea|journal=Archives of Internal Medicine|volume=170|issue=20|pages=1859–1860; author reply 1860|doi=10.1001/archinternmed.2010.398|issn=1538-3679|pmid=21059982}}</ref> Many clinicians have disregarded this [[dogma]] and administer beta-blockers for cocaine-related chest pain and acute coronary syndrome, especially when there is demand ischemia from uncontrolled tachycardia.<ref>{{Cite journal|last1=Dattilo|first1=Philip B.|last2=Hailpern|first2=Susan M.|last3=Fearon|first3=Kerrie|last4=Sohal|first4=Davendra|last5=Nordin|first5=Charles|date=2008-02-01|title=Beta-blockers are associated with reduced risk of myocardial infarction after cocaine use|journal=Annals of Emergency Medicine|volume=51|issue=2|pages=117–125|doi=10.1016/j.annemergmed.2007.04.015|issn=1097-6760|pmid=17583376}}</ref><ref>{{Cite journal|last1=Rangel|first1=Carlos|last2=Shu|first2=Richard G.|last3=Lazar|first3=Lawrence D.|last4=Vittinghoff|first4=Eric|last5=Hsue|first5=Priscilla Y.|last6=Marcus|first6=Gregory M.|date=2010-05-24|title=Beta-blockers for chest pain associated with recent cocaine use|journal=Archives of Internal Medicine|volume=170|issue=10|pages=874–879|doi=10.1001/archinternmed.2010.115|issn=1538-3679|pmid=20498415|doi-access=}}</ref><ref>{{Cite journal|last1=Ibrahim|first1=Morhaf|last2=Maselli|first2=Diego Jose|last3=Hasan|first3=Reham|last4=Hamilton|first4=Andrew|date=2013-03-01|title=Safety of β-blockers in the acute management of cocaine-associated chest pain|journal=The American Journal of Emergency Medicine|volume=31|issue=3|pages=613–616|doi=10.1016/j.ajem.2012.09.027|issn=1532-8171|pmid=23122421}}</ref><ref>{{Cite journal|last1=Fanari|first1=Zaher|last2=Kennedy|first2=Kevin K.|last3=Lim|first3=Michael J.|last4=Laddu|first4=Abhay A.|last5=Stolker|first5=Joshua M.|date=2014-06-01|title=Comparison of in-hospital outcomes for beta-blocker use versus non-beta blocker use in patients presenting with cocaine-associated chest pain|journal=The American Journal of Cardiology|volume=113|issue=11|pages=1802–1806|doi=10.1016/j.amjcard.2014.03.010|issn=1879-1913|pmid=24742472}}</ref><ref>{{Cite journal|last1=Gupta|first1=Navdeep|last2=Washam|first2=Jeffrey B.|last3=Mountantonakis|first3=Stavros E.|last4=Li|first4=Shuang|last5=Roe|first5=Matthew T.|last6=de Lemos|first6=James A.|last7=Arora|first7=Rohit|date=2014-03-01|title=Characteristics, management, and outcomes of cocaine-positive patients with acute coronary syndrome (from the National Cardiovascular Data Registry)|journal=The American Journal of Cardiology|volume=113|issue=5|pages=749–756|doi=10.1016/j.amjcard.2013.11.023|issn=1879-1913|pmid=24388623}}</ref> Of the 1,744 people in the aforementioned systematic review,<ref name=":1" /> only 7 adverse events were from putative cases of "unopposed alpha-stimulation" due to [[propranolol]] (n=3), [[esmolol]] (n=3), and [[metoprolol]] (n=1).<ref>{{Cite journal|last1=Ramoska|first1=Edward|last2=Sacchetti|first2=Alfred D|date=1985-11-01|title=Propranolol-induced hypertension in treatment of cocaine intoxication|journal=Annals of Emergency Medicine|volume=14|issue=11|pages=1112–1113|doi=10.1016/s0196-0644(85)80934-3|pmid=4051280|issn=0196-0644}}</ref><ref>{{Cite journal|last1=Fareed|first1=Fareed N.|last2=Chan|first2=Gar|last3=Hoffman|first3=Robert S.|date=2007-12-01|title=Death temporally related to the use of a Beta adrenergic receptor antagonist in cocaine associated myocardial infarction|journal=Journal of Medical Toxicology|volume=3|issue=4|pages=169–172|issn=1556-9039|pmc=3550023|pmid=18072171|doi=10.1007/bf03160934}}</ref><ref>{{Cite journal|last1=Sand|first1=I.Charles|last2=Brody|first2=Steven L.|last3=Wrenn|first3=Keith D.|last4=Slovis|first4=Corey M.|date=1991-03-01|title=Experience with esmolol for the treatment of cocaine-associated cardiovascular complications|journal=The American Journal of Emergency Medicine|volume=9|issue=2|pages=161–163|doi=10.1016/0735-6757(91)90182-j|pmid=1671639|issn=0735-6757}}</ref><ref>{{Cite journal|last1=Lange|first1=Richard A.|last2=Cigarroa|first2=Ricardo G.|last3=Flores|first3=Eduardo D.|last4=McBride|first4=Wade|last5=Kim|first5=Anatole S.|last6=Wells|first6=Peter J.|last7=Bedotto|first7=John B.|last8=Danziger|first8=Robert S.|last9=Hillis|first9=L. David|date=1990-06-15|title=Potentiation of Cocaine-Induced Coronary Vasoconstriction by Beta-Adrenergic Blockade|journal=Annals of Internal Medicine|volume=112|issue=12|pages=897–903|doi=10.7326/0003-4819-112-12-897|pmid=1971166|issn=0003-4819}}</ref><ref>{{Cite journal|last1=Izquierdo Gómez|first1=María Manuela|last2=Domínguez-Rodríguez|first2=Alberto|last3=Gálvez Rodríguez|first3=Manuel|last4=Marrero Rodríguez|first4=Francisco|date=2009-04-01|title=Reflections on beta-adrenergic receptor blockers and cocaine use. A case in point|journal=Revista Española de Cardiología|volume=62|issue=4|pages=455–456|issn=1579-2242|pmid=19401135|doi=10.1016/s1885-5857(09)71677-9|s2cid=43245025 }}</ref> Some detractors of beta-blockers for cocaine-induced chest pain have cited minimal acute mortality and the short half-life of the medication, making it unnecessary to aggressively treat any associated tachycardia and hypertension.<ref name=":2" /><ref>{{Cite web|url=http://freeemergencytalks.net/wp-content/uploads/2011/12/1-B-1100-Update-on-Cocaine-Myocardial-Ischemia-Judd-E.-Hollander-Pennsylvania.mp3|title=Update on Cocaine Myocardial Ischemia|last=Hollander|first=Judd|date=December 28, 2011|archive-url=https://web.archive.org/web/20170111122139/http://freeemergencytalks.net/wp-content/uploads/2011/12/1-B-1100-Update-on-Cocaine-Myocardial-Ischemia-Judd-E.-Hollander-Pennsylvania.mp3|archive-date=January 11, 2017|url-status=dead}}</ref> However, the long-term effect of cocaine use and development of heart failure, with early mortality, high morbidity, and tremendous demand on hospital utilization should be taken under consideration.<ref>{{Cite journal|last1=Casartelli|first1=Alessandro|last2=Dacome|first2=Lisa|last3=Tessari|first3=Michela|last4=Pascali|first4=Jennifer|last5=Bortolotti|first5=Federica|last6=Trevisan|first6=Maria Teresa|last7=Bosco|first7=Oliviero|last8=Cristofori|first8=Patrizia|last9=Tagliaro|first9=Franco|date=2014-01-01|title=Cocaine-associated increase of atrial natriuretic peptides: an early predictor of cardiac complications in cocaine users?|journal=Heart Asia|volume=6|issue=1|pages=100–107|doi=10.1136/heartasia-2013-010482|issn=1759-1104|pmc=4832714|pmid=27326180}}</ref><ref>{{Cite journal|last1=Liaudet|first1=Lucas|last2=Calderari|first2=Belinda|last3=Pacher|first3=Pal|date=2014-11-01|title=Pathophysiological mechanisms of catecholamine and cocaine-mediated cardiotoxicity|journal=Heart Failure Reviews|volume=19|issue=6|pages=815–824|doi=10.1007/s10741-014-9418-y|issn=1573-7322|pmid=24398587|s2cid=22420796|url=http://doc.rero.ch/record/326528/files/10741_2014_Article_9418.pdf}}</ref><ref>{{Cite journal|last1=Walsh|first1=David W.|last2=McVey|first2=Molly C.|last3=Gass|first3=Abigal|last4=Zhang|first4=Jingwen|last5=Mauldin|first5=Patrick D.|last6=Rockey|first6=Don C.|date=2016-06-24|title=Identification of high resource utilizing patients on internal medicine hospital services|journal=Journal of Investigative Medicine|volume=64|issue=7|doi=10.1136/jim-2016-000118|issn=1708-8267|pmid=27342424|pages=jim–2016–000118|s2cid=4547095}}</ref>
=== Calcium channel blockers === [[Calcium channel blocker]]s may also be used to treat hypertension and coronary arterial vasoconstriction,<ref>{{Cite journal|last1=Negus|first1=Brian H.|last2=Willard|first2=John E.|last3=Hillis|first3=L.David|last4=Glamann|first4=D.Brent|last5=Landau|first5=Charles|last6=Snyder|first6=Richard W.|last7=Lange|first7=Richard A.|date=1994-03-01|title=Alleviation of cocaine-induced coronary vasoconstriction with intravenous verapamil|journal=The American Journal of Cardiology|volume=73|issue=7|pages=510–513|doi=10.1016/0002-9149(94)90684-x|pmid=8141094|issn=0002-9149}}</ref> but fail to lower tachycardia based on all cocaine-related studies.<ref name=":1" /> Non-dihydropyridine calcium channels blockers such as [[diltiazem]] and [[verapamil]] are preferable, as dihydropyridine agents such as [[nifedipine]] have much higher risk of reflex tachycardia (however, clinicians can prevent reflex tachycardia by administering beta-blockers some minutes before using the latter class of CCBs).
== Legal implications == A situation wherein a person's cognitive faculties are impaired due to cocaine use is what constitutes ''drug intoxication'' per law in much of the United States, Europe, and most of the rest of the world, and can be a serious charge depending on one's actions while intoxicated (e.g., in [[Drug–impaired driving|drug-impaired driving]]), or other circumstances surrounding the acquisition of the drug.<ref>{{Cite web|title=Driving While Intoxicated ("DWI"): Texas Law|url=https://saputo.law/criminal-law/texas/intoxication-crimes/dwi/|access-date=2021-04-11|website=SAPUTO Law|language=en-US}}</ref><ref>{{Cite web|title=Legal Dictionary - Law.com|url=https://dictionary.law.com/Default.aspx?selected=1018|access-date=2021-04-11|website=Law.com Legal Dictionary|language=en}}</ref>
== See also == * [[Cocaine Anonymous]] * [[Cocaine dependence]] * [[Cocaine-Induced Midline Destructive Lesions]] * [[Cocaine#Cocaine nose|Cocaine § Cocaine nose]] * [[Crack cocaine#Crack lung|Crack cocaine § Crack lung]] *[[List of deaths from drug overdose and intoxication]]
==References== {{Reflist}}
{{Medical resources | DiseasesDB = | ICD10 ={{ICD10|F|14|0}} | ICD9 = {{ICD9|305.6}} | ICDO = | OMIM = | MedlinePlus = 000946 | eMedicineSubj = article | eMedicineTopic = 813959 | MeshID = D019970 }} {{Psychoactive substance use}}
{{DEFAULTSORT:Cocaine Dependence}} [[Category:Cocaine|Dependence]] [[Category:Substance intoxication]] [[Category:Disorders due to use of cocaine]]