Methadone
A synthetic opioid with analgesic activity. Methadone mimics the actions of endogenous peptides at CNS opioid receptors, primarily on the mu-receptor and has actions similar to those of morphine and morphine-like agents. The characteristic morphine-like effects include analgesia, euphoria, sedation, respiratory depression, miosis, bradycardia and physical dependence. However, the detoxification symptoms between morphine-like agents and methadone differ in that the onset of methadone’s withdrawal symptoms is slower, the course is more prolonged and the symptoms are less severe.
Methadone, sold under the brand name Dolophine among others, is an opioid used for opioid maintenance therapy in opioid dependence and for chronic pain management. Detoxification using methadone can be accomplished in less than a month, or it may be done gradually over as long as six months. Wikipedia
Formula: C21H27NO
Onset of action: Rapid
Metabolism: Liver (CYP3A4, CYP2B6 and CYP2D6-mediated)
Elimination half-life: 15 to 55 hours
Excretion: Urine, faeces
Bioavailability: 15-20% subcutaneous; 100% intravenous; 41–99% (by mouth)
Common brands: Diskets, Methadone Intensol, Methadose
Narcotic
It can treat moderate to severe pain. It can also treat narcotic drug addiction.
Brands: Diskets, Methadone Intensol, Methadose, and Dolophine
Availability: Prescription needed
Pregnancy: Consult a doctor
Alcohol: Avoid. Very serious interactions can occur
Drug class: Opioid
Methadone is a synthetic opioid with analgesic activity. Methadone mimics the actions of endogenous peptides at CNS opioid receptors, primarily on the mu-receptor and has actions similar to those of morphine and morphine-like agents. The characteristic morphine-like effects include analgesia, euphoria, sedation, respiratory depression, miosis, bradycardia and physical dependence. However, the detoxification symptoms between morphine-like agents and methadone differ in that the onset of methadone’s withdrawal symptoms is slower, the course is more prolonged and the symptoms are less severe.
NCI Thesaurus (NCIt)
Source: NCI Thesaurus (NCIt)
Record Name: Methadone
Description: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.
License Note: Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
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Methadone is a DEA controlled drug and a DEA Schedule II controlled substance. Substances in the DEA Schedule II have a high potential for abuse which may lead to severe psychological or physical dependence. Methadone is classified by the DEA as a Narcotics (Opioids) drug. Street names for Methadone are Amidone, Chocolate Chip Cookies, Fizzies, Maria, Pastora, Salvia, Street Methadone, and Water.
Drug Enforcement Administration (DEA)
Source: Drug Enforcement Administration (DEA)
Record Name: Methadone
URL: https://www.dea.gov/factsheets
Description: The U.S. Drug Enforcement Administration (DEA) enforces the controlled substances laws and regulations of the United States and brings to the criminal and civil justice system of the United States, or any other competent jurisdiction, those organizations and principal members of organizations, involved in the growing, manufacture, or distribution of controlled substances appearing in or destined for illicit traffic in the United States; and to recommend and support non-enforcement programs aimed at reducing the availability of illicit controlled substances on the domestic and international markets.
License Note: Unless otherwise indicated, information on Department of Justice websites is in the public domain and may be copied and distributed without permission. Citation of the Department of Justice as source of the information is appreciated, as appropriate.
License URL: https://www.justice.gov/legalpolicies
Methadone is a synthetic opioid which is used widely as an analgesic as well as maintenance therapy for persons with opioid dependency. Patients on chronic methadone therapy for opioid dependency often have underlying chronic viral hepatitis, but methadone itself has not been linked to serum enzyme elevations during therapy or to clinically apparent liver injury.
LiverTox
Source: LiverTox
Record Name: Methadone
URL: https://www.ncbi.nlm.nih.gov/books/n/livertox/Methadone/
Description: LIVERTOX provides up-to-date, accurate, and easily accessed information on the diagnosis, cause, frequency, patterns, and management of liver injury attributable to prescription and nonprescription medications, herbals and dietary supplements.
License URL: https://www.nlm.nih.gov/copyright.html
Synonyms - MeSH Entry Terms
Amidone
Biodone
Dolophine
Hydrochloride, Methadone
Metadol
Metasedin
Methaddict
Methadone
Methadone Hydrochloride
Methadose
Methex
Phenadone
Phymet
Physeptone
Pinadone
Symoron
(source)
Depositor-Supplied Synonyms
methadone
dl-Methadone
Dolophine
Phenadone
Amidone
Adanon
Diaminon
Dolophin
Ketalgin
Methadon
Physeptone
Algovetin
Heptadone
Heptanon
Sedo-Rapide
76-99-3
Racemic methadone
Amidon
(+-)-Methadone
(+/-)-Methadone
6-(dimethylamino)-4,4-diphenylheptan-3-one
Methadonum
Heptanon (pharmaceutical)
Metadone [DCIT]
Metadona [Spanish]
Methadonum [Latin]
Methadona [Spanish]
l-Methadone
Methadone [INN:BAN]
6-Dimethylamino-4,4-diphenyl-3-heptanone
Metadona [INN-Spanish]
Methadonum [INN-Latin]
Metasedin
3-Heptanone, 6-(dimethylamino)-4,4-diphenyl-
Polamivet
Hoechst 10820
Dolophine HCL
(RS)-methadones
Althose
Eptadone
Symoron
HSDB 3119
K 174
AN 148
EINECS 200-996-9
A 4624
BRN 3213669
rac-Methadone
CHEBI:6807
DEA No. 9250
Metadone
(+/-)-Methadone hydrochloride
Metadona
Methadona
6-(Dimethylamino)-4,4-diphenyl-3-heptanone
Levometadona [INN-Spanish]
Levomethadonum [INN-Latin]
UNII-UC6VBE7V1Z
Methadone (BAN)
(R)-6-(Dimethylamino)-4,4-diphenyl-3-hetpanone
3-14-00-00279 (Beilstein Handbook Reference)
Fenadone (*Hydrochloride*)
Heptanon (*Hydrochloride*)
Dolophine (*Hydrochloride*)
Heptadone (*Hydrochloride*)
Levomethadon
Phenadone (*Hydrochloride*)
Metadon
UC6VBE7V1Z
AN-148 (*Hydrochloride*)
BRN 3213667
BRN 3213668
(plusmn)-methadone
PHY
Hoescht 10820 (*Hydrochloride*)
Mecodin (Salt/Mix)
Methadone-HCL,(-)
Polamidon (Salt/Mix)
Polamidone (Salt/Mix)
(.+/-.)-Methadone
CHEMBL651
SCHEMBL34140
3-HEPTANONE, 6-(DIMETHYLAMINO)-4,4-DIPHENYL-, (S)-
DivK1c_000963
GTPL5458
IDS-NM-002
Adanon hydrochloride (Salt/Mix)
DTXSID7023273
BDBM82507
KBio1_000963
NINDS_000963
NSC_22266
STL455106
AKOS015962259
rac-Methadone 0.1 mg/ml in Methanol
rac-Methadone 1.0 mg/ml in Methanol
DB00333
IDI1_000963
NCGC00248116-01
NCGC00248116-02
297-88-1
AC-16055
LS-74485
LS-74486
LS-74487
SC-54552
2-Dimethylamino-4,4-diphenyl-5-heptanone
CAS_5967-73-7
DB-053574
6-(dimethylamino)-4,4-diphenyl-heptan-3-one
6481-EP1441224A2
6481-EP2275420A1
6481-EP2277875A2
6481-EP2280008A2
6481-EP2298764A1
6481-EP2298765A1
6481-EP2298776A1
6481-EP2305654A1
6481-EP2308509A1
6481-EP2308872A1
6481-EP2316829A1
C07163
D08195
L000874
Q179996
3-Hetpanone, 6-(dimethylamino)-4,4-diphenyl-, (R)-
3-Heptanone, 6-(dimethylamino)-4,4-diphenyl-, (.+/-.)-
DL-6-DIMETHYLAMINO-4,4-DIPHENYL-3-HEPTANONE-1,1,1-
(+/-)-Methadone solution, 1 mg/mL in methanol, ampule of 1 mL, certified reference material
(+/-)-Methadone solution, 100 mug/mL in methanol, ampule of 1 mL, certified reference material
(source)
Methadone Interactions
Using methadone with other opioids is extremely dangerous. For instance, a methadone and oxycodone interaction can increase the risk of respiratory depression, hypotension, coma, overdose and death. The same is true for mixing methadone and hydrocodone, heroin or any other known opiates.
Important Warning
Methadone may be habit forming. Take methadone exactly as directed. Do not take a larger dose, take it more often, or take it for a longer period of time or in a different way than prescribed by your doctor. While taking methadone, discuss with your healthcare provider your pain treatment goals, length of treatment, and other ways to manage your pain. Tell your doctor if you or anyone in your family drinks or has ever drunk large amounts of alcohol, uses or has ever used street drugs, or has overused prescription medications, or if you have or have ever had depression or another mental illness. There is a greater risk that you will overuse methadone if you have or have ever had any of these conditions. Talk to your healthcare provider immediately and ask for guidance if you think that you have an opioid addiction or call the U.S. Substance Abuse and Mental Health Services Administration (SAMHSA) National Helpline at 1-800-662-HELP.
Methadone may cause serious or life-threatening breathing problems, especially during the first 24 to 72 hours of your treatment and any time your dose is increased. Your doctor will monitor you carefully during your treatment. Tell your doctor if you have or have ever had slowed breathing or asthma. Your doctor will probably tell you not to take methadone. Also tell your doctor if you have or have ever had lung disease such as chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema), a head injury, or any condition that increases the amount of pressure in your brain. The risk that you will develop breathing problems may be higher if you are an older adult or are weak or malnourished due to disease. If you experience any of the following symptoms, call your doctor immediately or get emergency medical treatment: slowed breathing, long pauses between breaths, or shortness of breath.
Taking certain other medications during your treatment with methadone may increase the risk that you will experience serious, life-threatening side effects such as breathing problems, sedation, or coma. Tell your doctor if you are taking or plan to take any of the following medications: antipsychotics such as aripiprazole (Abilify), asenapine (Saphris), cariprazine (Vraylar), chlorpromazine, clozapine (Versacloz), fluphenazine, haloperidol (Haldol), iloperidone (Fanapt), loxapine, lurasidone (Latuda), molindone, olanzapine (Zyprexa), paliperidone (Invega), perphenazine, pimavanserin (Nuplazid), quetiapine (Seroquel), risperidone (Risperdal), thioridazine, thiothixene, trifluoperazine, and ziprasidone (Geodon); benzodiazepines such as alprazolam (Xanax), chlordiazepoxide (Librium), clonazepam (Klonopin), clorazepate (Gen-Xene, Tranxene), diazepam (Diastat, Valium), estazolam, flurazepam, lorazepam (Ativan), oxazepam, temazepam (Restoril), and triazolam (Halcion); opiate (narcotic) medications for pain and cough; medications for nausea or mental illness; muscle relaxants; sedatives; sleeping pills; or tranquilizers. Your doctor may need to change the doses of your medications and will monitor you carefully. If you take methadone with any of these medications and you develop any of the following symptoms, call your doctor immediately or seek emergency medical care: unusual dizziness, lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness. Be sure that your caregiver or family members know which symptoms may be serious so they can call the doctor or emergency medical care if you are unable to seek treatment on your own.
Drinking alcohol, taking prescription or nonprescription medications that contain alcohol, or using street drugs during your treatment with methadone increases the risk that you will experience serious, life-threatening side effects. Do not drink alcohol, take prescription or nonprescription medications that contain alcohol, or use street drugs during your treatment.
Do not allow anyone else to take your medication. Methadone may harm or cause death to other people who take your medication, especially children. Store methadone in a safe place so that no one else can take it accidentally or on purpose. Be especially careful to keep methadone out of the reach of children. Keep track of how many tablets or how much liquid is left so you will know if any medication is missing. Dispose of any unwanted methadone tablets or oral solution properly according to instructions. (See STORAGE and DISPOSAL.)
Methadone may cause a prolonged QT interval (a rare heart problem that may cause irregular heartbeat, fainting, or sudden death). Tell your doctor if you or anyone in your family has or has ever had long QT syndrome; or if you have or ever had a slow or irregular heartbeat; low blood levels of potassium or magnesium, or heart disease. Tell your doctor and pharmacist if you are taking or plan to take any of the following medications: antidepressants such as amitriptyline, amoxapine, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil); certain antifungals such as fluconazole (Diflucan), itraconazole (Onmel, Sporanox), ketoconazole, and voriconazole (Vfend); diuretics (‘water pills’); erythromycin (Eryc, Erythrocin, others); fludrocortisone; certain laxatives; medications for irregular heartbeat such as amiodarone (Nexterone, Pacerone), disopyramide (Norpace), dofetilide (Tikosyn), flecainide, ibutilide (Corvert), procainamide, and quinidine (in Nuedexta); nicardipine (Cardene); and risperidone (Risperdal); and sertraline (Zoloft). If you experience any of the following symptoms, call your doctor immediately: pounding heartbeat, dizziness, lightheadedness, or fainting.
Tell your doctor if you are pregnant or plan to become pregnant. If you take methadone regularly during your pregnancy, your baby may experience life-threatening withdrawal symptoms after birth. Tell your baby’s doctor right away if your baby experiences any of the following symptoms: irritability, hyperactivity, abnormal sleep, high-pitched cry, uncontrollable shaking of a part of the body, vomiting, diarrhea, or failure to gain weight.
Talk to your doctor about the risks of taking methadone for your condition.
Your doctor or pharmacist will give you the manufacturer’s patient information sheet (Medication Guide) when you begin treatment with methadone and each time you fill your prescription if a Medication Guide is available for the methadone product you are taking. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer’s website to obtain the Medication Guide.
Use of methadone to treat opiate addiction:
If you have been addicted to an opiate (narcotic drug such as heroin), and you are taking methadone to help you stop taking or continue not taking the drug, you must enroll in a treatment program. The treatment program must be approved by the state and federal governments and must treat patients according to specific federal laws. You may have to take your medication at the treatment program facility under the supervision of the program staff. Ask your doctor or the treatment program staff if you have any questions about enrolling in the program or taking or getting your medication.
What side effects can this medication cause?
Methadone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
headache
weight gain
stomach pain
dry mouth
sore tongue
flushing
difficulty urinating
mood changes
vision problems
difficulty falling asleep or staying asleep
Some side effects can be serious. If you experience any of the following symptoms or those mentioned in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical help:
seizures
itching
hives
rash
swelling of the eyes, face, mouth, tongue, or throat
hoarseness
difficulty breathing or swallowing
extreme drowsiness
agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination, nausea, vomiting, or diarrhea
nausea, vomiting, loss of appetite, weakness, or dizziness
inability to get or keep an erection
irregular menstruation
decreased sexual desire
Methadone may cause other side effects. Call your doctor if you have any unusual problems while you are taking this medication.
In case of emergency/overdose
In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call emergency services at 911.
While you are taking methadone, you may be told to always have a rescue medication called naloxone available (e.g., home, office). Naloxone is used to reverse the life-threatening effects of an overdose. It works by blocking the effects of opiates to relieve dangerous symptoms caused by high levels of opiates in the blood. You will probably be unable to treat yourself if you experience an opiate overdose. You should make sure that your family members, caregivers, or the people who spend time with you know how to tell if you are experiencing an overdose, how to use naloxone, and what to do until emergency medical help arrives. Your doctor or pharmacist will show you and your family members how to use the medication. Ask your pharmacist for the instructions or visit the manufacturer’s website to get the instructions. If someone sees that you are experiencing symptoms of an overdose, he or she should give you your first dose of naloxone, call 911 immediately, and stay with you and watch you closely until emergency medical help arrives. Your symptoms may return within a few minutes after you receive naloxone. If your symptoms return, the person should give you another dose of naloxone. Additional doses may be given every 2 to 3 minutes, if symptoms return before medical help arrives.
Symptoms of overdose may include the following:
small, pinpoint pupils (black circles in the center of the eyes)
slow or shallow breathing
drowsiness
cool, clammy, or blue skin
loss of consciousness (coma)
limp muscles
What other information should I know?
Keep all appointments with your doctor or clinic. Your doctor may order certain lab tests to check your response to methadone.
Before having any laboratory test (especially those that involve methylene blue), tell your doctor and the laboratory personnel that you are taking methadone.
This prescription is not refillable. If you continue to experience pain after you finish taking the methadone, call your doctor. If you take this medication on a regular basis, be sure to schedule appointments with your doctor so that you do not run out of medication.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
(source)
LABEL: methadone- methadone hydrochloride injection, solution
Description:
Methadone Hydrochloride Injection, USP, 10 mg/mL is an opioid analgesic.
Each milliliter of Methadone Hydrochloride Injection contains 10 mg (0.029 mmol) of methadone hydrochloride, equivalent to 8.95 mg of methadone free base.
Methadone hydrochloride is a white, crystalline material that is water-soluble.
Methadone hydrochloride is chemically described as 6-(dimethylamino)-4,4-diphenyl-3-hepatanone hydrochloride. Its molecular formula is C21H27NO•HCl and it has a molecular weight of 345.91. Methadone hydrochloride has a melting point of 235° C, and a pKa of 8.25 in water at 20°C. Its octanol/water partition coefficient at pH 7.4 is 117. A solution (1:100) in water has a pH between 4.5 and 6.5.
It has the following structural formula:
Methadone Hydrochloride Injection is a sterile injectable solution containing the following inactive ingredients: chlorobutanol, 0.5%, as a preservative, and sodium chloride. The pH of the sterile injectable solution may have been adjusted during manufacturing with sodium hydroxide and/or hydrochloric acid.
Indication and usage
For the treatment of moderate to severe pain not responsive to non-narcotic analgesics.
For use in temporary treatment of opioid dependence in patients unable to take oral medication.
Outpatient maintenance and outpatient detoxification treatment may be provided only by opioid treatment programs (OTPs) certified by the Federal Substance Abuse and Mental Health Services Administration (SAMHSA) and registered by the Drug Enforcement Administration (DEA). This does not preclude the maintenance treatment of a patient with concurrent opioid addiction who is hospitalized for conditions other than opioid addiction and who requires temporary maintenance during the critical period of hospitalization, or of a patient whose enrollment has been verified in a program which has been certified for maintenance treatment with methadone.
NOTE: INJECTABLE METHADONE PRODUCTS ARE NOT APPROVED FOR THE OUTPATIENT TREATMENT OF OPIOID DEPENDENCE. IN THIS PATIENT POPULATION, PARENTERAL METHADONE IS TO BE USED ONLY FOR PATIENTS UNABLE TO TAKE ORAL MEDICATION, SUCH AS HOSPITALIZED PATIENTS
Drug abuse and dependence
Methadone is a μ-agonist opioid with an abuse liability similar to that of morphine and is a Schedule II controlled substance. Methadone, like morphine and other opioids used for analgesia, has the potential for being abused and is subject to criminal diversion.
Abuse
Drug addiction is characterized by a preoccupation with the procurement, hoarding, and abuse of drugs for non-medicinal purposes. Drug addiction is treatable, utilizing a multi-disciplinary approach, but relapse is common.
“Drug seeking” behavior is very common to addicts and drug abusers. Drug seeking tactics include emergency calls or visits near the end of the office hours, refusal to undergo appropriate examination, testing or referral, repeated claims of loss of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). Doctor shopping (visiting multiple prescribers) to obtain additional prescriptions is common among drug abusers and people suffering from untreated addictions.
Physical Dependence and Tolerance
Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. Methadone Hydrochloride Injection, like other opioids, may be diverted for non-medical use. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised.
Abuse of Methadone Hydrochloride Injection poses a risk of overdose and death. This risk is increased with concurrent abuse of Methadone Hydrochloride Injection with alcohol and other substances. In addition, parenteral drug abuse is commonly associated with transmission of infectious disease such as hepatitis and HIV.
Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.
Infants born to mothers physically dependent on opioids may also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms.
(source)
In the news
Middletown methadone clinic proposal draws mixed reaction
Covid-19 has freed opioid addiction patients from daily methadone clinic visits
https://qz.com/1889461/covid-19-has-forced-a-relaxation-of-methadone-rules/
Study: Methadone Dosing Needs to be More Precise
Methadone Patients’ Data Poised to Be Entered Into PDMPs
https://filtermag.org/methadone-patients-prescription-drug-monitoring/
Methadone FAQ
Does methadone mess with your heart?
The main cardiac effects of methadone include prolongation of QT interval and torsade de pointes. Other effects include changes in QT dispersion, pathological U waves, Taku-Tsubo syndrome (stress cardiomyopathy), Brugada-like syndrome, and coronary artery diseases.
How often can you take methadone?
When methadone is used to relieve pain, it may be taken every 8 to 12 hours. If you take methadone as part of a treatment program, your doctor will prescribe the dosing schedule that is best for you.
What foods interact with methadone?
Grapefruit juice can increase the blood levels and effects of methadone. If you regularly consume grapefruits or grapefruit juice, you should be monitored for side effects and/or changes in methadone levels. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.
What anxiety medicine is safe to take with methadone?
If you have anxiety while taking methadone, you have options for reducing your symptoms.
Benzodiazepine medications for anxiety include:
Alprazolam (Xanax®)
Diazepam (Valium®)
Clonazepam (Klonopin®)
Lorazepam (Ativan®)
Chlordiazepoxide (Librium®)
Oxazepam (Serax®)
What should you not take with methadone?
Using methadone with other opioids is extremely dangerous. For instance, a methadone and oxycodone interaction can increase the risk of respiratory depression, hypotension, coma, overdose and death. The same is true for mixing methadone and hydrocodone, heroin or any other known opiates.
How often can you take methadone?
When methadone is used to relieve pain, it may be taken every 8 to 12 hours. If you take methadone as part of a treatment program, your doctor will prescribe the dosing schedule that is best for you.
What medications interact with methadone?
Moderate Interactions
LEVOMETHADONE; METHADONE/FLUVOXAMINE.
SELECTED OPIOID ANALGESICS/CIMETIDINE.
LEVOMETHADONE; METHADONE/POSSIBLE QT PROLONGING AGENTS.
LEVOMETHADONE; METHADONE/EFAVIRENZ; NEVIRAPINE.
LEVOMETHADONE; METHADONE/NELFINAVIR; RITONAVIR; TELAPREVIR.
SELECTED OPIOIDS/PHENOBARBITAL; PRIMIDONE.
Does methadone mess with your heart?
The main cardiac effects of methadone include prolongation of QT interval and torsade de pointes. Other effects include changes in QT dispersion, pathological U waves, Taku-Tsubo syndrome (stress cardiomyopathy), Brugada-like syndrome, and coronary artery diseases.