Methadone , sold under the brand name Dolophine , among others, is an opioid used to treat pain and as a maintenance therapy or to help taper in people with opioid dependence. Detoxification using methadone can be done relatively quickly in less than a month or gradually over a period of six months. While a single dose has a rapid effect, the maximum effect can take five days. The pain-relieving effect lasts about six hours after a single dose, similar to morphine. After long-term use, in people with normal liver function, the effect lasts 8 to 36 hours. Methadone is usually taken and rarely by injection into the muscles or veins.
Side effects are similar to other opioids. Usually this includes dizziness, drowsiness, vomiting, and sweating. Serious risks include opioid abuse and decreased attempts to breathe. An abnormal heart rhythm may also occur due to prolonged QT intervals. The number of deaths in the United States involving methadone poisoning decreased from 4,418 in 2011 to 3,300 by 2015. The risk is greater with higher doses. Methadone is made by chemical synthesis and acts on opioid receptors.
Methadone was developed in Germany from 1937 to 1939 by Gustav Ehrhart and Max BockmÃÆ'¼hl. It was approved for use in the United States in 1947. Methadone is on the World Health Organization's Essential Medicines List, the most effective and safe medication needed in the health system. Globally by 2013, about 41,400 kilograms are produced. This is set the same as other narcotic drugs. It's not too expensive in the United States.
Video Methadone
Medical use
Methadone maintenance
Methadone is used for the treatment of opioid dependence. It may be used as a long-term maintenance therapy or in a shorter period for detoxification without withdrawal symptoms.
The Cochrane Review of 2009 found that methadone is effective in keeping people in the treatment and the reduction or discontinuation of heroin use as measured by self-report and urine/hair analysis but does not affect criminal activity or the risk of death.
The treatment of people who depend on opioids with methadone will follow one of two routes. Methadone maintenance therapy (MMT) usually occurs as an outpatient. It is prescribed once or twice a day for those who want to distance themselves from drug use.
The duration of methadone treatment ranges from a few months to several years, or even a lifetime. Methadone reduction, called detoxification, is suitable for people who really want to stop taking drugs. The length of time a person remains in care depends on a number of factors. The initial dose depends on the type and amount of medication used at the onset of treatment. It also depends on how long the person has been using drugs and methods (ie oral, inhalation, or injected).
In addition, enrollment in methadone maintenance has the potential to reduce transmission of infectious diseases associated with opiate injection, such as hepatitis B and C, and/or HIV. The main goal of methadone maintenance is to reduce craving desire, suppress abstinence syndrome, and block the euphoric effects associated with opioids.
Both methadone abuse and legally determined use will ultimately lead to dependence. However, when used properly in care, maintenance therapy has been found to be medically safe, non-soothing, and can provide a slow recovery from opioid addiction. It is also indicated for pregnant women addicted to opioids.
Pain
Methadone is used as an analgesic in chronic pain. Because of its activity in NMDA receptors, it may be more effective against neuropathic pain; for the same reason, tolerance for analgesic effects may be less than other opioids.
People with long-term pain sometimes have to do what is called an opioid rotation . Opioid rotation involves switching from one opioid to another, usually at intervals of several weeks, or more commonly, several months. Opioid rotation allows lower equivalent doses, and therefore fewer side effects are likely to be found to achieve the desired effect. Then, over time, tolerance increases with new opioids, requiring higher doses. This, in turn, increases the likelihood of adverse reactions and toxicities. Then it's time to roll back to another opioid. Such opioid rotation is a standard practice for managing people with the development of tolerance. Usually when doing opioid rotation, a person can not get down to a completely naive dose, since there is cross-tolerance brought into a new opioid. Compared to other opioids, methadone has a lower cross tolerance when switching to other opioids. This means that methadone can start with a relatively lower dose than other opiates, and the time for subsequent changes will be longer.
Opioid Detox
Methadone is approved in the US, and many other parts of the world, for the treatment of opioid addiction. Its use for the treatment of addiction is usually strictly regulated. In the US, outpatient treatment programs must be certified by the Federal Substance Abuse and Mental Health Services Administration (SAMHSA) and registered by the Drug Enforcement Administration (DEA) to prescribe methadone for opioid addiction.
Maps Methadone
Adverse effects
On November 29, 2006, the US Food and Drug Administration issued a Public Health Adviser on methadone entitled "The Use of Methadone for Pain Control can Produce Changes That Threaten Death and Life That Threatens Respiratory and Cardiac Beating". The counselor said that "the FDA has received death reports and life-threatening side effects in patients taking methadone.These deaths and life-threatening side effects occur in patients who are just starting methadone to control pain and in patients who switch to methadone after being treated for pain with other potent opioid pain relievers Methadone may cause slow or shallow breathing and dangerous changes in the heartbeat that the patient may not feel. "The counsel urges doctors to be careful when prescribing methadone to people unfamiliar with drugs and that people take drugs exactly as directed.
Methadone side effects include:
- Sedasi
- Diarrhea or constipation
- Flushing
- Sweat and sweat
- Hot intolerance
- Dizziness or fainting
- Weakness
- Chronic fatigue, sleepiness and fatigue
- Sleep problems such as drowsiness, insomnia, and difficulty sleeping well
- Students are limited
- Dry mouth
- Nausea and vomiting
- Low blood pressure
- Hallucinations or confusion
- Headaches
- Heart problems such as chest pain or rapid/pounding heartbeat
- Abnormal heart rhythm
- Respiratory problems such as difficulty breathing, slow or shallow breathing (hypoventilation), slight dizziness, or fainting
- Loss of appetite, and in extreme cases of anorexia
- Weight
- Memory loss
- Abdominal pain
- Itch
- Difficulty urinating
- Swelling of hands, arms, legs, and feet
- Feeling uneasy or anxious
- Mood swings, euphoria, disorientation
- Nervous or anxious
- Blurred vision
- Libido decreases, menstrual periods are lost, difficulty reaching orgasm, or impotence
- Skin rash
- Seizures
- Sleep sleep apnea
Withdrawal symptoms
Physical symptoms
- Lightheadedness
- Rip the eye
- Mydriasis (dilated pupil)
- Photophobia (sensitivity to light)
- Hyperventilation syndrome (deep/deep breathing)
- Nose runny
- Yawning
- Sneeze
- Nausea, vomiting, and diarrhea
- Fever
- Sweating
- Chilling
- Tremor
- Akathisia (restless)
- Tachycardia (rapid heartbeat)
- Pain and pain, often in joints or feet
- Increased pain sensitivity
- Extremely high blood pressure (hypertension, can cause stroke)
Cognitive Symptoms
- Idea suicide
- Vulnerability to cravings
- Depression
- spontaneous orgasm
- Prolonged insomnia
- Delirium
- Hallucinations of hearing
- Visual hallucinations
- Increased perception odor (olfaction), real or shadow
- Mark the drop in or increase sex drive
- Agitation
- Anxiety
- Panic disorder
- Nervous
- Paranoia
- Delusions
- Apati
- Anorexia (symptoms)
Symptoms of methadone withdrawal were reported to be significantly more protracted than withdrawal from opioids with shorter half-lives.
Methadone is sometimes given as an oral solution. Methadone has been involved in contributing to significant tooth decay. Methadone causes dry mouth, reducing the protective role of saliva in preventing decay. Other putative mechanisms of methadone-related tooth decay include a desire for opioid-related carbohydrates, poor dental care, and a general decline in personal hygiene. These factors, combined with sedation, have been linked to the causes of extensive tooth decay.
Overdose
Most people who overdose methadone may show some of the following symptoms:
- Miosis (limited pupil)
- Vomit
- Hypoventilation (breathing is too slow/shallow)
- Drowsiness, drowsiness, disorientation, sedation, unresponsiveness
- Cold, moist (wet), and pale skin
- Muscle weakness, difficulty staying awake, nausea
- Unconscious and comma
- Off
Overdose respiratory depression may be treated with naloxone. Naloxone is preferred over longer-acting antagonist naltrexone. Although the duration of methadone is much longer compared to heroin and other short-acting agonists, and the need for repeated doses of naloxone antagonists, is still used for overdose therapy. Since naltrexone has a longer half-life, it is more difficult to do the titration. If too large doses of opioid antagonists are given to dependent people, it will produce withdrawal symptoms (may be severe). When using naloxone, naloxone will be rapidly removed and withdrawal will be short. The dose of naltrexone takes longer to be removed from the person's system. A common problem in treating methadone overdose is that, given the short course of naloxone (compared to longer-acting methadone), the dose of naloxone administered to people who overdose with methadone initially will work to bring people out of overdose, but once naloxone fades, if no naloxone is given, one can return to an overdose (based on time and dose of digestible methadone).
Tolerance and dependency
Like other opioid drugs, tolerance and dependence usually develop with repeated doses. There is some clinical evidence that tolerance to analgesia is less than methadone compared to other opioids; this may be due to its activity in NMDA receptors. Tolerance to various methadone physiological effects varies; Tolerance to analgesic properties may or may not develop rapidly, but tolerance to euphoria usually develops rapidly, while tolerance for constipation, sedation, and respiratory depression develops slowly (if ever).
Driving
Methadone treatments may impair driving ability. Drug users are significantly more involved in serious accidents than non-abusers in a study by the University of Queensland. In a study of a group of 220 drug users, most of them were drug abusers, 17 were involved in accidents that killed people, compared to a control group of randomly selected people not involved in fatal accidents. However, there are some studies that verify the patient's ability to maintain methadone for driving. In the UK, people prescribed Oral Methadone may continue to drive after they have satisfactorily completed an independent medical examination that will include a screen of urine for drugs. Licenses will be issued for 12 months at a time and even later, only after a favorable assessment of their own physician. Individuals prescribed methadone for IV or IM administration can not drive in the UK, mainly because of the increased sedation effects that can lead to this route of use.
Mortality
In the United States, deaths associated with methadone more than quadrupled in the five-year period between 1999 and 2004. According to the US National Center for Health Statistics, as well as the 2006 series in Charleston Gazette (West Virginia), medical examiners listed methadone as the cause of 3,849 deaths in 2004. That number rose from 790 in 1999. About 82 percent of these deaths were registered as accidents, and most deaths involved a combination of methadone with other drugs (especially benzodiazepines).
Although methadone deaths are on the rise, methadone-related deaths are not caused primarily by methadone for methadone treatment programs, according to an expert panel compiled by Substance Abuse and Mental Health Services Administration, which released a report entitled "Methadone Mortality Related, National Assessment Report". The consensus report concludes that "although the data remains incomplete, participants in the National Assessment meeting agree that methadone or diskettes distributed through channels other than opioid treatment programs are likely to be a major factor in methadone-related deaths."
In 2006, the US Food and Drug Administration issued a warning about methadone, titled "Methadone Usage for Pain Control May Cause Death." The FDA also revised the package of drugs that were included. This change removes previous information about the usual adult dose. The Charleston Gazette reported, "The old language of 'usual adult dose' is potentially lethal, according to a specialist in pain."
Detection in biological fluid
Methadone and its main metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), are often measured in the urine as part of a drug abusive testing program, in plasma or serum to confirm the diagnosis of poisoning in homicide victims sick, or with whole blood to assist in a traffic forensic investigation or other criminal offense or sudden death case. The history of methadone use considered to interpret results as chronic users may develop dose tolerance that would paralyze naive-opioid individuals. Chronic users often have high baseline values ​​of methadone and EDDP.
Pharmacology
Methadone acts by binding to μ-opioid receptors, but also has some affinity for the ionotropic NMOT glutamate receptor. Methadone is metabolized by CYP3A4, CYP2B6, CYP2D6 and is a substrate for P-glycoprotein in the gut and brain protein. Bioavailability and the elimination of the half-life of methadone depend on large inter-individual variability. The main route of administration is oral. Side effects include sedation, hypoventilation, constipation and miosis, in addition to tolerance, dependence and difficulty withdrawal. The withdrawal period can be much longer compared to other opioids, spanning anywhere from two weeks to several months. Many factors contribute to the rate of metabolism and excretion including individual body weight, history of use/abuse, metabolic dysfunction, renal system dysfunction, among others.
Metabolism of methadone life's life is different from its duration of action. Metabolic half-life is 8 to 59 hours (about 24 hours for opioid-tolerant people, and 55 hours in naive-opioid people), compared with half the life of 1 to 5 hours for morphine. The long half-life of methadone makes it possible to exhibit the effects of respiratory depression for long periods of time in naive-opioid people.
Action mechanism
Levomethadone (the R enantiomer) is a receptor-opioid agonist with higher intrinsic activity than morphine, but its affinity is lower. Dextromethadone (enantiomer S ) does not affect opioid receptors but binds to glutamatergic NMDA (N-methyl-D-aspartate) receptors, and thus acts as a receptor antagonist to glutamate. Methadone has been shown to reduce neuropathic pain in mouse models, especially through NMDA antagonism. Glutamate is a major excitation neurotransmitter on CNS. The NMDA receptors have a very important role in long-range excitation modulation and memory formation. NMDA antagonists such as dextromethorphan (DXM), ketamine (dissociative anesthesia), tiletamine (anesthesia of animals) and ibogaine (from the African tree Tabernanthe iboga ) are being studied for their role in reducing the development of opioid tolerance and possibly to eliminate addiction/tolerance/withdrawal, possibly by interrupting the memory circuit. Acting as an NMDA antagonist can be one of the mechanisms by which methadone decreases the desire for opioid and tolerance, and has been suggested as a possible mechanism for its prominent efficacy regarding the treatment of neuropathic pain. The dextrorotary form (d-methadone), which acts as an NMDA antagonist and without opioid activity, has been shown to produce analgesia in chronic pain experimental models. Methadone also acts as a potent, uncompetitive acetylcholine acetylcholine nicotine receptor antagonist? In rat receptors, expressed in human embryonic kidney cell lines.
Metabolism
Methadone has a slow metabolism and very high fat solubility, making it more durable than morphine-based drugs. Methadone has a typical elimination half-life of 15 to 60 hours with an average of about 22. However, the metabolic rate varies greatly between individuals, up to a factor of 100, ranging from at least 4 hours to as many as 130 hours, or even 190 hours. This variability appears to be due to genetic variability in the production of cytochrome enzymes associated with CYP3A4, CYP2B6 and CYP2D6. Many substances can also induce, inhibit or compete with these enzymes further affect the (sometimes harmful) part-time methadone. The longer half-life often allows for a one-time administration only once in the Opioid detox and maintenance program. People who metabolize methadone rapidly, on the other hand, may require twice-daily doses to get a moderate reduction of symptoms while avoiding excessive peaks and troughs in their blood concentrations and their associated effects. It can also allow lower dosage amounts in some such people. The analgesic activity is shorter than the pharmacological beak; dose to control the pain usually requires several doses per day usually dividing the daily dose for administration at an interval of 8 hours.
The main metabolic pathway involves N -demethylation by CYP3A4 in the liver and intestines to provide 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). This inactive product, as well as the inactive 2-ethyl-5-methyl-3,3-diphenyl-1-pyrrolidium (EMDP), produced by N -demethylation, can be detected in the urine. of those taking methadone. Methadone and its two main metabolites Administrative route
The most common administrative route in a methadone clinic is a racemic oral solution, although in Germany, only the R enantiomer (optical isomer L) has traditionally been used, as it is responsible for most of the desired opioid effect. Single-isomer forms become less common because of higher production costs.
Methadone is available in traditional pills, sublingual tablets, and two different formulations designed for people who drink. Drinkable forms include flue-free liquids (sold in the United States as Methadose), and "Diskettes" which are tablets designed to disperse rapidly in water for oral administration, used in a manner similar to Alka-Seltzer. The liquid form is the most common because it allows for smaller dose changes. Methadone is almost as effective when administered orally as with injections. In fact, methadone injections do not produce "rushes" as with some other powerful opioids such as morphine or hydromorphones, because the extremely high volume of distribution causes them to spread to other tissues in the body, especially fat tissue; the peak concentration in the blood is achieved at about the same time, whether the drug is injected or swallowed. Oral drugs are usually preferred because they offer safety, simplicity and represent a step away from substance-based injection abuse in those who are recovering from addiction. US federal regulations require an oral form in an addiction treatment program. Injecting a methadone pill may cause a collapsing vein, bruises, swelling, and possibly other harmful effects. Methadone pills often contain talc which, when injected, produces a bunch of small solid particles in the blood, causing many small blood clots. These particles can not be filtered before the injection, and will accumulate in the body over time, especially in the lungs and eyes, resulting in various complications such as pulmonary hypertension, irreversible and progressive disease. Formulations sold under the trademark Methadose (fluid-scented liquid suspensions for oral doses, usually used for maintenance purposes) should not be injected. Although it has been performed in very dilute concentrations, cardiac arrest events have been reported, as well as damaged blood vessels of sugar (even sugar free syrup can cause this damage due to the presence of artificial sweeteners that are harmful). US federal regulations require an oral form in an addiction treatment program.
Information leaflets included in British methadone tablet packaging state that tablets only for oral use and those used by other routes may cause serious harm. In addition to these warnings, additives have now been incorporated into tablet formulations to make their use by route IV more difficult.
History
Methadone was developed in 1937 in Germany by scientists working for I.G. Farbenindustrie AG in Farbwerke Hoechst who is looking for synthetic opioids that can be made with available precursors, to solve the problem of German opium shortage. On September 11, 1941 BockmÃÆ'¼hl and Ehrhart applied for a patent for a synthetic substance they called Hoechst 10820 or Polamidon (a name still used regularly in Germany) and its structure had little relation to opio morphine or alkaloids. (BockmÃÆ'¼hl and Ehrhart, 1949) It was brought to market in 1943 and was widely used by German soldiers during World War II.
In the 1930s, meperidine began to be produced in Germany; However, the production of methadone, then developed under the appointment of Hoechst 10820, was not brought forward due to the side effects found in the initial study. After the war, all German patents, trade names and research records were taken over and taken over by the Allies. Notes on research work I.G. Farbenkonzern at Farbwerke Hoechst was seized by the US Department of Commerce Intelligence, investigated by the US Department of State Technical Industry Committee and then taken to the United States. The report published by the committee notes that although methadone has the potential to cause addiction, it produces less sedation and respiratory depression than morphine and is thus attractive as a commercial drug.
In the early 1950s, methadone (most often a mixture of racemic HCl salts) was also investigated for use as antitrust.
From this study it came generally uncontrolled - or controlled to have the same precursors and effects of pure agonist agonists of an open chain type, this one a phenaloxam derivative, levopropoxyphene with optical isomerism and one that appears to have no narcotics. but antitussive nature that does have a dissociative effect if abused; the form of the isomers removed from the racemic salts produces dextromethorphan, or removes other isomers to purify dextropropoxyphene, or leave it to complete with a mixture of racemic dimethorphan salts. Open-chain opioids tend to have at least one isomer that is to some extent a pure opioid prescription drug that is strong.
Isomethadone, noracymethadol, LAAM, and normethadone were first developed in Germany, England, Belgium, Austria, Canada, and the United States within thirty years after the invention of petidin in 1937, the first synthetic opioid used in medicine, extending and increasing the length and depth of satiety opiates cravings and produces very strong analgesia (long metabolic half-life and strong receptor affinity in your opioid receptors, thus providing the full satiety and anti-addictive effects of methadone) by suppressing drug cravings and discovery in the early 1950s. antitussive properties of methadone were first tested in dogs in Europe in 1952-1955 with different inert placebo, active placebo such as codeine.
It was not until 1947 that the drug was given a generic name of "methadone" by the Council of Pharmacy and Chemistry of the American Medical Association. Due to the patent of I.G. Farbenkonzern and Farbwerke Hoechst are no longer protected any pharmaceutical company interested in that formula can buy the rights to commercial production of methadone for only a dollar (MOLL 1990).
Methadone was introduced to the United States in 1947 by Eli Lilly and Company as an analgesic under the trade name Dolophine, now registered with Roxane Laboratories. Since then, he is well known for his use in treating opioid dependence. Many anecdotal evidence is available "on the road" that methadone may prove to be effective in treating withdrawal of heroin and not infrequently used in hospitals and other dependency deprivation centers to increase complete opioid withdrawal rates. It was not until the study was conducted at Rockefeller University in New York City by Professor Vincent Dole, along with Marie Nyswander and Mary Jeanne Kreek, that methadone is systematically studied as potential substitution therapy. Their study introduces major changes in the notion that drug addiction does not necessarily defect simple characters, but rather a nuisance that must be treated in the same way as other diseases. To date, methadone maintenance therapy is the most systematically studied and most successful, and most politically polarized, of any pharmacotherapy for the treatment of people with drug addiction.
Methadone was first produced in the US by Eli Lilly, who obtained FDA approval on August 14, 1947, for Dolophine 5 mg and 10 mg Tablets. Mallinckrodt Pharmaceuticals received no approval until December 15, 1947 to produce their mass-forming powder. Mallinckrodt received approval for their branded generic, Methadose, on April 15, 1993 for their 5 mg and 10 mg Methadose Tablets. Mallinckrodt which also makes 5 mg mg, 10 mg and 40 mg in addition to their branded generic Methadose received approval for their regular tablets on April 27, 2004.
The trade name Dolophine was made by Eli Lilly after World War II and was used in the United States; claims that Nazi leader Adolf Hitler ordered the manufacture of methadone or that the brand name 'Dolophine' named after him was an urban legend. The term degrading "adolphine" (never a widely used name for medicine) appeared in the United States in the early 1970s as a reference to the urban myth above that the Dolophine trade name was a reference to Adolf Hitler.
Society and culture
Brand name
The brand names include Dolophine, Symoron, Amidone, Methadose, Physeptone, and Heptadon among others.
Cost
Metadon maintenance care
Methadone care clinics in the US are charged from $ 5 to $ 400 per week, which may be covered by private insurance or Medicaid.
In Germany, methadone maintenance (MMT) care is fully covered by all public and private insurance plans. The annual cost per person is less than 3000 euros, while the cost of heroin-assisted care reaches 10,000 euros per year.
The MMT cost analysis often compares the cost of clinic visits versus overall social costs of using illicit opioids.
By 2015 China has the largest methadone maintenance maintenance program with more than 250,000 people in more than 650 clinics in 27 provinces.
Medication
In the US, generic methadone tablets are not too expensive. The retail price ranges between $ 0.25 and $ 2.50 per specified daily dose. Branded methadone tablets can be more expensive.
Controversy
Substitution of methadone as a treatment of opioid addiction has been widely criticized in the social sciences because of its role in social control of addicts. It is recommended that methadone does not work much to curb addiction to divert it and retain dependence on official channels. Some authors apply Foucauldian's analysis of widespread prescription drugs and are used in institutions such as prisons, hospitals and rehabilitation centers. Such criticism centers on the idea that substance addiction is framed by disease models. Thus methadone, which mimics the effects of opioids and makes it addictive, is labeled as "treatment" and thus obscures the purpose of "managing undesirable" disciplines.
Rule
Methadone is a regulated substance of my Schedule in Canada and Schedule II in the United States, with ACSCN 9250 and an aggregate production quota of 31,875 kilos for sale. Methadone intermediate is also controlled, under ACSCN 9226 also under Schedule II, with a quota of 38,875 kilos. In most countries of the world, methadone is also limited. Methadone salts used were hydrobromide (free conversion ratio 0.793), hydrochloride (0.894), and HCl monohydrate (0.850). Methadone is also regulated internationally as a regulated substance. My schedule is controlled under the United Nations Single Convention on Drugs of 1961.
In Russia, methadone treatment is illegal. Gennadiy Onishchenko, Chief Inspector of Sanitation, claimed in 2008 that health workers were unsure about the efficacy of treatment. Instead, doctors encourage immediate cessation of drug use, rather than a gradual process that requires methadone substitution therapy. People are often given sedative and non-opioid analgesics to overcome withdrawal symptoms.
References
External links
- Methadone: Treatment and Treatment of Counseling, Substance Abuse and Mental Health Services, US Department of Health and Human Services
- Tapered from methadone maintenance
Source of the article : Wikipedia
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