Naltrexone , sold under the trademark of ReVia and Vivitrol among others, are drugs primarily used to manage alcohol or opioid dependence. The opioid-dependent person should not receive naltrexone prior to detoxification. This is taken by mouth or by injection into the muscle. The effect starts in 30 minutes. However, a decreasing desire for opioids can take several weeks.
Side effects may include difficulty sleeping, anxiety, nausea, and headaches. In those still using opioids, withdrawal of opioids may occur. Use is not recommended in people with liver failure. It is unclear whether the use is safe during pregnancy. Naltrexone is an opioid antagonist and works by blocking the effects of opioids, both from within and outside the body.
Naltrexone was first created in 1965 and approved for medical use in the United States in 1984. By 2017, the wholesale cost of tablets is about US $ 0.74 per day in the US. The cost-extension injections cost around $ 1,267 per month ($ 41.20 per day). Naltrexone, like bupropion/naltrexone, is also used to treat obesity.
Video Naltrexone
Medical use
Alcoholism
Naltrexone is best studied as a treatment for alcoholism. Naltrexone has been shown to decrease the amount and frequency of drinking. It does not seem to change the percentage of people who drink. The overall benefits have been described as "simple".
Acamprosate may work better than naltrexone to eliminate drinking, while naltrexone may lower the desire for alcohol to a greater extent.
The Sinclair method is a method of using opiate antagonists such as naltrexone to treat alcoholism. People take medication about one hour (and only later) before drinking to avoid side effects arising from chronic use. Opioid antagonists block the positive effects of alcohol and allow people to stop or reduce drinking.
Opioid use
Long-term injectable naltrexone decreases heroin use more than placebo. It has more benefits than methadone and buprenorphine in this case is not a restricted drug. This can reduce the desire for opioids after a few weeks, and reduce the risk of overdose. It is given once a month and has better adherence than oral formulation.
A 2011 review found insufficient evidence to determine the effect of naltrexone taken by mouth in opioid dependence. While some do well with this formulation, it should be taken daily, and the person who craves to be extraordinary can get opioid intoxication simply by passing the dose. Because of this problem, the usefulness of oral naltrexone in opioid usage disorders is limited by low retention in treatment. Naltrexone by mouth remains the ideal treatment for a small number of people with opioid use, usually those with a stable social and motivational situation. With the support of additional contingency management, naltrexone may be effective in a wider population.
More
Naltrexone is not useful for quitting smoking.
Available form
Naltrexone is available and most commonly used in the form of oral tablets (50 mg). Vivitrol, a naltrexone formulation for an injection depot containing 380 mg of drug per vial, is also available. In addition, surgically implanted naltrexone subcutaneous implants are also available. Although these are manufactured in Australia, they are not allowed to be used in Australia, but only for export. In 2009, naltrexone implants showed encouraging results.
Maps Naltrexone
Contraindications
Naltrexone should not be used by people with acute hepatitis or liver failure, or those with recent opioid usage (usually 7-10 days).
Side effects
The most common side effects reported with naltrexone are gastrointestinal complaints such as diarrhea and abdominal cramps. These side effects are analogous to the symptoms of opioid withdrawal, since your receptor blockade will increase GI motility.
Naltrexone has been reported to cause liver damage (when given at doses higher than recommended). It carries the FDA box warning for this rare side effect. Because of these reports, some doctors may check liver function tests before starting naltrexone, and periodically thereafter. Concerns for liver toxicity initially emerged from the study of obese patients who were unable to receive 300 mg of naltrexone. Subsequent studies showed limited toxicity in other patient populations.
Naltrexone should not start until some (usually 7-10) days of abstinence from opioids has been achieved. This is due to the risk of acute opioid withdrawal if naltrexone is removed, since naltrexone will replace most opioids of its receptor. The abstinent time may be shorter than 7 days, depending on the specific half-life of the opioid taken. Some doctors use the challenge of naloxone to determine if a person has any opioids left. Challenges involve dosing of naloxone test and monitoring for opioid withdrawal. If the withdrawal occurs, naltrexone should not start.
Pharmacology
Pharmacodynamics
Naltrexone and its active metabolite 6? -altrexol is a competitive antagonist of the -opioid receptor (MOR), the lower-acting -opioid (KOR) receptor, and, to a much lesser extent, at the -opioid receptor (DOR).
Action mechanism
Opioid receptor blockade is the basis behind the action of naltrexone in the management of opioid dependence - reversibly blocking or weakening opioid effects. Its mechanism of action in alcohol dependence is not fully understood, but as an opioid receptor antagonist is probably caused by the modulation of the mesolimbic dopaminergic pathway (one of the principal centers for gift-risk analysis in the brain, and tertiary) pleasure centers ") which is hypothesized to be a major center of reward-related with the addiction that all major drug abuse is believed to be activated.The mechanism of action may be endogenous opioid antagonisms such as tetrahydropapaveroline, whose production is coupled with the presence of alcohol.
Pharmacokinetics
Naltrexone metabolized in the liver mainly into 6? -altrexol by the enzyme dihydrodiol dehydrogenase. Other metabolites include 2-hydroxy-3-methoxy-6-naltrexol and 2-hydroxy-3-methoxy-naltrexone. This is further metabolized by conjugation with glucuronide. The half-life of plasma naltrexone and its metabolites is 6? -altrexol each about 4 hours and 13 hours.
Pharmacogenetic
A study of naltrexone treatment by Anton et al., Released by the National Institutes of Health in February 2008 and published in Archives of General Psychiatry, has shown that alcoholics have certain variants of the opioid receptor gene (G polymorphism SNP Rs1799971 in the OPRM1 gene), known as Asp40, exhibits a strong response to naltrexone and is far more likely to experience success in reducing or discontinuing alcohol intake altogether, while for those who lack the gene Variant, naltrexone does not seem to differ from placebo. The G allele of OPRM1 is most common in Asian-speaking individuals, with 60% to 70% of Chinese, Japanese and Indians having at least one copy, compared with 30% of Europeans and few Africans.
Due to the characteristics of a patient group in the US, the first study was performed on white patients, and the next regardless of ethnicity. Anton et al. found that patients of African descent did not have much success with naltrexone in treatment for alcohol dependence due to lack of relevant genes.
As white patients with genes had a five times greater success rate in reducing drinking when given naltrexone than patients without genes, when used in medical management protocols (MM), Anton et al. concluded,
"As nearly 25% of the population seeking treatment carry the Asp4 allele, individual genetic testing before naltrexone treatment may be worth the cost and effort, especially if structured behavior care is not considered." This will allow treatment to be targeted by genetics for patients to be most effective. They note, "Naltrexone is relatively easy to manage and is free from serious side effects, and as we observe the Asp40 operators we are studying, it seems very effective."
Studies have found naltreksone is more efficacious among certain white subjects, because the genetic basis, compared with black subjects, generally does not carry the relevant gene variant. A 2009 study of naltrexone as a treatment of alcohol dependence among African Americans failed to find statistically significant differences between naltrexone and placebo. Studies have shown that G allele carriers may experience higher levels of desire and are stronger "high" in alcohol consumption, compared with dominant allele carriers, and rather dull naltrexone this response, leading to decreased alcohol use in some studies.
Chemistry
Naltrexone can be described as a replaced oxymorphone - here tertiary methyl-amine substituents are replaced by methylcyclopropane. Naltrexone is an N-cyclopropylmethyl derivative of an oxymorphone.
Analogy
The closely related drug, methylnaltrexone, is used to treat opioid-induced constipation, but does not treat addiction because it does not cross the blood-brain barrier. Nalmefene is similar to naltrexone and is used for the same purpose as naltrexone. Naltrexone should not be equated with naloxone, which is used in emergency cases of opioid overdose. Other associated opioid antagonists include nalodeine and samidorphan.
History
Naltrexone was first synthesized in 1963 by Metossian at Endo Laboratories, a small pharmaceutical company in New York City. It was marked by Blumberg, Dayton, and Wolf in 1965 and was found as an oral opioid antagonist, active in a long, very powerful way. These drugs show advantages over previous opioid antagonists such as cyclazocine, nalorphine, and naloxone, including mouth activity, long duration of action that allows for once-daily administration, and lack of dysphoria, and are selected for further development. It was patented by Endo Laboratories in 1967 under the code name development EN-1639A and Endo Laboratories was acquired by DuPont in 1969. Clinical trials for opioid dependence began in 1973, and the DuPont development collaboration with the National Institute on Drug Abuse for this indication began next year in 1974. The drug was approved by the FDA for oral opioid drug treatment in 1984, under the brand name Trexan, and for oral treatment of alcohol dependence in 1995, when the brand name was changed by DuPont to ReVia. A depot formulation for intramuscular injection was approved by the FDA under the brand name Vivitrol for alcohol dependence in 2006 and opioid dependence in 2010.
Society and culture
Common names
Naltrexone is the generic name of the drug and INN , USAN , BAN , DCF , and DCIT , while naltrexone hydrochloride is < abbr title = "United States Pharmacopeia"> USP and BANM .
Brand name
Naltrexone has been or has been marketed under various brand names, including Adepend, Antaxone, Dye, Depade, Nalorex, Narcoral, Nemexin, Revia/ReVia, Trexan, and Vivitrol. It is also marketed in combination with bupropion (bupropion/naltrexone) as Contrave and marketed with morphine (morphine/naltrexone) as an Embeda. A combination of naltrexone with buprenorphine (buprenorphine/naltrexone) has been developed, but not yet marketed.
Controversy
The FDA allows the use of injectable naltrexone for opioid addiction using a single study led by Evgeny Krupitsky at the Bekhterev Research Psychoneurological Institute, St. Petersburg State Pavlov Medical University, St. Petersburg, Russia, a country where opioid agonists such as methadone and buprenorphine are not available. The study was a "double-blind, placebo-controlled, randomized", 24-week trial run "from 3 July 2008, to 5 October 2009" with "250 patients with opioid dependence disorder" at "13 clinical sites in Russia" on use naltrexone injection (XR-NTX) for opioid dependence. The study is funded by the Boston-based biotek Alcermes firm that manufactures and markets naltrexone in the United States. A 2011 article reported that a single trial of naltrexone was done not by comparing it with the best evidence-based treatment (methadone or buprenorphine), but by comparing it with placebo. The subsequent RCT in Norway compared naltrexone injections with buprenorphine and found they had similar results.
In May 2017, US Minister of Health and Human Services Tom Price, praised [Vivitrol] as the future of opioid addiction treatment after visiting a company plant in Ohio. His remarks sparked sharp criticism with nearly 700 experts in the field of substance abuse sending a letter to Price warning him of Vivitrol's "marketing tactics" and warning him that his comments "ignore the widely accepted knowledge". Experts point out that competitors Vivitrol, buprenorphine and methadone, "cheaper", "more widely used", and have been "studied closely".
Price has claimed that buprenorphine and methadone "only replace" for "illegal drugs" whereas according to the letter, "the substantial body of research evidence supporting this treatment is summarized in guidance from within your own agency, including Substance Abuse and Mental Health Services Administration To summarize briefly, buprenorphine and methadone have been shown to be very effective in managing the core symptoms of opioid use disorders, reducing the risk of relapse and fatal overdose, and promoting long-term recovery. "
According to the June 11, 2017 article, The New York Times, Alkermes has spent years persuading, with a strict lobbying strategy that has targeted lawmakers and law enforcement officials.The company has spent millions of dollars for contributions to officials who are struggling to stem the epidemic of opioid abuse.This also gives thousands of free doses to encourage the use of Vivitrol in jail and jail, which by default becomes a major detoxification center.
Research
Depersonalization
Naltrexone is sometimes used in the treatment of dissociative symptoms such as depersonalization and derealization. Some research suggests it might help. Other small preliminary studies also show benefits. KOR blockade by naltrexone and naloxone is considered to be responsible for their effectiveness in improving depersonalization and derealization. Because the drug is less efficacious in blocking KOR relative to MOR, higher doses than normally used seem to be needed.
Low dose
"Low-dose Naltrexone" (LDN) describes the use of low-dose "off-label" naltrexone for diseases unrelated to chemical or poisoning dependence, such as multiple sclerosis. More research needs to be done before it can be recommended for clinical use.
Although some scientific studies show its efficacy in some conditions such as fibromyalgia, other more dramatic claims for its use in conditions such as cancer and HIV lack scientific support. This treatment has received significant attention on the Internet, especially through websites run by organizations that promote its use.
​​Self-injury
Several studies have shown that self-defeating behaviors present in people with developmental disabilities (including autism) can sometimes be corrected with naltrexone. In this case, self-injury is believed to be done to release beta-endorphin, which binds to the same receptors as heroin and morphine. If the "rush" generated by the self-injury is removed, the behavior can stop.
Behavioral disorder
Some indications exist that naltrexone may be useful in the treatment of impulse control disorders such as kleptomania, compulsive gambling, or trichotillomania (compulsive hair pulling), but evidence of its effectiveness for conflicting gambling. A 2008 case study reported the successful use of naltrexone in suppressing and treating Internet pornography addiction.
Interferon alfa
Naltrexone is effective in suppressing cytokine-mediated neuropsychiatric effects of interferon alfa therapy.
See also
- opioid antagonists Ã,§ List of opioid antagonists
- One Little Pill (film 2014) - a documentary on using naltrexone to treat alcohol use disorders
References
Source of the article : Wikipedia
0 Comments