Nalokson , sold under the trademark Narcan among others, is a drug used to block the effects of opioids, especially in overdose. Naloxone can be combined with opioids (in the same pill) to reduce the risk of abuse. When administered intravenously, naloxone works in two minutes, and when injected into the muscle, it works within five minutes; it can also be sprayed onto the nose. The naloxone effect lasts about half an hour to an hour. Double doses may be necessary, since the duration of action of most opioids is greater than that of naloxone.
Administration for opioid-dependent individuals may cause withdrawal symptoms of opioids, including anxiety, agitation, nausea, vomiting, rapid heartbeat, and sweating. To prevent this, small doses every few minutes can be given until the desired effect is achieved. In those with previous heart disease or taking a drug that has a negative impact on the heart, further heart problems have occurred. It seems safe in pregnancy, after being given to a limited number of women. Naloxone is a non-selective and competitive opioid receptor antagonist. It works by reversing depression in the central nervous system and the respiratory system caused by opioids.
Nalokson patented in 1961 and was approved for an opioid overdose by the Food and Drug Administration in 1971. This is the List of Essential Medicines of the World Health Organization, the most effective and safe medicines needed in the health system. Naloxone is available as a generic drug. Wholesale prices in developing countries are between $ 0.50 and $ 5.30 per dose. Bottles of naloxone are not too expensive (less than $ 25) in the United States. Prices for two auto-injector packages in the US, however, have risen from $ 690 in 2014 to $ 4,500 by 2016.
Video Naloxone
Medical use
Opioid overdose
Naloxone is useful both in acute opioid overdose and in reducing respiratory or mental depression from opioids. Whether it is useful in those with cardiac arrest due to unclear opioid overdose.
This includes as part of an emergency overdose response kit distributed to heroin and other opioid drug users and emergency responders. This has been shown to reduce mortality from overdose. A prescription for naloxone is recommended if a person is at a high dose of opioid (100 mg equivalency of morphine/day), prescribed an opioid dose accompanied by benzodiazepine, or suspected or known to use nonmedical opioids. Prescribing naloxone should be accompanied by a standardized education that includes preventing, identifying, and responding to overdoses; rescue breath; and call emergency services.
Prevent opioid abuse
Naloxone is poorly absorbed when taken, so it is generally combined with a number of oral opioid preparations, including buprenorphine and pentazosin, so that when taken orally, only opioids have an effect, but if misused by injection, naloxone blocks the opioid effect. This combination is used in an attempt to prevent abuse. In Germany, tilidine is sold in a fixed combination with naloxone.
Other uses
Naloxone may be used in infants exposed to intrauterine opiates administered to the mother during labor. However, there is insufficient evidence for the use of naloxone to reduce cardiorespiratory and neurologic depression in these infants. Infants exposed to high opiates during pregnancy may develop central nervous system damage in perinatal asphyxia settings. Naloxone has been studied to improve results in this population, but current evidence is weak.
In people with shock, including septic shock, cardiogenic, haemorrhagic, or spinal, those receiving naloxone have improved blood flow. The importance of this is not clear.
Naloxone is also experimentally used in the treatment of congenital insensitivity to pain with anhidrosis, a very rare disorder (one of 125 million) that makes one unable to feel pain or distinguish the temperature.
Naloxone can also be used as an antidote to clonidine overdose, a drug that lowers blood pressure.
Naloxone can also be used to treat itching caused by the use of opioids.
Administrative route
Naloxone is most commonly injected intravenously for the fastest action, which usually causes the drug to act in one minute, and lasts up to 45 minutes. It can also be administered by intramuscular, subcutaneous injection, or nasal spray. There is a packaged nose spray that does not require assembly and provides a consistent dose. This can be repeated if necessary. FDA approved non-FDA spray devices attached to the syringe can be used to create a fog that delivers drugs to the nasal mucosa. This is useful near facilities where there are many overdoses that have injector stock.
If the response is minimal or absent within 2-3 minutes, the dose may be repeated every 2 minutes until a maximum dose of 10 mg has been achieved. If there is no current response, alternative diagnosis and treatment should be pursued. The effects of naloxone may disappear before opioids, and they may require repeated doses at a later time. Patients with effects should be monitored for respiratory rate, heart rate, blood pressure, temperature, ABG and level of consciousness. Those who are at greater risk for respiratory depression should be identified before administration and closely monitored.
In April 2014, the US Food and Drug Administration (FDA) approved a handheld pocket-sized, self-injected naloxone injection product and can be used in non-medical settings such as at home. It is designed for use by ordinary people, including family members and caregivers of opioid users at risk for opioid emergencies, such as overdose. The nasal spray was developed in partnership between LightLake Therapeutics and the National Institute on Drug Abuse. The approval process was quickly tracked as one of the initiatives to reduce the death toll caused by an overdose of opiates. At the time of approval, approximately 16,000 annual deaths were associated with an overdose of opioids prescribed in the US.
Naloxone can be used in conjunction with the controlled release of oxycodone and may help reduce opioid-associated constipation. Naloxone has a low systemic bioavailability when drunk because of first liver gastric metabolism, but blocking opioid receptors located in the intestine.
Maps Naloxone
Custom population
Pregnancy and breast-feeding
Naloxone is the category of pregnancy B or C in the United States. Studies in mice given a maximum dose of 10 mg of naloxone daily showed no harmful effects on the fetus, although human studies were lacking and the drug crossed the placenta, which can lead to fetal precipitation. In this setting, further research is needed before safety can be assured, so naloxone may only be used during pregnancy if it is a medical need.
Whether naloxone is excreted in breast milk is unknown.
Kidney and hepatic dysfunction
Currently, there are no personally performed clinical trials with inadequate kidney function or liver disease, and thus, these people should be closely monitored if naloxone is clinically indicated.
Cardiovascular Disease
Naloxone should be used with caution in people with cardiovascular disease as well as those who are taking medications that can have adverse effects on the cardiovascular system such as causing hypotension, pulmonary edema and arrhythmias. There are reports of sudden reversals with opioid antagonists that cause pulmonary edema and ventricular fibrillation.
Side effects
Naloxone has little effect if opioids do not exist. In people with opioids in their system, it can cause increased sweating, nausea, anxiety, tremor, vomiting, redness, and headache, and in rare cases is associated with changes in heart rhythm, seizures, and pulmonary edema.
In addition to the side effects listed above, naloxone also has other side effects, such as other cardiovascular effects (hypertension, hypotension, tachycardia, ventricular fibrillation, ventricular tachycardia) and central nervous system effects, such as agitation, body pain, brain disease, and coma.. In addition to these side effects, naloxone is also contraindicated in people with hypersensitivity to naloxone or its formulation components.
Nalokson has been shown to block the action of pain-reducing endorphins the body produces naturally. This endorphin is likely to operate on the same opioid receptor as the naloxone block. It is able to block a placebo-lowering response, if a placebo is administered simultaneously with a hidden or blind injection of naloxone. Other studies have found that placebo alone can activate the body's endophoric system-endorphins, providing pain relievers with the same receptor mechanisms as morphine.
Pharmacology
Pharmacodynamics
Naloxone is a lipophilic compound that acts as a non-selective and competitive opioid receptor antagonist. The pharmaceutically active isomer of naloxone is (-) - naloxone. () - Naloxone is relatively inactive on opioid receptors. The affinity of Naloxone binding is the highest for the -opioid receptors, then the -opioid receptors, and the lowest for the -opioid receptors; naloxone has a negligible affinity for nociceptin receptors. The affinity values ​​of K i of (-) - naloxone for receptors? -? -, and? -opioids have been reported as 0.559 nanomolar (nM), 4.91Ã, nM, and 36.5Ã, nM, respectively, whereas for () - naloxone, 3,550 nM, 8,950 nM, and 122,000 m, respectively, reported. Thus, (-) - naloxone appears to be an active isomer. In addition, this data suggests that (-) - naloxone is bound to the -opioid receptor by about 9 times greater affinity relative to the -opioid receptor and about 60 times greater affinity relative to the -opioid receptor.
If naloxone is administered in the absence of concurrent use of opioids, no functional pharmacological activity occurs, except the inability of the body to fight pain naturally. In contrast to direct opiate agonists, which cause withdrawal symptoms of opiates when stopped in people who are tolerant to opiates, there is no evidence to suggest the development of tolerance or dependence on naloxone. The mechanism of action is not fully understood, but research suggests it serves to produce withdrawal symptoms by competing for opiate receptor sites in CNS (competitive antagonists, not direct agonists), thereby preventing the action of endogenous and xenobiotic opiates on this. receptors without directly producing the effect itself.
Pharmacokinetics
When administered parenterally (nonorally or nonrectally, eg intravenously or by injection), as is most common, naloxone has a rapid distribution throughout the body. The average serum half-life has been shown to range from 30 to 81 minutes, shorter than the average half-life of some opiates, requiring re-dosing if the opioid receptor should be discontinued from the trigger for prolonged periods of time. Naloxone is primarily metabolized by the liver. Its main metabolite is naloxone-3-glucuronide, which is excreted in the urine.
Chemistry
Naloxone, also known as N-allylnoroxymorphone or 17-allyl-4,5? -epoxy-3,14-dihydroxymorphinan-6-one, is a synthetic morphine derivative derived from oxymorphone (14-hydroxydihydromorphinone), opioid analgesic. Oxymorphones, in turn, are derived from morphine, opioid analgesics and the natural constituents of opium poppy. Naloxone is a racemic mixture of two enantiomers, (-) - naloxone (levonaloxone) and () - naloxone (dextronaloxone), only the first active on opioid receptors. The drug is highly lipophilic, allowing it to rapidly penetrate the brain and reach the ratio of the brain to serum far greater than morphine. Opioid antagonists associated with naloxone include cyprodime, nalmefene, nalodeine, naloxol, and naltrexone.
History
Nalokson patented in 1961 by Jack Fishman, Mozes J. Lewenstein, and the company Sankyo. It was approved for the treatment of opioid abuse in 1971 by the FDA with abuse of opioid abuse that was distributed by many countries to people who were not medically trained from 1996. From the period 1996 to 2014, the CDC estimates more than 26,000 cases of opioid overdose have been reversed using a kit.
Society and culture
Name
Nalokson is the generic name of the drug and INN , BAN , DCF , DCIT , and JAN , while naloxone hydrochloride is USAN and BANM .
The patent for naloxone has expired; consequently, it is available in generics. Nalokson brand names include Narcan, Nalone, Evzio, Prenoxad Injection, Narcanti, Narcotan, and others.
Legal status
In the United States, naloxone is classified as a prescription drug, although it is not a controlled substance. While it is legal to prescribe naloxone in every state, the administration of drugs by professional medical personnel (including doctors or other licensed licensing) at the service point is subject to different rules under jurisdiction. In the following countries, it is possible to buy naloxone from a pharmacist directly without getting a prescription from a doctor: Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Minnesota, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, Ohio, Tennessee, Texas, Utah, Vermont, Washington, West Virginia Wisconsin.
While paramedics have been carrying naloxone for decades, law enforcement officers in many countries across the country are bringing naloxone to reverse the effects of heroin overdose when it reaches the site before the paramedics. On July 12, 2015, law enforcement departments in 28 countries were allowed or asked to bring naloxone to respond promptly to opioid overdose.
In Australia, beginning February 1, 2016, naloxone is now available "on the table" in pharmacies without a prescription. It comes in disposable syringes filled similar to law enforcement kits.
In Canada, naloxone disposable syringes are distributed and available in clinics and emergency rooms. Alberta Health Services increases the distribution points for naloxone devices in all emergency rooms, and various pharmacies and clinics throughout the province. Also in Alberta, home available naloxone kits are available and are generally distributed in most treatment or rehabilitation centers, as well as in pharmacies where pharmacists can distribute disposable naloxone kits or prescribe them to addicts. All Edmonton Police Service and the Calgary Police Police patrol service carry a disposable naloxone syringe kit. Some Canadian Mounted Police patrol vehicles also carry drugs, sometimes overkill to help distribute naloxone among users and family/friends concerned. Nurses, paramedics, medical technicians, and emergency medical respondents can also prescribe and distribute the drug.
After Alberta Health Services, Health Canada reviews the status of prescribed naloxone, so plan to remove it by 2016, allowing naloxone to be more accessible. Due to the increasing number of drug-related deaths across the country, Health Canada proposes a change to make Nalokson more available to Canadians in support of efforts to cope with the increasing number of opioid overdoses. In March 2016, Health Canada changed the status of naloxone recipes, because "pharmacies can now proactively provide naloxone to those who may have or have seen an opioid overdose."
Pre-hospital access
Laws in many jurisdictions have changed in recent years to allow for a wider distribution of naloxone. Some states have also moved to allow pharmacies to issue drugs without first seeing doctors or other non-apothecary professionals. Over 200 Naloxson distribution programs use licensed prescribers to distribute the drugs, often through the use of standing drug orders in which the drug is distributed under the medical authority of a doctor or other prescriber (such as a pharmacist under California's AB1535).
After the use of nasal spray devices by police officers at Staten Island in New York, an additional 20,000 police officers will begin carrying naloxone by mid 2014. The state Attorney General's office will provide US $ 1.2 million to supply nearly 20,000 kits. Police Commissioner William Bratton said: "Naloxone gives individuals a second chance to get help". Emergency Medical Service Providers (EMS) routinely administer naloxone, unless the Basic Emergency Medical Technician is prohibited by policy or by state law.
A survey of the US naloxone prescription program in 2010 revealed that 21 of the 48 programs reported challenges in obtaining naloxone in the months leading up to the survey, primarily due to increased costs that exceeded allocated funding or the inability of suppliers to fulfill orders. The estimated cost of 1 ml of the naloxone ampoule in the US is estimated to be significantly higher than in most Western countries.
These types of projects are underway in many cities in North America. CDC estimates that US programs for drug users and their caregivers who prescribe doses of naloxone and their home use training have prevented 10,000 deaths from opioid overdose. The healthcare-based naloxone prescription program has also helped reduce opioid overdose rates in North Carolina, and has been replicated in the US military. Police training programs and firefighters in opioid overdose responses using naloxone have also shown promise in the US, and increased efforts to integrate the prevention of opioid death in the overall response to the overdose crisis.
Pilot projects also began in Scotland in 2006. Also in Britain, in December 2008, the Welsh Assembly government announced its intention to build demonstration sites to bring home nalokson.
In February 2016, Pharmacies throughout Alberta and several other Canadian jurisdictions were allowed to distribute the take-home naloxone kit. In addition, the Minister of Health issued an order to change the scope of basic health care providers, within the EMS, to administer naloxone in case of suspected drug overdose. This is part of the government's plan to address the growing fentanyl drug crisis.
Identify
The naonal CAS number is 465-65-6; anhydrous hydrochloride salt has CAS 357-08-4 and a hydrochloride salt with 2 water molecules, hydrochloride dihydrate, has CAS 51481-60-8.
Media
2013 documentary Reach for Me: Striving to End an American Drug Overdose Interview of people involved in the naloxone program aimed at making naloxone available to opioid users and people with chronic pain.
See also
- Oxycodone/naloxone
References
External links
- Naloxson's Chicago Recovery Alliance distribution project
- Report Nalokson and other opiate antidote, by the International Program on Chemical Security
- What is Nalokson? through Substance Abuse and Mental Health Services Administration | SAMHSA
- Naloxone Overdose Prevention Laws | PDAPS.org
Source of the article : Wikipedia
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