Fentanyl , also spelled fentanyl , is an opioid used as a painkiller and along with other drugs for anesthesia. It has a fast onset and the effect generally lasts less than an hour or two. Fentanyl is available in a number of forms including by injection, as a skin patch, and is absorbed through tissues in the mouth.
Common side effects include nausea, constipation, drowsiness, and confusion. Serious side effects may include decreased attempts to breathe (respiratory depression), serotonin syndrome, low blood pressure, or addiction. Fentanyl works in part by activating the -opioid receptors. That's about 75 times stronger than morphine for a certain amount. Some fentanyl analogues may be as much as 10,000 times stronger than morphine.
Fentanyl was first created by Paul Janssen in 1960 and approved for medical use in the United States in 1968. It was developed by testing similar chemicals in a structure for petidin (meperidine) for opioid activity. By 2015, 1,600 kilograms (3,500 pounds) is used globally. In 2017, fentanyl is the most widely used synthetic opioid in medicine.
Patch Fentanyl is on the World Health Organization's Essential Drug List, the most effective and safe medication needed in the health system. The cost of grocery in developing countries by 2015 is between US $ 0.08 and US $ 0.81 per 100 microgram vial. In the United States this amount costs about US $ 0.40 by 2017. Fentanyl is also illegally made and used as recreational drugs often mixed with heroin or cocaine. By 2016, more than 20,000 deaths occur in the United States due to fentanyl and analog overdoses.
Video Fentanyl
Medical use
Intravenous and intrathecal
Intravenous fentanyl is often used for anesthesia and analgesia. During anesthesia it is often used along with hypnotic agents such as propofol. It is also administered in combination with benzodiazepines, such as midazolam, to produce sedation for procedures such as endoscopy, cardiac catheterization, and oral surgery, or in the emergency room. Often used in the management of chronic pain including cancer pain.
Fentanyl is sometimes given intrathecally as part of spinal or epidural anesthesia for epidural anesthesia and analgesia. Because of the high fat solubility of fentanyl, the effect is more localized than morphine, and some doctors prefer to use morphine to get wider spread of analgesia.
Patch
Transdermal fentanyl patch (Durogesic/Duragesic) is used in the management of chronic pain. The patch works by slowly releasing fentanyl through the skin into the bloodstream for 48 to 72 hours, allowing pain management to last forever. Dosage is based on the size of the patch, because, in general, the transdermal absorption rate is constant at constant skin temperature. Ingestion rate depends on a number of factors. Body temperature, skin type, body fat amount, and patch placement can have a major effect. Different delivery systems used by different manufacturers will also affect individual absorption rates. Under normal circumstances, the patch will achieve its full effect in 12 to 24 hours; thus, fentanyl patches are often prescribed with fast-acting opioids (such as morphine or oxycodone) to deal with breakthrough pain.
It is unclear whether fentanyl provides long-term pain relief to people with neuropathic pain.
In palliative care, transdermal fentanyl has a definite but limited role to:
- people are already stable in other opioids who have persistent swallowing problems and can not tolerate other parenteral routes such as subcutaneous administration.
- people with moderate to severe kidney failure.
- troublesome side effects of oral morphine, hydromorphone, or oxycodone.
Care must be taken to guard against external heat source applications (such as direct sunlight, heating pads, etc.) which in some circumstances may trigger the release of too many drugs and cause life-threatening complications.
Duragesic was first approved by the College ter Beoordeling van Geneesmiddelen, the Medicinal Evaluation Agency in the Netherlands, on 17 July 1995, as a formulation of 25, 50, 75 and 100 Âμg/h after a successful series of clinical trials, and on October 27, 2004, 12Ã,Âμg/h formulation (actually 12.5 Âμg/h) is also approved. On January 28, 2005, the US Food and Drug Administration approved the first generic formulation of 25, 50, 75, and 100 Ã,Âμg/hr of fentanyl transdermal system (manufactured by Mylan Technologies, Inc., the Duragesic brand name, made by Alza Corp.) Through an FTC agreement agreement that thwarts the possibility of a monopoly in the treatment of chronic pain breakthrough by Alza Corp. In some cases, doctors instruct patients to apply more than one patch at a time, giving a much wider dose range. For example, a patient may be prescribed a dose of 37.5 Ã,Âμg by applying one 12.5 Ã,Âμg patch and one 25 Âμg patch simultaneously, or depending on the large size (largest) 100 g/h patch, some patches are commonly prescribed. for doses that exceed 100? g/hour, such as two 75 Âμg/hour patches used to purchase a dosage regimen of 150 Âμg/hr. Although the usual dose level is 12/25/50/75/100 Âμg/h, the "12Ã,Âμg" patch actually releases 12.5 Âμg/hr. It is designed to release half the dose of 25Ã,Âμg/h patch dose.
In July 2009, the development of the Duragesic patch had been changed from the gel bag and the membrane design to a "drug-in-glue-adhesive formulation design", as described in prescribing information. This construction makes illegal use of fentanyl more difficult.
Storage and disposal
The fentanyl patch is one of a small number of drugs that may be very dangerous, and in some cases fatal, with only one dose, if used by anyone other than the person prescribed the drug. Unused fentanyl pairs should be stored in a safe location that is out of reach and reach of children, such as locked closets.
When patches can not be removed through a drug-taking program, rinsing is recommended for the fentanyl patch because it is the fastest and surest way to remove it from home so it can not harm children, pets and others who are not meant to use it..
Call back
In February 2004, a leading fentanyl supplier, Janssen Pharmaceutica Products, L.P., withdrew a lot, and later, many additional fentanyl (brand name: Duragesic) patches due to a seal offense that may have allowed the drug to leak from the patch. A series of reminiscences of Class II began in March 2004, and in February 2008 ALZA Corporation retracted their Duragesic 25 Ã,Âμg/h patch due to concerns that small cuts in the gel reservoir could result in unintentional exposure to patients or health care providers fentanyl gel.
In February 2011, manufacturers stopped production of all Duragesic patches due to quality control problems involving unspecified "microscopic crystallization" that were detected during the 100 Ã,Âμg/hour power-making process.
Intranasal
Intranasal fentanyl bioavailability is about 70-90%, but with some inaccuracies due to nasal congestion, ingestion of pharynx and false administration. For emergency and palliative use, intranasal fentanyl is available in doses of 50, 100, and 200 Âμg. In emergency medicine, intranasal fentanyl safe administration with low rates of adverse events and promising pain relief effects is demonstrated in prospective observational studies in approximately 900 outpatient outpatients.
In children, intranasal fentanyl is useful for the treatment of moderate and severe pain and is well tolerated.
Sublingual
Abstral dissolves rapidly and is absorbed through the sublingual mucosa to provide rapid analgesia. Fentanyl is a highly lipophilic compound, which is well absorbed subling and is generally well tolerated. Such forms are particularly useful for episodes of breakthrough cancer pain, often fast in onset, short duration and severe intensity.
Lozenges
Fentanyl lozenges ( Actiq ) is a solid formulation of fentanyl citrate on a lollipop in the form of a slowly soluble lollipop in the mouth for absorption of transmucosa. This throat lozenge is intended for individuals who are tolerant of opioids and are effective in treating breakthrough cancer pain. It has also been used to treat pain for patients with non-lethal pain (not cancer), but this application is controversial. This unit is a berry-flavored candy on wands that are wiped on the mucosal surface inside the mouth - inside the cheeks, below and on the tongue and gums - to release fentanyl quickly into the system. This is most effective when the sweets are consumed within 15 minutes. About 25% of the drug is absorbed through the oral mucosa, resulting in rapid onset, and the rest is swallowed and absorbed in the small intestine, acting more slowly. Sweets are less effective and act slower if swallowed whole, because despite the good absorbance of the small intestine there is an extensive first-track metabolism, leading to oral bioavailability of about 33% compared to 50% when used correctly, (25% via oral mucosa and 25% through the gut).
Actiq is produced by pharmaceutical company Cephalon on a plastic stick; this provides the means by which the drug can maintain its placement while it dissolves slowly in the mouth for absorption in the buccal mucosa, in a manner similar to the sublingual buprenorphine/naloxone strip. Actiq candy contains 2 grams of sugar (8 calories). Actiq has been linked to tooth decay, with some users who have no previous dental problems suffering from tooth loss, and in the US many users have started their own Facebook pages to educate users about the severe dental problems caused by so-called fentanyl lollipops. CBS News reported the issue of 28 September 2009. The sugar-free version status, called Actiq-SF , is unclear. Since the release of Fentora - an effervescent buccal fentanyl tablet for breakthrough cancer pain - Cephalon has postponed plans to release a sugar free version of Actiq.
Beginning in late September 2006, a transmittosal oral fentanyl citrate was made available by Barr Pharmaceuticals.
Pararescue The United States Air Force and the Swedish armed forces are battling medical personnel using lollipops with fentanyl. The naval corps working with the United States Marine Corps in Afghanistan use fentanyl lollipop on the victims of the IED bombings and other mechanisms of injury. Lollipop is attached to the victim's finger and inserted between the teeth and cheek (buccal area) of the patient. When enough medication has been absorbed, the finger will usually fall from the patient's mouth, thus indicating that the drug has become effectively administered.
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Some preparations such as nasal sprays and inhalers can produce a rapid response, but rapid onset of high blood levels may compromise safety. In addition, the cost of some of these tools can greatly reduce their cost effectiveness. In children it is unclear whether the intranasal fentanyl is the same or the same as morphine.
The patient-controlled transdermal system (PCTS) fentanyl is under development, which aims to enable patients to control fentanyl administration through the skin during perioperative pain treatment.
Maps Fentanyl
Adverse effects
The most common side effects of Fentanyl (more than 10% of patients) include diarrhea, nausea, constipation, dry mouth, somnolence, confusion, asthenia (weakness), sweating, and less frequent (3 to 10% of patients) abdominal pain, headache, fatigue, anorexia and weight loss, dizziness, nervousness, hallucinations, anxiety, depression, flu-like symptoms, dyspepsia, shortness of breath, hypoventilation, apnea, and urinary retention. The use of Fentanyl is also associated with aphasia.
Although the analgesics are stronger, fentanyl tends to induce less nausea, as well as less histamine-mediated itching, than morphine.
Fentanyl can produce longer respiratory depression than other opioid analgesics. In 2006, the US Food and Drug Administration (FDA) began investigating some respiratory deaths, but doctors in the UK were not warned about the risks with fentanyl until September 2008. The FDA reported in April 2012 that twelve small children had died and two more severe blisters caused by unintentional exposure to the fentanyl skin patch.
The exact reason for sudden respiratory depression is unclear, but there are several hypotheses:
- Saturation fat compartments in patients with rapid and deep body fat loss (patients with cancer, heart or infection caused by cachexia can lose 80% of their body fat).
- Early carbon dioxide retention causes skin vasodilation (more fentanyl release), along with acidosis, which reduces the fentanyl protein bond, releasing more fentanyl.
- Reduces sedation, loses a useful early warning sign of opioid toxicity and results in a level closer to the respiratory depressant level.
Fentanyl has a therapeutic index of 270.
Overdose
In July 2014, the UK's Agency for Medicines and Healthcare (MHRA) issued a warning about the potential life-threatening hazards of accidental exposure to transdermal fentanyl patches, especially in children, and suggested that they should be folded, with the adhesive side in , before disposal. Patches should be kept away from children, most at risk of fentanyl overdose.
Deaths from fentanyl overdose are expressed as a public health crisis in Canada in September 2015, and continue to be a significant public health problem. In 2016, deaths from a fatal fen- tilous overdose in British Columbia, Canada, an average of two people per day. By 2017 the mortality rate has risen by more than 100% with 368 death-related overdoses in British Columbia between January and April 2017.
The medical examiner concluded that Prince's musician died on 21 April 2016, from an accidental accidental overdose of fentanyl. Fentanyl is among the many substances identified in the fake pills found in his home, especially some of which are incorrectly labeled as Watson 385, a combination of hydrocodone and paracetamol. American rapper Lil Peep also died of an accidental fentanyl overdose on November 15, 2017. On January 19, 2018, a Los Angeles medical examiner announced that Tom Petty died of an accidental drug overdose as a result of mixing drugs. it includes fentanyl, acetyl fentanyl and despropionyl fentanyl (among others). He is reportedly treating "many serious diseases" that include hip fractures.
In the US, Fentanyl caused 20,100 deaths by 2016, up 540% over the past 3 years.
Pharmacology
Fentanyl provides some of the typical effects of other opioids through opioid receptor agonists. The strong potential in relation to morphine is largely due to its high lipophilicity, according to the Meyer-Overton correlation. Because of this, it can more easily penetrate the central nervous system.
Detection in biological fluid
Fentanyl can be measured in blood or urine to monitor harassment, confirm the diagnosis of poisoning, or assist in the investigation of medicolegal death. Commercially available immunoassays are often used as early screening tests, but chromatographic techniques are commonly used for confirmation and quantization. The concentration of blood or plasma fentanyl is expected to be in the range of 0.3-3.0 g/l in people taking therapeutically, 1-10? G/l in drunk patients and 3-300 Âμg/l in the victims of acute overdose.. Spray mass spectrometry (PS-MS) may be useful for initial sample testing.
History
Fentanyl was first synthesized by Paul Janssen under the relatively recently formed Janssen Pharmaceutica label in 1959. The widespread use of fentanyl triggered the production of fentanyl citrate (a salt formed by combining fentanyl and citric acid in a stoichiometric ratio of 1: 1). Fentanyl citrate entered medical use as a general anesthetic in 1968, produced by McNeil Laboratories under the trade name Sublimaze.
In the mid-1990s, Janssen Pharmaceutica was developed and introduced into the Duragesic patch clinical trial, which is the formation of inert gel alcohols infused with certain fentanyl doses, which are used to administer opioid administration constantly over a 48 to 72 day period. hour. After a series of successful clinical trials, Duragesic fentanyl patch was introduced into medical practice.
After the patch, a flavored lollipop of fentanyl citrate mixed with an inert filler was introduced in 1998 under the Actiq brand name, becoming the first rapid fentanyl formation for use with chronic breakthrough pain.
In 2009, the US Food and Drug Administration approved Onsolis (fentanyl buccal soluble film), a fentanyl drug in new dosage forms for the management of cancer pain in opioid-tolerant subjects. It uses a drug delivery technology called BEMA (BioErodible MucoAdhesive), a small dissolved polymer film containing various fentanyl doses applied to the inner lining of the cheek.
Fentanyl has a US DEA ACSCN 9801 and an annual aggregate production quota of 2,108.75 kg, unchanged from the previous year.
Society and culture
Brand name
The brand names include Sublimaze, Actiq, Durogesic, Duragesic, Fentora, Matrifen, Haldid, Onsolis, Instanyl, Abstral, Lazanda and others. Subss are sublingual fentanyl sprays produced by Therapeutics Insys.
Cost
The cost of grocery in developing countries by 2015 is between US $ 0.08 and US $ 0.81 per 100 microgram vial. In the United States this amount costs approximately US $ 0.40 by 2017. In the United States the cost of patches is US $ 11.22 for 12Ã,Âμg/jam and US $ 8.74 for version 100Ã,Âμg/hour.
Legal status
In the UK, fentanyl is classified as a controlled Class A drug under Drug Abuse 1971.
In the Netherlands, fentanyl is the substance of List of Opium Laws.
In the US, fentanyl is a substance set forth Schedule II per Controlled Substance Act. Abstral Distributors are required to apply FDA-approved risk and mitigation evaluation (REMS) programs. To prevent abuse, many health insurance companies have begun to require precertification and/or quantity limits for Actiq recipes.
Legal action
On June 19, 2007, a $ 5.5 million jury award was awarded in the US case against Johnson & Johnson's subsidiaries, Alza Corporation and Janssen Pharmaceutica Products, manufacturer of painless transfermal patch fentanyl Duragesic. This case, the first Federal trial involving the Duragesic fentanyl patch, was tried in the Federal District Court for the Southern District of Florida, West Palm Beach Division.
Public health advisor
The US Food and Drug Administration (FDA) has issued public health advisers related to the dangers of the fentanyl patch. Among other things, in July 2005, the FDA issued a Public Health Adviser, who notified that "deaths and overdoses have occurred in patients using both Duragesic and generic product brands." In December 2007, as part of this ongoing investigation, the FDA issued a second Public Health Advisor who stated, "The FDA continues to receive life-threatening reports and life-threatening side effects on patients using the fentanyl patch.The report shows that doctors have incorrectly prescribed patch fentanyl... In addition, the report indicates that patients continue to incorrectly use the fentanyl patch... "
Use of recreation
The illegal use of pharmaceutical and analog fentanyls first appeared in the mid-1970s in the medical community and continues to this day. More than 12 different fentanyl analogues, all not approved and produced clandestinely, have been identified in US drug traffic. The biological effects of fentanyl analogues are similar to heroin, with the exception that many users report much lower euphoric rates associated with drugs and stronger sedative and analgesic effects.
An analog fentanyl may be hundreds of times stronger than street heroin, and tends to produce more significant respiratory depression, making it much more dangerous than heroin for users. Fentanyl is used orally, smoked, snorted, or injected. Fentanyl is sometimes sold as heroin or oxycodone, often causing an overdose. Many fentanyl overdoses were initially classified as a heroin overdose. The use of recreation is not too broad in the EU with the exception of Tallinn, Estonia, where most have replaced heroin. Estonia has the highest 3-methylfentanyl overdose of death in the European Union, due to the high level of recreational use.
Fentanyl is sometimes sold on the black market in the form of transdermal fentanyl patches such as Duragesic, which is diverted from a legitimate medical supply. Gel from inside the patch may be ingested or injected.
Another form of fentanyl that appears on the streets is the Actiq lollipop formulation. Pharmaceutical retail prices range from $ 15 to $ 50 per unit based on candy power, with a black market price ranging from $ 5 to $ 25, depending on the dose. Connecticut and Pennsylvania public lawyers have launched their transition investigations from legitimate pharmaceutical markets, including "promotion and promotion of Cephalon for Provigil, Actiq and Gabitril".
The use of fentanyl by non-medical by individuals without opiate tolerance can be very dangerous and has caused many deaths. Even those with opiate tolerance have a high risk for overdose. Once the fentanyl is in the user's system, it is very difficult to stop it because of its absorption. Fentanyl powder that is synthesized illegally has also appeared in the US market. Due to the extremely high powder fentanyl strength, it is very difficult to liquefy properly, and often the resulting mixture may be too strong and, therefore, extremely dangerous.
Some heroin sellers mix fentanyl powder with heroin to increase the potency or compensation for low-quality heroin. In 2006, illegally produced, non-pharmaceutically produced fentanyl often mixed with cocaine or heroin led to an outbreak of overdose mortality in the United States and Canada, heavily concentrated in the cities of Dayton, Ohio; Chicago; Detroit; and Philadelphia.
A large number of illegally produced fentanyl have been seized by US law enforcement agencies. In June 2006, 945 grams (2.08 lb) of 83% of fentanyl-rure powder were seized by a Border Patrol agent in California from an incoming vehicle from Mexico. Mexico is the source of many illicit fentanyl for sale in the US. However, in April 2006, there was a domestic fentanyl laboratory found by law enforcement in Azusa, California. The laboratory is an artificial source of an 80-mg OxyContin tablet containing fentanyl, not oxycodone, as well as bulk fentanyl and other drugs. In November 2016, DEA discovered an operation that made fake oxycodone and Xanax from a house in Cottonwood Heights, Utah. They found about 70,000 pills in oxycodone appearance and over 25,000 in Xanax appearance. DEA reports that millions of pills can be distributed from this location all the time. The defendant had a press pill and ordered fentanyl in powder form from China.
The "White China" form of fentanyl refers to a number of silently-produced analogs, especially? -methylfentanyl (AMF). This Ministry of Justice document lists "China White" as a synonym for a number of fentanyl analogues, including 3-methylfentanyl and? -methylfentanyl, which is currently classified as a drug Schedule I in the United States. Part of the motivation for AMF is that, despite the extra difficulty from a synthetic point of view, the resulting drug is relatively more resistant to metabolic degradation. This results in a drug with increasing duration.
In June 2013, the US Centers for Disease Control and Prevention (CDC) issued a health advice for the emergency department that warned 14 deaths from overdoses among injection drug users in Rhode Island associated with acetylfentanyl, synthetic opioid fentanyl analogue that was never licensed for medical purposes. In a separate study conducted by the CDC, 82% of fentanyl overdose deaths involved illegally produced fentanyl, while only 4% were presumed to be prescribed.
Beginning in 2015, Canada has seen a large number of fentanyl overdoses. Authorities suspect that the drug was imported from Asia to the west coast by organized crime groups in powder form and pressed into pseudo-OxyContin tablets. Traces of this drug have also been found in other recreational drugs including cocaine, MDMA, and heroin. This drug has been involved in several deaths from the homeless to young professionals, including some teenagers and young parents. Due to the increasing demise across the country, especially in British Columbia where the death to 2016 was 668 and deaths for 2017 (January to October) was 999, Canadian Health was in a hurry on reviewing the status of naloxone only prescription efforts to combat drug overdose.
Fentanyl has been found for sale on the black market in Australia in 2017 and in New Zealand in 2018. In response, New Zealand experts called for greater availability of naloxone.
Incapacitating agent
Russian spetsnaz security forces used "fentanyl gas" to paralyze people quickly in a theater hostage crisis in Moscow in 2002. The siege was over, but about 130 of the 850 hostages died of gas. The Russian Health Minister later stated that the gas was based on fentanyl, but the exact chemical agent had not been identified.
Veterinary use
Fentanyl in the injection formulation is commonly used for analgesia and as a component of balanced sedation and general anesthesia in small animal patients. The potential and duration of its short work make it very useful in critically ill patients. In addition, it tends to cause less vomiting and regurgitation than other pure opioid agonists (morphine, hydromorphone) when administered as a continuous post operative infusion. Like other pure opioids, fentanyl can be associated with dysphoria in dogs and cats.
Transdermal fentanyl has also been used for many years in dogs and cats for postoperative analgesia. This is usually done with an off-label fentanyl patch produced for humans with chronic pain. In 2012 a highly concentrated transdermal solution (50mg/ml), the trade name Recuvyra , is commercially available for dogs only. It is FDA approved to provide four days of analgesia after one application before surgery. It is not approved for some doses or other species. The drug is also approved in Europe.
See also
- Fentanyl analogue list
References
External links
- National Health Institute (NIH) Medline Plus: Fentanyl Buccal (Transmucosal)
- DEA US Information: Fentanyl
- Fentanyl: Emergency Response Database. National Institute for Occupational Safety and Health
- US. National Medical Library: Drug Information Portal - Fentanyl
Source of the article : Wikipedia
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