Overview
Patches
Fentanyl transdermal patch (Durogesic / Duragesic / Matrifen) example used in the treatment of chronic pain. The patches act by slowly releasing fentanyl through the skin into the bloodstream for 48 to 72 hours, allowing you to control pain for a long time. The dosage depends on the size of the patch, since, in general, the rate of percutaneous absorption is constant at a constant skin temperature. The rate of absorption depends on a number of factors, such as body temperature, skin type, the amount of fat in the body and the location of the patch. Different delivery systems used by different manufacturers will also affect the rate of absorption. Under normal circumstances, the patch will begin to act in full force within Fentanyl hours; Thus, fentanyl patches are often prescribed with high-speed opioids (such as morphine or oxycodones) to deal with breakthrough pain. 4) In the case of palliative treatment, fentanyl patches can be used limitedly in the following groups of patients:
Lollipops
Fentanyl lozenges (Actiq) are a solid, sticky Braun of fentanyl citrate in the form of a lollipop that slowly dissolves in the mouth due to absorption through the mucosa. These pills are intended for people with opioid tolerance and are effective in treating breakthrough pain in case of cancer. In addition, they are also used in case of severe pain in patients with non-cancerous (non-cancerous) pain, but this use is controversial. Flavored berry lozenges on a stick dissolve on the surface of the mucous membrane of the oral cavity - inside the cheeks, under and on the tongue and gums, quickly releasing fentanyl. The greatest efficiency is observed when the tablet is resorbed for 15 minutes. About 25% of the drug is absorbed through the mucous membrane of the oral cavity, which is associated with a rapid onset of action, and the rest is swallowed and absorbed treatment for the small intestine, acting more slowly. When swallowed whole, the tablet is less effective and acts more slowly, because, despite good absorption from the small intestine, it undergoes extensive metabolism of the first pass, as a result of which its oral bioavailability is about 33% compared to 50% when used correctly ( 25% through the mucous membrane of the mouth and 25% through the intestines). 5)
Other
The American market has a wide range of fentanyl preparations, including resorption tablets, patches, nasal sprays, inhalers and active transdermal patches (thermal or electrical). Some drugs, such as nasal sprays and inhalers, can act quickly, but the rapid onset of action leads to high levels of the drug in the blood, which can jeopardize the safety of human health. In addition, overuse of certain drugs can significantly reduce their effectiveness. In children, it is unclear whether intranasal fentanyl is as effective as morphine. 6) Fentanyl is sometimes given intrathecally during spinal anesthesia or epidurally for epidural anesthesia and pain relief. Due to the high fat solubility of fentanyl, its effects are more localized than the effects of morphine, and some doctors prefer to use morphine for more extensive pain relief. A patient-controlled transdermal fentanyl delivery system is currently under development. The system aims to allow patients to control the administration of fentanyl through the skin during treatment of perioperative pain.
Veterinary use
Fentanyl (as an injection formula) is commonly used for pain relief and as a component for balanced sedation and general anesthesia in small animals. Its activity and short duration of action make it especially useful treatment for the treatment of seriously ill patients. In addition, fentanyl tends to cause less vomiting and regurgitation than other pure opioid agonists (morphine, hydromorphone) when used in the form of a continuous infusion after surgery. Like other pure opioids, fentanyl can cause dysphoria in dogs and cats. Transdermal fentanyl has long been also used for postoperative pain management in dogs and cats. This is often done through the use of fentanyl patches not for their intended purpose, made for use in people with chronic malignant pain. In 2012, a highly concentrated (50 mg / ml) transdermal solution under the trade name Recuvyra for Dogs entered the market. It has been approved by Fentanyl FDA to provide four-day pain relief (again, only in dogs) after a single application before surgery. It is not intended to be administered in multiple doses or for use in other animal species. The drug is also approved in Europe. 7)
Side effects
The most common side effects of fentanyl (observed in more than 10% of patients): diarrhea, nausea, constipation, dry mouth, drowsiness, confusion, asthenia (weakness) and sweating, and less often (observed in 3-10% of patients): pain in abdomen, headache, fatigue, anorexia and weight loss, dizziness, nervousness, hallucinations, anxiety, depression, flu-like symptoms, dyspepsia (indigestion), shortness of breath (shortness of breath), hypoventilation, apnea and urinary retention. The use of fentanyl has also been associated with aphasia. Although fentanyl is a more powerful pain reliever, it usually causes fewer symptoms such as nausea and histamine pruritus, compared to morphine. Fentanyl may produce longer respiratory depression than other opioid analgesics. 8) In 2006, the US FDA launched an investigation into several deaths from suffocation, but doctors in the United Kingdom were not warned of the risks associated with fentanyl until September 2008. 9) In April 2012, the FDA reported that several children died or became seriously ill as a result of the accidental exposure of the fentanyl patch to the skin. 10) The exact cause of sudden respiratory depression when taking fentanyl is unclear, but there are several hypotheses:
Fentanyl has a therapeutic index of 270.
Storage and disposal
Fentanyl is one of a small number of drugs that can be especially harmful to the body, and in some cases - deadly. Taking even one dose of the drug can be dangerous if it is not used by those to whom the drug was prescribed. All fentanyl preparations should be kept in a safe place out of the reach of children, for example, in a locked cabinet. If fentanyl preparations cannot be disposed of through the drug return program, it is recommended that you flush them Fentanyl the toilet, because this is the fastest and most reliable way to remove these potent drugs from your home so that they cannot harm children, pets, or other people. Fentanyl patches are recommended to flush into the toilet bowl after use. It is also worth doing the same with unused plasters as soon as they disappear. Detailed instructions for use, use and disposal of fentanyl patches are available on the FDA website.
Overdose
In July 2014, the More Health Surveillance Service (MHRA) issued a warning about the potential death hazard due to accidental exposure to the transdermal fentanyl patch, especially in children. 11) It is recommended that the plasters be folded with the adhesive side to each other before disposal. Patches should be kept out of the reach of children, as children are at greatest risk of overdose of fentanyl.
Analogs
Structural analogues of fentanyl include:
Mechanism of action
Fentanyl provides some of the effects characteristic of other opioids due to the opioid receptor agonism. Its strong potency compared to morphine is largely associated with its high lipophilicity, through the Meyer-Overton correlation. Because of this, it can more easily ingredient the central nervous system 12) .
Story
Fentanyl was first synthesized by Paul Janssen in his relatively newly formed company Janssen Pharmaceutica in 1959. 13) In the 1960s, fentanyl was introduced to the market as an intravenous anesthetic, under the brand name Sublimaze. In the mid-1990s, Janssen Pharmaceutica developed and introduced into clinical trials Mixture patch, which is an inert alcohol gel with a selected dose of fentanyl to ensure continuous administration of the opioid for 48-72 hours. After a series of successful clinical trials, Duragesic fentanyl patches were introduced into medical practice. After the patch, a flavored fentanyl citrate lollipop blended with inert fillers, marketed under the Actiq brand name, was launched on the market. This candy became the first fast-acting drug in which fentanyl was used to treat chronic breakthrough pain. More recently, fentanyl was developed in the form of an effervescent buccal absorption tablet similar to Actiq, after which a buccal spray was developed related pill provide rapid pain relief. Other methods for delivering the drug to the body are currently under development. Onsolis fentanyl product has been approved by the US FDA for the treatment of breakthrough pain in case of cancer. It uses the BEMA drug delivery technology (fentanyl buccal water-soluble film) in the form of a small disc placed in the mouth. Unlike many other fentanyl products, it is not possible to abuse the drug by crushing and inhaling it. Fentanyl has US DEA ACSCN 9801 and an annual cumulative production quota in 2013 of 2108.75 kg, unchanged from the previous year.
Other use
Recreational use
The illegal consumption of pharmaceutical fentanyl and its analogues first began for the first time in the mid-1970s and is currently ongoing. United States authorities classify fentanyl as a drug and opioid. To date, more than 12 different analogues of fentanyl are illegally produced. The biological effects of fentanyl analogues are similar to the effects of heroin, with the exception that many users report noticeably less pronounced euphoria and a stronger sedative and analgesic effect. Fentanyl analogs can be hundreds of times more powerful compared to street heroin and, as a rule, are associated with significantly more pronounced respiratory depression, which makes them somewhat more dangerous than heroin. Fentanyl is used orally, smoked, inhaled, or injected. Fentanyl is sometimes sold under the guise of heroin, which often leads to an overdose. Many cases of an overdose of fentanyl are initially classified as heroin overdoses. 14) In Estonia, due to the widespread use of recreational use, fentanyl causes more deaths than traffic accidents throughout the country. Fentanyl is sometimes sold on the black market as a Duragesic transdermal patch, which shipments are stolen from official sources. The patches can be cut and eaten, some smoke the gel from the inside of the patches. Another dosage form of fentanyl available on the black market is Actiq Fentanyl Candy, which is sold under the street name “percopop”. The ranges of retail prices in pharmacies range from $ 15 to $ 50 per piece (depending on the dosage of resorption tablets), while the cost on the black market is from $ 20 to $ 80 per piece, depending on the dosage. The non-medical use of fentanyl by people with no opiate tolerance can be very dangerous and involve many victims. 15) Even people with opiate tolerance may be at risk of overdose. After fentanyl is in the body of the user, it is extremely difficult to stop its action due to the nature of the absorption. Illegally synthesized fentanyl powder has also hit the United States market. Due to the extremely high activity of pure fentanyl powder, it is very difficult to properly dilute it, and often the resulting mixture can be too strong and therefore very dangerous to use. Some heroin dealers mix fentanyl powder with heroin to increase potency or compensate for the low quality of heroin. In 2006, illicitly manufactured, non-pharmaceutical fentanyl was often mixed with cocaine or heroin, causing an outbreak of overdose deaths in the United States, mainly in the cities of Dayton (Ohio), Chicago, Detroit and Philadelphia, as well as in Baltimore, Pittsburgh, St. Louis, Milwaukee and Camden (New Jersey). 16) Little Rock and Dallas were also affected. A mixture of fentanyl and heroin is known as “magic” or “bomb”. 17) Several large consignments of illegally produced fentanyl were seized by US law enforcement. In June 2006, 945 grams of 83% purity fentanyl powder was seized by border guards in California from a car sent from Mexico. 18) Mexico is the source of most of the illegal fentanyl for sale in the United States. However, in April 2006, law enforcement authorities discovered one internal fentanyl laboratory in Azusa, California. The lab was the source of fake 80 mg OxyContin tablets containing fentanyl instead of oxycodone, as well as fentanyl powder and other drugs. 19) “White Chinese” is another type of fentanyl belonging to any analogue from a Braun of secretly produced analogs, use this α-methylpentanil (AMP). 20) The Department of Justice lists “White Chinese” as a synonym for a number of fentanyl analogues, including 3-methylpentanil and alpha-methylpentanil, which is currently classified as Schedule I drug in the United States. Despite the additional difficulty from a synthetic point of view, AMP is relatively more resistant to metabolic decay, which is associated with a longer duration of action. In June 2013, the U.S. Centers for Disease Control and Prevention issued a recommendation 21) to emergency departments reporting 14 deaths from an overdose of injecting drug users in Rhode Island related to acetylfentanyl, a synthetic opioid analogue of fentanyl that has never been licensed for medical use. Since 2015, Canada has seen a worsening of the problem associated with overdoses of fentanyl throughout the country. Authorities suspect that the drug is being imported onto the west coast from Asia by organized criminal groups in the form of a powder and pressed into tablets under the guise of OxyContin. 22) Traces of the drug were also found in other recreational drugs, including cocaine, MDMA and Braun. The drug was associated with several deaths in various social circles, ranging from homeless to young professionals, including several teenagers and young parents. Due to rising mortality rates across the country, the Canadian Department of Health is doing everything to review the prescription status of naloxone to combat drug overdoses. 23)
Military use
Analgesic
