Fentanyl forms

Fentanyl was introduced to the United States in 1968 by the Janssen Pharmaceutical Company and marketed under the trade name Sublimaze. Its primary purpose was for use as an intravenous anesthetic and analgesic. It is 100 times more potent than morphine in reducing pain, and its duration of action is only 30 minutes (compared to morphine, which lasts several hours). Over the years, fentanyl has proved to be an extremely useful drug, and to date, it is still widely used for surgeries, childbirth, pain associated with cancer and other diseases, and the treatment of trauma-related injuries. Although fentanyl solutions are often given intravenously, pill forms of the drug are also available. 

Figure 7.2 China White powder, shown here, is a synthetic form of heroin that is very pure. China White that was tainted with illegal fentanyl analogues, which are hundreds of times more potent than heroin, caused numerous overdoses in heroin addicts in the late 1970s and early 1980s.

Reduction of Schiff base (XXXI) formed between l-phenethyl-4-piperidone and aniline, and acylation of the resultant dibase gives the highly potent analgesic [112] fentanyl(Sublimaze,XXXIla). In mice (tail-clip method), fentanyl... 

Concomitant anesthesia - Certain forms of conduction anesthesia, such as spinal anesthesia and some peridural anesthetics, can alter respiration by blocking intercostal nerves. Fentanyl can also alter respiration through other mechanisms. 

Opioid-induced muscle rigidity is a frequent complication of this form of anesthesia. It is most common with phenylpiperidine drugs and occurs even after low doses of fentanyl, such as those used in certain diagnostic or minor surgical procedures where a pain-free... 

The various forms of fentanyl can be hundreds of times more powerftil than heroin and its effects are indistinguishable. On the street, fentanyl is known as china white. ... 

High None Heroin, synthetic heroin, fentanyl First offense 10 years to (China white), morphine (pure life in prison 1 million forms) to 4 million fine. Second offense 20 years to life in prison 2 million to 8 million fine. 2 or more prior offenses Life imprisonment... 

Among the compounds that fall within this class are hydrocodone (e.g., Vicodin), oxycodone (e.g., OxyContin—an oral, controlled-release form of the drug), morphine, fentanyl, codeine, and related medications. Morphine and fentanyl are often used to alleviate severe pain, while codeine is used for milder pain. Other examples of opioids prescribed to relieve pain include propoxyphene (Darvon) hydromorphone (Dilaudid) and meperidine (Demerol), which is used less often because of its side effects. In addition to their effective pain-relieving properties, some of these medications can be used to relieve severe diarrhea (for example, Lomotil, also known as diphenoxylate) or severe coughs (codeine). 

Despite an intensive research effort over the past two decades involving many innovative approaches in the global academic community and by the pharmaceutical industry, the latter representing an aggregate investment in excess of 2.5 billion, the only new opioid-based pain medications either in clinical development or on the market are alternative dosage forms of the classical opioids, morphine, loperamide, and fentanyl, or compounds such as tramadol. ... 

A quantum leap in pain therapy with distinct advantages in the form of reduced side-effects and application frequency was achieved with transdermal opioid administration. Transdermal application requires a number of characteristics on the part of the active substance (Fig. 7), the most restrictive being the daily dose, and only very potent opioids which are effective in very low doses, such as fentanyl and buprenorphine, are an option (Sittl and Likar, 2001). 

Buprenorphine, the other option for transdermal application on account of its potency, is more difficult to apply dermally in therapeutic doses (Roy et al., 1994 Grond et al., 2000). A surrogate parameter for skin penetration, provided the other prerequisites are fulfilled (Fig. 7), is the melting point of the active substance. With buprenorphine base this is 209°C and about 260°C for buprenorphine hydrochloride, compared with, for example, 83°C for fentanyl base and 150°C for fentanyl dihydrogen citrate. The DDS developer LTS devised a technical solution for reliable transdermal buprenorphine administration in the form of a matrix patch (Fig. 9). 

Because faster onset of action is associated with higher potential for abuse, abuse-liability assessment should include consideration of whether a formulation can be altered to increase the speed of onset. There are numerous examples of abuse of a medication by a route other than that intended by the manufacturer. The sustained-release oral form of oxycodone, designed to deliver an initial rapid dose followed by slow release, has been widely abused by chewing the tablet, thus releasing the entire content of the tablet at once.65 There is also evidence for intravenous use of sublingual buprenorphine tablets.66 Transdermal systems developed to deliver medication slowly for extended periods of time have been prime targets for misuse,67 as discussed below in the case study of fentanyl. 

China white was popular on the West Coast of the United States in the early 1980s and was estimated at 6,000 times the potency of morphine. In the late 1980s, fentanyl was introduced into the club scene in New York, and designer variations were spawned. In the 1990s fentanyl was introduced as a lollipop for young cancer patients to treat their pain and suffering. In this form it entered into all-night raves and club parties. 

Fentanyl is also available in a patch form (much like a nicotine patch used for smoking cessation) that can also be used for long-term treatment. This form of administration is referred to as transdermal fentanyl and is sold under the trade name Duregasic. The fentanyl is absorbed directly into the skin from the patch and enters the bloodstream, which carries it to the mu receptors. This form of administration appears much easier than it... 

The street versions of fentanyl are ingested in the same ways as heroin. It is usually sold in a powder form and either smoked, snorted, or injected into a vein. Since fentanyl is water-soluble, the powder form can be cold-stirred into a solution and does not need to be boiled like other opioids. However, injection is the most common method used for ingestion on the street. It is so much more potent than heroin that in many of the overdose deaths, the user is found with the needle still in an arm, in some instances with plunger not fully compressed. Some of the designer fentanyl today is made into pill form, but in this form of ingestion, more time elapses before the user feels its effects. 

Fentanyl is also used in treating people who suffer from pain associated with long-term illnesses such as cancer. It is not, however, the most inexpensive method. Transdermal fentanyl costs roughly three times what an equivalent amount of sustained-release morphine sulfate, which has similar effects on the patient, would cost. For this reason it is not used as often as other forms of pain relief unless other avenues have failed. However, some health professionals believe fentanyl offers greater benefits in helping people cope with pain. Transdermal fentanyl is faster acting than other options and lasts up to 72 hours per application. Transdermal fentanyl is considered most beneficial for people who have a consistent... 

According to the makers of Duragesic, it is important not to also use slow-release forms of morphine or oxycodone while using the patch. This would include switching between the two forms of medication or using both at the same time. Other medications that can react negatively with fentanyl use include medicines for high blood pressure and seizures. 

Carbopol resins also have been used in controlled-release dosage forms. Especially, the resins Noven AA-1 USP and Carbopol 934P NF are being extensively developed in bioadhesive drug delivery systems for topical, bucal or nasal, ocular, and rectal applications (e.g., Fentanyl ). Noven CA-1 USP and CA-2 USP are used as oral laxative and antidiarrheal products in swallowable and chewable tablets. 

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