Introduction to Fentanyl[/FLOAT_LEFT]
3-D Molecular structure of Fentanyl
Fentanyl is an extremely potent opioid, approximately 50-100 times as potent as morphine, and is active in the sub-100 microgram range. It is prescribed for the treatment of acute and chronic pain, usually in patients who no longer respond to high doses of less potent opioids such as morphine or oxycodone. Drug users with no opiate tolerance should avoid using this most powerful of opioids.
Fentanyl is most commonly encountered in the form of patches which are applied to the skin (brand name: Duragesic) or as a "lollipop" which can be dissolved in the mouth (brand name: Actiq) transmucosally (through the mucous membrane). Fentanyl is soluble in lipids as well as water, therefore it is suitable for transdermal administration (through the skin).
Ways of Administration:Fentanyl dosage:
Fentanyl in the form of Duragesic patches comes in dosages of 1.25, 2.5, 5, 7.5, and 10mg. It is a continuous release product, and release depends on surface area. The sizes of the patches for each dose are 5, 10, 20, 30, and 40 cm, respectively. 2.5mcg/cm2 are released per hour. Users who abuse fentanyl, or take recreationally should take extreme caution. 100ug of fentanyl taken transdermally over an hour is equivalent to between 5-10 mg of IV morphine taken over an hour. It is unlikely that many people will ever encounter this patch size, but should be wary even of the smallest ones. Fentanyl has a bioavailability (the amount of a drug which remains unchanged and crosses the blood brain barrier, i.e has any effect on the user) of nearly 100% transdermally. This means that whereas taking an opiate orally enables perhaps a third of the drug to enter the brain- so 100mug of oral fentanyl is really around 35mug- when applied to the skin, nearly all of the fentanyl reaches the brain.
In the form of Actiq, because buccal bioavailability is only about half that of transdermal, dosages are 200, 400, 600, 800, 1200, and 1600 mcg. With Actiq, some of the fentanyl is absorbed transbucocally, while more of it is swallowed (ie passes through the liver), therefore first pass metabolism has a significant effect. That is why the dosages differ so greatly.
Duragesic patches were originally made with a gel in which the fentanyl was suspended, but quite recently the delivery system was changed, as leaky patches were associated with multiple deaths. However, it may still be possible to obtain gel patches, so information about their use is necessary. In addition, it is also be possible to chew the sans gel patches to attain a similar effect.
It is inadvisable for even the most opiate tolerant user to attempt injection of fentanyl. A much "safer" way to abuse the patch is to cut one end of the square off and suck on it in order to ingest the gel, although as mentioned earlier, ingestion would substantially decrease bioavailability, but would counter the time-release. Both of these are dangerous, as it is difficult to discern exactly how much fentanyl is really being put inside the body. For patches without gel, i.e Mylan brand patches, it is possible to cut off pieces and chew them. It is also possible to smoke the gel (after drying it), but this is inadvisable as opiates break down in the presence of extreme heat so it is a fairly inefficient route of administration.
As a precaution, keep in mind there is anecdotal literature about possible hepatoxicity associated with chronic ingestion of the gel.
In order to prepare for sublingual use the patches must be cut up evenly in order to obtain squares with equal amounts of fentanyl. Whilst the patches are designed for continual use over 72hours they contain much more fentanyl than is required:
12mcg/h - 5.25cm² - 2.1mg (2100ug) total content
25mcg/h - 10.5cm² - 4.2mg (4200ug) total content
50mcg/h - 21cm² - 8.4mg (8400ug) total content
75mcg/h - 31.5cm² - 12.6mg (12600ug) total content
100mcg/h - 42cm² - 16.8mg (16800ug) total content
Same total content for all equivalent strenghts. However they have a 12.5mcg/hr patch instead of a 12mcg/hr patch but both contain 2.1mg. They also have a 37.5mcg/hr patch which has 6.3mg in total.
Fentanyl Actavis and Ratiopharm:
12mcg/h patch has the total of 2.063mg of fentanyl (Ratiopharm only)
25mcg/h patch has the total of 4.125mg of fentanyl.
50mcg/h patch has the total of 8.25mg of fentanyl.
75mcg/h patch has the total of 12.375mg of fentanyl.
100mcg/h patch has the total of 16.5mg of fentanyl.
12mcg/h patch has the total of 1.38mg of fentanyl.
25mcg/h patch has the total of 2.75mg of fentanyl.
50mcg/h patch has the total of 5.5mg of fentanyl.
75mcg/h patch has the total of 8.25mg of fentanyl.
100mcg/h patch has the total of 11mg of fentanyl.
Example of how a patch may be divided up (Durogesic and Sandoz):
50mcg/hr patch containing 8400ug would be cut into 1/2, then 1/4s, then 1/8s then 1/16ths but cutting exactly in half each time. This would give 16 squares each with 525ug. These could then be cut into 5 to give 105ug squares. If chewed for sublingual absorption (bioavailability 50%) this would equate to 2.5-5mg of IV morphine. If swallowed (oral bioavailability 33%) it would be equal to 1.7-3.3mg of IV morphine. This method can be applied to 12mcg/hr, 25mcg/hr and 100mcg/hr by increasing or decreasing the amount of times cut in 1/2 proportionately to the reduction in strength i.e. 25mcg/hr would need cutting in 1/2 one time less than 50mcg/hr as it is half the strength. This method is applicable to 37.5mcg/hr and 75mcg/hr but the final squares are cut into 4 not 5. 37.5mcg/hr requiring 4 divisions by 2 and the 75mcg/hr needing 5 before each square is cut into 4 pieces.
For Activas and Radiopharm the same can be used producing squares with a very small amount less of Fentanyl. The same is not applicable to the Matrifen patches however. These each require differing amounts of division by different numbers:
To obtain 100ug pieces:
12mcg/hr cut in 3 then 4 (gives 115ug)
25mcg/hr cut in 3 then 3 then 3.
50mcg/hr cut in 3 then 3 then 3 then 2.
75mcg/hr cut in 3 then 3 then 3 then 3.
100mcg/hr cut in 3 then 3 then 3 then 4.
As well as being taken orally or sublingually the patches can be vaporized however this is far more likely to lead to an overdose as absorption is nearly 100%. 100ug smoked could be as strong as 10mg of IV morphine. Effects become apparent in seconds and can easily overpower even opiate tolerant users. Vaporizing is achieved by heating a piece of patch on tin foil and inhaling the vapour. This is the most dangerous method of consumption other than taking it IV.
Remember: the patches are designed for continuous release. Therefore when one cuts open the patch, a total of 5, 7.5, 10 etc mg are available. The patches are designed to release 100mcg fentanyl/10cm2/hr. 100mcg is equal to around 10 mg of morphine, and 10 mg of Fentanyl is equal to almost a gram of morphine. This would lead to fatalities in all but the highest of opiate tolerance users. Fentanyl has an LD50 (the dose at which 50% die) of .03 mg/kg. In humans it is undetermined, but this would mean perhaps 2.1mg of fentanyl (for a 70kg user) gives users a 1/2 chance of dying. If users don't have a legitimate prescription for Fentanyl, or are not heavily addicted to opiates, abuse of Fentanyl is highly- dangerous and should be avoided at all costs.
Effects of FentanylFentanyl, as an opioid, has similar effects to other opiates/opioids including, but not limited to:
- euphoria- said to be less than that of morphine
- feelings of relaxation
- pupil constriction
- slowed reaction time
- changes in focus, attention, and thought
- impaired thinking, confusion
- loss of appetite
- changes in vision
- nausea, vomiting
- dizziness, headache
- dry mouth
- fatigue, weakness
- light-headedness, fainting
- difficulty breathing
- respiratory depression, respiratory arrest
Combinations with FentanylFentanyl is an incredibly potent opioid. It should not be combined with any drug, especially with other CNS (central nervous system) depressants such as other opiates/opioids, alcohol, benzodiazepines, etc.
Different Uses for FentanylIndications include: the management of persistent, moderate to severe chronic pain, that requires continuous administration for extended periods of time and cannot be managed by other analgesics/opioids. It should only be used in opiate-tolerant individuals.
Fentanyl can also be used recreationally as outlined in the "Ways of Administration" section.
Pharmacology of Fentanyl
LD50 (mg/kg) (as the citrate) :
Mice : 62 subcutaneously, 11.2 intravenously
Fentanyl is a potent μ-opioid receptor agonist with relatively little effect on κ or δ receptors compared to most opioids. Being very lipid soluble, it penetrates the blood-brain barrier quickly and efficiently, which accounts for its high potency compared to traditional opioids. When taken orally, fentanyl undergoes extensive first-pass metabolism by CYP3A4 to non-active metabolites, and as such, CYP3A4 inhibitors (such as grapefruit juice) could potentially be very dangerous when coadministered with fentanyl.
Chemistry of Fentanyl
Column 1 Column 2 Systematic (IUPAC) name: N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenyl-propanamide Synonyms: N-phenyl-1-N-[1-(2-phenylethyl)-4-piperidinyl]propanamide, N-(1-phenethyl-4-piperidyl)propionanilide, N-(1-phenethyl-4-piperidinyl)-N-phenylpropionamide, phentanyl, R-4263, Matrifen, Duragesic, Durogesic; Abstral, Actiq, Fentanest, Leptanal, Sublimaze (citrate) Molecular Formula: C22H29N2O, C22H29N2O.C6H8O7 (citrate) Molar mass: 336.47 g/mol, 528.59 g/mol (citrate)  CAS Registry Number: 437-38-7, 990-73-8 (citrate) Melting Point: 83-84°C, 149-151°C (citrate) Boiling Point: 461.14°C Flash Point: 185.8±19.1 °C Solubility: Freebase: soluble in methanol; slightly soluble in water . Citrate : 1 g dissolves in about 40 mL water; soluble in methanol; slightly soluble in chloroform , ether  Additionnal data: Freebase partition coefficient (n-octanol/water) 860, pKa 8.4  Notes: Frebase aspect : crystals. Citrate aspect : white crystalline powder; bitter taste. 
Reagent color produced Marquis Orange
The dangers of FentanylFentanyl has a high potential for addiction. In addition, as an extremely potent opioid, overdose is easy for the opiate intolerant. A "recreational" dose of fentanyl (i.e. one used by someone who has enough tolerance to use fentanyl) has the potential to stop an opiate-naive user's breathing.
Fentanyl is contraindicated in:
Combining fentanyl with CYP3A4 inhibitors can increase fentanyl plasma concentrations.
- the opioid intolerant
- the management of acute pain or in those who only require acute analgesia
- the management of post-operative pain
- the management of mild pain
- the management of intermittent pain
Injecting FentanylDue to the extreme potency of fentanyl users should not attempt to inject fentanyl. There is no safe way to inject fentanyl outside of a medical environment.
There is no way to safely measure a dose of fentanyl without an extremely sensitive scale which would be well outside the price range of the typical consumer. Fentanyl is so powerful that it only takes a tiny difference in dosagee to be fatal. Injection is an extremely fast and efficient method of administration with no recourse if the dose was too high, excepting a naloxone injection which would have to administered very quickly by trained medical professionals.
Forms of FentanylSee "Ways of Administration". There are also a variety of fentanyl analogues which are of note:
Alfentanil (Alfenta), an ultra-short acting (5–10 minutes) analgesic.
Sufentanil (Sufenta), a potent analgesic (5 to 10 times more potent than fentanyl) for use in heart surgery. (7 day patch currently under FDA scrutiny)
Remifentanil (Ultiva), currently the shortest acting opioid, has the benefit of rapid offset, even after prolonged infusions.
Carfentanil (Wildnil) is an analogue of fentanyl with an analgesic potency 10,000 times that of morphine and is used in veterinary practice to immobilize certain large animals such as elephants.
Lofentanil is an analogue of fentanyl, with a potency slightly greater than Carfentanil.
Without advanced knowledge, tolerance and experience, users should never attempt to abuse these drugs.
Patches and 'lollipops' should be stored in a cool, dry place to avoid degradation.
Producing FentanylFentanyl is synthetized starting from 1-benzylpiperidin-5-one according to the following scheme .
Legal status of Fentanyl
Fentanyl is a controlled substance 21 CFR 1308.12
United NationsDescribes the legal situation according to the UN treaties. See: http://www.unodc.org/enl
USAFentanyl is a Schedule II drug in the US, meaning it is illegal to sell without a DEA license and illegal to buy or possess without a license or prescription.
EUDescribes the legal situation in the EU. See: http://europa.eu/scadplus/leg/en/lvb/l33215.htm
Describes the legal situation in other countries. See: http://www.unodc.org/enl/browse_countries.jsp
History of Fentanyl
Describe the history of the drug from an international perspective. NOT from a USA perspective.
More Fentanyl SectionsFentanyl Experiences Post & read experiences with fentanyl.
Fentanyl File Archive Upload and read research & articles on fentanyl.
Fentanyl Drug Info Thread Post and read about fentanyl.
Fentanyl Image Gallery Post and view pictures of fentanyl.
Addiction Calculator Do this small test to calculate your dependency.
The latest Opioids threads
Opiates & Opioids
Addiction -This thread, started by crono, has been deleted.
 Synthesis of Essential Drugs, 1st edition, Ruben Vardanyan & Victor Hruby, Elsevier
 Merck Index, fifteenth edition (2013)
 Calculated from Atomic Weights of the Elements, 2007
 Fentanyl monograph
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