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Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Saturday, October 30, 2010

Fentanyl & Analogues

Fentanyl


Basic:

Fentanyl is a potent and fast acting synthetic opioid. First synthesized in Europe by Dr. Paul Jannsen (Jannsen Pharmaceutica) who discovered its properties while doing binding assays of pethidine analogues.

Use:

In the US, fentanyl is used as a first or second line agent for a variety of indications including; emergency room, critical care, or post operative analgesia, a component of anaesthetic induction & maintenance of general anaesthesia, perioperative analgesia during 'conscious' procedures using regional anaesthesia, for procedural sedation often combined with a benzodiazapine prior to endotracheal intubation, etc, spinal analgesia, end of life palliative care (hospice), and in more recent years as a prescription non-parenteral analgesic for outpatient treatment of moderate to severe pain. Non parenteral fentanyl is delivered in doses of 100 to 1600 micrograms (instant release), or 12 to 100 micrograms per hour (sustained release). Parenteral fentanyl in the clinic or hospital setting is delivered in doses commonly ranging 25 to 150 micrograms as a single injection every few hours. In an surgical anaesthesia or critical care setting with the use of assisted ventilation, fentanyl is delivered in weight based doses as high as 50 to 150 micrograms per kilogram, depending on the degree of antinociception desired for the particular procedure. This is possible due to the use of assisted ventilation and extensive monitoring by the anaesthetist and team.

Fentanyl is typically the first choice among hospitalists for procedural sedation; i.e. setting broken bones, inserting catheters, obtaining CSF samples via lumbar puncture, or endotracheal intubation. The drgu can be be administered shortly before such a procedure along with midazolam or propofol - fentanyl provides analgesia while the sadative/hypnotic provides retrograde amnesia (the inability to remember the incident or discomfort). A trait which lends to its appeal in perioperative analgesia (anaesthesia) is its rapid onset & short duration; this allows a wider margin of safety in IV infusions during surgery, due to the continuous rate of elimination which takes place with the ongoing administration (the simplest way to describe this would be a revolving door effect) Furthermore, the short duration allows faster anaesthesia recovery time in the case of outpatient surgery, which in a busy facility promotes higher rates of patient turnover.

fentanyl transdermal patches
(used in treating chronic pain)
Fentanyl within the last 20 years has evolved as an effective opioid for outpatient use. The Duragesic transdermal patch was introduced to the US in the mid 90's - Duragesic is the original brand name for the transdermal fentanyl skin-patch, which when applied dermally delivers a set-hourly dose of the drug absorbed through the flesh. The patch lasts up to 72 hours, and comes in hourly dosages of 12ug/h, 25ug/h, 50ug/h, 75ug/h, 100ug/h. The patches exist in Europe as "Durogesic" - the US product is manufactured by ALZA corporation and marketed by Jannsen Pharmaceutica, both are subsidiaries of Johnson & Johnson.

In the years following introduction of transdermal fentanyl, fast acting buccal, sublingual, and intranasal forms have been introduced throughout the world - Currently available to the US market is Actiq; a bucally administered lolli-pop lozenge containting fentanyl citrate. Fentora; A simple fast dissolving buccal tablet containing the citrate form of the drug. Onsolis; A fast dissolving buccal film strip containing fentanyl citrate - These are available in generic form with the exception of the newly marketed Onsolis. Buccal IR fentanyl in the US comes in dosages of 100ug to 1600ug, or 1.6mg, and is indicated for use in opioid tolerant individuals with moderate to severe breakthrough cancer pain. No approval as of yet for the products in non malignant pain - meaning any use of this type is 'off label', and typically not covered by insurance carriers.

transdermal fentanyl to daily oral opioids -
dose conversion chart (right click to enlarge) 
The aforementioned long acting and short acting fentanyl preparations have caught on in the US. Transdermal Fentanyl is one of the most commonly prescribed and MD preferred XR opioid products in the US, and is used in patients who have climbed the dosing ladder with other opioids, or experience unmanageable side effects with morphine, etc. The reccomended dosing interval for the patch is every 72 hours, however, transdermal fentanyl was originally studied in end of life/hospice patients - a majority of subjects with compromised metabolism and renal/hepatic function - this considered, the dosing interval for such a subject may not be proper for an otherwise physically healthy subject treated for chronic pain. It was for this terminal care population that Duragesic was heavily aimed for - therefore, many subjects receiving transdermal fentanyl may require either changing the patch every 48 hours, or compensating with increased supplies of a short acting opioid for intermittent pain, which may be increased as needed during points of low fentanyl blood levels.

Because it is a strong opioid, fentanyl is used non medically just as morphine and other narcotics, by opioid tolerant individuals as a means of recreation or simply part of the pattern of habitual drug use. The long acting patch is particularly preferred due to its high fentanyl content; one patch of the strongest dose-size (100ug/hour) contains 10mg of the drug, which represents 100x the standard IV dose. Most of these opioid users apply a portion of the matrix-style patch to the cheek or gums, while those with the gel-style patch remove portions of the alcohol based gel and apply it buccally, make a liquid solution for intranasal or parenteral use, or in some cases swallow it (swallowing fentanyl is very ineffective, as a vast majority is destroyed in the gut/liver before reaching the bloodstream. Casual and experimental users with zero or low opioid tolerance should never use fentanyl by any route outside of the medical setting. Fentanyl is extremely potent and therefore offers little room for dosing misjudgement. An overdose of fentanyl can quickly progress from nausea and sedation to respiratory and cardiac arrest. Overdose of fentanyl by opioid naiive individuals causes frequent deaths among users, most often involving experimentation with the trasdermal patch leading to a massive overdose.

Those who are tolerant to high doses of strong opioids will often use fentanyl recreationally, in which case the optimal route for such use is simply to apply a patch transdermally - after all, the fentanyl patch is intended for opioid tolerant individuals, with the largest providing a morphine equivalent which is upwards of 540mg daily; not to mention the bioavailability of this route is upward of 90 percent, and a patch can last up to 72 hours (3 days). It is important for a user to be well familiar with their personal opioid tolerance, ideally in morphine units, and to equate morphine to fentanyl equivalents either themselves or via literature/internet.

Those who use fentanyl non medically via the transdermal route should never fall asleep until identifying their tolerance to fentanyl; there is typically a 12+ hour lag time between application of the patch and presence of clinically significant blood levels. Not to mention, peak levels are not reached until 24+ hours, meaning if an unfamiliar/naiive user were to fall asleep at some point before reaching significant blood levels (not to mention peak level), overdose may easily occur.

To transdermal users: Be vigilante of the degree of narcosis you feel, especially within the first 24 or so hours of application; if you experience strong effects earlier on in the experience, you could very well overdose by keeping the patch applied; hours worth of fentanyl has already absorbed to your tissue forming a depot beneath the skin, and has yet to release itself systemically (to your bloodstream). If you're already at the point of nausea and somnolence, imagine 12 hours from now when you will have had the >1000ug of fentanyl beneath your skin make it to your bloodstream. In these cases, remove the patch immediately and be sure to have a friend or family member monitor you for the next 12 to 24 hours.

Properties:

Fentanyl is part of a large family of piperidine derivatives, and is specifically a drug with an anilidopiperidine strucure.

Its synthesis is quite simple. N-phenethyl-4-piperidinone (NPP) is synthesized via reaction of 4-piperidinone with 2-phenylethylbromide. NPP is treated with aniline, followed by a reduction with sodium borohydride. This produces 4-anilino-N-phenethyl-piperidine (ANPP), which is then reacted with propionic anhydride to form fentanyl.

Fentanyl produces its analgesic and euphoric effects through its strong binding and agonism of the mu opioid receptor - it shows low affinity to kappa and delta receptors. Its extending N-phenethyl arm enhances binding by reaching further within the receptor complex - This applies to its structural analogues as well. The drug is ~100x more potent than morphine by weight, and ~750x stronger than its relative, pethidine (meperidine). Its doses are measured in micrograms (ug) rather than milligrams (mg) - 100ug of intravenous or intramuscular fentanyl is equianalgesic to 10mg parenteral morphine, or 75mg of pethidine.

Fentanyl is a highly lipophilic opioid; allowing it to quickly and efficiently penetrate the blood brain barrier, as well as attracting it to fat or skeletal muscle tissue. It is the most widely used opioid besides morphine for epidural and intrathecal (spinal) analgesia/anaesthesia - its lipid solubility allows it to A) more easily traverse spinal tissues and more effectively reach and penetrate the spinal cord. and B) distribute itself more directly to an incremental area of the spinal cord and minimally effect other areas/functions.

The drug is metabolized by P-450 enzymes forming inactive metabolites; fentanyl is itself responsible for its effects.

The systemic bioavailability of buccal ("transmucosal") fentanyl - actiq, fentora, onsolis - ranges 50 to 60%, but with a total mucosal absorbtion of around 50% to consider. The bioavailability of transdermally absorbed fentanyl is approximately 90 to 95%, suggesting the drug is not metabolized in the skin. Fentanyl's lipophilicity enhances its absorbtion transdermally - generally, highly lipophilic opioids make good canidates for transdermal delivery.

When fentanyl is administered via transdermal patch, peak blood levels occur from roughly 24 to 72 hours. With continued administration of the patch, steady state levels are acheived around the time for removal of the second patch which is after 4 to 6 days; from here, levels remain consistent with only slight fluctuation, assuming dosage is the same. Buccally absorbed fentanyl reaches peak blood levels at approx. 1 hour post administration.

When injected intravenously, fentanyl rapidly diffuses the blood brain barrier producing analgesia in seconds which lasts 30 to 60 minutes, with intramuscular injection coming on slower and lasting slightly longer. However it is important to be aware that fentanyl's depression of respiration tends to linger long after analgesic effects have passed, this is similar to longer acting opioids and due in part to its lipophilicity & accumulation in tissue. Also useful to note is that peak respiratory depression occurs at 5 to 15 minutes after IV injection (Hospira Corp).

Effects & Side Effects:

Through its activity at opioid receptors, fentanyl produces typical narcotic effects. Effects of fentanyl are much cleaner, or smoother than morphine in quality, owing to its favorably less incidence of side effects - Fentanyl in therapeutic doses has been shown to effect histamine release to a lesser degree than other opioids such as morphine - in studies, doses up to 50ug/kg were shown rarely to produce clinically significant histamine release. Fentanyl generally produces a lesser incidence of emesis (nausea & vomiting) than morphine. Other possible side effects include sedation or somnolence, miosis, constipation, supression of cough reflex, and the possibility of bradycardia. Orthostatic hypotension is possible, and is a result of peripheral vasodilation caused by histamine release.

Centrally mediated effects include analgesia, anxiolysis, euphoria and positive mood, empathetic tendencies and sociability, a sense of contentment, motivation & productivity, and an inhibition of stress/worry and depression. In terms of analgesia, widespread reports and clinical experience suggest a very profound antinociceptive effect. Patients treated for chronic pain commonly rank fentanyl as most effective of all opioids for this purpose.

The pleasurable effects of fentanyl are largely dependent on the route administered - IV injection of fentanyl produces an intense rush and is described as extremely clean in effect. Injected fentanyl will typically produce the warm 'punch in the gut' sensation of hydromorphone, the sudden strange tension of the body followed instantly by a complete/profound release of tension, and generally lacks the often overwhelming pins and needles of morphine considered by some to be uncomfortable.

The overall quality of the fentanyl experience can perhaps best be described by documenting the most commonly reported impressions of fentanyl: Users sometimes report a less pronounced euphoria with fentanyl, and some describe it as simply a happy, content and mellow mood lacking of depression and stress. Some report that the physically experienced narcosis (i.e. body buzz) is more prominent while euphoria is subtle. Some report fentanyl to be more sedating or dreamy and 'nod' condusive than euphoric. Others describe the effects as attributable to heroin.

Sufentanil
 
Basic:

Sufentanil is a potent synthetic opioid analgesic. It is an analogue of fentanyl with about 7x the potency of fentanyl, and is used in the hospital setting under the same indications as similar fentanyl based opioids.

Use:

Use of sufentanil is currently limited to the hospital/clinical setting, where it is used as a strong analgesic and adjunct to anaesthesia.

Sufentanil is used for procedural sedation during routine but painful procedures such as intubation, CSF spinal tap, biopsy, setting of dislocated bones, among others. It is most often administered with a sedative such as a benzodiazapine, usually midazolam.

Sufentanil is used along with benzodiazapines for the induction of general anaesthesia, When given in a weight based dose of 8mg/kg, fentanyl induces deep hypnotic anaesthesia and profound analgesia without any need for an additional induction agent such as a benzodiazapine or barbiturate.

The drug is used additionally as an analgesic component during the maintenance phase of general anaesthesia, given as a continuous infusion by the IV route alongside a neuromuscular blocking agent, a general anaesthetic in volataile or liquid form, and perhaps an additional sedative, along with supplemental oxygen and nitrous oxide. Anaesthesia protocols with enhanced means of airway/O2 management allow for the safe use of much higher opioid doses, which are often required for invasive procedures producing a strong degree of stimuli. Weight based doses as high as 25 to 30ug/kg have been shown to effectively block sympathetic response to surgical stress while maintaining cardiovascular stability and steady blood O2 levels.

Sufentanil may be used for post-operative analgesia by various parenteral routes, given as either fixed doses, continuous infusion, or a PCA (patient controlled analgesia) device.

Sufentanil has been used off label via intraspinal routes. It may be used for post-operative analgesia (via an epidural or subdural/intrathecal infusion), or as a component to regional anaesthesia via these routes in combination with local anaesthetics such as bupivicaine. The high lipid solubility of sufentanil (and all fentanyl analogues in general) allows rapid onset and esay dural penetration, with a lesser degree of respiratory depression. Fentanyl tye drugs however come with several drawbacks by this route; drug distribution is mostly limited to the immediate area of administration, also due their tendency not to linger in CSF fluid, the effects are limited in duration comared to a lipophobic+hydrophilic agent such as morphine. This transient duration is irrelevant when the drug is given via continuous infusion.

After over a decade of success with long acting transdermal fentanyl, researchers have developed a similar transdermal preparation of sufentanil - "TransDUR" Sufentanil, the transdur label is a patent dermal delivery system licensed to Durect Corporation, and may be utilized for additional medications - The available dosage-sizes of these transdermal units will correspond to equianalgesic dosages of the fentanyl patch, but will deliver a continuous dose of fentanyl for an entire 7 days. The patch is currently in development / testing and no release date has been set

Because of its restricted availability, non medical use of sufentanil is rarely heard of. Any unapproved use of the drug is likely to take place among medical professionals such as anaesthetists or surgeons, and perhaps more sophisticated or experienced narcotic users with close friends or family in such a medical position.

Properties:

Suentanyl is a synthetic opioid of the anilidopiperidine subtype. It is a potent fentanyl analogue - Studies suggest it to be approximately 7.5x the potency of fentanyl thus several hundred times more potent than morphine; 12-15ug of sufentanil is roughly equianalgesic to 100ug of fentanyl, or 10mg of morphine, each by the intravenous or intramuscular route. Given in a weight based dosing protocol, literature suggests a sufentanil dose ratio of 1/5 to 1/7 relative to fentanyl.

Sufentanil is a fairly selective opioid. It has (very) high affinity for the mu opioid receptor, and low affinities at kappa and delta receptors.

Fentanyl is highly lipid soluble. Upon IV administration, fentanyl is rapidly distributed within 1 minute, and redistributed within 15 minutes. It has a rapid analgesic onset (within seconds) and an elimination half life of 148 minutes. Sufentanil has a lesser tendency of accumulation than fentanyl, and is rapidly eliminated from tissue, leading to a faster offset of effect and relatively quick post-anaesthesia recovery time. This also lessens the likelihood of delayed respiratory depression, lending favorably to its safety profile.

Effects & Side Effects:

Side effect profile is similar to that of other fentanyl analogues, and typical of mu agonists - the most serious of which may include respiratory depression, sedation, bradycardia, and orthostatic hypotension. Other effects include somnolence, dizziness, constipation, miosis, myoclonus, dry skin & mouth, emesis, urinary retention, and inhibition of libido. Evidence has shown that sufentanil does not produce elevation in histamine levels or cause histamine release; significant pruritis and itching are therefore unlikely.

Like its relatives, when used in the hospital setting these side effects are not likely to be of any relevance; as subjects are typically incapacitated with with other agents, or completely unconscious via anaesthesia.

As it is a potent mu agonist, sufentanil will produce euphoria, anxiolysis, relaxation, subjective warmth, positive mood, inhibition of depression, a care-free state of contentment, and a dreamlike state pseudo-sleep (nodding).

Alfentanil

Basic:

Alfentanil is an analogue of fentanyl, discovered by Jannsen Pharmaceutica in the 1970's. It is an opioid analgesic and is used primarily in the hospital/clinical setting.

Use:

Alfentanil is typically used to provide procedural analgesia & sedation in the Surgical, Emergency, or Critical Care setting. Its short duration of action lend it well to short-lived surgeries or infusion driven protocols with a fast recovery time.

It may be given via injection as an analgesic prior to minor routine procedures such as endotracheal intubation or lumbar puncture along with a benzodiazapine such as midazolam to provide sedation and induce amnesia.

It may be given by injection as a pre-operative sedative/euphoriant to relieve patient apprehension or anxiety which may compromise vitals prior to surgery.

It may be given as a single IV loading dose to induce general anaesthesia along with a benzodiazapine or propofol - AND/OR - may be given as a maintenance agent in general anaesthesia and administered via a continuous IV infusion along with the additional basic components of anaesthesia.

It may also be given for analgesia in the conscious patient, during surgeries using regional/local anaesthesia, in this case usually along with a sedative such as midazolam; both together provide effective sedation and amnesia with fast recovery time and without some of the risks of general anaesthesia.

Numerous anaesthesia protocols using alfentanil are described below:

Alfentanil anaesthesia . For simple conscious procedural sedation; the typical dose range is 5-10ug/kg. For use as an analgesic during short-lived surgical procedures, manufacturer reccomends doses of 8 to 40ug per kilogram. For longer surgical procedures, doses of 50 to 75ug per kg may be used . When used for induction of general anaesthesia, doses of 130 to 245ug/kg are common. Use of alfentanil as an induction agent in adequate anaesthetic doses (130ug/kg) has proven to allow much lower doses of volatile inhalation anaesthetics during the initial stages of surgery. These initial doses depending on the procedure, may be followed by a venous infusion of the drug at an infusion rate of 0.5 to 3ug per kg per minute - Infusions of alfentanil along with a nitrous oxide/O2 combination provides inhibition of sympathetic pain response with a shorter recovery time than traditional 'flurane' agents. Alfentanil provides a similar recovery time as fentanyl.

There have been no documented cases of non-medical or illicit use of alfentanil in the US. Due to its exclusion to primarily the hospital/clinical setting, instances of diversion are likely rare. In the case of recreational use of alfentanil, this would most likely occur among medical professionals such as anaesthesiologists, surgeons, or nurse anaesthetists.

Properties:

Compared with fentanyl; alfentanil is rapid acting with a short duration. It's is less potent than fentanyl (approximately 10x stronger than morphine) - similar in potency to levorphanol or oxymorphone, with 1000ug alfentanil (1mg) being equianalgesic to about 100ug fentanyl, or 10mg morphine, by the IV route.

Alfentanil is a mu-receptor agonist with similar pharmacology to other fentanyl-type opioids; with a high affinity for mu-receptor, and negligible binding at delta & kappa receptors.

Effects & Side Effects:

Side effects of alfentanil may include the expected effects of opioid agonists. Pruritis & itching, peripheral vasodilation, emesis, constipation, urinary retention, dizziness, miosis, and possible myoclonus.

Compared to fentanyl, respiratory depression may occur at to a greater relative extent. Side effects are generally transient in nature, due to its short half life.

Alfentanil produces pleasant opioid-typical effects mediated via the CNS; these are very short lived and include analgesia, anxiolysis, euphoria, relaxation and sedation or somnolence. Patients given the drug however will rarely have the opportunity to fully distinguish or even remember these effects, much less enjoy them - as use of alfentanil is excluded to primarily the hospital anaesthesia setting, and usually administered along with sedatives or anaesthetics, directly before or during procedures.

Remifentanil

Basic:

Remifentanil is a synthetic narcotic related to fentanyl, available in the US as "Ultiva". It is used in medicine much like other fentanyl analogues as an analgesic administered by the parenteral route.

Use:

Remifentanil is available in the US and Canada as the brand name Ultiva, available as a solution for parenteral use. Remifentanil may also be given off label by the epidural or intrathecal route.

The drug is used as a preoperative analgesic or induction agent in general anaesthesia, typically in doses of 0.5 to 1ug/kg per minute by infusion. Single IV loading doses are not reccomended in the absence of endotracheal intubation and cardiopulmonary resuscitative equipment.

Remifentanil is given during procedures as a maintenance agent, typically through an IV infusion, alongside other anaesthetics and assisted ventilation. The reccomended infusion rate is 0.05 to 2ug/kg per minute, depending on the general anaesthetic used, the invasiveness of the procedure, and individual response. In the case of inadequate anaesthesia or adverse sympathetic response to surgical stress, supplemental bolus are reccomended in doses of 0.5 to 1ug/kg, only as needed. As with similar analgesics, adjunctive use of remifentanil in this setting has been shown to facilitate as much as 75% reductions in requirements for volatile anaesthetics & sedatives. Compared to fentanyl and sufentanil, remifentanil may be preferable for short and/or outpatient procedures where a rapid recovery time is ideal - Its elimination is rapid even after long, high dose infusions.

Aside from general anaesthesia, remifentanil is used as an analgesic of choice during minor surgical or diagnostic procedures, given along with a benzodiazepine (typically midazolam).

Properties:

Remifentanil is a potent fentanyl analogue with a rapid onset and offset. It is an opioid agonist with high affinity and selectivity for the mu receptor. Effects at kappa and dela sites are clinically irrelevant.

Peak levels are acheived almost immediately upon administration. Upon slow IV injection, the drug is rapidly distributed within 60 seconds, and redistributed over 5 to 6 minutes, where it binds for a short period with high affinity to mu opioid receptors in the brain & spinal cord.

The pharmacodynamic effects of the drug will correllate very closely with blood levels, more so than with other analgesics. During infusion, response is observed rapidly with any change in infusion rate; steady state levels are reached within 5 to 10 minutes of any adjustment of dose. This allows rapid titration to effect due to precision in dosing, and a desireable safety profile during anaesthesia.

Remifentanil is hydrolyzed by esterase enzymes in the plasma and tissues to form an inavactive metabolite which is excreted via the kidneys; this pathway making up over 95% of its metabolism.

With cessasion of infusion, analgesia will not be present more than 5 to 10 minutes, with the possibility of delayed respiratory depression for up to 30 minutes (generally never past 30 minutes). With remifentanil's limited degree of distribution and rapid clearance, its elimation half life is roughly 3 to 10 minutes. Remifentanil is unique from fentanyl in that its duration of analgesia does not increase with continuous administration. Even after a 12 hour infusion, the drug is rapidly cleared with effects lasting no more than 5 to 10 minutes.

Effects:

Remifentanil produces effects typical of any mu agonist, however with a single dose administration, these effects are transient in nature. Serious side effects may include respiratory depression, orthostatic hypotension, bradycardia and tachycardia. The latter three are most common among the elderly (>65 years), and may occur more frequently than with similar opioids. Other effects typically include sedation, somnolence, emesis, miosis, peripheral vasodilation, muscle rigidity, pruritis, or headache.

The most clinically significant function of remifentanil is to suppress the physiological response to surgical stress (which is mediated via the sympathetic nervous system). Remifentanil (along with other opioids) acheive this via their analgesic actions throughout the spinal cord and brain. In high enough doses, which is possible with the use of intubated ventilation, fentanyl type opioids may produce a deep anaesthetic & unconscious state; effectively blocking nociceptive input to the brain, not to mention inhibiting any degree of physiological response whatsoever to pain.

A reliable account of remifentanil's subjective effects is likely to be rare, as its use is limited to the perioperative anaesthetic setting, and it is often combined with strong hypnotics which produce amnesia.

Remifentanil can be expected to produce euphoria and positive mood as with any mu opioid agonist. The drug has been shown to be highly reinforcing in animals, and may produce more of a rush upon injection than other narcotics. Remifentanil is liable to produce a high degree of physical and/or psychological dependence.


Carfentanil


Fentanyl analogue first synthesized by Paul Janssen's research team.

High affinity opioid agonist with high selectivity for the mu receptor.

One of the most potent opioids known. Strongest opioid available commercially. About 10,000x more potent than morphine and 100x stronger than fentanyl.

Not marketed for human use. Available by the brand name Wildnil which is used in the veterinary setting as an analgesic, anaesthetic, sedative and tranquilizer - mainly in large animals such as bears, horses, lions, giraffes, etc.

Has increasingly taken over the role of etorphine in the veterinary setting due to its favorable therapeutic index and selective pharmacodynamic profile.

Active in humans at around 1 microgram.

High dependence potential. Very high tolerance potential - Continuous use of carfentanyl is likely to produce marked tachyphylaxis (i.e. a an unusually rapid development of tolerance, pronounced with each use)

4 comments:

  1. 'absence of a 5-hydrogen feature replaced with a 5-alpha-epoxy feature instead'?

    Indeed? Check again. Lack of epoxy bridge seen in Levorphanol & butorphanol - all other phenanthracene opioids have the feature...

    BTW - a hydrogen is not a 'feature' in organic chemistry!

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  2. What about remifentanil? important drug!

    Alfentanil, BTW, is used because it has a much faster onset (due to pKa of drug). It is more controllable...

    ReplyDelete
  3. "'absence of a 5-hydrogen feature replaced with a 5-alpha-epoxy feature instead'?"

    I don't see how this would pertain to any fentanyl type drug.. If that line is actually in my blog somewhere I'd appreceiate being pointed in the right direction so I can fix it.

    If that line had been in here it may have been intended for another section; most likely referring to one of the 3-hydroxymorphinans, as you mention.

    I'm aware that levorphanol and butorphanol are not epoxymorphinans, as the many phenanthrene based opioids.

    MWL

    ReplyDelete
  4. Great Post, !!!!!!!...... Thanks For Sharing info....The Fentanyl Drug Testing looks for the presence of drugs in urine specimens. It is available for use in multi-panels, cassettes, strips, or cup formats.

    ReplyDelete