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ω×™’Þ§×{|}¥≡\While the US |±| WORLD moves forward in opening up, the attorney opportunities in lateral land look to be following suit.  As a legal recruiter, I constantly monitor attorney job openings on numerous law firms’ websites and other job boards.   In particular, I focus on mid-large firms around the DMV area with an emphasis on our capitol.  While there are over 1500, I closely monitor 175 firms that are either part of the top AmLaw 200 with locations in the DMV, or have 40 or more attorneys in an office within the area.  Near the beginning of last week, I started noticing a nice uptick in lateral job postings, especially given how anemic or frozen some of these same boards looked in April and May.  I started a project on Friday 6/12/20 to literally go through these 175 firms and count the openings.  This took through the weekend as notes were taken relating to their recruiting viability of represented candidates which are the #ELITE  #HIR/r #PURPOSED #UNITg #CAREER #PATH #GOAL #ORIENTED #VISUALIZE #SUCCESS #LLC #4U #DRip #41

Counted 115 experienced or lateral attorney openings, which equates to around .65 openings per firm, which is not bad given the time of year which is typically heavily focused on the summer associate hiring.  While I did not physically count the openings in April or May, my guesstimate would be that number was cut in half or possibly even less than 50 (.285) total opening.  I will probably do another follow up project near the end of the summer and am expecting that we will see the number above a 1:1 ratio with over 175 total openings.  I believe laterals bottomed out around the end of May. Make no mistake, some firms and paths may forever be broken. I’ve noticed a lot of talented attorneys simply reassessing their paths in this pandemic. Stay tuned for future trends, hot openings and opportunities – Geoff Wexler 202.505.7481 | geoff@legalinkconfidential.com | 704.576.0933 ©

 

 

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Ω0mega updates on our Blog as we’ll be instilling more than just LEGAL+ CODES to keep us all balanced and learning.  Coming from a Jewish family of educators you’ll notice my passions center outside of the capitalistic pieces we must   succeed in to help the masses a UTILITARIAN Principle I learned back in my HS debate years.  Consequently, expect more than just|ice/the unexpected.í≡î=ICUTEIQTπIFLEX while the middle MSKS.ELON.ed≡g

While an upside down A looks odd, it actually is very inclusive and stands for ALL4 .  We promote it to blend the greek, latin along with newage emojis to promote fluidity or masks when appropriate.

 

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ωñ≡∞.∑.eduk8 Vice/P.s  https://en.wikipedia.org/wiki/Fentanyl

Overdose

Further information: Opioid overdose and U.S. drug overdose death rates and totals over time ft. Wiki ≡gAbe +PERDUE PHARMA SERVñ

 

2 milligrams of fentanyl, a lethal dose for most people when injected.[53] Diameter of a US penny is 19.05 mm, or 0.75 inches.

Naloxone can completely or partially reverse an opioid overdose.[54] In July 2014, the Medicines and Healthcare products Regulatory Agency (MHRA) of the UK issued a warning about the potential for life-threatening harm from accidental exposure to transdermal fentanyl patches, particularly in children,[55] and advised that they should be folded, with the adhesive side in, before being discarded. The patches should be kept away from children, who are most at risk from fentanyl overdose.[56] In the US, fentanyl and fentanyl analogs caused over 29,000 deaths in 2017, a large increase over the previous four years.[57][38]

Actiq-30-pack-600mcg-fentanyl-base.jpg

 

Death from fentanyl overdose continues to be a public health issue of national concern in Canada since September 2015.[58] In 2016, deaths from fentanyl overdoses in the province of British Columbia averaged two persons per day.[59] In 2017 the death rate rose over 100% with 368 overdose- related deaths in British Columbia between January and April 2017.[60]

Fentanyl has started to make its way into heroin as well as illicitly-manufactured opioid and benzodiazepines. Fentanyl contamination in cocaine, methamphetamine, ketamine, MDMA , and other drugs is becoming increasingly common.[61][62] A kilogram of heroin laced with fentanyl may sell for more than US$100,000, but the fentanyl itself may be produced far more cheaply for about US$6,000 per kilogram. Fentanyl was often produced in China and exported illegally to the U.S.[63][64] The UK drug market is no longer reliant on China as domestic production is replacing imports.[65]

As of 2018 fentanyl was the most commonly listed opioid in overdose drug deaths, surpassing heroin. From 2013 until 2016, overdose deaths involving fentanyl increased 113% per year.[66]

The intravenous dose causing 50% of opioid-naive experimental subjects to die (LD50) is “3 mg/kg in rats, 1 mg/kg in cats, 14 mg/kg in dogs, and 0.03 mg/kg in monkeys.”[67] The LD50 in mice has been given as 6.9 mg/kg by intravenous administration, 17.5 mg/kg intraperitoneally, 27.8 mg/kg by oral administration.[68] The LD50 in humans is unknown,[69][70] but a lethal dose for the average person is estimated to be 2 mg.[53]

Contrary to what has been reported in some media outlets, topical (via the skin) exposure to fentanyl is extremely unlikely to cause intoxication or overdose (except in cases of prolonged exposure with very large quantities of fentanyl), and first-responders such as paramedics and police officers are at minimal risk of fentanyl poisoning through accidental contact with intact skin.[71][72]

Pharmacology[edit]

Classification[edit]

Fentanyl is a synthetic opioid in the phenylpiperidine family, which includes sufentanilalfentanilremifentanil, and carfentanil.[73][74]

Structure-activity[edit]

The structures of opioids share many similarities. Whereas opioids like codeine, hydrocodone, oxycodone, and hydromorphone are synthesized by simple modifications of morphine, fentanyl and its relatives are synthesized by modifications of meperidine.[49] Meperidine is a fully synthetic opioid, and other members of the phenylpiperidine family like alfentanil and sufentanil are complex versions of this structure.[49]

Like other opioids, fentanyl is a weak base that is highly lipid-soluble, protein-bound, and protonated at physiological pH.[49] All of these factors allow it to rapidly cross cellular membranes, contributing to its quick effect in the body and the central nervous system.[40][73]

Mechanism of action[edit]

Fentanyl at opioid receptors[75]
AffinitiesKi Ratio
MOR DOR KOR MOR:DOR:KOR
0.39 nM >1,000 nM 255 nM 1:>2564:654

Fentanyl, like other opioids, acts on opioid receptors. These receptors are G-protein-coupled receptors, which contain seven transmembrane portions, intracellular loops, extracellular loops, intracellular C-terminus, and extracellular N-terminus.[49] The extracellular N-terminus is important in differentiating different types of binding substrates.[49] When fentanyl binds, downstream signaling leads to the inhibitory effects, such as decreased cAMP production, decreased calcium ion influx, and increased potassium efflux.[49] This inhibits the ascending pathways in the central nervous system to increase pain threshold by changing the perception of pain; this is mediated by decreasing propagation of nociceptive signals, resulting in analgesic effects.[76][77]

As a μ-receptor agonist, fentanyl binds 50 to 100 times more potently than morphine.[76] It can also bind to the delta and kappa opioid receptors but with a lower affinity. It has high lipid solubility, allowing it to more easily penetrate the central nervous system.[73][40] It attenuates “second pain” with primary effects on slow-conducting, unmyelintated C-fibers and is less effective on neuropathic pain and “first pain” signals through small, myelinated A-fibers.[49]

Fentanyl can produce the following clinical effects strongly, through μ-receptor agonism.[78]

  • Supraspinal analgesia (μ1)
  • Respiratory depression (μ2)
  • Physical dependence
  • Muscle rigidity

It produces sedation and spinal analgesia through Κ-receptor agonism.[78]

Therapeutic effects[edit]

  • Pain relief: Primarily, fentanyl provides the relief of pain by acting on brain and spinal μ-receptors.[49]
  • Sedation: Fentanyl produces sleep and drowsiness, as dosage is increased, and can produce the δ-waves often seen in natural sleep on electroencephalogram.[49]
  • Suppression of the cough reflex: Fentanyl can decrease the struggle against an endotracheal tube and excessive coughing by decreasing the cough reflex, becoming useful when intubating people who are awake and have compromised airways.[49] After receiving a bolus dose of fentanyl, people can also experience paradoxical coughing, which is a phenomenon that is not well understood.[49]

Detection in biological fluids[edit]

Fentanyl may be measured in blood or urine to monitor for abuse, confirm a diagnosis of poisoning, or assist in a medicolegal death investigation. Commercially available immunoassays are often used as initial screening tests, but chromatographic techniques are generally used for confirmation and quantitation. The Marquis Color test may also be used to detect the presence of fentanyl. Using formaldehyde and sulfuric acid, the solution will turn purple when introduced to opium drugs. Blood or plasma fentanyl concentrations are expected to be in a range of 0.3–3.0 μg/L in persons using the medication therapeutically, 1–10 μg/L in intoxicated people and 3–300 μg/L in victims of acute overdosage.[79] Paper spray-mass spectrometry (PS-MS) may be useful for initial testing of samples.[80][81]

History[edit]

Fentanyl was first synthesized in Belgium by Paul Janssen under the label of his relatively newly formed Janssen Pharmaceutica in 1959.[82] It was developed by screening chemicals similar to pethidine (meperidine) for opioid activity.[83] The widespread use of fentanyl triggered the production of fentanyl citrate (the salt formed by combining fentanyl and citric acid in a 1:1 stoichiometric ratio).[84] Fentanyl citrate entered medical use as a general anaesthetic in 1968, manufactured by McNeil Laboratories under the trade name Sublimaze.[85]

In the mid-1990s, Janssen Pharmaceutica developed and introduced into clinical trials the Duragesic patch, which is a formulation of an inert alcohol gel infused with select fentanyl doses, which are worn to provide constant administration of the opioid over a period of 48 to 72 hours. After a set of successful clinical trials, Duragesic fentanyl patches were introduced into medical practice.

Following the patch, a flavoured lollipop of fentanyl citrate mixed with inert fillers was introduced in 1998 under the brand name of Actiq, becoming the first quick-acting formation of fentanyl for use with chronic breakthrough pain.[86]

In 2009, the US Food and Drug Administration approved Onsolis (fentanyl buccal soluble film), a fentanyl drug in a new dosage form for cancer pain management in opioid-tolerant subjects.[87] It uses a medication delivery technology called BEMA (BioErodible MucoAdhesive), a small dissolvable polymer film containing various fentanyl doses applied to the inner lining of the cheek.[87]

Fentanyl has a US DEA ACSCN of 9801 and a 2013 annual aggregate manufacturing quota of 2,108.75 kg, unchanged from the prior year.

Society and culture[edit]

Legal status[edit]

In the UK, fentanyl is classified as a controlled Class A drug under the Misuse of Drugs Act 1971.[88]

In the Netherlands, fentanyl is a List I substance of the Opium Law.

In the U.S., fentanyl is a Schedule II controlled substance per the Controlled Substance Act. Distributors of Abstral are required to implement an FDA-approved risk evaluation and mitigation strategy (REMS) program.[89][90] In order to curb misuse, many health insurers have begun to require precertification and/or quantity limits for Actiq prescriptions.[91][92][93]

In Canada, fentanyl is considered a Schedule I drug as listed in Canada’s Controlled Drugs and Substances Act.[94]

Estonia in known to have been home to the world’s longest documented fentanyl epidemic, especially following the Taliban ban on opium poppy cultivation in Afghanistan.[95]

A 2018 report by The Guardian indicated that many major drug suppliers on the dark web have voluntarily banned the trafficking of fentanyl.[96]

Recreational use[edit]

Illicit use of pharmaceutical fentanyl and its analogues first appeared in the mid-1970s in the medical community and continues in the present. More than 12 different analogues of fentanyl, all unapproved and clandestinely produced, have been identified in the U.S. drug traffic. In February 2018, the U.S. Drug Enforcement Administration indicated that illicit fentanyl analogs have no medically valid use, and thus applied a “Schedule I” classification to them.[97]

Fentanyl analogues may be hundreds of times more potent than heroin. Fentanyl is used orally, smoked, snorted, or injected. Fentanyl is sometimes sold as heroin or oxycodone, sometimes leading to overdoses. Many fentanyl overdoses are initially classified as heroin overdoses.[98] The recreational use is not particularly widespread in the EU with the exception of Tallinn, Estonia, where it has largely replaced heroin. Estonia has the highest rate of 3-methylfentanyl overdose deaths in the EU, due to its high rate of recreational use.[99]

Fentanyl is sometimes sold on the black market in the form of transdermal fentanyl patches such as Duragesic, diverted from legitimate medical supplies. The gel from inside the patches is sometimes ingested or injected.[100]

Another form of fentanyl that has appeared on the streets is the Actiq lollipop formulation. The pharmacy retail price ranges from US$15 to US$50 per unit based on the strength of the lozenge, with the black market cost ranging from US$5 to US$25, depending on the dose.[101] The attorneys general of Connecticut and Pennsylvania have launched investigations into its diversion from the legitimate pharmaceutical market, including Cephalon’s “sales and promotional practices for Actiq. [101]

Non-medical use of fentanyl by individuals without opioid tolerance can be very dangerous and has resulted in numerous deaths.[100] Even those with opiate tolerances are at high risk for overdoses. Like all opioids, the effects of fentanyl can be reversed with naloxone, or other opiate antagonists. Naloxone is increasingly available to the public. Long acting or sustained release opioids may require repeat dosage. Illicitly synthesized fentanyl powder has also appeared on the United States market. Because of the extremely high strength of pure fentanyl powder, it is very difficult to dilute appropriately, and often the resulting mixture may be far too strong and, therefore, very dangerous.[102]

Some heroin dealers mix fentanyl powder with heroin to increase potency or compensate for low-quality heroin. In 2006, illegally manufactured, non-pharmaceutical fentanyl often mixed with cocaine or heroin caused an outbreak of overdose deaths in the United States and Canada, heavily concentrated in the cities of Dayton, Ohio; Chicago; Detroit; and Philadelphia.[103]

Enforcement[edit]

 

Fentanyl powder (23% fentanyl) seized by a sheriff[104]

Several large quantities of illicitly produced fentanyl have been seized by U.S. law enforcement agencies. In November 2016, the DEA uncovered an operation making counterfeit oxycodone and Xanax from a home in Cottonwood Heights, Utah. They found about 70,000 pills in the appearance of oxycodone and more than 25,000 in the appearance of Xanax. The DEA reported that millions of pills could have been distributed from this location over the course of time. The accused owned a tablet press and ordered fentanyl in powder form from China.[105][106] A seizure of a record amount of fentanyl occurred on February 2, 2019, by U.S. Customs and Border Protection in Nogales, Arizona. The 254 pounds (115 kg) of fentanyl, which was estimated to be worth US$3.5M, was concealed in a compartment under a false floor of a truck transporting cucumbers.[107] The “China White” form of fentanyl refers to any of a number of clandestinely produced analogues, especially α-methylfentanyl (AMF).[108] One US Department of Justice publication lists “China White” as a synonym for a number of fentanyl analogues, including 3-methylfentanyl and α-methylfentanyl,[109] which today are classified as Schedule I drugs in the United States.[108] Part of the motivation for AMF is that, despite the extra difficulty from a synthetic standpoint, the resultant drug is more resistant to metabolic degradation. This results in a drug with an increased duration.[110]

In June 2013, the United States Centers for Disease Control and Prevention (CDC) issued a health advisory[111] to emergency departments alerting to 14 overdose deaths among intravenous drug users in Rhode Island associated with acetylfentanyl, a synthetic opioid analog of fentanyl that has never been licensed for medical use. In a separate study conducted by the CDC, 82% of fentanyl overdose deaths involved illegally manufactured fentanyl, while only 4% were suspected to originate from a prescription.[112]

Beginning in 2015, Canada has seen a number of fentanyl overdoses. Authorities suspected that the drug was being imported from Asia to the western coast by organized crime groups in powder form and being pressed into pseudo-OxyContin tablets.[113] Traces of the drug have also been found in other recreational drugs including cocaine, MDMA, and heroin. The drug has been implicated in multiple deaths from the homeless to young professionals, including multiple teens and young parents.[114] Because of the rising deaths across the country, especially in British Columbia where the deaths for 2016 is 668 and deaths for 2017 (January to October) is 999,[115]Health Canada is putting a rush on a review of the prescription-only status of naloxone in an effort to combat overdoses of the drug.[116]

Fentanyl has been discovered for sale in illicit markets in Australia in 2017[117] and in New Zealand in 2018.[118] In response, New Zealand experts called for wider availability of naloxone.[119]

In 2020, the Myanmar military and police confiscated 990 gallons of methyl fentanyl, as well as precursors for the illicit synthesis of the drug. According to the United Nations Office on Drugs and Crime, the Shan State of Myanmar has been identified as a major source for fentanyl derivatives. In 2021, the agency reported a further drop in opium poppy cultivation in Burma, as the region’s synthetic drug market continues to expand and diversify.[120][121]

Recalls[edit]

In February 2004, a leading fentanyl supplier, Janssen Pharmaceutica Products, L.P., recalled one lot, and later, additional lots of fentanyl (brand name: Duragesic) patches because of seal breaches which might have allowed the medication to leak from the patch. A series of Class II recalls was initiated in March 2004, and in February 2008 ALZA Corporation recalled their 25 µg/h Duragesic patches due to a concern that small cuts in the gel reservoir could result in accidental exposure of patients or health care providers to the fentanyl gel.[122]

Brand names[edit]

Brand names include Sublimaze,[39] Actiq, Durogesic, Duragesic, Fentora, Matrifen, Haldid, Onsolis,[123] Instanyl,[124] Abstral,[125] Lazanda[126] and others.[127]

Cost[edit]

In the United States, the 800 mcg tablet was 6.75 times more expensive as of 2020 than the lozenge.[128][129]

Storage and disposal[edit]

The fentanyl patch is one of a few medications that may be especially harmful, and in some cases fatal, with just one dose, if used by someone other than the person for whom the medication was prescribed.[130] Unused fentanyl patches should be kept in a secure location out of children’s sight and reach, such as a locked cabinet.

In British ColumbiaCanada where there are environmental concerns about toilet flushing or garbage disposal, pharmacists recommend that unused patches be sealed in a child-proof container which is then returned to a pharmacy.[131] In the United States where patches cannot always be returned through a medication take-back program, flushing is recommended for fentanyl patches because it is the fastest and surest way to remove them from the home to prevent them from ingestion by children, pets or others not intended to use them.[130][132]

Notable deaths[edit]

  • Medical examiners concluded that musician Prince died on April 21, 2016, from an accidental fentanyl overdose.[133] Fentanyl was among many substances identified in counterfeit pills recovered from his home, especially some that were mislabeled as Watson 385, a combination of hydrocodone and paracetamol.[133][134]
  • Author & journalist Michelle McNamara died on April 21, 2016, from an accidental overdose; medical examiners determined fentanyl was a contributing factor.[135][136]
  • American rapper Lil Peep died of an accidental fentanyl overdose on November 15, 2017.[137][138]
  • On January 19, 2018, the medical examiner-coroner for the county of Los Angeles said musician Tom Petty died from an accidental drug overdose as a result of mixing medications that included fentanyl, acetyl fentanyl and despropionyl fentanyl (among others). He was reportedly treating “many serious ailments” that included a broken hip.[139]
  • In 2018, American rapper Mac Miller died from an accidental overdose of fentanyl, cocaine and alcohol.[140]
  • On December 16, 2018, American tech entrepreneur Colin Kroll, founder of social media video-sharing app Vine and quiz app HQ Trivia, died from an overdose of fentanyl, heroin, and cocaine.[141]
  • On August 20, 2020, Justin Townes Earle died from an accidental overdose caused by cocaine laced with fentanyl.[142]

State use[edit]

In August 2018, the United States used fentanyl for the first time to execute a prisoner.[143][144][145] Carey Dean Moore, at the time one of the United States’ longest-serving death row inmates,[146] was executed at the Nebraska State Penitentiary. Moore received a lethal injection, administered as an intravenous series of four drugs that included fentanyl citrate to inhibit breathing and render the subject unconscious. The other drugs included diazepam as a tranquilizer, cisatracurium besylate as a muscle relaxant, and potassium chloride to stop the heart.[147][148] The use of fentanyl in execution caused concern among death penalty experts because it was part of a previously untested drug cocktail.[143][145] The execution was also protested by anti-death penalty advocates at the prison during the execution and later at the Nebraska capitol building.[147][148]

Russian Spetsnaz security forces used a fentanyl analogue or derivative to incapacitate people rapidly in the Moscow theater hostage crisis in 2002. The siege was ended, but some hostages may have died from the gas after their health was severely taxed during the days long siege.[citation needed] The Russian Health Minister later stated that the gas was based on fentanyl,[149] but the exact chemical agent has not been identified.

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 From their website Qs

Manufacturing

Purdue Pharmaceuticals L.P.
4701 Purdue Drive
Wilson, NC 27893

Main Phone: 203‑588‑8000
Main Fax: 203‑588‑8850

 

 

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