In the US, oxycodone is only approved for use by mouth, available as tablets and oral solutions. Parenteral formulations of oxycodone (brand name OxyNorm) are also available in other parts of the world, however, and are widely used in the European Union.[34][35][36] In Spain, the Netherlands and the United Kingdom, oxycodone is approved for intravenous (IV) and intramuscular (IM) use. When first introduced in Germany during World War I, both IV and IM administrations of oxycodone were commonly used for postoperative pain management of Central Powers soldiers.[4]
Purdue sales representatives were instructed to encourage doctors to write prescriptions for larger 12-hour doses instead of more frequent dosing. An August 1996 memo to Purdue sales representatives in Tennessee entitled "$$$$$$$$$$$$$ It's Bonus Time in the Neighborhood!" reminded the representatives that their commissions would dramatically increase if they were successful in convincing doctors to prescribe larger doses. Los Angeles Times journalists argue using interviews from opioid addiction experts that such high doses of OxyContin spaced 12 hours apart create a combination of agony during opiate withdrawal (lower lows) and a schedule of reinforcement that relieves this agony, fostering addiction.[85]
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The first clinical use of the drug was documented in 1917, the year after it was first developed.[18][11] It was first introduced to the U.S. market in May 1939. In early 1928, Merck introduced a combination product containing scopolamine, oxycodone, and ephedrine under the German initials for the ingredients SEE, which was later renamed Scophedal (SCOpolamine, ePHEDrine, and eukodAL) in 1942. It was last manufactured in 1987, but can be compounded. This combination is essentially an oxycodone analogue of the morphine-based "twilight sleep", with ephedrine added to reduce circulatory and respiratory effects.[93] The drug became known as the "Miracle Drug of the 1930s" in Continental Europe and elsewhere and it was the Wehrmacht's choice for a battlefield analgesic for a time. The drug was expressly designed to provide what the patent application and package insert referred to as "very deep analgesia and profound and intense euphoria" as well as tranquillisation and anterograde amnesia useful for surgery and battlefield wounding cases. Oxycodone was allegedly chosen over other common opiates for this product because it had been shown to produce less sedation at equianalgesic doses compared to morphine, hydromorphone (Dilaudid), and hydrocodone (Dicodid).[94]
Oxycodone is the most widely recreationally used opioid in America. In the United States, more than 12 million people use opioid drugs recreationally.[103] The U.S. Department of Health and Human Services estimates that about 11 million people in the U.S. consume oxycodone in a non-medical way annually.[104]
The recent formulations of oxycodone, particularly Purdue Pharma's crush-, chew-, injection- and dissolve-resistant OxyNEO[120] which replaced the banned OxyContin product in Canada in early 2012, have led to a decline in the recreational use of this opiate but have increased the recreational use of the more potent drug fentanyl.[121] According to a Canadian Centre on Substance Abuse study quoted in Maclean's magazine, there were at least 655 fentanyl-related deaths in Canada in a five-year period.[122]
Much of the legislative activity has stemmed from Purdue Pharma's decision in 2011 to begin a modification of Oxycontin's composition to make it more difficult to crush for snorting or injecting. The new formulation, OxyNeo, is intended to be preventive in this regard and retain its effectiveness as a painkiller. Since introducing its Narcotics Safety and Awareness Act, Ontario has committed to focusing on drug addiction, particularly in the monitoring and identification of problem opioid prescriptions, as well as the education of patients, doctors, and pharmacists.[139] This Act, introduced in 2010, commits to the establishment of a unified database to fulfil this intention.[140] Both the public and medical community have received the legislation positively, though concerns about the ramifications of legal changes have been expressed. Because laws are largely provincially regulated, many speculate a national strategy is needed to prevent smuggling across provincial borders from jurisdictions with looser restrictions.[141]
Under the Controlled Substances Act, oxycodone is a Schedule II controlled substance whether by itself or part of a multi-ingredient medication.[152] The DEA lists oxycodone both for sale and for use in manufacturing other opioids as ACSCN 9143 and in 2013 approved the following annual aggregate manufacturing quotas: 131.5 metric tons for sale, down from 153.75 in 2012, and 10.25 metric tons for conversion, unchanged from the previous year.[153] In 2020, oxycodone possession was decriminalized in the U.S. state of Oregon.[154]
Breaking Dawn (stylized as breaking dawn) is the 2008 fourth novel in The Twilight Saga by American author Stephenie Meyer. Divided into three parts, the first and third sections are written from Bella Swan's perspective, and the second is written from the perspective of Jacob Black. The novel directly follows the events of the previous novel, Eclipse, as Bella and Edward Cullen get married, leaving behind a heartbroken Jacob. When Bella faces unexpected and life-threatening situations, she willingly risks her human life and possible vampire immortality.
Breaking Dawn was released on August 2, 2008 at midnight release parties in over 4,000 bookstores throughout the US.[4] From its initial print run of 3.7 million copies, over 1.3 million were sold in the US and 20,000 in the UK in the first 24 hours of the book's release, setting a record in first-day sales performance for the Hachette Book Group USA.[5] The book was highly successful, selling over 6 million copies in 2008, and was the third best-selling novel of 2008 behind Twilight and New Moon.
Unlike the series' previous three entries, Breaking Dawn received mixed reviews from critics. It is also the most controversial book of the series, as adult themes and concepts are explored more directly than in its predecessors. However, the novel was awarded the British Book Award for "Children's Book of the Year". It was translated in 38 languages with rights sold to over 50 countries. The book has been adapted into a two-part movie, with the first part released on November 18, 2011, and the second part released on November 16, 2012.
Breaking Dawn is divided into three parts. The first part details Bella's marriage and honeymoon with Edward, which they spend on Isle Esme, a private island off the coast of Brazil that Carlisle owns. Two weeks into their honeymoon, Bella realizes that she is pregnant. Because the fetus is part-vampire, her condition progresses at an unnaturally accelerated rate. Bella and Edward immediately return home to Forks, Washington, where the fetus continues to develop at an abnormal speed, causing Bella severe physical and emotional distress.
The second part of the book is written from the perspective of Jacob Black, a Quileute Native American who, like other members of his tribe, can shapeshift into a wolf. Knowing of Bella's wish to become a vampire, he is immediately suspicious when she returns from her honeymoon and the Cullens keep her father, Charlie, from seeing her. Believing the Cullens have broken their treaty not to bite another human, he advances on their home intending to kill Edward. He arrives and discovers that Bella is undergoing a difficult pregnancy in which the fetus is draining her life away. Jacob begs Bella to abort the fetus to save her life, as neither Carlisle, a doctor, nor Alice who can see the future, are optimistic about Bella's prognosis.
The part that took Meyer the longest time to write in Breaking Dawn was the half-chapter describing the 3 months after Bella's transformation into a vampire because "the amount of time per word put into that section was probably ten times what it was in any other part of the book" and Meyer liked to write minute by minute, but didn't think it would be exciting.[8]
The title, Breaking Dawn, is a reference to the beginning of Bella's life as a newborn vampire.[7] Wanting to add a "sense of disaster" to the title to match the novel's mood, she called it Breaking Dawn. Another reason for giving the book this particular title is that it matches the book's plot, which centers on "a new awakening and a new day and there's also a lot of problems inherent in it".[14]
Entertainment Weekly magazine released an excerpt of Breaking Dawn on May 30, 2008.[16] Stephenie Meyer also revealed a 'Quote of the Day' from Breaking Dawn for about three weeks prior to its August 2, 2008 release. The first quote was released on Meyer's website on July 12, 2008.[17] The first chapter of Breaking Dawn, "Engaged", was released in the special edition of Eclipse.[18] Breaking Dawn was officially released on August 2, 2008 through midnight release parties in over 4,000 bookstores,[4] most of which involved costume and trivia contests, crafts, and face painting.[19]
Godiva also made a Twilight-themed chocolate bar, which was released in Barnes & Noble book stores at the release parties.[20] A four-city Breaking Dawn Concert Series, featuring Stephenie Meyer and Blue October's Justin Furstenfeld, coincided with the novel's release. The concert series sold out three of its four locations on the day that tickets went on sale,[21] selling out in under an hour in one city.[22]
Summit Entertainment announced in November 2008 that they had obtained the rights to the fourth book in Stephenie Meyer's series, Breaking Dawn.[43] The studio greenlit an adaptation of The Twilight Saga: Breaking Dawn in April 2010. The film was split into two parts; the first part of the film was released on November 18, 2011,[44] and the second part was released on November 16, 2012.[45] 2ff7e9595c
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