text:
(Redirected from Eukodal)
Oxycodone, sold under brand name OxyContin among others, is an opioid medication used for treatment of moderate to severe pain.[11] It is usually taken by mouth, and is available in immediate-release and controlled-release formulations.[11] Onset of pain relief typically begins within 15 minutes and lasts for up to six hours with the immediate-release formulation.[11] In the United Kingdom, it is available by injection.[12] Combination products are also available with paracetamol (acetaminophen) or aspirin.[11]
ɒksɪˈkəʊdəʊn
OxyContin, others
Eukodal, eucodal; dihydrohydroxycodeinone, 7,8-dihydro-14-hydroxycodeinone, 6-deoxy-7,8-dihydro-14-hydroxy-3-O-methyl-6-oxomorphine[3]
AHFS/Drugs.com
AU: C
US: B (No risk in non-human studies)
High[1]
Routes of
By mouth, sublingual, intramuscular, intravenous, intranasal, subcutaneous, transdermal, rectal, epidural[2]
N02AA05 (WHO)
N02AA55 (WHO) (in combinations)
AU: S8 (Controlled)
CA: Schedule I
DE: Anlage III (Special prescription form required)
UK: Class A
US: Schedule II
By mouth: 60–87%[4][6]
45%[4]
Liver: mainly CYP3A, and, to a much lesser extent, CYP2D6 (~5%);[4] 95% metabolized (i.e., 5% excreted unchanged)[5]
• Noroxycodone (25%) [7][5]
• Noroxymorphone (15%, free and conjugated)[7][5]
• Oxymorphone (11%, conjugated)[7][5]
• Others (e.g., minor metabolites)[5]
IR: 10–30 minutes[6][5]
CR: 1 hour[8]
By mouth (IR): 2–3 hrs (same t1/2 for all ROAs)[5][6]
By mouth (CR): 4.5 hrs[9]
By mouth (IR): 3–6 hrs[5]
By mouth (CR): 10–12 hrs[10]
Urine (83%)[4]
(5R,9R,13S,14S)-4,5α-Epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one
76-42-6 Y
IUPHAR/BPS
4447649 Y
CD35PMG570
ChEMBL656 Y
CompTox Dashboard (EPA)
DTXSID5023407
Chemical and physical data
315.364 g/mol g·mol−1
3D model (JSmol)
219 °C (426 °F)
HCl: 166 mg/mL (20 °C)
O=C4[C@@H]5Oc1c2c(ccc1OC)C[C@H]3N(CC[C@]25[C@@]3(O)CC4)C
InChI=1S/C18H21NO4/c1-19-8-7-17-14-10-3-4-12(22-2)15(14)23-16(17)11(20)5-6-18(17,21)13(19)9-10/h3-4,13,16,21H,5-9H2,1-2H3/t13-,16+,17+,18-/m1/s1 Y
Key:BRUQQQPBMZOVGD-XFKAJCMBSA-N Y
(verify)
Common side effects include constipation, nausea, sleepiness, dizziness, itching, dry mouth, and sweating.[11] Severe side effects may include addiction, respiratory depression (a reduction in breathing), and low blood pressure.[11] Those allergic to codeine may also be allergic to oxycodone.[11] Use of oxycodone in early pregnancy appears relatively safe.[11] Opioid withdrawal may occur if rapidly stopped.[11] Oxycodone acts by activating the μ-opioid receptor.[13] When taken by mouth, it has roughly 1.5 times the effect of the equivalent amount of morphine.[14]
Oxycodone was first made in Germany in 1916 from thebaine.[15] It is available as a generic medication.[11] In the United States, the wholesale cost per dose is less than US$0.30 as of 2018.[16] In 2016, it was the 54th most prescribed medication in the United States, with more than 14 million prescriptions.[17] Oxycodone has been a common drug of abuse.[18] A number of abuse-deterrent formulations are available, such as in combination with naloxone.[18][19]
1 Medical uses
1.1 Available forms
2.1 Dependence and withdrawal
2.2 Hormone levels
3 Overdose
4 Interactions
5 Pharmacology
5.1 Pharmacodynamics
5.1.1 Active metabolites
5.1.2 κ-opioid receptor
5.2 Pharmacokinetics
5.2.1 Instant-release absorption profile
5.2.2 Distribution
5.2.3 Metabolism
5.2.4 Elimination
5.2.5 Duration of action
6.1 Biosynthesis
6.2 Detection in biological fluids
8 Society and culture
8.1 Names
8.2 Legal status
8.2.1 General
8.2.3.1 Canadian legislative changes
8.2.3.2 Canadian lawsuits
8.2.5 Hong Kong
8.2.7 Singapore
8.3 Recreational use
8.3.1 Effects
8.3.2 Preventive measures
8.4 Economics
8.5 Lawsuits
Medical usesEdit
Oxycodone is used for managing moderate to severe acute or chronic pain when other treatments are not sufficient.[11] It may improve quality of life in certain types of pain.[20] It is unclear if use in chronic pain results in improved quality of life or ongoing pain relief.[11]
Oxycodone is available as controlled-release tablet, intended to be taken every 12 hours.[21] A July 1996 study independent of Purdue Pharma, the drug's originator, found the controlled-release formulation had a variable duration of action ranging from 10–12 hours.[10] A 2006 review found that controlled-release oxycodone is comparable to immediate-release oxycodone, morphine, and hydromorphone in management of moderate to severe cancer pain, with fewer side effects than morphine. The author concluded that the controlled-release form is a valid alternative to morphine and a first-line treatment for cancer pain.[21] In 2014, the European Association for Palliative Care recommended oxycodone by mouth as a second-line alternative to morphine by mouth for cancer pain.[22]
In the U.S., extended-release oxycodone is approved for use in children as young as 11 years old. The approved uses is for relief of cancer pain, trauma pain, or pain due to major surgery, in children already treated with opioids, who can tolerate at least 20 mg per day of oxycodone; this provides an alternative to Duragesic (fentanyl), the only other extended-release opioid analgesic approved for children.[23]
Available formsEdit
See also: Oxycodone/paracetamol, Oxycodone/aspirin, Oxycodone/ibuprofen, and Oxycodone/naloxone
Both sides of a single 10mg OxyContin pill.
Oxycodone is available in a variety of formulations for by mouth or under the tongue:[6][24][25][26]
Immediate-release oxycodone (OxyFast, OxyIR, OxyNorm, Roxicodone)
Controlled-release oxycodone (OxyContin, Xtampza ER) – 10-12 hour duration[10]
Oxycodone tamper-resistant (OxyContin OTR)[27]
Immediate-release oxycodone with paracetamol (acetaminophen) (Percocet, Endocet, Roxicet, Tylox)
Immediate-release oxycodone with aspirin (Endodan, Oxycodan, Percodan, Roxiprin)
Immediate-release oxycodone with ibuprofen (Combunox)[28]
Controlled-release oxycodone with naloxone (Targin, Targiniq, Targinact)[29] – 10-12 hour duration[10]
Controlled-release oxycodone with naltrexone (Troxyca) – 10-12 hour duration[10][30]
In the U.S., 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 Europe.[31][32][33] 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.[2]
Side effectsEdit
Main side effects of oxycodone[34]
Two tablets (10 mg) of oxycodone and safety blisters
Serious side effects of oxycodone include reduced sensitivity to pain (beyond the pain the drug is taken to reduce), euphoria, anxiolysis, feelings of relaxation, and respiratory depression.[35] Common side effects of oxycodone include constipation (23%), nausea (23%), vomiting (12%), somnolence (23%), dizziness (13%), itching (13%), dry mouth (6%), and sweating (5%).[35][36] Less common side effects (experienced by less than 5% of patients) include loss of appetite, nervousness, abdominal pain, diarrhea, urine retention, dyspnea, and hiccups.[37] Most side effects generally become less intense over time, although issues related to constipation are likely to continue for the duration of use.[38] Oxycodone in combination with naloxone in managed-release tablets, has been formulated to both deter abuse and reduce "opioid-induced constipation".[39]
Dependence and withdrawalEdit
See also: Opioid dependence
The risk of experiencing severe withdrawal symptoms is high if a patient has become physically dependent and discontinues oxycodone abruptly. Medically, when the drug has been taken regularly over an extended period, it is withdrawn gradually rather than abruptly. People who regularly use oxycodone recreationally or at higher than prescribed doses are at even higher risk of severe withdrawal symptoms. The symptoms of oxycodone withdrawal, as with other opioids, may include "anxiety, panic attack, nausea, insomnia, muscle pain, muscle weakness, fevers, and other flu-like symptoms".[40]
Withdrawal symptoms have also been reported in newborns whose mothers had been either injecting or orally taking oxycodone during pregnancy.[41]
Hormone levelsEdit
See also: Opioid § Low sex hormone levels
As with other opioids, chronic use of oxycodone (particularly with higher doses) often causes concurrent hypogonadism (low sex hormone levels).[42]
OverdoseEdit
In high doses, overdoses, or in some persons not tolerant to opioids, oxycodone can cause shallow breathing, slowed heart rate, cold/clammy skin, pauses in breathing, low blood pressure, constricted pupils, circulatory collapse, respiratory arrest, and death.[37]
In 2011, it was the leading cause of drug-related deaths in the U.S.[43] However, from 2012 onwards, heroin and fentanyl have become more common causes of drug-related deaths.[43]
Oxycodone overdose has also been described to cause spinal cord infarction in high doses and ischemic damage to the brain, due to prolonged hypoxia from suppressed breathing.[44]
InteractionsEdit
Oxycodone is metabolized by the enzymes CYP3A4 and CYP2D6, and its clearance therefore can be altered by inhibitors and inducers of these enzymes, increasing and decreasing half-life, respectively.[32] (For lists of CYP3A4 and CYP2D6 inhibitors and inducers, see here and here, respectively.) Natural genetic variation in these enzymes can also influence the clearance of oxycodone, which may be related to the wide inter-individual variability in its half-life and potency.[32]
Ritonavir or lopinavir/ritonavir greatly increase plasma concentrations of oxycodone in healthy human volunteers due to inhibition of CYP3A4 and CYP2D6.[45] Rifampicin greatly reduces plasma concentrations of oxycodone due to strong induction of CYP3A4.[46] There is also a case report of fosphenytoin, a CYP3A4 inducer, dramatically reducing the analgesic effects of oxycodone in a chronic pain patient.[47] Dosage or medication adjustments may be necessary in each case.[45][46][47]
PharmacologyEdit
PharmacodynamicsEdit
Oxycodone (and metabolite) at opioid receptors
Affinities (Ki)
MOR:DOR:KOR
Oxycodone 18 nM 958 nM 677 nM 1:53:38 [48]
Oxymorphone 0.78 nM 50 nM 137 nM 1:64:176 [49]
Equianalgesic doses[50][51][52]
Codeine PO 200 mg
Hydrocodone PO 20–30 mg
Hydromorphone PO 7.5 mg
Hydromorphone IV 1.5 mg
Morphine PO 30 mg
Morphine IV 10 mg
Oxycodone PO 20 mg
Oxycodone IV 10 mg
Oxymorphone PO 10 mg
Oxymorphone IV 1 mg
Oxycodone, a semi-synthetic opioid, is a highly selective full agonist of the μ-opioid receptor (MOR).[31][32] This is the main biological target of the endogenous opioid neuropeptide β-endorphin.[13] Oxycodone has low affinity for the δ-opioid receptor (DOR) and the κ-opioid receptor (KOR), where it is an agonist similarly.[31][32] After oxycodone binds to the MOR, a G protein-complex is released, which inhibits the release of neurotransmitters by the cell by decreasing the amount of cAMP produced, closing calcium channels, and opening potassium channels.[53] Opioids like oxycodone are thought to produce their analgesic effects via activation of the MOR in the midbrain periaqueductal gray (PAG) and rostral ventromedial medulla (RVM).[54] Conversely, they are thought to produce reward and addiction via activation of the MOR in the mesolimbic reward pathway, including in the ventral tegmental area, nucleus accumbens, and ventral pallidum.[55][56] Tolerance to the analgesic and rewarding effects of opioids is complex and occurs due to receptor-level tolerance (e.g., MOR downregulation), cellular-level tolerance (e.g., cAMP upregulation), and system-level tolerance (e.g., neural adaptation due to induction of ΔFosB expression).[57]
Taken orally, 20 mg of immediate-release oxycodone is considered to be equivalent in analgesic effect to 30 mg of morphine,[58][59] while extended release oxycodone is considered to be twice as potent as oral morphine.[60]
Similarly to most other opioids, oxycodone increases prolactin secretion, but its influence on testosterone levels is unknown.[31] Unlike morphine, oxycodone lacks immunosuppressive activity (measured by natural killer cell activity and interleukin 2 production in vitro); the clinical relevance of this has not been clarified.[31]
Active metabolitesEdit
A few of the metabolites of oxycodone have also been found to be active as MOR agonists, some of which notably have much higher affinity for (as well as higher efficacy at) the MOR in comparison.[61][62][63] Oxymorphone possesses 3- to 5-fold higher affinity for the MOR than does oxycodone,[5] while noroxycodone and noroxymorphone possess one-third of and 3-fold higher affinity for the MOR, respectively,[5][63] and MOR activation is 5- to 10-fold less with noroxycodone but 2-fold higher with noroxymorphone relative to oxycodone.[64] Noroxycodone, noroxymorphone, and oxymorphone also have longer biological half-lives than oxycodone.[61][65]
Pharmacology of oxycodone and metabolites[35][64]
Oxycodone 16.0 nM 343 nM 23.2 ± 8.6 ng/mL 236 ± 102 ng/h/mL
Oxymorphone 0.36 nM 42.8 nM 0.82 ± 0.85 ng/mL 12.3 ± 12 ng/h/mL
Noroxycodone 57.1 nM 1930 nM 15.2 ± 4.5 ng/mL 233 ± 102 ng/h/mL
Noroxymorphone 5.69 nM 167 nM ND ND
Ki is for [3H]diprenorphine displacement. (Note that diprenorphine is a non-selective opioid receptor ligand, so this is not MOR-specific.) EC50 is for hMOR1 GTPyS binding. Cmax and AUC levels are for 20 mg CR oxycodone.
However, despite the greater in vitro activity of some of its metabolites, it has been determined that oxycodone itself is responsible for 83.0% and 94.8% of its analgesic effect following oral and intravenous administration, respectively.[62] Oxymorphone plays only a minor role, being responsible for 15.8% and 4.5% of the analgesic effect of oxycodone after oral and intravenous administration, respectively.[62] Although the CYP2D6 genotype and the route of administration result in differential rates of oxymorphone formation, the unchanged parent compound remains the major contributor to the overall analgesic effect of oxycodone.[62] In contrast to oxycodone and oxymorphone, noroxycodone and noroxymorphone, while also potent MOR agonists, poorly cross the blood–brain barrier into the central nervous system, and for this reason are only minimally analgesic in comparison.[61][64][62][63]
κ-opioid receptorEdit
In 1997, a group of Australian researchers proposed (based on a study in rats) that oxycodone acts on KORs, unlike morphine, which acts upon MORs.[66] Further research by this group indicated the drug appears to be a high-affinity κ2b-opioid receptor agonist.[67] However, this conclusion has been disputed, primarily on the basis that oxycodone produces effects that are typical of MOR agonists.[68] In 2006, research by a Japanese group suggested the effect of oxycodone is mediated by different receptors in different situations.[69] Specifically in diabetic mice, the KOR appears to be involved in the antinociceptive effects of oxycodone, while in nondiabetic mice, the μ1-opioid receptor seems to be primarily responsible for these effects.[69][70]
PharmacokineticsEdit
Instant-release absorption profileEdit
Oxycodone can be administered orally, intranasally, via intravenous, intramuscular, or subcutaneous injection, or rectally. The bioavailability of oral administration of oxycodone averages within a range of 60 to 87%, with rectal administration yielding the same results; intranasal varies between individuals with a mean of 46%.[71]
After a dose of conventional (instant-release) oral oxycodone, the onset of action is 10 to 30 minutes,[5][6] and peak plasma levels of the drug are attained within roughly 30 to 60 minutes;[5][6][61] in contrast, after a dose of OxyContin (an oral controlled-release formulation), peak plasma levels of oxycodone occur in about three hours.[37] The duration of instant-release oxycodone is 3 to 6 hours, although this can be variable depending on the individual.[5]
DistributionEdit
Oxycodone has a volume of distribution of 2.6L/kg,[72] in the blood it is distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, and brain.[37] Conventional oral preparations start to reduce pain within 10 to 15 minutes on an empty stomach; in contrast, OxyContin starts to reduce pain within one hour.[11]
MetabolismEdit
The metabolism of oxycodone in humans occurs in the liver mainly via the cytochrome P450 system and is extensive (about 95%) and complex, with many minor pathways and resulting metabolites.[5][73] Around 10% (range 8–14%) of a dose of oxycodone is excreted essentially unchanged (unconjugated or conjugated) in the urine.[5] The major metabolites of oxycodone are noroxycodone (70%), noroxymorphone ("relatively high concentrations"),[35] and oxymorphone (5%).[61][64] The immediate metabolism of oxycodone in humans is as follows:[5][9][74]
N-Demethylation to noroxycodone predominantly via CYP3A4
O-Demethylation to oxymorphone predominantly via CYP2D6
6-Ketoreduction to 6α- and 6β-oxycodol
N-Oxidation to oxycodone-N-oxide
In humans, N-demethylation of oxycodone to noroxycodone by CYP3A4 is the major metabolic pathway, accounting for 45% ± 21% of a dose of oxycodone, while O-demethylation of oxycodone into oxymorphone by CYP2D6 and 6-ketoreduction of oxycodone into 6-oxycodols represent relatively minor metabolic pathways, accounting for 11% ± 6% and 8% ± 6% of a dose of oxycodone, respectively.[5][31]
Several of the immediate metabolites of oxycodone are subsequently conjugated with glucuronic acid and excreted in the urine.[5] 6α-Oxycodol and 6β-oxycodol are further metabolized by N-demethylation to nor-6α-oxycodol and nor-6β-oxycodol, respectively, and by N-oxidation to 6α-oxycodol-N-oxide and 6β-oxycodol-N-oxide (which can subsequently be glucuronidated as well).[5][9] Oxymorphone is also further metabolized, as follows:[5][9][74]
3-Glucuronidation to oxymorphone-3-glucuronide predominantly via UGT2B7
6-Ketoreduction to 6α-oxymorphol and 6β-oxymorphol
N-Demethylation to noroxymorphone
The first pathway of the above three accounts for 40% of the metabolism of oxymorphone, making oxymorphone-3-glucuronide the main metabolite of oxymorphone, while the latter two pathways account for less than 10% of the metabolism of oxymorphone.[74] After N-demethylation of oxymorphone, noroxymorphone is further glucuronidated to noroxymorphone-3-glucuronide.[74]
Because oxycodone is metabolized by the cytochrome P450 system in the liver, its pharmacokinetics can be influenced by genetic polymorphisms and drug interactions concerning this system, as well as by liver function.[37] Some people are fast metabolizers of oxycodone, resulting in reduced effects, while others are slow metabolizers, resulting in increased effects and toxicity.[75][76] While higher CYP2D6 activity increases the effects of oxycodone (owing to increased conversion into oxymorphone), higher CYP3A4 activity has the opposite effect and decreases the effects of oxycodone (owing to increased metabolism into noroxycodone and noroxymorphone).[77] The dose of oxycodone must be reduced in patients with reduced liver function.[78]
EliminationEdit
The clearance of oxycodone is 0.8 L/min.[79] Oxycodone and its metabolites are mainly excreted in urine.[80] Therefore, oxycodone accumulates in patients with kidney impairment.[78] Oxycodone is eliminated in the urine 10% as unchanged oxycodone, 45% ± 21% as N-demethylated metabolites (noroxycodone, noroxymorphone, noroxycodols), 11 ± 6% as O-demethylated metabolites (oxymorphone, oxymorphols), and 8% ± 6% as 6-keto-reduced metabolites (oxycodols).[80][81]
Duration of actionEdit
Oxycodone has a half-life of 4.5 hours.[72] It is available as a generic medication.[11] Its manufacturer Purdue Pharma claimed in their 1992 patent application that the duration of action of OxyContin, oxycodone's controlled-release preparation, is 12 hours in "90% of patients." It has never performed any clinical studies in which OxyContin was given at more frequent intervals. In a separate filing, Purdue claims that controlled-release oxycodone "provides pain relief in said patient for at least 12 hours after administration."[82] However, in 2016 an investigation by the Los Angeles Times found that "the drug weans off hours early in many people," inducing symptoms of opiate withdrawal and intense cravings for OxyContin. One doctor Lawrence Robbins told journalists that over 70% of his patients would report that OxyContin would only provide 4–7 hours of relief. Doctors in the 1990s often would switch their patients to a dosing schedule of once every eight hours when they complained that the duration of action for OxyContin was too short to be only taken twice a day.[82][83]
Purdue strongly discouraged the practice: Purdue's medical director Robert Reder wrote to one doctor in 1995 that "OxyContin has been developed for [12-hour] dosing...I request that you not use a [8-hourly] dosing regimen." Purdue repeatedly released memos to its sales representatives ordering them to remind doctors not to deviate from a 12-hour dosing schedule. One such memo read, "There is no Q8 dosing with OxyContin... [8-hour dosing] needs to be nipped in the bud. NOW!!"[82] The journalists who covered the investigation argue that Purdue Pharma has insisted on a 12-hour duration of action for nearly all patients, despite evidence to the contrary, in order to protect the reputation of OxyContin as a 12-hour drug and the willingness of health insurance and managed care companies to cover OxyContin despite its high cost relative to generic opiates such as morphine.[82]
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.[82]
ChemistryEdit
See also: List of opioids
Oxycodone's chemical name is derived from codeine. The chemical structures are very similar, differing only in that
Oxycodone has a hydroxy group at carbon-14 (codeine has just a hydrogen in its place)
Oxycodone has a 7,8-dihydro feature. Codeine has a double bond between those two carbons; and
Oxycodone has a carbonyl group (as in ketones) in place of the hydroxyl group of codeine.
It is also similar to hydrocodone, differing only in that it has a hydroxyl group at carbon-14.[78]
Oxycodone is marketed as various salts, most commonly as the hydrochloride salt. The free base conversion ratios of different salts are: hydrochloride (0.896), bitartrate (0.667), tartrate (0.750), camphosulfonate (0.576), pectinate (0.588), phenylpriopionate (0.678), sulfate (0.887), phosphate (0.763), and terephthalate (0.792). The hydrochloride salt is the basis of most American oxycodone products whilst bitartrate, tartrate, pectinate, terephthalate and phosphate salts are also available in European products. Methyiodide and hydroiodide are mentioned in older European publications.
BiosynthesisEdit
In terms of biosynthesis, oxycodone has been found naturally in nectar extracts from the orchid family Epipactis helleborine; together along with another opioid: 3-{2-{3-{3-benzyloxypropyl}-3-indol, 7,8-didehydro- 4,5-epoxy-3,6-d-morphinan.[84]
Detection in biological fluidsEdit
Oxycodone and/or its major metabolites may be measured in blood or urine to monitor for clearance, abuse, confirm a diagnosis of poisoning, or assist in a medicolegal death investigation. Many commercial opiate screening tests cross-react appreciably with oxycodone and its metabolites, but chromatographic techniques can easily distinguish oxycodone from other opiates.[85]
Freund and Speyer of the University of Frankfurt in Germany first synthesized oxycodone from Thebaine in 1916,[15] a few years after the German pharmaceutical company Bayer had stopped the mass production of heroin due to hazardous use, harmful use, and dependence. It was hoped that a thebaine-derived drug would retain the analgesic effects of morphine and heroin with less dependence. Unfortunately, this was ultimately not found to be the case.
The first clinical use of the drug was documented in 1917, the year after it was first developed.[15][10] 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.[86] 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 morphine, hydromorphone, and hydrocodone for this product because of oxycodone having subjective elements in its side effect profile similar to cocaine.[87]
During Operation Himmler, Skophedal was also reportedly injected in massive overdose into the prisoners dressed in Polish Army uniforms in the staged incident on 1 September 1939 which opened the Second World War.[86][88]
The personal notes of Adolf Hitler's physician, Theodor Morell, indicate Hitler received repeated injections of "eukodal" (oxycodone) and Scophedal, as well as Dolantin (pethidine) codeine, and morphine less frequently; oxycodone could not be obtained after late January 1945 and it is likely that Hitler went through full-scale withdrawal.[89][90] Eukodal, Dicodid (hydrocodone), cocaine, and methamphetamine in different proportions were the basis of a combat drug tested by the Nazis late in 1944; the ninth in the series of ten formulae, called D IX (Drug no. 9) with 3 mg methamphetamine, 5 mg cocaine, and 5 mg eukodal with no Dicodid was given to mini-sub captains in a disastrous roll-out which led to the end of that combat drug programme.[91] Hermann Göring was taken into custody by the Americans with thousands of doses of oxycodone as well as the entire world supply of dihydrocodeine in two large suitcases.[92][93]
In the early 1970s, the U.S. government classified oxycodone as a schedule II drug.
Purdue Pharma — a privately held company based in Stamford, Connecticut, developed the prescription painkiller OxyContin. Upon its release in 1995, OxyContin was hailed as a medical breakthrough, a long-lasting narcotic that could help patients suffering from moderate to severe pain. The drug became a blockbuster, and has reportedly generated some US$35 billion in revenue for Purdue.[94]
Society and cultureEdit
NamesEdit
Expanded expressions for the compound oxycodone in the academic literature include "dihydrohydroxycodeinone",[3][95][96] "Eucodal",[95][96] "Eukodal",[2][10] "14-hydroxydihydrocodeinone",[3][95] and "Nucodan".[95][96] In a UNESCO convention, the translations of "oxycodone" are oxycodon (Dutch), oxycodone (French), oxicodona (Spanish), الأوكسيكودون (Arabic), 羟考酮 (Chinese), and оксикодон (Russian).[97] The word "oxycodone" should not be confused with "oxandrolone", "oxazepam", "oxybutynin", "oxytocin", or "Roxanol".[98]
Other brand names include Longtec and Shortec.[99]
Legal statusEdit
GeneralEdit
Oxycodone is subject to international conventions on narcotic drugs. In addition, oxycodone is subject to national laws that differ by country. The 1931 Convention for Limiting the Manufacture and Regulating the Distribution of Narcotic Drugs of the League of Nations included oxycodone.[100] The 1961 Single Convention on Narcotic Drugs of the United Nations, which replaced the 1931 convention, categorized oxycodone in Schedule I.[101] Global restrictions on Schedule I drugs include "limit[ing] exclusively to medical and scientific purposes the production, manufacture, export, import, distribution of, trade in, use and possession of" these drugs; "requir[ing] medical prescriptions for the supply or dispensation of [these] drugs to individuals"; and "prevent[ing] the accumulation" of quantities of these drugs "in excess of those required for the normal conduct of business".[101]
AustraliaEdit
Oxycodone is in Schedule I (derived from the Single Convention on Narcotic Drugs) of the Commonwealth's Narcotic Drugs Act 1967.[102] In addition, it is in Schedule 8 of the Australian Standard for the Uniform Scheduling of Drugs and Poisons ("Poisons Standard"), meaning it is a "controlled drug... which should be available for use but require[s] restriction of manufacture, supply, distribution, possession and use to reduce abuse, misuse and physical or psychological dependence".[103]
CanadaEdit
Oxycodone is a controlled substance under Schedule I of the Controlled Drugs and Substances Act (CDSA).[104]
Canadian legislative changesEdit
Canadian oxycodone HCL/acetaminophen 5/325 mg tablet
In February 2012, Ontario passed legislation to allow the expansion of an already existing drug-tracking system for publicly funded drugs to include those that are privately insured. This database will function to identify and monitor patient's attempts to seek prescriptions from multiple doctors or retrieve from multiple pharmacies. Other provinces have proposed similar legislation, while some, such as Nova Scotia, have legislation already in effect for monitoring prescription drug use. These changes have coincided with other changes in Ontario's legislation to target the misuse of painkillers and high addiction rates to drugs such as oxycodone. As of February 29, 2012, Ontario passed legislation delisting oxycodone from the province's public drug benefit program. This was a first for any province to delist a drug based on addictive properties. The new law prohibits prescriptions for OxyNeo except to certain patients under the Exceptional Access Program including palliative care and in other extenuating circumstances. Patients already prescribed oxycodone will receive coverage for an additional year for OxyNeo, and after that, it will be disallowed unless designated under the exceptional access program.[105]
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 preventative 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.[106] This Act, introduced in 2010, commits to the establishment of a unified database to fulfil this intention.[107] 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.[108]
In 2015, Purdue Pharma's abuse-resistant OxyNEO and six generic versions of OxyContin had been on the Canada-wide approved list for prescriptions since 2012. In June 2015, then federal Minister of Health Rona Ambrose announced that within three years all oxycodone products sold in Canada would need to be tamper-resistant. Some experts warned that the generic product manufacturers may not have the technology to achieve that goal, possibly giving Purdue Pharma a monopoly on this opiate.[109]
Canadian lawsuitsEdit
Several class action suits across Canada have been launched against the Purdue group of companies and affiliates. Claimants argue the pharmaceutical manufacturers did not meet a standard of care and were negligent in doing so. These lawsuits reference earlier judgments in the United States, which held that Purdue was liable for wrongful marketing practices and misbranding. Since 2007, the Purdue companies have paid over CAN$650 million in settling litigation or facing criminal fines.
GermanyEdit
The drug is in Appendix III of the Narcotics Act (Betäubungsmittelgesetz or BtMG).[110] The law allows only physicians, dentists, and veterinarians to prescribe oxycodone and the federal government to regulate the prescriptions (e.g., by requiring reporting).[110]
Hong KongEdit
Oxycodone is regulated under Part I of Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance.[111]
JapanEdit
Oxycodone is a restricted drug in Japan. Its import and export is strictly restricted to specially designated organizations having prior permit to import it. In a high-profile case an American who was a top Toyota executive living in Tokyo, who claimed to be unaware of the law, was arrested for importing oxycodone into Japan.[112][113]
SingaporeEdit
Oxycodone is listed as a Class A drug in the Misuse of Drugs Act of Singapore, which means offences in relation to the drug attract the most severe level of punishment. A conviction for unauthorized manufacture of the drug attracts a minimum sentence of 10 years of imprisonment and corporal punishment of 5 strokes of the cane, and a maximum sentence of life imprisonment or 30 years of imprisonment and 15 strokes of the cane.[114] The minimum and maximum penalties for unauthorized trafficking in the drug are respectively 5 years of imprisonment and 5 strokes of the cane, and 20 years of imprisonment and 15 strokes of the cane.[115]
United KingdomEdit
Oxycodone is a Class A drug under the Misuse of Drugs Act.[116] For Class A drugs, which are "considered to be the most likely to cause harm", possession without a prescription is punishable by up to seven years in prison, an unlimited fine, or both.[117] Dealing of the drug illegally is punishable by up to life imprisonment, an unlimited fine, or both.[117] In addition, oxycodone is a Schedule 2 drug per the Misuse of Drugs Regulations 2001 which "provide certain exemptions from the provisions of the Misuse of Drugs Act 1971".[118]
United StatesEdit
Under the Controlled Substances Act, oxycodone is a Schedule II controlled substance whether by itself or part of a multi-ingredient medication.[119] 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.[120]
Recreational useEdit
EffectsEdit
Oxycodone, like other opioid analgesics, tends to induce feelings of euphoria, relaxation and reduced anxiety in those who are occasional users.[121] These effects make it one of the most commonly abused pharmaceutical drugs in the United States.[122]
Preventive measuresEdit
In August 2010, Purdue Pharma reformulated their long-acting oxycodone line, marketed as OxyContin, using a polymer, Intac,[123] to make the pills extremely difficult to crush or dissolve[124] in water to reduce OxyContin abuse.[125] The FDA approved relabeling the reformulated version as abuse-resistant in April 2013.[126]
Pfizer manufactures a preparation of short-acting oxycodone, marketed as Oxecta, which contains inactive ingredients, referred to as tamper-resistant Aversion Technology.[127] It does not deter oral abuse. Approved by the FDA in the U.S. in June 2011, the new formulation makes crushing, chewing, snorting, or injecting the opioid impractical because of a change in its chemical properties.[128]
The non-medical use of oxycodone existed from the early 1970s, but by 2015, 91% of a national sample of injecting drug users in Australia had reported using oxycodone, and 27% had injected it in the last six months.[129]
Opioid-related deaths in Ontario had increased by 242% from 1969 to 2014.[130] By 2009 in Ontario there were more deaths from oxycodone overdose than from cocaine overdose.[131] Deaths from opioid pain relievers had increased from 13.7 deaths per million residents in 1991 to 27.2 deaths per million residents in 2004.[132] The abuse of oxycodone in Canada became a problem. Areas where oxycodone is most problematic are Atlantic Canada and Ontario, where its abuse is prevalent in rural towns, and in many smaller to medium-sized cities.[133] Oxycodone is also widely available across Western Canada, but methamphetamine and heroin are more serious problems in the larger cities, while oxycodone is more common in rural towns. Oxycodone is diverted through doctor shopping, prescription forgery, pharmacy theft, and overprescribing.[133][134]
The recent formulations of oxycodone, particularly Purdue Pharma's crush-, chew-, injection- and dissolve-resistant OxyNEO[135] which replaced the banned OxyContin product in Canada in early 2012, have led to a decline in the abuse of this opiate but have increased the abuse of the more potent drug fentanyl.[136] 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.[137]
In Alberta, the Blood Tribe police claimed that from the fall of 2014 through January 2015, oxycodone pills or a lethal fake variation referred to as Oxy 80s[138] containing fentanyl made in illegal labs by members of organized crime were responsible for ten deaths on the Blood Reserve, which is located southwest of Lethbridge, Alberta.[139] Province-wide, approximately 120 Albertans died from fentanyl-related overdoses in 2014.[138]
Abuse and diversion of oxycodone in the UK commenced in the early- to mid-2000s.[140] The first known death due to overdose in the UK occurred in 2002.[141] However, recreational use remains relatively rare.
Further information: Opioid epidemic in the United States
In the United States, more than 12 million people use opioid drugs recreationally.[142] Opioids were responsible for 49,000 of the 72,000 drug overdose deaths in the U.S. in 2017.[143] In September 2013, the FDA released new labeling guidelines for long acting and extended release opioids requiring manufacturers to remove moderate pain as indication for use, instead stating the drug is for "pain severe enough to require daily, around-the-clock, long term opioid treatment."[144] The updated labeling will not restrict physicians from prescribing opioids for moderate, as needed use.[142]
Oxycodone is the most widely recreationally used opioid in America. 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.[145] In 2007, about 42,800 emergency room visits occurred due to "episodes" involving oxycodone.[146] Diverted oxycodone may be taken orally or ingested through insufflation; used intravenously, or the heated vapors inhaled. In 2008, recreational use of oxycodone and hydrocodone were involved in 14,800 deaths. Some of the cases were due to overdoses of the acetaminophen component, resulting in fatal liver damage.[147]
Reformulated OxyContin is causing some recreational users to change to heroin, which is cheaper and easier to obtain.[148]
EconomicsEdit
The International Narcotics Control Board estimated 11.5 short tons (10.4 t) of oxycodone were manufactured worldwide in 1998;[149] by 2007 this figure had grown to 75.2 short tons (68.2 t).[149] United States accounted for 82% of consumption in 2007 at 51.6 short tons (46.8 t). Canada, Germany, Australia, and France combined accounted for 13% of consumption in 2007.[149][150] In 2010, 1.3 short tons (1.2 t) of oxycodone were illegally manufactured using a fake pill imprint. This accounted for 0.8% of consumption. These illicit tablets were later seized by the U.S. Drug Enforcement Administration, according to the International Narcotics Control Board.[151] The board also reported 122.5 short tons (111.1 t) manufactured in 2010. This number had decreased from a record high of 135.9 short tons (123.3 t) in 2009.[152]
LawsuitsEdit
In October 2017, The New Yorker published a story on Mortimer Sackler and Purdue Pharma regarding their ties to the production and manipulation of the oxycodone markets.[94] The article links Raymond and Arthur Sackler's business practices with the rise of direct pharmaceutical marketing and eventually to the rise of addiction to oxycodone in the United States. The article implies that Sackler bears some responsibility for the opioid epidemic in the United States.[153] In 2019 the New York Times ran a piece confirming Sackler told company officials in 2008 to "measure our performance by Rx's by strength, giving higher measures to higher strengths."[154] This was verified with documents tied to a lawsuit – which was filed by the Massachusetts attorney general, Maura Healey – claiming that Purdue Pharma and members of the Sackler family knew that high doses of OxyContin over long periods would increase the risk of serious side effects, including addiction.[155] Despite Purdue Pharma's proposal for a US$12 billion settlement of the lawsuit, the attorneys general of 23 states, including Massachusetts, rejected the settlement offer in September, 2019.[156]
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^ Baselt, R. (2017) Disposition of Toxic Drugs and Chemicals in Man, 11th edition, Biomedical Publications, Foster City, CA, pp. 1604–1607.
^ a b Defalque, Ray; Wright, Amos (October 2003). "Schophedal (SEE) Was it a Fad or a Miracle Drug?". Bulletin of Anesthesia History. 21 (4): 12–14. doi:10.1016/S1522-8649(03)50051-8. PMID 17494237.
^ William S Burroughs 1952 letter to Allen Ginsburg concerning Eukodal, in Collected Correspondance, pp 141-2
^ Merck 1930 package insert for Skophedal (German)
^ Breitenbach, Dagmar (9 September 2015). "A fresh light on the Nazis' wartime drug addiction". Deutsche Welle. Retrieved 2016-04-24.
^ Blitzed: Drugs In The Third Reich, Normal Ohler, 2017, pp 194 et seq
^ Ohler, pp 194
^ Dihydrocodeine
^ a b Keefe, Patrick Radden (2017-10-23). "The Family That Built an Empire of Pain". The New Yorker. ISSN 0028-792X. Retrieved 2019-02-02.
^ a b c d Eddy NB (1973). The National Research Council involvement in the opiate problem, 1928–1971. Washington: National Academy of Sciences.
^ a b c May EL, Jacobson AE (1989). "The Committee on Problems of Drug Dependence: a legacy of the National Academy of Sciences. A historical account". Drug Alcohol Depend. 23 (3): 183–218. doi:10.1016/0376-8716(89)90083-5. PMID 2666074.
^ United Nations Educational, Scientific; Cultural Organization (2005). "International convention against doping in sport" (PDF). Retrieved 2009-04-04.
^ Hicks RW, Becker SC, Cousins DD, eds. (2008). MEDMARX data report. A report on the relationship of drug names and medication errors in response to the Institute of Medicine's call for action (PDF). Rockville, MD: Center for the Advancement of Patient Safety, US Pharmacopeia. Retrieved 2009-04-04. [permanent dead link]
^ postlethwaite, Julia. "Oxycodone Longtec Patient Leaflet" (PDF). Great Western Hospitals NHS Foundation Trust. Great Western Hospitals NHS Foundation Trust. Retrieved 23 March 2019.
^ League of Nations (1931). "Convention for limiting the manufacture and regulating the distribution of narcotic drugs" (PDF). Retrieved 2009-04-04.
^ a b "United Nations conference for the adoption of a single convention on narcotic drugs. Final act" (PDF). 1961. Archived from the original (PDF) on 2011-08-17. Retrieved 2009-04-04.
^ Commonwealth of Australia. "Narcotic Drugs Act 1967 – first schedule". Australasian Legal Information Institute. Retrieved 2009-04-06.
^ Australian Government. Department of Health and Aging. Therapeutic Goods Administration (June 2008). Standard for the uniform scheduling of drugs and poisons no. 23 (PDF). Canberra: Commonwealth of Australia. ISBN 978-1-74186-596-7. Retrieved 2009-04-06.
^ Canada Department of Justice (2009-02-27). "Controlled Drugs and Substances Act (1996, c. 19)". Retrieved 2009-03-23.
^ Olgilvie, Megan. "Ontario delisting OxyContin and its substitute from drug benefit program" Toronto Star (2012-02-17)
^ Narcotics Safety and Awareness Act. 2010. Ministry of Health and Long Term Care.
^ Dhalla, Irfan; Born, Karen (2012-02-22). "Opioids". healthydebate.ca. Archived from the original on March 21, 2015.
^ Ontario OxyContin Rules: New Restrictions Applauded But National Rules Needed. Huffington Post. Canadian Press (2012-02-20)
^ Weeks, Carly; Howlett, Karen (August 4, 2015). "New oxycodone rules would give drug maker a monopoly in Canada, experts warn". Globe and Mail. Toronto, Ontario. Retrieved December 15, 2015.
^ a b German Federal Ministry of Justice (2009-01-19). "Act on the circulation of narcotics (Narcotics Act – BtMG)" (in German). Retrieved 2009-04-06.
^ Hong Kong Special Administrative Region, People's Republic of China. "Dangerous drugs ordinance – chapter 134". Hong Kong Legal Information Institute. Archived from the original on 2007-12-15. Retrieved 2009-04-08.
^ "Toyota's American PR chief arrested for suspected drug violation". Retrieved 11 February 2018.
^ "Toyota: American exec did not intend to break Japan law". Archived from the original on 19 June 2015. Retrieved 11 February 2018.
^ Misuse of Drugs Act (Cap. 185, 2008 Rev. Ed.) (Singapore), section 6(1).
^ Misuse of Drugs Act (Singapore), section 5(1).
^ "List of drugs currently controlled under the Misuse of Drugs legislation" (PDF). UK. Home Office. 2009. Archived from the original (PDF) on 2007-02-05. Retrieved 2009-04-08.
^ a b "Class A, B and C drugs". UK. Home Office. Archived from the original on 2007-08-04. Retrieved 2009-04-08.
^ "Statutory instrument 2001 No. 3998. The Misuse of Drugs regulations 2001". UK. Office of Public Sector Information. Retrieved 2009-04-08.
^ DEA. "Controlled substance scheduling". Drug information and scheduling. Drug Enforcerment Administration. Archived from the original on 21 November 2015. Retrieved 23 November 2015.
^ "DEA Diversion Control CSA". US Dept of Justice – DEA. Retrieved 23 May 2013.
^ "OxyContin: Pain Relief vs. Abuse". Retrieved 11 February 2018.
^ "Top 10 Most Commonly Abused Prescription Medications". 28 April 2014. Retrieved 11 February 2018.
^ "New Abuse Deterrent Formulation Technology for Immediate-Release Opiods" (PDF). Grünenthal Group. Grünenthal Group Worldwide. 2010. Archived from the original (PDF) on 2015-12-22. Retrieved December 15, 2015.
^ Diep, Francie (May 13, 2013). "How Do You Make a Painkiller Addiction-Proof". Popular Science. Bonnier Corporation. Retrieved January 30, 2019.
^ Coplan, Paul (2012). Findings from Purdue's Post-Marketing Epidemiology Studies of Reformulated OxyContin's Effects (PDF). NASCSA 2012 Conference. Scottsdale, Arizona. Archived from the original (PDF) on June 14, 2013.
^ "Press Announcements; FDA approves abuse-deterrent labeling for reformulated OxyContin". US Government – FDA. Retrieved 23 May 2013.
^ "Pfizer and Acura Announce FDA Approval of Oxectatm (Oxycodone HCL, USP) CII". Pfizer News and Media. Pfizer Inc. Retrieved December 15, 2015.
^ Fiore, Kristina (June 20, 2011). "FDA Okays New Abuse-Resistant Opioid". MedPage Today. MedPage Today. Retrieved December 15, 2015.
^ Black E (2008). Australian drug trends 2007. Findings from the Illicit Drug Reporting System (IDRS) (PDF). Sydney: National Drug and Alcohol Research Centre, University of New South Wales. ISBN 978-0-7334-2625-4. Archived from the original (PDF) on 2008-07-21.
^ Boyle, Theresa (7 July 2014), "Opioid deaths soaring, study finds Opioid-related deaths in Ontario jumped by a whopping 242 per cent over two decades, according to a study by ICES and St. Mike's", The Star, Toronto, Ontario, retrieved 23 January 2015
^ Donovan, Kevin (10 February 2009), "Oxycodone found to be more deadly than heroin", The Star, Toronto, Ontario, retrieved 23 January 2015
^ "Study finds huge rise in oxycodone deaths". CTV News. Retrieved 2009-12-07.
^ a b "OxyContin Fact Sheet" (PDF). ccsa.ca. Archived from the original (PDF) on 2008-11-17. Retrieved 2012-05-10.
^ "Health Canada – Misuse and Abuse of Oxycodone-based Prescription Drugs". Hc-sc.gc.ca. 2010-01-11. Archived from the original on 2011-11-26. Retrieved 2012-05-10.
^ Kirkey, Sharon (May 23, 2012). "OxyNEO another prescription for disaster?". Globe and Mail. Toronto, Ontario.
^ Criger, Erin (August 17, 2015). "Death of OxyContin behind rise of fentanyl?". CityNews. Rogers Digital Media. Retrieved February 7, 2019.
^ Gatehouse, Jonathon; Macdonald, Nancy (June 22, 2015). "Fentanyl: The King of all Opiates, and a Killer Drug Crisis". Macleans. Rogers Media. Retrieved December 15, 2015.
^ a b Southwick, Reid (December 2, 2015). "Fentanyl brings tragedy to Blood Tribe". Calgary Herald. Calgary, Alberta. Retrieved December 15, 2015.
^ Police believe organized crime is flooding the Blood Tribe reserve with an illegal drug that has been linked to 10 deaths, Alberta, 23 January 2015, archived from the original on 2016-01-24, retrieved 23 January 2015
^ Gordon T (2008-03-30). "Scots' use of 'hillbilly heroin' rises by 430%". Sunday Times (London).
^ Thompson T (2002-03-24). "Epidemic fear as 'hillbilly heroin' hits the streets". Society Guardian. Retrieved 2009-04-16.
^ a b Girioin, Lisa; Haely, Melissa (11 September 2013). "FDA to require stricter labeling for pain drugs". Los Angeles Times. pp. A1 and A9.
^ "Overdose Death Rates". www.drugabuse.gov. 29 January 2019. Retrieved 11 May 2019.
^ "ER/LA Opioid Analgesic Class Labeling Changes and Postmarket Requirements" (PDF). FDA. Retrieved 12 September 2013.
^ Now a counselor, she went from stoned to straight, San Francisco Chronicle, November 2. 2015.
^ "Oxycontin and Addiction". consumer.healthday.com. Retrieved 2016-04-24.
^ Policy Impact: Prescription Pain Killer Overdoses Centers for Disease Control and Prevention. Retrieved 24 December 2013.
^ Reformulated OxyContin reduces abuse but many addicts have switched to heroin, The Pharmaceutical Journal, 16 March 2015.
^ a b c International Narcotics Control Board (2009). Narcotic drugs: estimated world requirements for 2009; statistics for 2007. Report E/INCB/2008/2 (PDF). New York: United Nations. ISBN 978-92-1-048124-3.
^ "Availability of Opioid Analgesics in the World and Asia, With a special focus on: Indonesia, Philippines, Thailand" (PDF). University of Wisconsin Pain & Policy Studies Group/World Health Organization (WHO) Collaborating Center for Policy and Communications in Cancer Care. United Nations. Archived from the original (PDF) on 26 April 2012. Retrieved 27 November 2011.
^ Narcotic Drugs: Estimated World Requirements for 2012 and Statistics for 2010[permanent dead link]. International Narcotics Control Board (2011).
^ Narcotic Drugs: Estimated World Requirements for 2012 and Statistics for 2010. International Narcotics Control Board (2011).
^ Keefe, Patrick Radden (23 October 2017). "The Family That Built an Empire of Pain". The New Yorker. ISSN 0028-792X. Retrieved 18 November 2017.
^ Meier, Barry (2019-01-31). "Sackler Scion's Email Reveals Push for High-Dose OxyContin, New Lawsuit Disclosures Claim". The New York Times. ISSN 0362-4331. Retrieved 2019-02-03.
^ Martha Bebinger; Christine Willmsen (15 January 2019). "Mass. AG Implicates Family Behind Purdue Pharma In Opioid Deaths". WBUR Boston. Retrieved 19 September 2019.
^ Nik DeCosta-Klipa (17 September 2019). "Maura Healey explains why she refused to join the Purdue Pharma settlement". Boston.com. Boston Globe Media Partners, LLC. Retrieved 19 September 2019.
Coluzzi, F.; Mattia, C. (July–August 2005). "Oxycodone. Pharmacological profile and clinical data in chronic pain management" (PDF). Minerva Anestesiol. 71 (7–8): 451–60. PMID 16012419. Archived from the original (PDF) on March 9, 2006.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Oxycodone&oldid=936301252"


Champagne – day or night in Marbella!
On this page, we look at some interesting things relating to food and drink.
To help you when ordering food in a Spanish restaurant, tapas bar or café, we have provided translations for some of the most important types of food. There are details of some of the more popular types of coffee and their Spanish names to help you order your perfect cup and there is a brief history of Spanish coffee.
There are of course plenty of bars in Marbella that specialize in cocktails or offer cocktails as an alternative to the usual selection of drinks. Its great fun to try all the different ones on offer. But, many of us enjoy making cocktails at home – especially when entertaining. We have provided details here of how to make some of the more popular cocktails to enjoy with friends on a hot Marbella night.
Visiting Spain? You may find this helpful when eating out.
Spanish restaurants and tapas bars can be an absolute delight. Some of the best restaurants in Europe can be found in Spain and they are usually in the major cities or in tourist areas. Unfortunately, many of us are not fluent in Spanish. So, when we encounter a restaurant with a Spanish menu, it is sometimes difficult to know what is on offer.
Coffee was originally brought to Spain by Turkish immigrants during the 17th century. Huge coffee plantations were later created in Central and South America by the descendants of Spanish conquistadors.
Drinking coffee has become a way of life in Spain. Spanish people will typically have a coffee first thing in the morning with their breakfast to get them started for the day. Then, at around 11.00 am, they will stop for a "merienda" (a short break) and have another coffee with a light snack – perhaps a pitufo or a bocadillo.


BRING YOUR BEST OFFER - MOTIVATED SELLERS! MOVE RIGHT IN! NEW FURNITURE AND FURNISHINGS INCLUDED IN PRICE! Imagine a pond/park view outside your front window – your view will not be another home! Quiet and serene surroundings yet you are minutes to shopping, I-75 and restaurants! What could be better? How about a saltwater pool and fenced yard (double lot) for entertaining to round out the lovely surroundings. Now imagine a newer built home (2017) with 1617 sq. ft. under air, spacious lanai, 3 bedrooms along with a den/dining room, kitchen with newer appliances, 2 bathrooms, 2 car garage, indoor laundry (washer and dryer convey) complete with security features, irrigation system (ask your agent for a complete list attached to this listing!). This home has been lovingly built and cared for by meticulous owners. The pictures tell the tale – why wait for a new build when you can have it all right here! NOTE: STREET VIEW MAP SHOWS THE LOT BEFORE THE BUILD.


The Triumph Speed Triple is a series of motorcycles produced by Triumph Motorcycles. In . "First Ride: Triumph Speed Triple R". Motorcyclist. Origins - Generations - T - and beyond. 20 Jan A gentleman's supernaked - Visordown is the world's fastest growing motorcycle website with all the latest motorbike reviews, motorcycle news. The purest, hardest performing and most rewarding naked sports motorcycle available today. We took the Speed Triple, the world's first and best factory.
Przyjrzyjmy się najpotężniejszym i najzwinniejszym motocyklom Speed Triple, zupełnie nowemu Speed Triple S oraz stanowiącej ukoronowanie linii wersji RS. 25 Jan You have to hand it to Triumph Motorcycles for staying true to its soul with the Speed Triple. Triumph has always had a certain sense of attitude. TRIUMPH SPEED TRIPLE R used motorbikes and new motorbikes for sale on MCN. Buy and sell TRIUMPH SPEED TRIPLE R bikes through MCN's. 5 Feb Triumph didn't reinvent the wheel, but it took two great performance Triple RS which replaces the Speed Triple R at the top of Triumph's line of "roadsters. Triumph is touting a good new sound for these bikes which we've. Our Triumph Motorcycles are located in the Euro Center inside of Bert's Mega Mall. Description: The Triumph Motorcycles Speed Triple R comes in two colors.
Find new and used Triumph Speed Triple Motorcycles for sale by motorcycle .. Triumph Speed Triple R Ultimate Performance One of the most iconic. Triumph Speed Triple would be launching in India around November with Powering the motorcycle is a cc, triple-cylinder motor developing. Come with Bike on a quick trip to Spain to see the new Triumph Speed Triple R. You can read the full first test in the April issue of Bike magazine, on sale. 22 Feb - 9 min - Uploaded by Bike World We joined Bruce from Fast Bikes mag for the launch of the new Triumph Speed Triple RS.


This black tote features the Owl print in grey. This sweet image was originally hand drawn in pencil. The main section of the bag measures approx. 37cm wide x 41cm high making it ideal for casual wear & shopping as well as college & work as will easily fit your A4 books/folders.


Understanding the difficulty of winning back a majority with Republicandrawn. Raleigh, NC North Carolina and the Wake County Board of Elections are. Pennsylvania could be the next key battleground in the fight for redistricting reform following recent incremental victories against gerrymandering in places like North. The Delaware Countybased 7th District Democrats a tally that hasnt. A byproduct of the Republican takeover of Wisconsin state government, the case. A dramatic redistricting effort spearheaded by North Carolina Republicans a. Kennedy suggested, as he did in another redistricting case 13 years ago, that courts perhaps could be involved in placing limits on extremely partisan electoral maps But he did the courts in Maryland and North Carolina In Wisconsin,. The measure gives $435,000 to help Wilmingtonarea utilities and the University of North Carolina at Wilmington to help treat and remove the chemical GenX from the Cape Fear River A Bladen County plant promotes fairness in maps. Understanding the difficulty of winning back a majority with Republicandrawn.


Controversial song, "F--- Donald Trump," featuring Hussle was played on a hacked Evansville Catholic radio station after the president's inauguration.
EVANSVILLE, Ind. – Grammy-nominated rapper Nipsey Hussle was shot to death in Los Angeles Sunday night.
The 33-year-old rapper, whose real name is Ermias Asghedom, was one of three people shot Sunday outside his clothing company, called the Marathon Store, in South Los Angeles. TMZ was the first to report the shooting.
A controversial song that Hussle wrote, along with fellow rapper YG, was played by a hacked Evansville Catholic radio station back in January 2017, weeks after President Trump's inauguration. YG released the song. Hussle was featured on the track.
The station, 103.5 WIAH-FM, had its regular Catholic-themed content interrupted with a 15-minute-loop of the song "FDT (F--- Donald Trump)." The song has a repetitive hook the same as its title.
The station was one of several across the country that were allegedly hacked to play the song.
The station is operated independently by nonprofit Mother of the Redeemer Radio. But the Evansville Diocese approved the channel as a Catholic entity.
According to website Heat Street, the person or people responsible likely exploited an unsecured backdoor in an IP device used to transmit broadcasts. The low-wattage station is based on the North Side of town, and its reach covers large parts of Evansville.
WIAH-FM was not the only station that was reportedly hacked in the incident. Reports show the song was played on radio stations in Murfreesboro, Tennessee; Salem, South Carolina; San Angelo, Texas; and several others.
A nonprofit radio station in Louisville, Kentucky, was also reportedly affected, according to the Courier-Journal.
A native of Crenshaw, Hussle said in a 2014 interview with Vlad TV that he had joined the Rollin 60s Neighborhood Crips as a teen.
In the years before his death, Hussle was invested in technology and community development.
Last year, he cut the ribbon on a co-working space and STEM center in his neighborhood with the goal connecting it to Silicon Valley and increasing diversity in those fields.
"In our culture, there's a narrative that says, 'Follow the athletes, follow the entertainers,'" he told The Los Angeles Times last year. "And that's cool, but there should be something that says, 'Follow Elon Musk, follow (Mark) Zuckerberg.'"
Steve Soboroff, president of the Los Angeles Police Commission, revealed on Twitter that he and Police Chief Michel Moore had a Monday meeting scheduled with Hussle and entertainment company Roc Nation, "to talk about ways he could help stop gang violence and help us help kids. I'm so very sad."
At this year's Grammy Awards, Hussle's debut studio album, "Victory Lap," was nominated for best rap album.
Hussle leaves behind a 2-year-old son with actress Lauren London and a daughter from a previous relationship.


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redpajama_set_name: RedPajamaGithub


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The Truth about Hot Shots
The use of electricity to make animals perform
This is the Power-Mite electric prod, manufactured by Hot-Shot Products Company, Inc. It is a very small device -- easily concealable -- which makes it a perfect weapon for rodeo animal abusers.
The electric prod was not designed to be cruel. It was designed to make large animals move when needed. One example might be to get a sick or injured animal up for absolutely necessary medical treatment.
In rodeos the prods are more often used on animals in pens who are unable to move or even turn around. The rodeo people use the pain of the prod to force the animals to "perform" -- to run or buck against their nature and beyond their natural abilities. This can result in injury and even death for the animal victims of the Rodeo Mafia.
The Hot-Shot Power-Mite easily generates between 4,000-5,000 volts of electrical pain, but don't believe us: Click here.
This horse is about to receive a shock near his head.
Rodeos use the Hot-Shot device in defiance of the manufacturer's own recommendations, which state:
"We do not recommend our products be used in rodeos."
"We only recommend our products be used on hogs and cattle. Do not use on horses, they are much more sensitive."
"Any use for entertainment purposes is not something we support or condone."
"Our prods should only be used on the rear of animals, never near the head or eyes."
"The Hot-Shot Power-Mite livestock prod is designed, manufactured, and marketed for use to aid in the movement of cattle and hogs. Hot-Shot does not condone the use of the Power-Mite or any Hot-Shot electric prod for use on horses, including horses in a rodeo environment."
--Jim Bartel, Marketing Director, Miller Manufacturing Company, Inc.
Rodeo people claim that the prod "just pinches a little." But a radio talk show host in Las Vegas who tried the prod likened it to, "...a thousand white hot needles going in and out of me."
The prod hurts, and the Rodeo Mafia knows it. That's why they use it on their animal victims, in violation of the prod manufacturer's intentions. That's also why rodeo people refuse to take a jolt from the prod, even though SHARK president Steve Hindi has taken the prod himself, and offered rodeo people as much as $300 to do the same for just an instant.
"We don't condone the use of this on horses and not in rodeos"
--Amy Scheel, Marketing Director, Miller Manufacturing Company, Inc.
The bottom line is -- the Rodeo Mafia can't take what it dishes out.
We've gathered a multitude of video evidence of these devices being used in rodeos. From "backyard rodeos", to PRCA rodeos, IPRA rodeos, and all the way up to the PRCA's National Finals Rodeo in Las Vegas, Nevada.
Hot-Shotted Horse Dies, July, 2013
Horses Electro-Shocked at 2013 Tucson Rodeo
Corporate Cruelty Sponsors
Sponsor Victories!
Cowboy Criminals
Are Animals Injured?
Individual Rodeos
Shame On Cheyenne
Rodeo "Family Values"
Rodeo Vet Speaks Out!
Voices Against Rodeo
Groups Against Rodeo
Welfare Cowboys
People and Assocs
PRCA 'Humane' Rules
SHARK Rodeo Media
Rodeo: Take Action
SHARK Teams with Canadians to Expose Illegality of Rodeo

redpajama_set_name: RedPajamaCommonCrawl


text:
Panhandle Church Offers Concealed Handgun License Classes
"We've always attempted to think outside the box as far as what the needs of the community are," said Rev. Brad Foster, Calvary Baptist Church's senior pastor.
Texas Monthly and Madelyn Herzog
https://www.texasmonthly.com/politics/panhandle-church-offers-concealed-handgun-license-classes/
Calvary Baptist Church, located 50 miles north of Amarillo in the state's panhandle, will be hosting its first concealed handgun license class on March 2 in an effort to promote self-defense and safety in the community.
The church's senior pastor, Rev. Brad Foster, told the Amarillo Globe-News there has been high demand for the class and that the church will continue to offer classes as long as there is interest. "We've always attempted to think outside the box as far as what the needs of the community are, and I think this melds well with that philosophy," he said.
The 10-hour class will be taught by state-certified instructor Mike Cearley and will cover the safety and legal parameters of carrying a concealed handgun. Sunday School Director Jim Edlin suggested the idea months ago, reported Amarillo local news channel KFDA–prior to the Newtown shooting. Foster said they are not trying to make a political statement, though they "don't mind being associated with being in support of the Second Amendment."
Foster said he views the current debate over gun control from a Biblical standpoint, arguing that we have a responsibility to be "protectors of innocents" and that "Jesus has a special place in his heart for children and innocents."
More than half of enrollees have been women and some are teachers, Edlin said.
Calvary Baptist isn't the only religious institution in Texas to dip its toes into firearm education. As Fox News reported, The Lighthouse Worship Center in Beaumont began offering free concealed handgun classes for teachers after the school shooting in Connecticut. Pastor James McAbee, locally known as the pistol-packing preacher, said he wants teachers to be prepared to defend themselves and their students.
Like Foster, McAbee said he believes the right to bear arms is sacred. "Jesus asked his disciples if they had swords and when they said they didn't, he told them to go out and buy one–for protection," he said. "I think firearms are the modern-day swords."
Over 150 teachers showed up to The Lighthouse Worship Center's first class this month, and March's is already full.
"I'm trying to do my part," McAbee told Fox News. "We live in evil days."
Tags: Politics, Religion, Guns
Texans Sure Like to Pack Guns in Their Carry-On Bags
Court's 3D Printer Ruling Does Not Halt DIY Ghost Guns
Houston Police Chief Art Acevedo Speaks About His Controversial 'Gun Rights' Stance
By Andy Langer
Investigators Want Apple to Turn Over Data from the Sutherland Springs Shooter's iPhone
Greg Abbott's Rejection of Refugees is Baffling—and Boneheaded
Texas Should Be the First Primary State, Obviously
Bull Session: Texas Republicans Rally Around Ricky Gervais and Enrique Iglesias Dances to the Tune of $485,000
The White Settlement Shooting and When It's Okay to Politicize a Tragedy
What Democrats Lose With the End of Julián Castro's Campaign
By Carlos Sanchez


WASHINGTON, DC - FEB 13, 2012: Rescue 1 of Fire Department ambulance, siren blaring, races past downtown rush hour commuters. Rescue 1 began in DC in 1925; is now located in Chinatown firehouse.
hd01:00Equipment of gel electrophoresis is a method of gel electrophoresis used in biochemistry, molecular biology, genetics, and clinical chemistry in lab.
hd00:05MOSCOW - DEC 3: (Timelapse) Sixth Food Festival Food Show at Arcade Moscow, on Dec 3, 2012 in Moscow, Russia. The festival was organized by gastronomic festival Food Show - LLC NTA group Media Event.
4k00:17KUALA LUMPUR, MALAYSIA - JANUARY 2016: sunny day city road pay point bus driver view circa january 2016 kuala lumpur, malaysia.


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The State of Connecticut, United States of America
This certifies that the heraldic arms of The State of Connecticut, United States of America are registered as an original design and are described by the blazon below
Blazon adopted by state legislature: A shield of rococo design of white field, having in the center three grape vines, supported and bearing fruit. The vine located in the center of the shield and the vine located on the right side of the shield shall ascend in a counterclockwise manner. The vine located on the left side of the shield shall ascend in a clockwise manner. The bordure to the shield shall consist of two bands bordered by fine lines adorned with clusters of white oak leaves (Quercus alba) bearing acorns. Below the shield shall be a white streamer, cleft at each end, bordered with two fine lines, and upon the streamer shall be in block letters the motto 'QUI TRANSTULIT SUSTINET.'
The historical note is quoted from FOTW Flags Of The World website at URL http://flagspot.net/flags/. Original author is Joe McMillan.
Image from FCIC website at URL http://www.pueblo.gsa.gov/
The Connecticut coat of arms is defined by � 3-105 of Connecticut General Statutes as follows: "A shield of rococo design of white field, having in the center three grape vines, supported and bearing fruit. The vine located in the center of the shield and the vine located on the right side of the shield shall ascend in a counterclockwise manner. The vine located on the left side of the shield shall ascend in a clockwise manner. The bordure to the shield shall consist of two bands bordered by fine lines adorned with clusters of white oak leaves (Quercus alba) bearing acorns. Below the shield shall be a white streamer, cleft at each end, bordered with two fine lines, and upon the streamer shall be in block letters the motto 'QUI TRANSTULIT SUSTINET.'"
The seal of the old Saybrook Colony in what is now Connecticut, introduced in 1639, depicted 15 grapevines, with a hand issuing from clouds in the upper left corner holding a scroll inscribed "Sustinet qui transtulit (He who transplanted sustains)." This seal was transferred to the Connecticut Colony when it purchased the land and fort of the Saybrook settlement in 1644 and used de facto by the colony's General Court (legislature). On October 9, 1662, coincident with the promulgation of Connecticut's royal charter, the seal was formally adopted by the general assembly as the seal of the colony. It was used until 1687, when James II's despotic royal governor Edmund Andros abolished self-government throughout New England; the original seal disappeared during this period. The charter of Connecticut was restored in 1689. On October 25, 1711, the governor and council (upper house of the General Assembly) directed the purchase of a new seal, which was essentially that in use today. The grapevines were reduced to three--perhaps to represent the three original colonies of New Haven, Saybrook, and Connecticut (Hartford). The motto scroll was moved to the bottom of the oval seal and the words rearranged to read "Qui transtulit sustinet." The only change to the seal of Connecticut since then was made in May 1784, after independence, changing inscription on the rim from SIGILLUM COLONIAE CONNECTICUTENSIS to SIGILLUM REIPUBLICAE CONNECTICUTENSIS (Seal of the State of Connecticut).
From an early period, the three grapevines were used on a shield as the arms of Connecticut, appearing in that form on state military colors among other places. The current official depiction of the arms on a rococo shield was in use by 1880; it was officially adopted by the General Assembly on March 24, 1931.
State, US, C


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Hamas arson balloons set fire to two nature reserves in Israel
Aug 13, 2021 | News
Israeli warplanes struck a number of sites in the Gaza Strip Saturday night in response to a wave of arson balloon attacks launched at Israel from the coastal enclave a day earlier, the military said.
The airstrikes came after at least four brush fires were ignited in southern Israel by balloons carrying incendiary devices that were launched from the Hamas-run Strip on Friday.
Three of the fires ignited in the Kissufim forest, and another one in the Be'eri forest, two nature reserves located on the border of Israel and Gaza, a spokesperson for the Jewish National Fund said.
The IDF said it struck a camp and a rocket-launching position in the Strip belonging to Hamas, adding that it would "continue to respond with strikes to terror attempts from Gaza."
Residents of the Palestinian enclave and of Israeli communities near the border reported hearing blasts in the northern Gaza Strip.
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F.I.N. was born in the 2006, when my old Gothic/Doom band "The Sad Darkness of thy Love" was broken. From these moment I work on the keyboards and do the Demo Tierra de Olvido in the same year under the line of Atmosphere/Drone Funeral Doom. Time after, F.I.N. was members that works on our first Single & Split's works un der the FunerART Label, splits with one band from Egypt (Grave Solace), another with one from Singapore (Overhaul In Damnation) and a 3-Way Split with the Chilean pioneers of Uden & Voice Transmissions with the Deceased (Both from Chlie). After of it, they get out to bring life to herself projects as Funeral Memories, Frustration Emotions & La Vermut.
In the 2008 F.I.N. launch their fist EP called LAYIL on the north american label Gelid Glacier Records, it sold out in weeks, after the FunerART Label make a second edition on Chile with a Bonustrack. After it we work with the Russian guys of Korolev Zond in one split released under Kapustin Yar Records (U.S.A.). and after we work with the Mexican (((O))) in one Split/Lp of only one track called EL CICLO DE LA IMPOTENCIA DE LA CONCIENCIA made by Nokturnal Transmissions Records (U.S.A.). both splits on the 2009 under the line up of Sammael on guitar and me in keyboards & Voice.
2010 carry us a new line-up, when we create new tracks and doing a new impression on the stage to our followers. On our sound we was more in the line of black, and the local zines was called us a Black/Drone/Funeral Doom band. in March, we see the launch of our last 3-way Split for the moment. this split was called Architectes and was between Tomhet (Canada) & Throudos (Norway/Chile) produced by the North American Label 9th Meridian Records.
On this year, we released our first LP called LA ESPERANZA QUE NUNCA SE PIERDE... ES LA DE MORIR under the Japan label Sabbathid Records, who was made of it an amazing release, a mix of art with the factory. This Lp are reviewed in U.S.A., Germany, Brazil, Mexico and with very good comments.
We define our-self as postmodernist doom, because the people are call & define us as Atmosphere, Ethereal, Drone, Minimal, Funeral Doom, Black Doom, etc... by it, we prefer call our work as postmodernist doom
If you want to make you an idea of how sound the postmodernist doom... We are influenced by bands from different styles as In The Woods..., Lvna In Caelo, Ved Buens Ende..., Bitterdusk, Green Carnation, Tristitia, Aghast, Until Death Overtakes Me and many more... Too we are influenced by the Poetry, literature, Art & Design.
Why should a metalhead buy your albums?
You can check it on the websites of the labels, here a list with the label and the disc that you can find on these website:
LA ESPERANZA QUE NUNCA SE PIERDE... ES LA DE MORIR (Lp 2010) - Sabbathid Records (Japan) - www.myspace.com/sabbathid, www.sound.jp/disnecro/releases.html
ARCHITECTES - 9th Meridian Records (U.S.A.) - www.myspace.com/9thmeridianrecords
EL CICLO DE LA IMPOTENCIA DE LA CONCIENCIA - Nokturnal Transmissions Records (U.S.A.) - www.myspace.com/nokturnaltransmissions, www.nokturnaltransmissionsrecords.com
COSMO-CREATION OF THE LOST SOULS - Kapustin Yar Records (U.S.A.) - www.myspace.com/kapustinyarrecords, www.artektronic.nu/kapustinyar.swf
LAYIL (EP 2008) - Gelid Glacier Records (U.S.A.) SOLD OUT, FunerART (Chile) SOLD OUT, Portaldisc.com AVAILABLE www.portaldisc.com/disco.php?id=716
TRINIDAD, CLOSING IN... & Other's - Under the FunerART Distro - www.myspace.com/funerarttheexperimentalul, www.funerart.org
You can find some releases at Ebay.com too ;)
We have a very interesting list of releases... it contain one Demo, one Single, four Split's & Two 3-Way Split's + one Ep (With 3 editions) and one LP.
we are very good reviewed on the countries where our works was launched and the people & Zines are received it very good. we thanks to all for the support through this years. Thanks to it we are part of diverse compilations around the world
We play in very special show, so much of it was private sessions because our performance is of a conceptual character and not to all people like it on Chile. We play more on Festivals organized by FunerART in Chile.
We are a postmodernist doom band, we have a "Strange" porpoise and vision about the music, we are art... if you like it, fantastic!
Some labels are interested in release a Best Of... of our works between2008-2010.
This year we are working hard to reform the band, create new sounds for the second LP upcoming for the 2011 under Sabbathid Records.
In the 2011 we will play on the DOOM VOICE CONVERSATION III, one of the msot important Funeral & Drone Fest from Chile and South America
I invit you to visit our official website & Myspace on where you can listen us and know our art: www.fin.funerart.org, www.myspace.com/doomfin