Question:

What is the difference between oxycontin and oxycone?

Answer:

They are pretty much the same. The main difference between oxycontin and oxycodone is simply the rate at which they are absorbed.

More Info:


Hydromorphone
InChI=1S/C17H19NO3/c1-18-7-6-17-10-3-5-13(20)16(17)21-15-12(19)4-2-9(14(15)17)8-11(10)18/h2,4,10-11,16,19H,3,5-8H2,1H3/t10-,11+,16-,17-/m0/s1Yes 
Key:WVLOADHCBXTIJK-YNHQPCIGSA-NYes  Hydromorphone, a more common synonym for dihydromorphinone (not to be confused by Dihydromorphine, which is a different derivative of the morphine family), commonly a hydrochloride (brand names Palladone, Dilaudid, and numerous others) is a very potent centrally acting analgesic drug of the opioid class. It is a derivative of morphine; to be specific, a hydrogenated ketone thereof, and it can be said that hydromorphone is to morphine as hydrocodone is to codeine and, therefore, a semi-synthetic drug. It is, in medical terms, an opioid analgesic and, in legal terms, a narcotic. Hydromorphone is commonly used in the hospital setting, mostly intravenously (IV) because its bioavailability orally, rectally, and intranasally is very low. Sublingual administration is usually superior to swallowing for bioavailability and effects. Hydromorphone is much more soluble in water than morphine and therefore hydromorphone solutions can be produced to deliver the drug in a smaller volume of water.][ Very small quantities of hydromorphone are detected in assays of opium on rare occasions; it appears to be produced by the plant under circumstances and by processes which are not understood at this time and may include the action of bacteria. A similar process and/or other metabolic processes in the plant may very well be responsible for the very low quantities of hydrocodone also found on rare occasions in opium and alkaloid mixtures derived therefrom; dihydrocodeine, oxymorphol, oxycodone, oxymorphone, metopon and possibly other derivatives of morphine and/or hydromorphone also are found in trace amounts in opium. Hydromorphone was first synthesized and researched][ in Germany in 1924; Knoll introduced it to the mass market in 1926 under the brand name Dilaudid, indicating its derivation and degree of similarity to morphine (by way of laudanum)—compare Dicodid (hydrocodone), Dihydrin (dihydrocodeine) and Dinarkon (oxycodone). The brand name Dilaudid is more widely known than generic term hydromorphone, and because of this, Dilaudid is often used—generically to mean any form of hydromorphone. Hydromorphone is used to relieve moderate to severe pain and severe, painful dry coughing. Hydromorphone is becoming more popular in the treatment of chronic pain in many countries, including the United States.][ Hydromorphone displays superior solubility and speed of onset, a less troublesome side effect profile, and lower dependence liability as compared to morphine and diamorphine. It is thought to be 6–8 times stronger than morphine][, but with a lower risk of dependency. Hydromorphone is therefore preferred over morphine in many areas ranging from the ongoing treatment of chronic pain syndromes, the emergency department to the operating suite.][ It is a common alternative for those tending to have hallucinations from fentanyl administered through dermal patches and other dosage forms.][ Hydromorphone, a semi-synthetic μ-opioid agonist, is a hydrogenated ketone of morphine and shares the pharmacologic properties typical of opioid analgesics. Hydromorphone and related opioids produce their major effects on the central nervous system and gastrointestinal tract. These include analgesia, drowsiness, mental clouding, changes in mood, euphoria or dysphoria, respiratory depression, cough suppression, decreased gastrointestinal motility, nausea, vomiting, increased cerebrospinal fluid pressure, increased biliary pressure, pinpoint constriction of the pupils, increased parasympathetic activity and transient hyperglycemia. The chemical modification of the morphine molecule to produce hydromorphone results in a drug with higher lipid solubility and ability to cross the blood–brain barrier and, therefore, more rapid and complete central nervous system penetration. The results shows hydromorphone to be somewhat faster-acting and about eight to ten times more potent than morphine and about three to five times more potent than heroin on a per milligram basis][. The effective morphine to hydromorphone conversion ratio can vary from patient to patient by a significant amount with relative levels of some liver enzymes being the main cause; the normal human range appears to be of 8:1. It is not uncommon, for example, for the 2-mg tablet to have an effect similar to that of 30 mg of morphine sulfate or a similar morphine preparation. Patients with kidney problems must exercise caution when dosing hydromorphone. In those with renal impairment, the half-life of hydromorphone can increase to as much as 40 hours. This could cause an excess buildup of the drug in the body, and result in fatality. The typical half-life of intravenous hydromorphone is 2.3 hours. Peak plasma levels usually occur between 30 and 60 minutes after oral dosing. Hydromorphone is extensively metabolized via glucuronidation in the liver, with greater than 95% of the dose metabolized to Hydromorphone-3-glucuronide along with minor amounts of 6-hydroxy reduction metabolites. Hydromorphone lacks the toxic metabolites (e.g., norpethidine) of many opioids related to pethidine and some of the methadone class. CNS depressants, such as other opioids, anesthetics, sedatives, hypnotics, barbiturates, phenothiazines, chloral hydrate, dimenhydrinate and glutethimide may enhance the depressant effects of hydromorphone. MAO inhibitors (including procarbazine), first-generation antihistamines (brompheniramine, promethazine, diphenhydramine, chlorpheniramine), beta-blockers, and alcohol may also enhance the depressant effect of hydromorphone. When combined therapy is contemplated, the dose of one or both agents should be reduced. Adverse effects of hydromorphone are similar to those of other potent opioid analgesics, such as morphine and heroin. The major hazards of hydromorphone include dose-related respiratory depression and sometimes circulatory depression. More common side effects include light-headedness, dizziness, sedation, itching, constipation, nausea, vomiting, and sweating. Massive overdoses are rarely observed in opioid-tolerant individuals, but, when they occur, they may lead to circulatory system collapse. A particular problem that may occur with hydromorphone is accidental administration in place of morphine due to a mix-up between the similar names, either at the time the prescription is written or when the drug is dispensed. This has led to several deaths and calls for hydromorphone to be distributed in distinctly different packaging from morphine to avoid confusion. The effects of overdose can be exaggerated by dose dumping if the medication is taken with alcohol or benzodiazepines. Like other opiates, hydromorphone can be used recreationally. Its reinforcing effects are mediated via its strong affinity for the μ-opioid receptor, inducing euphoria, sedation, reduced anxiety, respiratory depression, and other prototypical morphinian effects . Although such effects make it particularly susceptible to abuse, many patients using it for analgesia are able to use it for extended periods of time without developing drug-seeking behavior. Although users of hydromorphone will develop a physical dependence on the drug from extended use, this is not considered true addiction unless they are psychologically dependent on the drug and are compelled to continue taking it against the instructions of the prescribing doctor. In abusers, there can be a strong psychological dependence, thus creating an addiction with repeated use. While physical dependence causes withdrawal, psychological dependence can create strong compulsions to use the drug which can persist for days or weeks after the physical dependence is broken, and has been known to induce anxiety, insomnia, depression, and a range of other persistent mental illnesses. For this reason, psychotherapy is often included in detox programs, sometimes augmented with pharmacological therapies. Despite producing similar effects, hydromorphone is more expensive on the illicit market than heroin is,][ causing the abuse rates of hydromorphone to be lower than heroin and similar opiates in many areas. Even in the medical community, hydromorphone is quite scare; opiates like hydrocodone, oxycodone, and fentanyl are typically prescribed more often, due in part to the fact that most doctors are more familiar with those medications and the side effects and interactions thereof][. The short length of action of hydromorphone and other metabolic factors mean that the abstinence syndrome, or withdrawal, is brief but intense. A low dosing user of hydromorphone opting or otherwise forced to quit "cold turkey" can expect a withdrawal syndrome as intense as that of morphine but much more severe. It is compressed into a spike, peaking in 14 to 21 hours and resolving in 36 to 72 hours, provided the user is not taking other longer-acting opioids and has normal liver and kidney function. All of the effects of hydromorphone and its attendant withdrawal syndrome can be significantly lengthened by such factors. Possible but less common is the opposite: some patients require oral doses of hydromorphone as frequently as every 90 minutes, and the withdrawal syndrome can peak in as little as 9 hours. Users taking over 40 milligrams per day can experience painful withdrawal lasting up to two weeks with symptoms including constant shaking, cold sweats, diarrhea, vomiting, muscle pain, body cramps, and insomnia. Even after the withdrawal, long-term users of this drug can experience symptoms for months, even years after, however, those symptoms are usually psychological, including drug cravings, feelings of self-doubt, of "emptiness", moderate depression, mild anxiety, and sometimes slight insomnia, though these symptoms occurring after the initial withdrawal are usually much more prominent in users who use the drug (or other drugs) recreationally, likely because recreational users enjoy the effects that it has on their mood. Opiate withdrawal is almost never life threatening in and of itself although it can result in behaviors which make a sufferer a danger to themselves and others. For this reason, enduring withdrawal is safer when under the care of a qualified physician. Mild psychological issues can be treated with therapy, while more severe symptoms of psychological distress (incessant crying, suicidal/homicidal thoughts/actions, severe mood swings, etc.) may be treated with antidepressants and/or anxiolytics. If (and only if) a patient is experiencing intense physical withdrawal symptoms such as hyperalgesia, diarrhea, and photosensitivity, doctors may consider prescribing a long acting opiate substitute (such as methadone) and then slowly tapering the down the dose (usually over a period of days or weeks) until the patient is on a low enough dose to discontinue the drug completely. Even after quiting the drug completely, most doctors will recommend that the patient continue to attend therapy and take all other prescribed medicines as instructed until the root cause of the patients drug abuse is identified and addressed, and the ex-addict has developed a healthy support network to prevent relapse. Hydromorphone is known in various countries around the world by the brand names Hydal, Dimorphone, Sophidone LP, Dilaudid, Hydrostat, Hydromorfan, Hydromorphan, Hymorphan, Laudicon, Opidol, Palladone, Hydromorph Contin and others. An extended-release version of hydromorphone called Palladone was available for a short time in the United States before being voluntarily withdrawn from the market after a July 2005 FDA advisory warned of a high overdose potential when taken with alcohol. As of March 2010, it is still available in the United Kingdom under the brand name Palladone SR, Nepal under the brand name Opidol, and in most other European countries. Hydromorphone is most commonly detected via blood and urine testing. Hydromorphone is usually detectable via blood screen for up to 24 hours and via urine screen from 3 to 8 days. Urine screen depends on several factors such as age, frequency of use, weight and duration of use. Extremes: a 20-year-old patient with a normal BMI, who is administered a small dosage (<8 mg per day for <5 days) would screen positive for up to 3 days in 95% of clinical tests. Conversely, patients who are >35 years of age and have been administered a heavy dosage (>16 mg per day) with an overweight to obese BMI tend to test positive up to 7 to 8 days in 85% of clinical cases. Another option for prolonged administration is an implantable pump loaded with 90 days' worth of hydromorphone; the device consists of two small titanium tubes arranged into a piston with a semi-permeable membrane on one end which operates the pump by means of osmotic pressure, as the device is placed in areas under the skin which have a salinity gradient. Like morphine—which also has an identical molecular weight—hydromorphone can be dissolved in DMSO and applied externally to allow the body to pull the solution into the bloodstream. Hydromorphone can also be made into an emulsion for IM or SC injection which can continue to release the drug into the system in sufficient quantities to maintain therapeutic concentrations for up to a week. In the United States, the main drug control agency, the Drug Enforcement Administration, reports an increase in annual aggregate production quotas of hydromorphone from 766 kilograms in 1998 to 3,300 kilograms in 2006, and an increase in prescriptions in this time of 289%, from about 470,000 to 1,830,000.][ Like all opioids used for analgesia, hydromorphone is potentially habit-forming and is listed in Schedule II of the United States' Controlled Substances Act of 1970 as well as in similar levels under the drugs laws of practically all other countries and is listed in the Single Convention On Narcotic Drugs. In the United States, the state of Ohio has approved the use of an intramuscular injection of hydromorphone and midazolam as a backup means of carrying out executions when a suitable vein cannot be found for intravenous injection. Hydromorphone is made from morphine either by direct re-arrangement (made by reflux heating of alcoholic or acidic aqueous solution of morphine in the presence of platinum or palladium catalyst) or reduction to dihydromorphine (usually via catalytic hydrogenation), followed by oxidation with benzophenone in presence of potassium tert butoxide or aluminium tert butoxide (Oppenauer oxidation). The 6 ketone group can be replaced with a methylene group via the Wittig reaction to produce 6-Methylenedihydrodesoxymorphine, which is 80× stronger than morphine. Changing morphine into hydromorphone increases its activity and, therefore, makes hydromorphone about eight times stronger than morphine on a weight basis, all other things being equal.][ Changed also is lipid solubility, contributing to hydromorphone's having a more rapid onset of action and alterations to the overall absorption, distribution, metabolism, and elimination profile as well as the side effect profile (in general, less nausea and itching) versus that of morphine. The semi-synthetic opiates, of which hydromorphone and its codeine analogue hydrocodone are among the best-known and oldest, include a huge number of drugs of varying strengths and with differences among themselves both subtle and stark, allowing for many different options for treatment. Hydromorphone is made from morphine via catalytic hydrogenation and is also produced in trace amounts by human and other mammalian metabolism of morphine and occasionally appears in assays of opium latex in very small quantities, apparently forming in the plant in an unknown percentage of cases under poorly understood conditions. Some bacteria have been shown to be able to turn morphine into closely related drugs including hydromorphone and dihydromorphine among others. The bacterium Pseudomonas putida serotype M10 produces a naturally occurring NADH-dependent morphinone reductase that can work on unsaturated 7,8 bonds, with result that, when these bacteria are living in an aqueous solution containing morphine, significant amounts of hydromorphone form, as it is an intermediary metabolite in this process; the same goes for codeine being turned into hydrocodone. The process gave rise to various concentrations of hydromorphone, dihydromorphine, hydromorphinol, and oxymorphone during the experiments. Three paths were found: from morphine to hydromorphone with dihydromorphine as the penultimate step, from morphine to hydromorphone with morphinone as the penultimate step, and from morphine to hydromorphinol to hydromorphone. M: CNS anat (n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp noco (m/d/e/h/v/s)/cong/tumr, sysi/epon, injr proc, drug (N1A/2AB/C/3/4/7A/B/C/D) M: RES anat (n, x, l, c)/phys/devp noco (c, p)/cong/tumr, sysi/epon, injr proc, drug (R1/2/3/5/6/7) M: CNS anat (n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp noco (m/d/e/h/v/s)/cong/tumr, sysi/epon, injr proc, drug (N1A/2AB/C/3/4/7A/B/C/D)

Oxycodone
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/s1Yes 
Key:BRUQQQPBMZOVGD-XFKAJCMBSA-NYes  Oxycodone is a semi-synthetic opioid synthesized from poppy-derived thebaine. It is a narcotic analgesic generally indicated for relief of moderate to severe pain. It was developed in 1916 in Germany as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids. Oxycodone is available as single ingredient medication in immediate release and controlled release. Combination products formulated with non-narcotic ingredients such as NSAIDs and paracetamol are also available as immediate release formulation. Oxycodone has been in clinical use since 1917. and it is used for managing moderate to moderately severe acute or chronic pain. It has been found to improve quality of life for those with many types of pain. Controlled release oral tablet form is indicated for cancer and other chronic pains and intended to be taken every 12 hours. Immediate release forms are used more commonly for management of moderate pain. An Italian study concluded from investigating multiple studies that controlled release oxycodone is comparable to instant release oxycodone, morphine and hydromorphone in management of moderate to severe cancer pain. It indicated that side effect appears to be lesser than morphine and that it is a valid alternative to morphine and a first-line treatment for cancer pain. In 2001, the European Association for Palliative Care recommended that oral oxycodone could be taken as a second-line alternative to oral morphine for cancer pain. Oxycodone can be administered by parenteral or oral route. Starting dose of 5–15 mg oral every 4 to 6 hours or 10 mg controlled release every 12 hours. Maintenance dose of 10–30 mg every 4 hours or 20–640 mg controlled release form oxycodone per day for cancer pain with indication to use immediate release tablets as needed for break-through pain. Common side effects include constipation, fatigue, dizziness, nausea, vomiting, dry mouth, anxiety, itching, and sweating. Less common side effects (experienced by less than 5% of patients) include loss of appetite, nervousness, abdominal pain, diarrhea, urine retention, dyspnea, and hiccups, In high doses, overdoses, or in patients not tolerant to opiates, oxycodone can cause shallow breathing, bradycardia, cold-clammy skin, apnea, hypotension, miosis, circulatory collapse, respiratory arrest, and death. The risk of experiencing severe withdrawal symptoms is high if a patient has become physically dependent or addicted and discontinues oxycodone abruptly. Therefore, particularly in cases where the drug has been taken regularly over an extended period of time, use should be discontinued gradually rather than abruptly. People who use oxycodone in a recreational, hazardous, or harmful fashion (not as intended by the prescribing physician) are at even higher risk of severe withdrawal symptoms, as they tend to use higher-than-prescribed doses. The symptoms of oxycodone withdrawal are the same as for other opiate-based painkillers, and may include "anxiety, panic attack, nausea, insomnia, muscle pain, muscle weakness, fevers, and other flu-like symptoms". Withdrawal symptoms have also been reported in newborns whose mothers had been either injecting or orally taking oxycodone during pregnancy. 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. In 1997, a group of Australian researchers proposed (based on a study in rats) that oxycodone acts on κ-opioid receptors, unlike morphine, which acts upon μ-opioid receptors. Further research by this group indicated the drug appears to be a κ2b-opioid agonist. However, this conclusion has been disputed, primarily on the basis that oxycodone produces effects that are typical of μ-opioid agonists, mainly because oxycodone is metabolized in the liver to oxymorphone as a metabolite, which is a more potent opioid agonist with stronger/higher binding affinity to μ-opioid receptors compared to oxycodone. In 2006, research by a Japanese group suggested the effect of oxycodone is mediated by different receptors in different situations. Specifically in diabetic mice, the κ-opioid receptor 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. After a dose of conventional oral oxycodone, peak plasma levels of the drug are attained in about one hour; in contrast, after a dose of OxyContin (an oral controlled-release formulation), peak plasma levels of oxycodone occur in about three hours. Oxycodone in the blood is distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, and brain. Conventional oral preparations start to reduce pain within 10–15 minutes on an empty stomach; in contrast, OxyContin starts to reduce pain within one hour. Oxycodone is metabolized to α and β oxycodol; oxymorphone, then α and β oxymorphol and noroxymorphone; and noroxycodone, then α and β noroxycodol and noroxymorphone (N-desmethyloxycodone). (14-Hydroxydihydrocodeine that in turn becomes 14-Hydroxydihydromorphine) These metabolites are true only for humans. As many as six metabolites for oxycodone (14-hydroxydihydromorphinone, 14-hydroxydihydrocodeine, 14-hydroxydihydrocodeinone N-oxide {oxycodone N-oxide}, 14-hydroxydihydroisocodeine, 14-hydroxydihydrocodeine N-oxide, and noroxycodone) have been found in rabbits, several of which are thought to be active metabolites to some extent, although a study using conventional oral oxycodone concluded oxycodone itself, and not its metabolites, is predominantly responsible for the drug's opioid effects on the brain. Oxycodone is metabolized by the cytochrome P450 enzyme system in the liver, making it vulnerable to drug interactions. Some people are fast metabolizers, resulting in reduced analgesic effect, but increased adverse effects, while others are slow metabolisers, resulting in increased toxicity without improved analgesia. The dose of OxyContin must be reduced in patients with reduced hepatic function. Oxycodone and its metabolites are mainly excreted in the urine and sweat; therefore, it accumulates in patients with renal impairment. Oxycodone can be administered orally, intranasally, via intravenous, intramuscular, or subcutaneous injection, or rectally. The bioavailability of oral administration of oxycodone averages 60–87%, with rectal administration yielding the same results; intranasal varies between individuals with a mean of 46%. Taken orally, the conversion ratio between morphine to extended release oxycodone is reported as 2:1 Oxycodone's chemical name is derived from codeine. The chemical structures are very similar, differing only in that It is also similar to hydrocodone, differing only in that it has a hydroxyl group at carbon-14. Expanded expression for the compound oxycodone in the academic literature include "dihydrohydroxycodeinone", "Eucodal", "Eukodal", "14-hydroxydihydrocodeinone", and "Nucodan". In a UNESCO convention, the translations of "oxycodone" are oxycodon (Dutch), oxycodone (French), oxicodona (Spanish), الأوكسيكودون (Arabic), 羟考酮 (Chinese), and оксикодон (Russian). The word "oxycodone" should not be confused with "oxandrolone", "oxazepam", "oxybutynin", "oxytocin", or "Roxanol". Freund and Speyer of the University of Frankfurt in Germany first synthesized oxycodone from thebaine in 1916, 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. To some extent this was achieved, as oxycodone does not have the same immediate effect as heroin or morphine, nor does it last as long.][ The first clinical use of the drug was documented in 1917, the year after it was first developed. It was first introduced to the US 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)—this combination is essentially an oxycodone analogue of the morphine-based Twilight Sleep with ephedrine added to reduce circulatory and respiratory effects. As of May 2013, extended release version in the United States is only available as OxyContin brand. The International Narcotics Control Board estimated 11.5 tons (23,000 lbs) of oxycodone were manufactured worldwide in 1998; by 2007, this figure had grown to 75.2 tons (150,400 lbs). United States accounted for 82% of consumption in 2007 at 51.6 tons. Canada, Germany, Australia and France combined accounted for 13% of consumption in 2007. pp. 92 In August 2010, Purdue Pharma reformulated their OxyContin product line to use an abuse-resistant polymer designed to decrease abuse potential by defeating the release mechanism. The FDA approved relabeling the reformulated version as abuse-resistant in April 2013. The non-medical use of OxyContin began in Australia in the early 2000s. By 2007, 51% of a national sample of injection drug users in Australia had reported using oxycodone, and 27% had injected it in the last six months. Deaths from opioid pain relievers increased from 13.7 deaths per million residents in 1991 to 27.2 deaths per million residents in 2004.] [ 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. 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. Abuse and diversion of oxycodone in the UK commenced in the early- to mid-2000s. The first known death due to overdose in the UK occurred in 2002. However, recreational use remains relatively rare. 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. The 1961 Single Convention on Narcotic Drugs of the United Nations, which replaced the 1931 convention, categorized oxycodone in Schedule I. 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". Oxycodone is in Schedule I (derived from the Single Convention on Narcotic Drugs) of the Commonwealth's Narcotic Drugs Act 1967. 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". Oxycodone is a controlled substance under Schedule I of the Controlled Drugs and Substances Act (CDSA). 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. Much of the legislative activity has stemmed from Purdue Pharma’s decision in 2011 to begin a modification of oxycodone’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 pain killer. 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. This Act, introduced in 2010, commits to the establishment of a unified database to fulfill this intention. 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. 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 $650 million in settling litigation or facing criminal fines. The drug is in Appendix III of the Narcotics Act (Betäubungsmittelgesetz or BtMG). The law allows only physicians, dentists, and veterinarians (Ärzte, Zahnärzte und Tierärzte) can prescribe oxycodone, and the federal government can regulate the prescriptions (e.g., by requiring reporting). Oxycodone is regulated under Part I of Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. 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 five strokes of the cane, and a maximum sentence of life imprisonment or 30 years of imprisonment and 15 strokes of the cane. The minimum and maximum penalties for unauthorized trafficking in the drug are respectively five years of imprisonment and five strokes of the cane, and 20 years of imprisonment and 15 strokes of the cane. Oxycodone is a Class A drug under the Misuse of Drugs Act. 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. Dealing of the drug illegally is punishable by up to life imprisonment, an unlimited fine, or both. 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". Oxycodone is a Schedule II controlled substance
M: CNS anat (n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp noco (m/d/e/h/v/s)/cong/tumr, sysi/epon, injr proc, drug (N1A/2AB/C/3/4/7A/B/C/D)

MS Contin
MS Contin is a brand of a time-released formulation of morphine sulfate, usually taken every twelve hours for chronic pain. MS Contin is a trademark of Purdue Pharma. In the United States, MS Contin is available in tablet and liquid formulas in doses of 15mg, 20mg, 30mg, 60mg, 100mg and 200mg. In Australia, MS Contin tablets are available in doses of  5mg, 10mg, 15mg, 30mg, 60mg, 100mg and 200mg, and as a suspension, in doses of 20mg, 30mg, 60mg, 100mg and 200mg. It is typically prescribed in cases of severe pain where prolonged opioid therapy is indicated. MS Contin is a DEA Schedule II substance in the United States, and is a Schedule 8 (controlled) drug in Australia. Alternative sustained release morphine sulfate formulations made and marketed by other pharmaceutical companies include King Pharmaceuticals' Avinza and Actavis Pharmaceuticals' Kadian. Kadian is available in various strengths. There has been some concern][ regarding the issue that some capsules contain pellets (made by the process of extrusion and Spheronization (a trademark of Caleva Process Solutions) while others contain powder. Pellet (spheroid) formulations (made by extrusion and spheronization) can be used for controlled release of the drug in the body whereas powder filled pellets generally cannot.

Hydrocodone
InChI=1S/C18H21NO3/c1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19/h3,6,11-12,17H,4-5,7-9H2,1-2H3/t11-,12+,17-,18-/m0/s1Yes 
Key:LLPOLZWFYMWNKH-CMKMFDCUSA-NYes  Hydrocodone is a semi-synthetic opioid derived from codeine. Hydrocodone is used orally as narcotic analgesic and antitussive, often in combination with paracetamol (acetaminophen) or ibuprofen. Hydrocodone is prescribed predominantly in the United States. International Narcotics Control Board reports that 99% of worldwide supply in 2007 was consumed in the United States. Hydrocodone is used to treat moderate to severe pain and as an antitussive to treat cough. It is approximately 1.5 times less potent opioid than oxycodone. Analgesic action of hydrocodone begins 20–30 minutes after taking it and lasts 4–8 hours. Common side effects of hydrocodone are nausea, vomiting, constipation, drowsiness, dizziness, lightheadedness, fuzzy thinking, anxiety, abnormally happy or sad mood, dry throat, difficulty urinating, rash, itching, and narrowing of the pupils. Serious side effects include slowed or irregular breathing and chest tightness. Several cases of progressive bilateral hearing loss unresponsive to steroid therapy have been described as an infrequent adverse reaction to hydrocodone/acetaminophene abuse. This adverse effect has been considered due to the ototoxicity of hydrocodone. Recently, researchers suggested that acetaminophen is the primary agent responsible for the ototoxicity. It is in FDA pregnancy category C. No adequate and well-controlled studies in humans have been conducted. A newborn of a mother taking opioid medications regularly prior to the birth will be physically dependent. The baby may also exhibit respiratory depression if the opioid dose was high. An epidemiological study indicated that opioid treatment during early pregnancy results in increased risk of various birth defects. Symptoms of hydrocodone overdose include narrowed or widened pupils; slow, shallow, or stopped breathing; slowed or stopped heartbeat; cold, clammy, or blue skin; excessive sleepiness; loss of consciousness; seizures; and death. Hydrocodone can be habit-forming, causing physical and psychological dependence. Its abuse liability is similar to morphine and less than oxycodone. Patients consuming alcohol, other opioids, antihistamines, antipsychotics, antianxiety agents, or other central nervous system (CNS) depressants together with hydrocodone may exhibit an additive CNS depression. Hydrocodone may interact with serotonergic medications. As a narcotic, hydrocodone relieves pain by binding to opioid receptors in the CNS. It acts primarily on μ-opioid receptors, with about six times lesser affinity to δ-opioid receptors. In blood, 20-50% of hydrocodone is bound to protein. Studies have shown hydrocodone is stronger than codeine but only one-tenth as potent as morphine at binding to receptors and reported to be only 59% as potent as morphine in analgesic properties. However, in tests conducted on rhesus monkeys, the analgesic potency of hydrocodone was actually higher than morphine. Per os hydrocodone has a mean equivalent daily dosage (MEDD) factor of .4, meaning that 1 mg of hydrocodone is equivalent to .4 mg of intravenous morphine. However, because of morphine's low oral bioavailability, there is a 1:1 correspondence between orally administered morphine and orally administered hydrocodone. Hydrocodone is biotransformed by the liver into several metabolites, and has a serum half-life that averages 3.8 hours. The hepatic cytochrome P450 enzyme CYP2D6 converts it into hydromorphone, a more potent opioid. However, extensive and poor cytochrome 450 CYP2D6 metabolizers had similar physiological and subjective responses to hydrocodone, and CYP2D6 inhibitor quinidine did not change the responses of extensive metabolizers, suggesting that inhibition of CYP2D6 metabolism of hydrocodone has no practical importance. Ultrarapid CYP2D6 metabolizers (1-2% of the population) may have an increased response to hydrocodone; however, hydrocodone metabolism in this population has not been studied. A major metabolite, norhydrocodone, is predominantly formed by CYP3A4-catalyzed oxidation. Inhibition of CYP3A4 in a child who was, in addition, a poor CYP2D6 metabolizer, resulted in a fatal overdose of hydrocodone. Approximately 40% of hydrocodone metabolism is attributed to non-cytochrome catalyzed reactions. Commercial hydrocodone preparations are always combined with another medication. The rationale of combining hydrocodone with other pain-killers is that the combination may increase efficacy, and the adverse effects may be reduced as compared with an equally effective dose of a single agent. A combination of hydrocodone and ibuprofen was more effective than either of the drugs on their own in relieving postoperative pain. The overall effect of the combination could be presented as a sum of the effects of ibuprofen and hydrocodone, which is consistent with differing mechanisms of action of these drugs. Similar results were observed for hydrocodone-acetaminophen combination. Four pharmaceutical companies (Purdue Pharma, Cephalon, Zogenix, and Egalet) are developing extended-release formulations of hydrocodone by itself. These formulations are expected to avoid the issue of hepatotoxicity of acetaminophen containing formulations. They may also have lower abuse potential. Many users of hydrocodone report a sense of satisfaction, especially at higher doses. A number of users also report a warm or pleasant numbing sensation throughout the body, one of the best known effects of narcotics.][ Withdrawal symptoms may include, but are not limited to; severe pain, pins and needles sensation throughout body, sweating, extreme anxiety and restlessness, sneezing, watery eyes, fever, depression, stomach cramps, diarrhea, and extreme drug cravings, among others.][ Taking over 4,000 milligrams (4 grams) of paracetamol in a period of 24 hours can result in paracetamol overdose and severe hepatotoxicity; doses in the range of 15,000–20,000 milligrams a day have been reported as fatal. Taking hydrocodone with grapefruit juice is one of the measures believed to enhance its narcotic effect. It is believed that CYP3A4 inhibitors in grapefruit juice may decrease metabolism of hydrocodone, although there has been no research into this issue. Hydrocodone may be quantitated in blood, plasma or urine to monitor for misuse, confirm a diagnosis of poisoning or assist in a medicolegal death investigation. Many commercial opiate screening tests cross-react appreciably with hydrocodone and its metabolites, but chromatographic techniques can easily distinguish hydrocodone from other opiates. Blood or plasma hydrocodone concentrations are typically in the 5-30 µg/L range in persons taking the drug therapeutically, 100-200 µg/L in abusers and 0.1-1.6 mg/L in cases of acute fatal overdosage. In Australia, hydrocodone is a Schedule 8 (S8) or Controlled Drug. Hydrocodone is regulated in the same fashion as in Germany (see below) under the Austrian Suchtmittelgesetz; since 2002 it has been available in the form of German products and those produced elsewhere in the European Union under Article 76 of the Schengen Treaty—prior to this, no Austrian companies produced hydrocodone products, with dihydrocodeine and nicomorphine being more commonly used for the same levels of pain and the former for coughing. In Belgium, hydrocodone is no longer available for medical use. In France, hydrocodone (Vicodin) is no longer available for medical use. Hydrocodone is a prohibited narcotic. In Germany, hydrocodone is no longer available for medical use. Hydrocodone is listed under the Betäubungsmittelgesetz as a Suchtgift in the same category as morphine. In Luxembourg, hydrocodone is available by prescription under the name Biocodone. Prescriptions are more commonly given for use as a cough suppressant (antitussive) rather than for pain relief (analgesic). In the Netherlands, hydrocodone is not available for medical use and is classified as a List 1 drug under the Opium Law. Hydrocodone is no longer available for medical use. The last remaining formula was banned in 1967. In the UK, hydrocodone is not available for medical use and is listed as a Class A drug under the Misuse of Drugs Act 1971. Various formulations of dihydrocodeine, a weaker opioid, are frequently used as an alternative for the aforementioned indications of hydrocodone use. In the U.S., formulations containing more than 15 mg per dosage unit are considered Schedule II drugs, as would any formulation consisting of just hydrocodone alone. Those containing less than or equal to 15 mg per dosage unit in combination with acetaminophen or another non-controlled drug are called hydrocodone compounds and are considered Schedule III drugs. Hydrocodone is typically found in combination with other drugs such as acetaminophen, aspirin, ibuprofen and homatropine methylbromide. The purpose of the non-controlled drugs in combination is often twofold: 1) To provide increased analgesia via drug synergy. 2) To limit the intake of hydrocodone by causing unpleasant and often unsafe side effects at higher-than-prescribed doses. Hydrocodone is not commercially available in pure form in the United States due to a separate regulation, and is always sold with an NSAID, paracetamol, antihistamine, expectorant, or homatropine. Pure hydrocodone is a more strictly controlled Schedule II drug and sold by compounding pharmacies. The cough preparation Codiclear DH is the purest commercial US hydrocodone item, containing guaifenesin and small amounts of ethanol as active ingredients. Under the Controlled Substances Act (CSA), hydrocodone is listed as both a Schedule II and Schedule III substance depending on the formulation. Hydrocodone was until recently the active antitussive in more than 200 formulations of cough syrups and tablets sold in the United States. In late 2006, the FDA began forcing the recall of many of these formulations due to reports of deaths in infants and children under the age of six. The legal status of drug formulations originally sold between 1938 and 1962—before FDA approval was required—was ambiguous. As a result of FDA enforcement action, by August 2010, 88% of the hydrocodone-containing medications had been removed from the market.][ At the present time][, doctors, pharmacists, and codeine-sensitive or allergic patients or sensitive to the amounts of histamine released by its metabolites must choose among rapidly dwindling supplies of the Hycodan-Codiclear-Hydromet type syrups, Tussionex—an extended-release suspension similar to the European products Codipertussin (codeine hydrochloride), Paracodin suspension (dihydrocodeine hydroiodide), Tusscodin (nicocodeine hydrochloride) and others—and a handful of weak dihydrocodeine syrups. The low sales volume and Schedule II status of Dilaudid cough syrup predictably leads to under-utilisation of the drug. There are several conflicting views concerning the US availability of cough preparations containing ethylmorphine (also called dionine or codethyline)—Feco Syrup and its equivalents were first marketed circa 1895 and still in common use in the 1940s and 1950s, and the main ingredient is treated like codeine under the Controlled Substances Act of 1970.][ In the U.S., hydrocodone is always found in combination with other drugs such as paracetamol (also called acetaminophen), aspirin, an NSAID, ibuprofen, an antihistamine, an expectorant, or homatropine methylbromide due to compounding regulations. These combinations are considered C-III substances, prescriptions for which are generally valid for 6 months, including refills. The purpose of the non-controlled drugs in combination is often twofold: The cough preparation Codiclear DH is the purest US hydrocodone item, containing guaifenesin and small amounts of ethanol as active ingredients.][ As of July 2010, the FDA was considering banning some hydrocodone and oxycodone fixed-combination proprietary prescription drugs—based on the paracetamol content and the widespread occurrence of liver problems. FDA action on this suggestion would ostensibly also affect codeine and dihydrocodeine products such as the Tylenol With Codeine and Panlor series of drugs.][ In 2010, it was the most prescribed drug in the USA, with 131.2 million prescriptions of hydrocodone (combined with paracetamol) being written. Hydrocodone was first synthesized in Germany in 1920 by Carl Mannich and Helene Löwenheim. It was approved by the Food and Drug Administration on 23 March 1943 for sale in the United States and approved by Health Canada for sale in Canada under the brand name Hycodan. M: CNS anat (n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp noco (m/d/e/h/v/s)/cong/tumr, sysi/epon, injr proc, drug (N1A/2AB/C/3/4/7A/B/C/D) M: RES anat (n, x, l, c)/phys/devp noco (c, p)/cong/tumr, sysi/epon, injr proc, drug (R1/2/3/5/6/7)

Doctor shopping
Doctor shopping or double doctoring refers to the practice of a patient requesting care from multiple physicians, often simultaneously, without making efforts to coordinate care or informing the physicians of the multiple caregivers. This usually stems from a patient's addiction to, or reliance on, certain prescription drugs or other medical treatment. Usually a patient will be treated by their regular physician and be prescribed a drug that is necessary for the legitimate treatment of their current medical condition. Some patients will then actively seek out other physicians to obtain more of the same medication, often by faking or exaggerating the extent of their true condition, in order to feed their addiction to that drug. Not all patients seeking inappropriate multiple prescriptions of drugs are doing so because of addiction or an intention to abuse the drugs for their recreational effects. In the United States, increasing scrutiny of prescribing practices and high-profile prosecutions of doctors for allegedly over-prescribing drugs such as opiate painkillers and benzodiazepine tranquilizers has made many doctors extremely reluctant to prescribe large doses or repeat prescriptions of these drugs, even to patients with a legitimate medical need. To accurately determine which patients are suffering from genuine pain and not necessarily abusing medications, a physician must distinguish between patient tolerance, dependence, and addiction. Tolerance happens when a patient is no longer responding to a drug in the way they initially did. Dependence develops when the neurons adapt to the repeated drug exposure or only function normally in the presence of the drug. Addiction is a chronic relapsing brain disease. It is characterized by compulsive drug seeking and use. The cause of increased abuse may be connected to an emphasis in modern medicine to relieve pain. This has inadvertently led to an increased supply of these medications that is more easily available. Some view prescription drugs as a "safer" way to get high compared to street drugs. Others become dependent or addicted when the medication is inappropriately prescribed or when they have been necessary in the treatment of a long-term illness or injury. Some seek prescriptions to sell because they have a high street value. In the United States, most sedatives can only be legally dispensed with a prescription, because they have some potential for addiction and dependence. If sedatives are prescribed, it is sometimes in small quantities, which will last one week or even less. Examples of such drugs include zolpidem (Ambien), alprazolam (Xanax), and diazepam (Valium). Dependence on such medications usually arises because the patient comes to rely on the effects of the drug to fall asleep, or to prevent anxiety attacks. Prescription pain medications that contain an opiate or opioid painkiller have a high potential for addiction and abuse, including oxycodone (common brand names Percocet, OxyContin), hydrocodone (Vicodin, Lortab), meperidine (brand name Demerol), hydromorphone (Palladone, Dilaudid), oxymorphone (Opana, Numorphan), and morphine (MS Contin, Kadian, Avinza). Less powerful opiates and opioids (such as codeine, propoxyphene), and tramadol are generally less addictive. Tramadol is a novel, non-scheduled analgesic similar in effect to other narcotic painkillers, but has a high risk of inducing seizures. Newer medications of abuse include various preparations of the extremely potent and potentially addictive narcotic analgesic fentanyl, including Duragesic (a self-adhesive skin patch, available in five strengths which are 12mcg/hr, 25mcg/hr, 50mcg/hr, 75mcg/hr, and 100mcg/hr each to be applied for 3 days) and Actiq (berry-flavored lollipops that dissolve slowly in the mouth for absorption across the buccal mucosa, available in six strengths). All of these are categorized as Schedule II drugs under the U.S. Controlled Substances Act (with the exception of tramadol and some preparations of codeine and hydrocodone) and have stringent physical security associated with them. They must remain under lock and key at all times; every tablet must be precisely accounted for; no refills are permitted on prescriptions; and no telephone orders are accepted, with the exception of palliative care facilities (i.e., to discourage prescription fraud). Because of the widespread abuse of prescription drugs in both the United States and around the world, regulatory authorities have been discouraging the practice by cracking down on the process of doctor shopping, with some U.S. states even criminalizing the practice. Doctors have also undergone both education and training in recent years about the dangers of prescribing unneeded medication.

Oxycinchophen
InChI=1S/C16H11NO3/c18-15-13(16(19)20)11-8-4-5-9-12(11)17-14(15)10-6-2-1-3-7-10/h1-9,18H,(H,19,20) 
Key:XAPRFLSJBSXESP-UHFFFAOYSA-N  Oxycinchophen is an antirheumatic agent. M: JNT anat (h/c, u, t, l)/phys noco (arth/defr/back/soft)/cong, sysi/epon, injr proc, drug (M01C, M4)

Codeine
InChI=1S/C18H21NO3/c1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19/h3-6,11-13,17,20H,7-9H2,1-2H3/t11-,12+,13-,17-,18-/m0/s1Yes 
Key:OROGSEYTTFOCAN-DNJOTXNNSA-NYes  Codeine or 3-methylmorphine (a natural isomer of methylated morphine) is an opiate used for its analgesic, antitussive, antidiarrheal, antihypertensive, anxiolytic, antidepressant, sedative and hypnotic properties. It is also used to suppress premature labor contractions, myocardial infarction, and has many other potential and indicated uses. Codeine is the second-most predominant alkaloid in opium, at up to three percent. Although codeine can be extracted from natural sources, a semi-synthetic process is the primary source of codeine for pharmaceutical use. It is considered the prototype of the weak to midrange opioids (tramadol, dextropropoxyphene, dihydrocodeine, hydrocodone, oxycodone). Codeine is used to treat mild to moderate pain and to relieve cough. Codeine is also used to treat diarrhea and diarrhea predominant irritable bowel syndrome, although loperamide (which is available OTC for milder diarrhea), diphenoxylate, paregoric or even laudanum (also known as Tincture of Opium) are more frequently used to treat severe diarrhea. Codeine is marketed as both a single-ingredient drug and in combination preparations with paracetamol (as co-codamol: e.g., brands Paracod, Panadeine. Paramol, and the Tylenol-with-codeine series, including Tylenol 3 and 1,2,4); with aspirin; (as co-codaprin); or with ibuprofen (as Nurofen Plus). These combinations provide greater pain relief than either agent alone (drug synergy). Codeine is also commonly marketed in products containing codeine with other pain killers or muscle relaxers, as well as codeine mixed with phenacetin (Emprazil With Codeine No. 1, 2, 3, 4 and 5), naproxen, indomethacin, diclofenac, and others, as well as more complex mixtures, including such mixtures as aspirin + paracetamol + codeine ± caffeine ± antihistamines and other agents, such as those mentioned above. Codeine-only products can be obtained with a prescription as a time release tablet (e.g., Codeine Contin 100 mg and Perduretas 50 mg). Codeine is also marketed in cough syrups with zero to a half-dozen other active ingredients, and a linctus (e.g., Paveral) for all of the uses for which codeine is indicated. Injectable codeine is available for subcutaneous or intramuscular injection; intravenous injection can cause a serious reaction that can progress to anaphylaxis. Codeine suppositories are also marketed in some countries. Common adverse effects associated with the use of codeine include drowsiness and constipation. Less common are euphoria, itching, nausea, vomiting, dry mouth, miosis, orthostatic hypotension, urinary retention, depression, and, paradoxically, coughing. Rare adverse effects include anaphylaxis, seizure, and respiratory depression. As with all opiates, longer-term effects can vary but can include diminished libido, apathy and memory loss. Some people may also have an allergic reaction to codeine, such as the swelling of skin and rashes. Codeine and morphine as well as opium were used for control of diabetes until relatively recently, and still are in rare cases in some countries, and the hypoglycemic effect of codeine, although usually weaker than that of morphine, diamorphine, or hydromorphone, can lead to cravings for sugar. Tolerance to many of the effects of codeine develops with prolonged use, including therapeutic effects. The rate at which this occurs develops at different rates for different effects, with tolerance to the constipation-inducing effects developing particularly slowly for instance. A potentially serious adverse drug reaction, as with other opioids, is respiratory depression. This depression is dose-related and is the mechanism for the potentially fatal consequences of overdose. As codeine is metabolized to morphine, morphine can be passed through breast milk in potentially lethal amounts, fatally depressing the respiration of a breastfed baby. In August 2012, the Federal Drug Administration issued a warning about deaths in pediatric patients < 6 years old after ingesting "normal" doses of acetaminophen with codeine after tonsillectomy. Some patients are very effective converters of codeine to its active form, hydromorphone, resulting in lethal blood levels. The FDA presently is recommending very cautious use of Codeine in young tonsillectomy patients: use the drug in the lowest amount that can control the pain, use "as needed" and not "around the clock", and seek immediate medical attention if a child on codeine exhibits excessive sedation or abnormally noisy breathing. As with other opiate-based pain killers, chronic use of codeine can cause physical dependence. When physical dependence has developed, withdrawal symptoms may occur if a person suddenly stops the medication. Withdrawal symptoms include: drug craving, runny nose, yawning, sweating, insomnia, weakness, stomach cramps, nausea, vomiting, diarrhea, muscle spasms, chills, irritability, and pain. To minimize withdrawal symptoms, long-term users should gradually reduce their codeine medication under the supervision of a healthcare professional. Codeine is metabolized to codeine-6-glucuronide (C6G) by uridine diphosphate glucuronosyl transferase UGT2B7, and, since only about 5% of codeine is metabolized by cytochrome P450 CYP2D6, the current evidence is that C6G is the primary active compound. Claims about the supposed "ceiling effect" of codeine doses are based on the assumption that high doses of codeine saturate CYP2D6, preventing further conversion of codeine to morphine, however it is now known that C6G is the main metabolite responsible for codeine's analgesia. There is also no evidence that CYP2D6 inhibition is useful in treating codeine dependence, though the metabolism of codeine to morphine (and hence further metabolism to glucuronide morphine conjugates) does have an effect on the abuse potential of codeine. However, CYP2D6 has been implicated in the toxicity and death of neonates when codeine is administered to lactating mothers, particularly those with increased 2D6 activity ("ultra-rapid" metabolizers). The conversion of codeine to morphine occurs in the liver and is catalysed by the cytochrome P450 enzyme CYP2D6. CYP3A4 produces norcodeine and UGT2B7 conjugates codeine, norcodeine, and morphine to the corresponding 3- and 6- glucuronides. Srinivasan, Wielbo and Tebbett speculate that codeine-6-glucuronide is responsible for a large percentage of the analgesia of codeine, and, thus, these patients should experience some analgesia. Many of the adverse effects will still be experienced in poor metabolizers. Conversely, 0.5-2% of the population are "extensive metabolizers"; multiple copies of the gene for 2D6 produce high levels of CYP2D6 and will metabolize drugs through that pathway more quickly than others. Some medications are CYP2D6 inhibitors and reduce or even completely block the conversion of codeine to morphine. The most well-known of these are two of the selective serotonin reuptake inhibitors, paroxetine (Paxil) and fluoxetine (Prozac) as well as the antihistamine diphenhydramine and the antidepressant, bupropion (Wellbutrin, also known as Zyban). Other drugs, such as rifampicin and dexamethasone, induce CYP450 isozymes and thus increase the conversion rate. CYP2D6 converts codeine into morphine, which then undergoes glucuronidation. Life-threatening intoxication, including respiratory depression requiring intubation, can develop over a matter of days in patients who have multiple functional alleles of CYP2D6, resulting in ultra-rapid metabolism of opioids such as codeine into morphine. Studies on codeine's analgesic effect are consistent with the idea that metabolism by CYP2D6 to morphine is important, but some studies show no major differences between those who are poor metabolizers and extensive metabolizers. Evidence supporting the hypothesis that ultrarapid metabolizers may get greater analgesia from codeine due to increased morphine formation is limited to case reports.
The active metabolites of codeine, notably morphine, exert their effects by binding to and activating the μ-opioid receptor. Codeine has been used in the past as the starting material and prototype of a large class of mainly mild to moderately strong opioids; such as hydrocodone (1920 in Germany), oxycodone (1916 in Germany), dihydrocodeine (1908 in Germany), and its derivatives such as nicocodeine (1956 in Austria).][ However, these opiates are no longer synthesized from codeine and are usually synthesized from other opioid alkaloids; specifically thebaine.][ Other series of codeine derivatives include isocodeine and its derivatives, which were developed in Germany starting around 1920. As an analgesic, codeine compares moderately to other opiates. Related to codeine in other ways are codoxime, thebacon, -oxideNcodeine- (genocodeine), related to the nitrogen morphine derivatives as is codeine methobromide, and heterocodeine, which is a drug six times stronger than morphine and 72 times stronger than codeine due to a small re-arrangement of the molecule, viz. moving the methyl group from the 3 to the 6 position on the morphine carbon skeleton. Drugs bearing resemblance to codeine in effects due to close structural relationship are variations on the methyl groups at the 3 position including ethylmorphine a.k.a. codethyline (Dionine) and benzylmorphine (Peronine). While having no narcotic effects of its own, the important opioid precursor thebaine differs from codeine only slightly in structure. Pseudocodeine and some other similar alkaloids not currently used in medicine are found in trace amounts in opium as well. Codeine, or 3-methylmorphine, is an alkaloid found in the opium poppy, Papaver somniferum var. album, a plant in the papaveraceae family. Opium poppy has been cultivated and utilized throughout human history for a variety of medicinal (analgesic, anti-tussive and anti-diarrheal) and hypnotic properties linked to the diversity of its active components, which include morphine, codeine and papaverine. Codeine is found in concentrations of 10 to 3.0 per cent in opium prepared by the latex method from unripe pods of Papaver somniferum. The name codeine is derived from the Greek word kodeia (κώδεια) for "poppy head". The relative proportion of codeine to morphine, the most common opium alkaloid at 4 to 23 per cent, tends to be somewhat higher in the poppy straw method of preparing opium alkaloids. Until the beginning of the 19th century, raw opium was used in diverse preparations known as laudanum (see Thomas de Quincey's "Confessions of an English Opium-Eater", 1821) and paregoric elixirs, a number of which were popular in England since the beginning of the 18th century; the original preparation seems to have been elaborated in Leiden, the Netherlands around 1715 by a chemist named Lemort; in 1721 the London Pharmocopeia mentions an Elixir Asthmaticum, replaced by the term Elixir Paregoricum ("pain soother") in 1746. The progressive isolation of opium's several active components opened the path to improved selectivity and safety of the opiates-based pharmacopeia. Morphine had already been isolated in Germany by German pharmacist Friedrich Sertürner in 1804. Codeine was first isolated decades later in 1832 in France by Pierre Robiquet, a French chemist and pharmacist already famous for the discovery of alizarin, the most widespread red dye, while working on refined morphine extraction processes. This paved the way for the elaboration of a new generation of safer, codeine-based specific antitussive and antidiarrheal formulations. Codeine is currently the most widely-used opiate in the world, and is one of the most commonly used drugs overall according to numerous reports by organizations including the World Health Organization and its League of Nations predecessor agency. It is one of the most effective orally administered opioid analgesics and has a wide safety margin. Its strength ranges from 8 to 12 percent of morphine in most people; differences in metabolism can change this figure as can other medications, depending on its route of administration. While codeine can be directly extracted from opium, its original source, most codeine is synthesized from the much more abundant morphine through the process of O-methylation. By 1972, the effects of the Nixon War On Drugs had caused across-the-board shortages of illicit and licit opiates because of a scarcity of natural opium, poppy straw, and other sources of opium alkaloids, and the geopolitical situation was growing difficult for the United States. After a large percentage of the opium and morphine in the US National Stockpile of Strategic & Critical Materials was tapped in order to ease severe shortages of medicinal opiates — the codeine-based antitussives in particular — in late 1973, researchers were tasked with finding a way to synthesize codeine and its derivatives. They quickly succeeded using petroleum or coal tar and a process developed at the United States' National Institutes of Health. Numerous codeine salts have been prepared since the drug was discovered. The most commonly used are the hydrochloride (freebase conversion ratio 0.805), phosphate (0.736), sulphate (0.859), and citrate (0.842). Others include a salicylate NSAID, codeine salicylate (0.686), and at least four codeine-based barbiturates, the cyclohexenylethylbarbiturate (0.559), cyclopentenylallylbarbiturate (0.561), diallylbarbiturate (0.561), and diethylbarbiturate (0.619). Codeine can be used as a recreational drug. In some countries, cough syrups and tablets containing codeine are available without prescription; some potential recreational users are reported to buy codeine from multiple pharmacies so as not to arouse suspicion. In countries like Canada, in an effort to reduce recreational use, all OTC purchases of codeine are electronically recorded, and any pharmacy can access these records if desired. A heroin addict may use codeine to ward off the effects of a withdrawal. Codeine is also available in conjunction with the anti-nausea medication promethazine in the form of a syrup. Brand named as Phenergan with Codeine or in generic form as promethazine with codeine. Called 'syrup', this medication is quickly becoming one of the most commonly misused codeine preparations. Rapper Pimp C, from the group UGK, died from an overdose of this combination. Codeine is also demethylated by reaction with pyridine to illicitly synthesize morphine, which can then be acetylated to make heroin (diacetylmorphine). Pyridine is toxic and possibly carcinogenic, so morphine illicitly produced in this manner (and potentially contaminated with pyridine) may be particularly harmful. Codeine can also be turned into α-chlorocodide, which is used in the clandestine synthesis of desomorphine (Permonid) (desomorphine attracted attention in 2010 in Russia due to an upsurge in clandestine production, presumably due to its relatively simple synthesis from codeine.][ The drug is easily made from codeine, iodine and red phosphorus, in a similar process to the manufacture of methamphetamine from pseudoephedrine, but desomorphine made this way is highly impure and contaminated with various toxic and corrosive byproducts.). Codeine and/or its major metabolites may be quantitated in blood, plasma or urine to monitor therapy, confirm a diagnosis of poisoning or assist in a medicolegal death investigation. Drug abuse screening programs generally test urine, hair, sweat or oral fluid. Many commercial opiate screening tests directed at morphine cross-react appreciably with codeine and its metabolites, but chromatographic techniques can easily distinguish codeine from other opiates and opioids. It is important to note that codeine usage results in significant amounts of morphine as an excretion product. Furthermore, heroin contains codeine (or acetylcodeine) as an impurity and its use will result in excretion of small amounts of codeine. Poppy seed foods represent yet another source of low levels of codeine in one's biofluids. Blood or plasma codeine concentrations are typically in the 50–300 µg/L range in persons taking the drug therapeutically, 700–7000 µg/L in chronic users and 1000–10,000 µg/L in cases of acute fatal overdosage. In Australia, Canada, New Zealand, Romania, Russia, Sweden, the United Kingdom, the United States, and many other countries, codeine is regulated under various narcotic control laws. In some countries it is available without prescription in combination preparations from licensed pharmacists in doses up to 15 mg/tablet in Australia, New Zealand, Poland, Romania (Codamin), and Costa Rica, 12.8 mg/tablet in the UK, 10 mg/tablet in Israel and 8 mg/tablet in Canada and Estonia.][ In Australia, codeine preparations must be sold only at a pharmacy. Preparations will often be a combination of paracetamol (500 mg), ibuprofen (200 mg) and doxylamine succinate (5 mg), and the codeine content may range from 5 mg to 15 mg; preparations with in excess of 30 mg per tablet are S4 (schedule 4, or Prescription Only) medications. The item is given over the counter, no prescriptions, at the discretion of the Pharmacist. Most preparations are considered S3 (schedule 3, or Pharmacist Only) medications, meaning that they must be sold with the direct involvement of a pharmacist. It must be labelled and usage history monitored by the Pharmacist to help deter misuse and dependence. The exception to this rule is cold and flu preparations such as "Codral". These preparations contain phenylephrine (5 mg), paracetamol(500 mg) and codeine(9.5 mg).
Preparations containing pure codeine (e.g., codeine phosphate tablets or codeine phosphate linctus) are available on prescription and are considered S8 (schedule 8, or Controlled Drug (Possession without authority illegal)). Schedule 8 preparations are subject to the strictest regulation of all medications available to consumers. In Denmark codeine is sold over the counter with max 9.6 mg in mixture.][ The item is given over the counter, no prescriptions. The strongest available over the counter preparation containing codeine has 9.6 mg (with aspirin, brand name Kodimagnyl); anything stronger requires a prescription. In France, most preparations containing codeine do not require a doctor's prescription. Example products containing codeine include Néocodion (cough pills, ad sirup), Codoliprane (codeine with paracetamol), Prontalgine and Migralgine (codeine, paracetamol and caffeine). Codeine is listed under the Betäubungsmittelgesetz in Germany and the similarly named narcotics and controlled substances law in Switzerland. In Austria, the drug is listed under the Suchtmittelgesetz in categories corresponding to their classification under the Single Convention on Narcotic Drugs. Dispensing of products containing codeine and similar drugs (dihydrocodeine, nicocodeine, benzylmorphine, ethylmorphine etc.), in general, requires a prescription order from a doctor or the discretion of the pharmacist. Municipal and provincial regulations may impact availability, in particular in Austria and Switzerland, which allows cities and provinces to regulate the selling of the least-regulated schedule of the SMG/BtMG; and, of course, individual chemists' shops can opt out of providing them or imposing volume, frequency, or single-purchase limitations and other things of the same store. Plain codeine hydrochloride tablets (which in the USA would share CSA Schedule II with drugs like morphine, cocaine, hydromorphone, and bezitramide) as well as other non-injectable forms of codeine and its midrange derivatives can be dispensed in this way; the same goes for most chemical classes of benzodiazepines, the majority of non-barbiturate sedative/hypnotics, and at least a handful of barbiturates. Title 76 of the Schengen treaty has made it possible for countries within the signatory states to import and export drugs with various provisos, recording and ordering requirements, and various other rules. Codeine is classed as an illegal drug in Greece, and individuals possessing it could conceivably be arrested, even if they were legitimately prescribed it in another country. It is sold only with a doctor's prescription (Lonarid-N, Lonalgal). In Hong Kong, codeine is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. It can be used legally only by health professionals and for university research purposes. The substance can be given by pharmacists under a prescription. Anyone who supplies the substance without prescription can be fined $10,000 (HKD). The maximum penalty for trafficking or manufacturing the substance is a $5,000,000 (HKD) fine and life imprisonment. Possession of the substance for consumption without license from the Department of Health is illegal with a $1,000,000 (HKD) fine and/or 7 years of jail time. However, codeine is available without prescription from licensed pharmacists in doses up to 0.1% (5 mg/5ml) according to Hong Kong "Dangerous Drugs Ordinance". Preparations of paracetamol and codeine require a prescription in Iceland. These tablets are known as Parkódín. Codeine preparations require a prescription in India. A preparation of paracetamol and codeine is available in India. Codeine is also present in various cough syrups as Codeine Phosphate. In the Republic of Ireland, new regulations came into effect on August 1, 2010 concerning codeine, due to worries about the overuse of the drug. Codeine remains a semi non-prescriptive, over-the-counter drug up to a limit of 12.8 mg per pill, but codeine products must be out of the view of the public to facilitate the legislative requirement that these products “are not accessible to the public for self-selection”. In practice, this means customers must ask pharmacists for the product containing codeine in name, and the pharmacist makes a judgement whether it is suitable for the patient to be using codeine, and that patients are fully advised of the correct use of these products. Products containing more than 12.8 mg codeine are available on prescription only. Codeine tablets or preparations require a prescription in Italy. A preparation of paracetamol and codeine is available in Italy as Co-Efferalgan. Codeine and similar mid-level centrally acting agents in combination with non-opioid analgesics, antihistamines, vitamins, inert GI agents like kaolin & pectin, mild laxatives, antacids, and herbal preparations, can be purchased over the counter, with 10 mg being the ceiling for OTC dispensing. This is also true of ethylmorphine and dihydrocodeine, and also diphenoxylate, some weak relatives of the thiambutene opioid family. According to ITAR-Tass and Austria Presse-Agentur, OTC availability of codeine products was rescinded nationwide in 2012 because of the discovery of the Krokodil method of underground desomorphine synthesis. Opponents of the move point out that codeine has not been available OTC in 22 of Russia's oblasts for years and the demand will call forth its own supply, meaning that only legitimate end users are negatively impacted (activist quoted in Pravda story on issue) Codeine preparations are available as over the counter pharmacy medicines in Sri Lanka. The most common preparation is Panadeine, which contains 500 mg of Paracetamol and 8 mg of Codeine. Narcotic content number in the US names of codeine tablets and combination products like Tylenol With Codeine No. 3, Emprin With Codeine No. 4, and pure codeine tablets are as follows: No. 1 - 7½ or 8 mg (1/8 grain), No. 2 - 15 or 16 mg (1/4 grain), No. 3 - 30 or 32 mg (1/2 grain), No. 4 - 60 or 64 mg (1 grain). The Canadian "Frosst 222" series is identical to the above list: "222" contains 8 mg codeine, "282" 15 mg, "292" 30 mg, and "293" 60 mg. This system, which is also used at present in the trade names of some dihydrocodeine and ethylmorphine products both in and outside of North America, was inaugurated with the Pure Food and Drug Act of 1906 and related legislation and refined since. Equivalent scales for labeling stronger opioids such as diacetylmorphine (heroin), morphine, opium salts mixtures, and others were in common use in the past, and on occasion one can find past references to brand names for hydrocodone (invented 1920, introduced in US 1943), hydromorphone (invented 1924), oxycodone (invented 1916), paregoric and similar drugs containing narcotic content numbers. For example. from circa 1900 to 1925, the most common cough medicine was terpin hydrate With Heroin Elixir No. 2. Contrary to the advertising matter of some pharmacies, 60 mg is No. 4, not No. 6, and tablets with 45 mg of codeine are not No. 4 and would in all likelihood be classified as No. 3½ under that system. Whether the scale goes to No. 5 and higher is moot at this point, as in the United States and Canada single-dose-unit concentrations of more than 64 mg are not manufactured. The United States Controlled Substances Act of 1970 does place dosage unit strengths of 90 mg of codeine and higher in Schedule II, even if mixed with another active ingredient. Oral tablets, hypodermic tablets, liquid forms, and capsules of less common doses are available in some cases the equivalent dihydrocodeine, dionine, benzylmorphine, and opium dosages were previously available in North America (and in most cases still are in other countries, particularly the 45 mg paracetamol/codeine and 50 and 100 mg single-ingredient codeine tablets). In the United States, codeine is regulated by the Controlled Substances Act. Federal law dictates that codeine be a Schedule II controlled substance when used in products for pain-relief that contain codeine alone or more than 90 mg per dosage unit. Tablets of codeine in combination with aspirin or acetaminophen (paracetamol/Tylenol) made for pain relief are listed as Schedule III; and cough syrups are Schedule III or V, depending on formula. The acetaminophen/codeine pain-relief elixir (trade name Tylenol Elixir with Codeine) is a Schedule IV controlled substance. Some states, however, have chosen to classify Schedule V codeine preparations into a more restrictive schedule in order to cut down the abuse of prescription codeine preparations. Minnesota, for instance, has chosen to reclassify Schedule V codeine preparations (such as Cheratussin) as a Schedule II controlled substance. Preparations for cough or diarrhea containing small amounts of codeine in combination with two or more other active ingredients are Schedule V in the US, and in some states may be dispensed in amounts up to 4 fl. oz. per 48 hours (one or two states set the limit at 4 fl. oz. per 72 hours) without a prescription. Schedule V specifically consigns the product to state and local regulation beyond certain required record-keeping requirements (a dispensary log must be maintained for two years in a ledger from which pages cannot easily be removed and/or are pre-numbered, and the pharmacist must ask for photo identification) and also maintain controlled substances in the closed system at the root of the régime intended by the Controlled Substances Act of 1970; the codeine in these products was a Schedule II substance when the company making the Schedule V product acquired it for mixing up the end-product. In locales where dilute codeine preparations are non-prescription, anywhere from very few to perhaps a moderate percentage of pharmacists will sell these preparations without a prescription. However, many states have their own laws that do require a prescription for Schedule V drugs. The December 2008 issue of The Bulletin of the National Codeine OTC Lobby (Vol. XVIII, No. 4) listed 12 states with some kind of OTC access to codeine, noting that small independent pharmacies are the most likely to have it. This situation is roughly equivalent to that in February 1991, when the aforementioned organisation undertook its first comprehensive study of Schedule V and overall codeine, dihydrocodeine, ethylmorphine, and hydrocodone availability. Other drugs that are present in Schedule V narcotic preparations like the codeine syrups are ethylmorphine and dihydrocodeine. Paregoric and hydrocodone were transferred to Schedule III from Schedule V even if the preparation contains two or more other active ingredients, and diphenoxylate is usually covered by state prescription laws even though this relative of pethidine is a Schedule V substance when adulterated with atropine to prevent abuse. Around the world, codeine is, contingent on its concentration, a Schedule II and III drug under the Single Convention on Narcotic Drugs. Codeine tablets or preparations require a prescription in Spain, although this is often not enforced and many pharmacies will sell codeine products without the requirement of a prescription.][ The UAE takes an infamously strict line on medicines, with many common drugs, notably anything with containing codeine being banned unless you have a notarized and authenticated doctor's prescription. Visitors breaking the rules, even inadvertently, have found themselves deported or jailed. The US Embassy to the UAE maintains an unofficial list of what may not be imported. In the United Kingdom, neat codeine and higher-strength codeine formulations - such as 30/500 co-codamol (where 30 mg of codeine phosphate is combined with 500 mg paracetamol) are prescription-only medicines (POM). Lower-strength combinations, such as 8/500 (various brands) or 12.8/500 (Panadol Ultra, Solpadeine MAX and others) are available as pharmacy medicines over the counter. Codeine is also available combined with Ibuprofen; a common formulation is 12.8 mg codeine alongside 200 mg Ibuprofen. It is also available 'behind the counter' with aspirin in doses of 8 mg codeine phosphate and 500 mg aspirin (Codis). Codeine Linctus of 15 mg per 5ml is also available behind the counter at some pharmacies, although a purchaser would have to request it specifically from the pharmacist. Under the Misuse of Drugs Act 1971, possession of codeine is legal without a prescription in quantities of up to 12.5 mg when in tablet form. As with most opioids, possession of neat codeine without a prescripion is illegal in quantities over 12.5 mg and is currently a class B controlled drug. However, if it prepared for intra-muscular injection, it is then considered to be a class A controlled drug. Thus it is legal for a person to carry neat codeine in quantities over 12.5 mg assuming that they possess a valid prescription, subject to the quantities carried being for personal use only and with no indication that there is intent to supply. M: CNS anat (n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp noco (m/d/e/h/v/s)/cong/tumr, sysi/epon, injr proc, drug (N1A/2AB/C/3/4/7A/B/C/D) M: DIG anat (t, g, p)/phys/devp/enzy noco/cong/tumr, sysi/epon proc, drug (A2A/2B/3/4/5/6/7/14/16), blte M: RES anat (n, x, l, c)/phys/devp noco (c, p)/cong/tumr, sysi/epon, injr proc, drug (R1/2/3/5/6/7)
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Organic chemistry

Organic chemistry is a chemistry subdiscipline involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms. Study of structure includes using spectroscopy and other physical and chemical methods to determine the chemical composition and constitution of organic compounds and materials. Study of properties includes both physical properties and chemical properties, and uses similar methods as well as methods to evaluate chemical reactivity, with the aim to understand the behavior of the organic matter in its pure form (when possible), but also in solutions, mixtures, and fabricated forms. The study of organic reactions includes both their preparation—by synthesis or by other means—as well as their subsequent reactivities, both in the laboratory and via theoretical (in silico) study.

The range of chemicals studied in organic chemistry include hydrocarbons, compounds containing only carbon and hydrogen, as well as compositions based on carbon but containing other elements. Organic chemistry overlaps with many areas including medicinal chemistry, biochemistry, organometallic chemistry, and polymer chemistry, as well as many aspects of materials science.

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