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derivative of opium; used as an antitussive (to relieve coughing) and an analgesic (to relieve pain)

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コデイン(アヘンから作られる鎮痛剤・せき止め薬)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/07/22 20:28:12」(JST)

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This article is about the drug. For the US rock band, see Codeine (band). For other uses, see Codeine (disambiguation).

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).

1 Medical uses
- 1.1 Formulations
2 Adverse effects
- 2.1 Withdrawal and dependence
3 Pharmacokinetics
4 Relation to other opiates
5 History
6 Recreational use
- 6.1 Detection
7 Legal status
- 7.1 Australia
- 7.2 Denmark
- 7.3 France
- 7.4 Germany, Switzerland and Austria
- 7.5 Greece
- 7.6 Hong Kong
- 7.7 Iceland
- 7.8 India
- 7.9 Ireland
- 7.10 Italy
- 7.11 Japan
- 7.12 Russia
- 7.13 Sri Lanka
- 7.14 North America
  - 7.14.1 Narcotic content numbers
  - 7.14.2 United States
- 7.15 Spain
- 7.16 United Arab Emirates
- 7.17 United Kingdom
8 References

Medical uses[edit]

Codeine is used to treat mild to moderate pain and to relieve cough.^[2] 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.^[3]

Formulations[edit]

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.

Adverse effects[edit]

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.^[4] 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.^[5]

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.^[6]^[7] 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.^[8] 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.

Withdrawal and dependence[edit]

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.^[9]

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.^[10] 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.^[11] There is also no evidence that CYP2D6 inhibition is useful in treating codeine dependence,^[12] 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.^[13] 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).^[14]^[15]

Pharmacokinetics[edit]

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.^[16] 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.^[17]^[18]^[19]

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.^[20]

The active metabolites of codeine, notably morphine, exert their effects by binding to and activating the μ-opioid receptor.

Relation to other opiates[edit]

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).^{[citation needed]} However, these opiates are no longer synthesized from codeine and are usually synthesized from other opioid alkaloids; specifically thebaine.^{[citation needed]} 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, codeine-N-oxide (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.

History[edit]

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.^[21] 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,^[22]^[23] 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.^[23]^[24]

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).

Recreational use[edit]

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.^[25]

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.^[26] Rapper Pimp C, from the group UGK, died from an overdose of this combination.^[27]

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.^[28] 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.^{[citation needed]} The drug is easily made from codeine, iodine and red phosphorus,^[29] 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.).

Detection[edit]

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.^[30]^[31]^[32]

Legal status[edit]

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.^{[citation needed]}

Australia[edit]

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).^[33]
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.

Denmark[edit]

In Denmark codeine is sold over the counter with max 9.6 mg in mixture.^{[citation needed]} 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.

France[edit]

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).^[34]

Germany, Switzerland and Austria[edit]

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.

Greece[edit]

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).^[35]

Hong Kong[edit]

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".

Iceland[edit]

Preparations of paracetamol and codeine require a prescription in Iceland. These tablets are known as Parkódín.

India[edit]

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.

Ireland[edit]

In the Republic of Ireland, new regulations came into effect on August 1, 2010^[36] 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”.^[37] 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.^[38]

Italy[edit]

Codeine tablets or preparations require a prescription in Italy. A preparation of paracetamol and codeine is available in Italy as Co-Efferalgan.

Japan[edit]

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.

Russia[edit]

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)

Sri Lanka[edit]

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.

North America[edit]

Narcotic content numbers[edit]

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"^[39] 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).

United States[edit]

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.^[40] 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.^[41]

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.^[42]

Spain[edit]

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.^{[citation needed]}

United Arab Emirates[edit]

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.

United Kingdom[edit]

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.^[43]

References[edit]

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^ "FDA Drug Safety Communication: Codeine use in certain children after tonsillectomy and/or adenoidectomy may lead to rare, but life-threatening adverse events or death". Food and Drug Administration.
^ Alberta Health Services; AADAC (April 16, 2007). "The ABCs - Codeine and Other Opioid Painkillers". Alberta Alcohol and Drug Abuse Commission. Retrieved Sep 12 2008.
^ Armstrong SC, Cozza KL (2003). "Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, Part II". Psychosomatics 44 (6): 515–20. doi:10.1176/appi.psy.44.6.515. PMID 14597688.
^ Vree TB, van Dongen RT, Koopman-Kimenai PM (2000). "Codeine analgesia is due to codeine-6-glucuronide, not morphine". Int. J. Clin. Practa. 54 (6): 395–8. PMID 11092114.
^ Fernandes LC, Kilicarslan T, Kaplan HL, Tyndale RF, Sellers EM, Romach MK (June 2002). "Treatment of codeine dependence with inhibitors of cytochrome P450 2D6". J Clin Psychopharmacol 22 (3): 326–9. doi:10.1097/00004714-200206000-00014. PMID 12006904.
^ Kathiramalainathan K, Kaplan HL, Romach MK, et al. (2000). "Inhibition of cytochrome P450 2D6 modifies codeine abuse liability". J Clin Psychopharmacol 20 (4): 435–44. doi:10.1097/00004714-200008000-00008. PMID 10917405.
^ Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder SJ (2006). "Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother". Lancet 368 (9536): 704. doi:10.1016/S0140-6736(06)69255-6. PMID 16920476.
^ Willmann S, Edginton AN, Coboeken K, Ahr G, Lippert J (2009). "Risk to the Breast-Fed Neonate From Codeine Treatment to the Mother: A Quantitative Mechanistic Modeling Study". Clinical Pharmacology & Therapeutics 86 (6): 634–43. doi:10.1038/clpt.2009.151.
^ Srinivasan V, Wielbo D, Tebbett IR (1997). "Analgesic effects of codeine-6-glucuronide after intravenous administration". European Journal of Pain 1 (3): 185–90. doi:10.1016/S1090-3801(97)90103-8. PMID 15102399.
^ Lurcott G (1998). "The effects of the genetic absence and inhibition of CYP2D6 on the metabolism of codeine and its derivatives, hydrocodone and oxycodone". Anesth Prog 45 (4): 154–6. PMC 2148980. PMID 10483388.
^ Gasche Y, Daali Y, Fathi M, et al. (December 2004). "Codeine intoxication associated with ultrarapid CYP2D6 metabolism". N. Engl. J. Med. 351 (27): 2827–31. doi:10.1056/NEJMoa041888. PMID 15625333.
^ Caraco Y (December 2004). "Genes and the response to drugs". N. Engl. J. Med. 351 (27): 2867–9. doi:10.1056/NEJMe048278. PMID 15625340.
^ Gardiner, S. J.; Begg, E. J. (2006). "Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice". Pharmacological Reviews 58 (3): 521–590. doi:10.1124/pr.58.3.6. PMID 16968950. edit
^ Andreas Luch (2009). Molecular, clinical and environmental toxicology. Springer. p. 20. ISBN 3-7643-8335-6.
^ Opiates.com - Codeine
^ ^a ^b Science Daily (March 2010) - "Unlocking the Opium Poppy's Biggest Secret: Genes That Make Codeine, Morphine"
^ Elmhurt College - Narcotic Analgesic Drugs
^ Boekhout van Solinge, Tim (1996). "7. La politique de soins des années quatre-vingt-dix". L'héroïne, la cocaïne et le crack en France. Trafic, usage et politique (in French). Amsterdam: CEDRO Centrum voor Drugsonderzoek, Universiteit van Amsterdam. pp. 247–262.
^ Leinwand, Donna (2006-10-18). "DEA warns of soft drink-cough syrup mix". USA Today. Retrieved 2006-10-23.
^ http://www.chron.com/entertainment/music/article/Pimp-C-s-death-caused-by-overdose-and-sleep-1629962.php
^ Hogshire, Jim (June 1999). Pills-A-Go-Go: A Fiendish Investigation into Pill Marketing, Art, History & Consumption. Los Angeles: Feral House. pp. 216–223. ISBN 978-0-922915-53-8.
^ Savchuk, S. A.; Barsegyan, S. S.; Barsegyan, I. B.; Kolesov, G. M. (2011). "Chromatographic study of expert and biological samples containing desomorphine". Journal of Analytical Chemistry 63 (4): 361–70. doi:10.1134/S1061934808040096.
^ Thevis M, Opfermann G, Schänzer W (2003). "Urinary concentrations of morphine and codeine after consumption of poppy seeds". J. Anal. Toxicol. 27 (1): 53–6. PMID 12587685.
^ Cone EJ, Welch P, Paul BD, Mitchell JM (1991). "Forensic drug testing for opiates, III. Urinary excretion rates of morphine and codeine following codeine administration". J. Anal. Toxicol. 15 (4): 161–6. PMID 1943064.
^ Baselt, R. (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City CA: Biomedical Publications. pp. 355–360.
^ "Codeine crackdown comes into effect". ABC.net.au. Retrieved 2010-11-22.
^ "vital list of codein". vidal.com. Retrieved 2011-01-12.
^ "Pharmacies in Greece". About.com. Retrieved 2009-10-10.
^ "Codeine regulations cause a few headaches". The Irish Times. 08 Aug 2010.
^ Office of The Attorney General, Regulation 5(1)(e) of the Regulation of Retail Pharmacy Businesses Regulations 2008 (S.I. 488 of 2008)
^ Non-Prescription Medicinal Products Containing Codeine: Draft Guidance for Pharmacists. Pharmaceutical Society of Ireland.
^ Business and History - Merck Frosst Canada Inc. | Western Libraries
^ Valeant Pharmaceuticals. "Prescribing Information for Capital with Codeine (acetaminophen with codeine) showing Schedule V designation" (PDF). Retrieved 2011-02-25.
^ "152.02 SCHEDULES OF CONTROLLED SUBSTANCES". State of Minnesota. Retrieved 15:01, 30 May 2013 (UTC).
^ International Narcotics Control Board. "List of Narcotic Drugs under International Control" (PDF). Retrieved 2006-05-24.
^ http://www.legislation.gov.uk/ukpga/1971/38/schedule/2

English Journal

Larger corpus callosum and reduced orbitofrontal cortex homotopic connectivity in codeine cough syrup-dependent male adolescents and young adults.

Qiu YW1,2,3, Lv XF4, Jiang GH5, Su HH5, Ma XF5, Tian JZ5, Zhuo FZ6.
European radiology.Eur Radiol.2017 Mar;27(3):1161-1168. doi: 10.1007/s00330-016-4465-5. Epub 2016 Jun 21.
OBJECTIVES: To characterize interhemispheric functional and anatomical connectivity and their relationships with impulsive behaviour in codeine-containing cough syrup (CCS)-dependent male adolescents and young adults.METHODS: We compared volumes of corpus callosum (CC) and its five subregion and vox
PMID 27329520

Chronic Use of Opioids Before and After Total Knee Arthroplasty: A Retrospective Cohort Study.

Hansen CA1, Inacio MC2, Pratt NL2, Roughead EE2, Graves SE3.
The Journal of arthroplasty.J Arthroplasty.2017 Mar;32(3):811-817.e1. doi: 10.1016/j.arth.2016.09.040. Epub 2016 Oct 4.
BACKGROUND: Opioids are commonly used for the management of preoperative and postoperative pain among patients undergoing total knee arthroplasty (TKA). There is limited literature on the chronic use of opioids pre-TKA and post-TKA. The aim of this study was to characterize the use of opioids in TKA
PMID 27836577

Drug safety and adverse drug reaction reporting behavior related to outpatient opioid replacement therapy: Results from a survey among physicians.

Gahr M1, Eller J2, Cabanis M3, Hiemke C4, Freudenmann RW2, Connemann BJ2, Lang D5, Schönfeldt-Lecuona C2.
Journal of substance abuse treatment.J Subst Abuse Treat.2017 Mar;74:7-15. doi: 10.1016/j.jsat.2016.12.002. Epub 2016 Dec 14.
To study drug safety and the reporting behavior of adverse drug reactions (ADR) related to agents used for opioid replacement therapy (ORT) we conducted a cross-sectional questionnaire-based telephone survey among physicians who provide outpatient ORT in Germany (n=176; response rate=55.7%). Most re
PMID 28132703

Related Pictures

Pics Photos - Codeine Or 3 Methylmorphine METHYLMORPHINE SULFATE SALT;CODEINE Morphine Molecule Structure cornellbiochem - 3-methylmorphine Codeine or 3-methylmorphine (a naturally methylmorphine; n-methylmorphine

★リンクテーブル★

リンク元	「麻薬性鎮痛薬」「コデイン」「codeine」

「麻薬性鎮痛薬」

Codeine
Systematic (IUPAC) name
	(5α,6α)-7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a682065
Pregnancy cat.	C (US)
Legal status	Controlled (S8) (AU) Schedule I (CA) POM (UK) Schedule II (US)
Dependence liability	Moderate
Routes	Oral, intra-rectally, SC, IM
Pharmacokinetic data
Bioavailability	~90% Oral
Metabolism	Hepatic, via CYP2D6 (cytochrome P450 2D6)
Half-life	2.5–3 h
Identifiers
CAS number	76-57-3
ATC code	R05DA04; combinations: N02AA59, N02AA79
PubChem	CID 5284371
IUPHAR ligand	1673
DrugBank	DB00318
ChemSpider	4447447
UNII	Q830PW7520
KEGG	C06174
ChEBI	CHEBI:16714
ChEMBL	CHEMBL485
Chemical data
Formula	C18H21NO3
Mol. mass	299.364 g/mol
	SMILES CN1CC[C@]23c4c5ccc(c4O[C@H]2[C@H](C=C[C@H]3[C@H]1C5)O)OC;
	InChI 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/s1 ; Key:OROGSEYTTFOCAN-DNJOTXNNSA-N ;
(what is this?) (verify);

　　[★]

英: narcotic analgesic, narcotic analgesics
同: オピオイド鎮痛薬、モルフィン鎮痛薬？？？
関: オピオイド

モルフィン鎮痛薬

内因性オピオイド

外因性オピオイド

合成

phenylheptylamines

メタドン methadone

phenylpiperadines

オピオイド受容体拮抗薬

ナロキソン naloxone

麻酔薬として

心臓手術やハイリスク患者の麻酔に用いる。
使用される薬にはクエン酸ファンタネルやモルヒネがある。
脳神経に存在する麻酔特有の受容体(オピオイド受容体)をしげきする
鎮痛作用は協力
麻酔薬なので常習性がある。
副作用：呼吸抑制、精神神経作用、消化器症状がある。
注意：患者さんの状態に合わせて、睡眠作用のある薬を使用。すなわち、これ単独では眠らない(記憶を失わない)
○強力な鎮痛・鎮静。血圧安定
×術中覚醒。呼吸抑制。筋硬直。徐脈。術中高血圧

パンクロニウム(長時間使用で頻脈になる)を併せて使うことがある。

依存性

麻薬(オピオイド)には精神依存性・身体依存性がある。
慢性的に疼痛が持続しているような癌患者では、κ受容体が賦活され、μ受容体(身体・精神依存性に関与)が抑制されている。このため、依存は起こらない。(SAN.411改変)

副作用

(高頻度)悪心・嘔吐、(高頻度)便秘、眠気、譫妄

「コデイン」

　　[★]

英: codeine
同: メチルモルヒネ methylmorphine
化: リン酸コデインコデインリン酸塩 codeine phosphate codeini phosphas、codeine polistirex、codeine sulfate
商: ブロチンコデイン(桜皮、コデイン)、サリパラ・コデイン
関: モルフィン鎮痛薬、オピオイド受容体。ジヒドロコデイン; アヘンアルカロイド系麻薬

麻薬性鎮咳薬

薬理作用

鎮痛作用: モルヒネの約l/6 (鎮痙作用はモルヒネの1/4)
鎮咳作用
呼吸抑制、悪心、便秘作用は弱い。

適応

鎮咳：気管支炎、咽頭炎、喉頭炎、肺炎等の咳。乾性咳に有効 (湿性咳には去痰薬を)
鎮痛
激しい下痢の抑制

慎重

前立腺肥大があると尿閉を来しやすいので使いづらい。　→　デキストロメトルファン考慮
便秘　→　便秘になることを説明する。重症の便秘の人には使わない。

処方例

鎮咳薬:リン酸コデインとして 60mg 分3

「codeine」

　　[★] コデイン。メチルモルヒネ methylmorphine 　　

[1] Shen H, He MM, Liu H, et al (August 2007). "Comparative metabolic capabilities and inhibitory profiles of CYP2D6.1, CYP2D6.10, and CYP2D6.17". Drug Metab. Dispos. 35 (8): 1292–300. doi:10.1124/dmd.107.015354. PMID 17470523.

[AHFS-2] "Codeine". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.

[3] Stefano Guandalini; Haleh Vaziri (November 8, 2010). Diarrhea: Diagnostic and Therapeutic Advances. New York, USA: Humana Press. p. 452. ISBN 1-60761-182-1.

[4] "Codeine - adverse effects". Medscape reference - Drugs, Diseases & Procedures. WebMD LLC. Retrieved 27 Sep 2012.

[Drugs.com-5] Codeine Information from Drugs.com

[6] CTV News, Codeine use while breastfeeding may be dangerous, Wed. Aug. 20 2008 9:42 PM ET.

[7] Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder SJ (August 2006). "Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother". Lancet 368 (9536): 704. doi:10.1016/S0140-6736(06)69255-6. PMID 16920476.

[8] "FDA Drug Safety Communication: Codeine use in certain children after tonsillectomy and/or adenoidectomy may lead to rare, but life-threatening adverse events or death". Food and Drug Administration.

[9] Alberta Health Services; AADAC (April 16, 2007). "The ABCs - Codeine and Other Opioid Painkillers". Alberta Alcohol and Drug Abuse Commission. Retrieved Sep 12 2008.

[10] Armstrong SC, Cozza KL (2003). "Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, Part II". Psychosomatics 44 (6): 515–20. doi:10.1176/appi.psy.44.6.515. PMID 14597688.

[Vree2000-11] Vree TB, van Dongen RT, Koopman-Kimenai PM (2000). "Codeine analgesia is due to codeine-6-glucuronide, not morphine". Int. J. Clin. Practa. 54 (6): 395–8. PMID 11092114.

[12] Fernandes LC, Kilicarslan T, Kaplan HL, Tyndale RF, Sellers EM, Romach MK (June 2002). "Treatment of codeine dependence with inhibitors of cytochrome P450 2D6". J Clin Psychopharmacol 22 (3): 326–9. doi:10.1097/00004714-200206000-00014. PMID 12006904.

[13] Kathiramalainathan K, Kaplan HL, Romach MK, et al. (2000). "Inhibition of cytochrome P450 2D6 modifies codeine abuse liability". J Clin Psychopharmacol 20 (4): 435–44. doi:10.1097/00004714-200008000-00008. PMID 10917405.

[14] Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder SJ (2006). "Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother". Lancet 368 (9536): 704. doi:10.1016/S0140-6736(06)69255-6. PMID 16920476.

[15] Willmann S, Edginton AN, Coboeken K, Ahr G, Lippert J (2009). "Risk to the Breast-Fed Neonate From Codeine Treatment to the Mother: A Quantitative Mechanistic Modeling Study". Clinical Pharmacology & Therapeutics 86 (6): 634–43. doi:10.1038/clpt.2009.151.

[Srinivasan_V.2C_Wielbo_D.2C_Tebbett_IR_1997_185.E2.80.9390-16] Srinivasan V, Wielbo D, Tebbett IR (1997). "Analgesic effects of codeine-6-glucuronide after intravenous administration". European Journal of Pain 1 (3): 185–90. doi:10.1016/S1090-3801(97)90103-8. PMID 15102399.

[17] Lurcott G (1998). "The effects of the genetic absence and inhibition of CYP2D6 on the metabolism of codeine and its derivatives, hydrocodone and oxycodone". Anesth Prog 45 (4): 154–6. PMC 2148980. PMID 10483388.

[18] Gasche Y, Daali Y, Fathi M, et al. (December 2004). "Codeine intoxication associated with ultrarapid CYP2D6 metabolism". N. Engl. J. Med. 351 (27): 2827–31. doi:10.1056/NEJMoa041888. PMID 15625333.

[19] Caraco Y (December 2004). "Genes and the response to drugs". N. Engl. J. Med. 351 (27): 2867–9. doi:10.1056/NEJMe048278. PMID 15625340.

[20] Gardiner, S. J.; Begg, E. J. (2006). "Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice". Pharmacological Reviews 58 (3): 521–590. doi:10.1124/pr.58.3.6. PMID 16968950. edit

[21] Andreas Luch (2009). Molecular, clinical and environmental toxicology. Springer. p. 20. ISBN 3-7643-8335-6.

[opiates-22] Opiates.com - Codeine

[sciencedaily-23] Science Daily (March 2010) - "Unlocking the Opium Poppy's Biggest Secret: Genes That Make Codeine, Morphine"

[24] Elmhurt College - Narcotic Analgesic Drugs

[25] Boekhout van Solinge, Tim (1996). "7. La politique de soins des années quatre-vingt-dix". L'héroïne, la cocaïne et le crack en France. Trafic, usage et politique (in French). Amsterdam: CEDRO Centrum voor Drugsonderzoek, Universiteit van Amsterdam. pp. 247–262.

[26] Leinwand, Donna (2006-10-18). "DEA warns of soft drink-cough syrup mix". USA Today. Retrieved 2006-10-23.

[27] ttp://www.chron.com/entertainment/music/article/Pimp-C-s-death-caused-by-overdose-and-sleep-1629962.php

[28] Hogshire, Jim (June 1999). Pills-A-Go-Go: A Fiendish Investigation into Pill Marketing, Art, History & Consumption. Los Angeles: Feral House. pp. 216–223. ISBN 978-0-922915-53-8.

[29] Savchuk, S. A.; Barsegyan, S. S.; Barsegyan, I. B.; Kolesov, G. M. (2011). "Chromatographic study of expert and biological samples containing desomorphine". Journal of Analytical Chemistry 63 (4): 361–70. doi:10.1134/S1061934808040096.

[30] Thevis M, Opfermann G, Schänzer W (2003). "Urinary concentrations of morphine and codeine after consumption of poppy seeds". J. Anal. Toxicol. 27 (1): 53–6. PMID 12587685.

[31] Cone EJ, Welch P, Paul BD, Mitchell JM (1991). "Forensic drug testing for opiates, III. Urinary excretion rates of morphine and codeine following codeine administration". J. Anal. Toxicol. 15 (4): 161–6. PMID 1943064.

[32] Baselt, R. (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City CA: Biomedical Publications. pp. 355–360.

[33] "Codeine crackdown comes into effect". ABC.net.au. Retrieved 2010-11-22.

[34] "vital list of codein". vidal.com. Retrieved 2011-01-12.

[35] "Pharmacies in Greece". About.com. Retrieved 2009-10-10.

[36] "Codeine regulations cause a few headaches". The Irish Times. 08 Aug 2010.

[37] Office of The Attorney General, Regulation 5(1)(e) of the Regulation of Retail Pharmacy Businesses Regulations 2008 (S.I. 488 of 2008)

[38] Non-Prescription Medicinal Products Containing Codeine: Draft Guidance for Pharmacists. Pharmaceutical Society of Ireland.

[39] Business and History - Merck Frosst Canada Inc. | Western Libraries

[Valeant_Pharmaceuticals_Prescribing_Information_for_Capital_with_Codeine_Oral_Suspension-40] Valeant Pharmaceuticals. "Prescribing Information for Capital with Codeine (acetaminophen with codeine) showing Schedule V designation" (PDF). Retrieved 2011-02-25.

[Minnesota.3B_Schedules_of_controlled_substances-41] "152.02 SCHEDULES OF CONTROLLED SUBSTANCES". State of Minnesota. Retrieved 15:01, 30 May 2013 (UTC).

[INCB-Yellow-42] International Narcotics Control Board. "List of Narcotic Drugs under International Control" (PDF). Retrieved 2006-05-24.

[43] ttp://www.legislation.gov.uk/ukpga/1971/38/schedule/2

匿名

検索

案内

methylmorphine