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| {{drugbox |
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| | IUPAC_name = (5α,6α)-7,8-didehydro-4,5-epoxy-<br />3-methoxy-17-methylmorphinan-6-ol
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| | image = Codein - Codeine.svg
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| | CAS_number = 76-57-3
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| | ATC_prefix = R05
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| | ATC_suffix = DA04
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| | ATC_supplemental = {{ATC|N02|AA59}}
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| | PubChem = 5284371
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| | DrugBank = APRD00120
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| | C=18 | H=21 | N=1 | O=3
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| | molecular_weight = 299.364 g/mol
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| | bioavailability = ~90% Oral
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| | elimination_half-life = 2.5–3 hours
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| | metabolism = [[Liver|Hepatic]], via [[CYP2D6]] (Cytochrome P450 2D6)<ref>Drug Metab Dispos. 2007 Aug;35(8):1292-300</ref>
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| | legal_AU = S8
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| | legal_CA = Schedule I
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| | legal_NZ = Class C
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| | legal_SG = Class B
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| | legal_UK = Class B
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| | legal_US = Schedule II
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| | legal_status =
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| | routes_of_administration = oral, intra-rectally, [[subcutaneous|SC]], [[intramuscular|IM]]
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| }}
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| {{SI}}
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| {{CMG}}
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| ==Overview==
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| '''Codeine''' ([[International Nonproprietary Name|INN]]) or '''methylmorphine''' is an [[opiate]] used for its [[analgesic]], [[Cough medicine|antitussive]] and [[Antidiarrhoeal|antidiarrheal]] properties. It is by far the most widely used opiate in the world and very likely most commonly used drug overall according to numerous reports over the years by organizations such as the [[World Health Organization]] and its League of Nations predecessor agency and others. It is one of the most effective orally-administered [[opioid]] [[analgesics]] and has a wide safety margin. It is from 8 to 12 percent of the strength of morphine in most people; differences in metabolism can change this figure as can other medications.
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| Codeine is an [[alkaloid]] found in [[opium]] and other poppy saps like ''Papaver bracteatum'' the Iranian poppy. It was first isolated in 1830 in [[France]] by [[Pierre Jean Robiquet|Jean-Pierre Robiquet]], in concentrations ranging from 0.3 to 3.0 [[percent]]. While codeine can be extracted from opium, most codeine is synthesized from [[morphine]] through the process of O-[[methylation]].
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| Although it is a naturally-occurring opiate, codeine can also be made by complete synthesis as well. The effects of the Nixon [[War On Drugs]] by 1972 or so 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 getting less helpful for the United States. After a large percentage of the opium and morphine in the [[Defense National Stockpile Center|US National Stockpile of Strategic & Critical Materials]] had to be tapped in order to ease severe shortages of medicinal opiates -- the codeine-based antitussives in particular -- in late 1973, researchers were tasked with and quickly succeeded in finding a way that codeine and its derivatives and precursors can be synthesized from scratch from petroleum or coal tar using a process developed at the United States' National Institutes of Health.
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| Codeine is marketed as the salts codeine sulphate and codeine phosphate in the United States and Canada. Codeine hydrochloride is more commonly marketed in continental Europe and other regions, and codeine hydroiodide and codeine bitartrate round out the top five most-used codeine salts worldwide. Codeine is usually present in raw opium as free alkaloid in addition to codeine meconate, codeine pectinate, and possibly other naturally-occurring codeine salts. Dozens of other salts of codeine have been developed over the last 175 years including some with special properties of other drug groups such as codeine [[salicylate]] and codeine-based salts of barbituric acid ([[barbiturates]]). Codeine citrate, nitrate, picrate, acetate, hydrobromide and others are occasionally encountered on the pharmaceutical market and in research.
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| Codeine is the starting material and prototype of a large class of mainly mild to moderately strong opioids such as [[hydrocodone]], [[dihydrocodeine]] and its derivatives such as [[nicocodeine]], [[oxycodone]] etc. Related to codeine in other ways are [[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.
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| ==Indications==
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| Approved indications for codeine include:
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| *[[Cough]], though its efficacy in low dose [[Over-the-counter drug|over the counter]] formulations has been disputed.<ref name="Cochrane2004-Schroeder">{{cite journal | author=Schroeder K, Fahey T | title=Over-the-counter medications for acute cough in children and adults in ambulatory settings. | journal=Cochrane Database Syst Rev | pages=CD001831 | date=2001 | doi=10.1002/14651858.CD001831 | id=PMID 15495019}}</ref>
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| *[[Diarrhea]]
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| *Moderate to severe [[Pain and nociception|pain]]
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| *[[Irritable bowel syndrome]]
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| Codeine is sometimes marketed in combination preparations with [[paracetamol]] (acetaminophen) as [[co-codamol]] or paracod (best known in North America as Tylenol 3), with [[aspirin]] as [[co-codaprin]] or with [[ibuprofen]]. These combinations provide greater pain relief than either agent alone (drug synergy). Codeine is also commonly compounded with other pain killers or muscle relaxers such as Fioricet with Codeine, Soma Compound/Codeine, etc. Codeine-only products can be obtained with a prescription as a time release tablet (eg. Codeine Contin(r) 100mg).
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| The narcotic content number in the US names of codeine tablets and combination products like Tylenol With Codeine No. 3, Emprin With Codeine No. 4 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 222 series is identical to the above list 222=1/8 grain, 292=1/4 grain, 293=1/2 grain, and 294=1 grain of codeine.
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| Injectable codeine is available for subcutaneous or intramuscular injecton; intravenous injection can cause a serious reaction which can progress to anaphylaxis. Codeine suppositories are also marketed in some countries.
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| ==Controlled substance==
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| In [[Australia]], [[New Zealand]], [[Romania]], [[Canada]] and many other countries, codeine is regulated. In some countries it is available without prescription in combination preparations from licensed pharmacists in doses up to 15 mg/tablet in Australia, 8 mg/tablet in Canada, 20 mg/tablet in New Zealand, and 10mg/tablet in Israel.
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| In Canada, codeine can be sold over the counter only in combination with two or more ingredients, which has resulted in the prevalence of AC&C ([[aspirin]], codeine, and [[caffeine]]), and similar combinations using acetaminophen ([[paracetamol]]) rather than aspirin. Caffeine, being a stimulant, tends to offset the sedative effects of codeine. It also can [[synergy#Examples|increase]] the effectiveness and absorption rate of analgesics in some circumstances.<ref>{{cite web | title = Headache Triggers: Caffeine | publisher = WebMD | date = June 2004 | url = http://www.webmd.com/content/article/46/1826_50681.htm | accessdate = 2007-03-23 }}</ref>
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| Codeine is listed under the ''Betäubungsmittelgesetz'' in [[Germany]] and the similarly-named narcotics & 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 &c.) generally require a prescription order from a doctor or the discretion of the pharmacist. Municipal and provincial regulations may impact the range of products which can be dispensed in the latter case.
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| In [[Hong Kong]], codeine is regulated under Schedule 1 of [[Hong Kong|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([[Hong Kong dollar|HKD]]). The 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.
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| However, codeine is available without prescription from licensed pharmacists in doses up to 0.1% (5mg/5ml) according to Hong Kong "Dangerous Drugs Ordinance".<ref>{{cite web | title = Common Drugs in Hong Kong | publisher = Hong Kong Police Force | url = http://www.police.gov.hk/hkp-text/english/nb/common_drugs.htm#cough | accessdate = 2007-08-13 }}</ref>
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| In the [[United Kingdom]], codeine tablets are prescription only medicines, with the exception of co-codamol 8/500 where 8mg of codeine phosphate is combined with 500mg paracetamol which is available as a pharmacy supervised medicine. This applies as well to Nurofen Plus, which contains 200mg [[Ibuprofen]] with 12.8mg Codeine per tablet. [[Intramuscular injection]] of codeine is a controlled drug under the [[Misuse of Drugs Act 1971]].
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| In the [[United States]], codeine is regulated by the [[Controlled Substances Act]]. It is a Schedule II controlled substance for pain-relief products containing codeine alone or more than 90 mg per dosage unit. In combination with aspirin or acetaminophen ([[paracetamol]]/Tylenol) it is listed as Schedule III or V, depending on formula. Preparations for cough or diarrhoea 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 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 a picture ID such as a driving licence) and also which maintain controlled substances in the closed system at the root of the régime intended by the Controlled Substances Act of 1970 -- e.g. 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. Other drugs which 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.
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| Codeine is also available outside the United States as an [[over-the-counter drug]] in liquid cough-relief formulations. Internationally, codeine is a Schedule II drug under the [[Single Convention on Narcotic Drugs]].<!--
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| --><ref name="INCB-Yellow">{{cite web | author =International Narcotics Control Board | authorlink =International Narcotics Control Board | url =http://www.incb.org/pdf/e/list/46thedition.pdf | title =List of Narcotic Drugs under International Control | format =PDF | accessdate =2006-05-24}}</ref>
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| ==Pharmacokinetics==
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| Codeine is considered a [[prodrug]], since it is metabolised ''[[in vivo]]'' to the primary active compounds [[morphine]] and [[codeine-6-glucuronide]].<ref>{{cite journal |author=Vree TB, van Dongen RT, Koopman-Kimenai PM |title=Codeine analgesia is due to codeine-6-glucuronide, not morphine |journal=Int. J. Clin. Pract. |volume=54 |issue=6 |pages=395–8 |year=2000 |pmid=11092114 |doi=}}</ref><ref>{{cite journal |author=Srinivasan V, Wielbo D, Tebbett IR |title=Analgesic effects of codeine-6-glucuronide after intravenous administration |journal=European journal of pain (London, England) |volume=1 |issue=3 |pages=185–90 |year=1997 |pmid=15102399 |doi=}}</ref> Roughly 5-10% of codeine will be converted to morphine, with the remainder either free, conjugated to form codeine-6-glucuronide (~70%), or converted to [[norcodeine]] (~10%) and [[hydromorphone]] (~1%). It is less potent than morphine and has a correspondingly lower [[drug addiction|dependence]]-liability than morphine.<ref>{{cite journal |author=Vree TB, van Dongen RT, Koopman-Kimenai PM |title=Codeine analgesia is due to codeine-6-glucuronide, not morphine |journal=Int. J. Clin. Pract. |volume=54 |issue=6 |pages=395–8 |year=2000 |pmid=11092114 |doi=}}</ref> Like all opiates, codeine is addictive unless used infrequently. However, the withdrawal symptoms are relatively mild and as a consequence codeine is considerably less addictive than the other opiates.
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| Theoretically, a dose of approximately 200 mg (oral) of codeine must be administered to give analgesia equivalent to 30 mg (oral) of morphine (Rossi, 2004). However, codeine is generally not used in single doses of greater than 60 mg (and no more than 240 mg in 24 hours). When analgesia beyond this is required, stronger opioids such as [[hydrocodone]] or [[oxycodone]] are favored. Because codeine needs to be metabolized to an active form, there is a [[ceiling effect]] around 400-450 mg. This low ceiling further contributes to codeine being less addictive than the other opiates.
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| 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. Approximately 6–10% of the Caucasian population, 2% of Asians, and 1% of Arabs<ref>{{cite web |url=http://codeine.50g.com/info/codeine.html |title=Codeine Information - Facts - Codeine |accessdate=2007-07-16 |format= |work=}}</ref> have poorly functional CYP2D6 and codeine should be less effective for analgesia in these patients (Rossi, 2004), although it is speculated that codeine-6-glucuronide is responsible for a large percentage of the analgesia of codeine and thus these patients should experience some analgesia.<ref>{{cite journal |author=Srinivasan V, Wielbo D, Tebbett IR |title=Analgesic effects of codeine-6-glucuronide after intravenous administration |journal=European journal of pain (London, England) |volume=1 |issue=3 |pages=185–90 |year=1997 |pmid=15102399 |doi=}}</ref> Many of the adverse effects will still be experienced in those deficient in 2D6. Conversely, 0.5-2% of the population has multiple copies of the 2D6 gene and will metabolise 2D6 dependent drugs more efficiently than others.
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| Some medications are CYP2D6 inhibitors and reduce or even completely eliminate the efficacy of codeine. The most well-known of these are the [[selective serotonin reuptake inhibitor]]s, such as [[fluoxetine]] (Prozac) and [[citalopram]] (Celexa). Other drugs, such as [[rifampicin]] and [[dexamethasone]], induce expression of CYP450 isozymes and thus increase the rate of metabolism.
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| It is important to note that whereas usually a CYP2D6 extensive metaboliser (EM) will need a higher dose of 2D6-metabolized drug for a sufficient therapeutic effect and a poor metaboliser (PM) may suffer from drug toxicity due to excessive plasma concentration, with the pro-drug Codeine, the opposite is true. Thus, an EM may have an adverse toxicity effect and a PM may have little or no pain relief.
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| ==Pharmacology==
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| {{main|Opioid receptor}}
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| Codeine is a [[prodrug]], itself inactive, but demethylated to the active [[morphine]] by the liver enzyme [[CYP2D6]]. Because of the wide variability in CYP2D6 activity among humans, the effect of codeine can vary between individuals. In persons with little or no CYP2D6 function, codeine has little or no effect.
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| ==Adverse effects==
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| Common adverse drug reactions associated with the use of codeine include itching, nausea, vomiting, drowsiness, dry mouth, [[miosis]], [[orthostatic hypotension]], urinary retention and constipation.<!--
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| --><ref name="AMH2004">{{cite book | author = Australian Medicines Handbook | authorlink = Australian Medicines Handbook | editor = Rossi S | title = Australian Medicines Handbook | year = 2004 | publisher = Australian Medicines Handbook | location = Adelaide | id = ISBN 0-9578521-4-2}}</ref>
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| 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.
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| 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.
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| Another side effect commonly noticed is the lack of sexual drive.<ref>http://www.drugs.com/codeine.html</ref>
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| Codeine has also been known to interact negatively with some [[psychiatric]] [[medication]]s such as [[reboxetine]] and [[venlafaxine]].
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| Some people may also have an allergic reaction to codeine, which may cause severe allergic reactions such as the swelling of skin and rashes. <ref>http://www.drugs.com/codeine.html</ref>
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| ==Recreational use==
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| Codeine can be used as a [[recreational drug]], however it has much less abuse potential than some other opiates or opioids such as oxycodone and hydrocodone. When it is taken for recreational use, it is commonly referred to as "cilly" (pronounced silly) because of the way most people react to it. Another name that might refer to it is "loopy c," also for the way it makes most people act. Codeine is also known as juice (cough syrup), school boy, codys (tablets), little c, T1s, T2s, T3s, and T4s.
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| Codeine is the opioid which causes itching at most for a good percentage of users and its presence along with [[acetylcodeine]] in illicitly-produced heroin causes most of the itching associated with that drug.
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| In combination with the [[sedative-hypnotic]] Doriden ([[Glutethimide]]) it is known as Dors & Fours or a six-pack (two Doriden tablets and four tablets of [[Tylenol With Codeine]] No. 4). Like [[dihydrocodeine]] and [[hydrocodone]], codeine is also mixed with [[carisoprodol]] to intensify the effect. Both for control of itching and potentiation, codeine and its derivatives are often combined with antihistamines in both clinical and recreational settings, with [[hydroxyzine]], [[diphenhydramine]], [[orphenadrine]], [[brompheniramine]], [[dexbrompheniramine]], [[chlorpheniramine]], [[dexchlorpheniramine]], [[carbinoxamine]], [[bromdiphenhydramine]], and [[tripelennamine]].
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| Three favourite opioid-potentiator combinations using this knowledge are narcotic cough syrup and ginger ale, codeine, dihydrocodeine, hydrocodone and similar tablets or liquids with the green label Alka Seltzer Cold Medicine, and the opioids above with naproxen and cyclobenzaprine with caffeine if desired. Note that these are not only for recreational use -- they have significant efficacy against pain and concurrent misery and reduce the quantity of opioid needed in a given case.
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| The antihistamine [[promethazine]] (Phenergan) is not only an antihistamine but a Cytochrome P450 II-D-6 booster which can double the percentage of the codeine that the liver turns into morphine. For the same reason [[cimetidine]] (Tagamet) should be avoided with codeine but can help out dihydrocodeine and other codeine derivatives which have direct action of their own before being demethylated in the liver. Mixing opioids with depressant medications such as those above is certainly not without risks of its own.
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| Codeine can also be snorted, taken as a rectal solution, turned into freebase and smoked, or injected into the skin or muscle as well. Intravenous injection is particularly dangerous as discussed elswehere in this article.
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| In some countries codeine has easy availability [[Over-the-counter drug|over the counter]] or on [[Medical prescription|prescription]] in combination products (which, in certain countries, are scheduled lower than codeine as a single-agent). People use it in order to obtain the [[euphoria|euphoric]] effects associated with use of opioids. Codeine-containing cough syrups are often taken whole by drinking the syrup; combination pills may be taken whole or crushed and mixed with water for faster absorption into the body, or the codeine may be extracted using methods like [[cold water extraction]].
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| Therapeutic use of codeine falls in the category of 10-60 mg at once for the starting dose. As indicated in this article tolerance can build with time. The ceiling for codeine use in the clinical setting is often set at 120 mg per dose and 640-1000 mg per 24 hours and/or the 1000 mg/dose and 4000 mg per day limit for paracetamol as histamine-related side effects may become difficult to manage and are not as likely to decrease with time as much as the direct narcotic effects. Some patients with tolerance have been able to handle a regimen of 8 single-ingredient tablets of codeine hydrochloride (240 mg), combined with one 100 mg tablet of Atarax ([[hydroxyzine]] hydrochloride) and 500 mg of [[Naproxen]] q6h under doctor's orders as related in ''Inside Narcotics'' (pp. 32–33 of fourth edition (2000)).
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| The recreational dose of codeine is between 60 mg and 400 mg; the liver cannot metabolize any more than that amount at once. This is also the reason for which the entire dose should be taken at one time and at least two hours allowed between doses.
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| In some countries, cough syrups and tablets containing codeine are available without prescription; some potential recreational users are reported to buy the aforementioned from multiple pharmacies so as not to incur suspicion. It is reported that in [[France]], 95% of the consumption of Néo-codion cough preparation, containing codeine, can be attributed to non-medical use. A heroin addict may use codeine to ward off the effects of a [[withdrawal]].<!--
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| --><ref>{{cite book | last = Boekhout van Solinge | first = Tim | title = L'héroïne, la cocaïne et le crack en France. Trafic, usage et politique | origyear = 1996 | publisher = CEDRO Centrum voor Drugsonderzoek, Universiteit van Amsterdam | location = Amsterdam | language = French | pages = 247–262 | chapter = 7. La politique de soins des années quatre-vingt-dix | chapterurl = http://www.cedro-uva.org/lib/boekhout.heroine.fr.7.html}}</ref>
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| Codeine is also available in conjunction with the anti-nausea medication [[promethazine]] in the form of a syrup. Brand named as Phenergan VC with Codeine or generically as promethazine with codeine this medication is quickly becoming one of the most highly abused codeine preparations. Although there are various forms of this syrup varying in strengths, the highly publicized "purple" version (grape flavored) is the most sought after. In this form, there are 60mg of codeine per liquid ounce which makes it the strongest of the codeine syrups. This "[[Purple Drank]]" is frequently referenced and praised in the [[southern rap]] and [[Houston]]-based hip-hop community where it is mixed with the soft drink [[Sprite (soft drink)|Sprite]]. There are many songs that mention this narcotic mixed drink, such as [[Three Six Mafia]]'s "[[Sippin' On Some Syrup]]" and [[Paul Wall]]'s "[[Sippin' The Barre]]". The common nicknames associated with codeine infused cough syrup are purple, yellow, red, barre, drank, Texas tea, purple drank, hulk, syrup, sizzerp and there continues to be more added everyday.<ref>{{cite news |publisher = [[USA Today]] |first = Donna | last = Leinwand |title = DEA warns of soft drink-cough syrup mix | date= |url = http://www.usatoday.com/news/nation/2006-10-18-lean_x.htm?csp=34 |date = [[2006-10-18]] |accessdate = 2006-10-23}}</ref>
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| In the [[United Kingdom]], [[Ireland]], [[Australia]], [[New Zealand]], and [[Canada]] tablets which combine codeine and [[paracetamol]] (acetaminophen) are widely available, and these can be consumed at higher-than-recommended doses for recreational effect. In doing so, users run the serious risk of [[hepatotoxicity]] associated with large doses of paracetamol. While the combination of codeine with [[paracetamol]] at higher-than-recommended doses can possibly cause hepatotoxicity ([[liver]] damage), combination with [[ibuprofen]] can result in [[kidney]] problems/failure and additional [[stomach]] pain and [[nausea]], and combination with [[aspirin]] can lead to internal [[hemorrhage|hemorrhaging]], particularly [[gastrointestinal]] hemorrhage.
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| Codeine is also demethylated by reaction with [[pyridine]] to illicitly synthesize morphine. Pyridine is toxic and [[carcinogenic]], so morphine illicitly produced in this manner (and potentially contaminated with pyridine) may be particularly harmful.<!--
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| --><ref>{{cite book | last = Hogshire | first = Jim | authorlink = Jim Hogshire | title = Pills-A-Go-Go: A Fiendish Investigation into Pill Marketing, Art, History & Consumption | publisher = Feral House | year = 1999 | month = June | location = Los Angeles | pages = 216–223 | id = ISBN 0-922915-53-9}}</ref>
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| ==References==
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| {{Reflist|2}}
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| {{Analgesics}}
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| {{Opioids}}
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| {{Cough and cold preparations}}
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| [[Category:Drugs]]
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| [[Category:Substance abuse]]
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| [[Category:Abuse]]
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| [[ar:كودين]]
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| [[ast:Codeína]]
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| [[fr:Codéine]]
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| [[id:Kodein]]
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| [[simple:Codeine]]
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| [[Category:Antitussives]]
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