This article is about the drug.

Codeine
Systematic (IUPAC) name
(5α,6α)-7,8-didehydro-4,5-epoxy- 3-methoxy-17-methylmorphinan-6-ol
Identifiers
CAS number	76-57-3
ATC code	R05DA04 N02AA59
PubChem	5284371
DrugBank	APRD00120
Chemical data
Formula	C18H21NO3
Mol. mass	299.364 g/mol
Pharmacokinetic data
Bioavailability	~90% Oral
Metabolism	Hepatic, via CYP2D6 (Cytochrome P450 2D6)[1]
Half life	2.5–3 hours
Excretion	?
Therapeutic considerations
Pregnancy cat.	? Codeine is an American indie rock/slowcore band formed in 1989 by members Stephen Immerwahr (vocal, bass), Chris Brokaw (drums), and John Engle (guitar). ... Image File history File links This is a lossless scalable vector image. ... IUPAC nomenclature is a system of naming chemical compounds and of describing the science of chemistry in general. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A section of the Anatomical Therapeutic Chemical Classification System. ... A section of the Anatomical Therapeutic Chemical Classification System. ... PubChem is a database of chemical molecules. ... The DrugBank database available at the University of Alberta is a unique bioinformatics and cheminformatics resource that combines detailed drug (i. ... A chemical formula is an easy way of expressing information about the atoms that constitute a particular chemical compound. ... For other uses, see Carbon (disambiguation). ... This article is about the chemistry of hydrogen. ... General Name, symbol, number nitrogen, N, 7 Chemical series nonmetals Group, period, block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... This article is about the chemical element and its most stable form, or dioxygen. ... The molecular mass (abbreviated Mr) of a substance, formerly also called molecular weight and abbreviated as MW, is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. ... The liver is the largest internal organ in the human body, and is an organ present in vertebrates and some other animals. ... Cytochrome P450 2D6 (CYP2D6), a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. ... The biological half-life of a substance is the time required for half of that substance to be removed from an organism by either a physical or a chemical process. ... The kidneys are important excretory organs in vertebrates. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. ...
Legal status	Controlled (S8)(AU) Schedule I(CA) Class B(UK) Schedule II(US) The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ... The Standard for the Uniform Scheduling of Drugs and Poisons, abbreviated SUSDP, is a document used in the regulation of drugs and poisons in Australia. ... For other uses, see Australia (disambiguation). ... The Controlled Drugs and Substances Act is Canadas federal drug control statute. ... Motto (Latin for From Sea to Sea) Anthem O Canada Royal anthem: God Save the Queen Capital Ottawa Largest city Toronto Official languages English, French Government Parliamentary democracy and federal constitutional monarchy  -  Monarch Queen Elizabeth II  -  Governor General Michaëlle Jean  -  Prime Minister Stephen Harper Establishment  -  Act of Union February... The Misuse of Drugs Act 1971 is an Act of Parliament, by which the United Kingdom aims to control the possession and supply of numerous drugs and drug-like substances, as listed under the Act, and to enable international co-operation against illegal drug trafficking. ... This box:      The Controlled Substances Act (CSA) was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. ... For other uses of terms redirecting here, see US (disambiguation), USA (disambiguation), and United States (disambiguation) Motto In God We Trust(since 1956) (From Many, One; Latin, traditional) Anthem The Star-Spangled Banner Capital Washington, D.C. Largest city New York City National language English (de facto)1 Demonym American...
Routes	oral, intra-rectally, SC, IM

Codeine (INN) or methylmorphine is an opiate used for its analgesic, antitussive and 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. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body. ... The subcutis is the layer of tissue directly underlying the cutis. ... Intramuscular injection is an injection of a substance directly into a muscle. ... An International Nonproprietary Name (INN) is the official non-proprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization. ... For other uses see Opiate (disambiguation), or for the class of drugs see Opioid. ... An analgesic (colloquially known as a painkiller) is any member of the diverse group of drugs used to relieve pain (achieve analgesia). ... Cough medicine often contains cough suppressants and expectorants. ... An antidiarrhoeal drug is any medication which provides symptomatic relief for diarrhoea. ... WHO redirects here. ... An opioid is a chemical substance that has a morphine-like action in the body. ... For other uses of painkiller, see painkiller (disambiguation) An analgesic (colloquially known as painkiller) is any member of the diverse group of drugs used to relieve pain. ...

Codeine is an alkaloid found in opium, first isolated in 1830 in France by 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. Chemical structure of ephedrine, a phenethylamine alkaloid An alkaloid is a nitrogen-containing naturally occurring compound, produced by a large variety of organisms, including fungi, plants, animals, and bacteria. ... This article is about the drug. ... A percentage is a way of expressing a proportion, a ratio or a fraction as a whole number, by using 100 as the denominator. ... This article is about the drug. ... Methylation is a term used in the chemical sciences to denote the attachment or substitution of a methyl group on various substrates. ...

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 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 synthesised from scratch from petroleum or coal tar using a process developed at the United States' National Institutes of Health. For the Barenaked Ladies song War on Drugs, see Everything to Everyone. ... The Defense National Stockpile Center (DNSC) is a branch of the Defense Logistics Agency whose purpose it is to store, secure, and sell raw materials. ...

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. Salicylic acid is a colorless, crystalline organic carboxylic acid. ... Barbiturates are drugs that acts as central nervous system (CNS) depressants, and by virtue of this they produce a wide spectrum of effects, from mild sedation to anesthesia. ...

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. Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from two of the naturally occurring opiates, codeine and thebaine. ... Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and by the brand names of Synalgos DC, Panlor DC, Panlor SS, SS Bron, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine, Didrate, Dihydrin, Hydrocodin, Nadeine, Novicodin, Rapacodin, Fortuss, Dico, and DF-118 amongst others, is a semi-synthetic opioid... Nicocodeine (Lyopect) is an opiate derivative developed as a cough suppressant and analgesic. ... Not to be confused with oxytocin. ... Heterocodeine (6-methylmorphine) is an opiate derivative, the 6-methyl ether of morphine, and a structural isomer of codeine. ... Ethylmorphine is a drug in the class of both opiates (representing a minor synthetic change from morphine) and opioids (being effective in the CNSs opioid reception system) . Its effects in humans mainly stem from its metabolic conversion to morphine. ... This article needs additional references or sources to facilitate its verification. ... A minor constituent of opium, thebaine or paramorphine (C19H21NO3) is chemically similar to both morphine and codeine, but produces stimulatory rather than depressant effects. ...

Indications

Approved indications for codeine include:

• Cough, though its efficacy in low dose over the counter formulations has been disputed.^[2]
• Diarrhoea
• Mild to severe pain
• Irritable bowel syndrome

Codeine is sometimes marketed in combination preparations with the analgesic, acetaminophen (paracetamol), as co-codamol, paracod, panadiene, or Tylenol 3, with the analgesic, acetylsalicylic acid (aspirin), as co-codaprin or with the NSAID (non-steroidal anti-inflammatory drug), ibuprofen, as Herron Blue or Nurofen Plus. 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) and Perduretas (50 mg). Over-the-counter (OTC) drugs are medicines that may be sold without a prescription, in contrast to prescription drugs. ... Diarrhoea is the correct way to spell the word Diarrhoea. ... Pain redirects here. ... Acetaminophen (USAN) or paracetamol (INN), is a popular analgesic and antipyretic drug that is used for the relief of fever, headaches, and other minor aches and pains. ... Paracetamol (INN) (IPA: ) or acetaminophen (USAN), is the active metabolite of phenacetin, a so-called coal tar analgesic. ... Co-codamol (BAN) is a non-proprietary name used to denote a combination of codeine phosphate and paracetamol (acetaminophen). ... Codeine (INN) or methylmorphine is an opiate used for its analgesic, antitussive and antidiarrheal properties. ... A very old bottle of Aspirin Aspirin or acetylsalicylic acid is a drug in the family of salicylates, often used as an analgesic (against minor pains and aches), antipyretic (against fever), and anti-inflammatory. ... This article is about the drug. ... Co-codaprin (BAN) is a non-proprietary name used to denote a combination of codeine phosphate with aspirin. ... Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAIDs, are drugs with analgesic, antipyretic and anti-inflammatory effects - they reduce pain, fever and inflammation. ... Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation. ... Coated 200 mg ibuprofen tablets Ibuprofen (INN) (IPA: ) (from the earlier and no longer correct nomenclature iso-butyl-propanoic-phenolic acid) is a non-steroidal anti-inflammatory drug (NSAID) originally marketed as Brufen, and since then under various other trademarks (see tradenames section), most notably Advil. ... It has been suggested that this article or section be merged into Nurofen. ... Synergy (from the Greek synergos, συνεργός meaning working together, circa 1660) refers to the phenomenon in which two or more discrete influences or agents acting together create an effect greater than that predicted by knowing only the separate effects of the individual agents. ...

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.

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.

Controlled substance

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.^{[citation needed]}

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 increase the effectiveness and absorption rate of analgesics in some circumstances.^[3] This article is about the drug. ... For other uses, see Caffeine (disambiguation). ... Paracetamol (INN) (IPA: ) or acetaminophen (USAN), is the active metabolite of phenacetin, a so-called coal tar analgesic. ... Synergy (from the Greek synergos, συνεργός meaning working together, circa 1660) refers to the phenomenon in which two or more discrete influences or agents acting together create an effect greater than that predicted by knowing only the separate effects of the individual agents. ...

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. Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and by the brand names of Synalgos DC, Panlor DC, Panlor SS, SS Bron, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine, Didrate, Dihydrin, Hydrocodin, Nadeine, Novicodin, Rapacodin, Fortuss, Dico, and DF-118 amongst others, is a semi-synthetic opioid...

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 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. ISO 4217 Code HKD User(s) Hong Kong Inflation 2. ...

However, codeine is available without prescription from licensed pharmacists in doses up to 0.1% (5mg/5ml) according to Hong Kong "Dangerous Drugs Ordinance".^[4]

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. Coated 200 mg ibuprofen tablets Ibuprofen (INN) (IPA: ) (from the earlier and no longer correct nomenclature iso-butyl-propanoic-phenolic acid) is a non-steroidal anti-inflammatory drug (NSAID) originally marketed as Brufen, and since then under various other trademarks (see tradenames section), most notably Advil. ... Intramuscular injection is the injection of a substance directly into a muscle. ... The Misuse of Drugs Act 1971 is an Act of Parliament, by which the United Kingdom aims to control the possession and supply of numerous drugs and drug-like substances, as listed under the Act, and to enable international co-operation against illegal drug trafficking. ...

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. This box:      The Controlled Substances Act (CSA) was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. ... Paracetamol (INN) (IPA: ) or acetaminophen (USAN), is the active metabolite of phenacetin, a so-called coal tar analgesic. ... Ethylmorphine is a drug in the class of both opiates (representing a minor synthetic change from morphine) and opioids (being effective in the CNSs opioid reception system) . Its effects in humans mainly stem from its metabolic conversion to morphine. ... Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and by the brand names of Synalgos DC, Panlor DC, Panlor SS, SS Bron, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine, Didrate, Dihydrin, Hydrocodin, Nadeine, Novicodin, Rapacodin, Fortuss, Dico, and DF-118 amongst others, is a semi-synthetic opioid... Paregoric, or camphorated tincture of opium, is a medication known for its antidiarrheal, antitussive, and analgesic properties. ... Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from two of the naturally occurring opiates, codeine and thebaine. ... On opiod agonist used for the treatment of diarrhea. ... Pethidine (INN) or meperidine (USAN) (also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil®; Alodan®; Centralgin®; Demerol®; Dispadol®; Dolantin®; Dolargan® (in Poland);[1] Dolestine®; Dolosal®; Dolsin®; Mefedina®) is a fast-acting opioid analgesic drug. ...

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.^[5] Over-the-counter (OTC) drugs are medicines that may be sold without a prescription, in contrast to prescription drugs. ... Single Convention on Narcotic Drugs Opened for signature March 30, 1961 at New York Entered into force December 13, 1964[1] Conditions for entry into force 40 ratifications Parties 180[2] The Single Convention on Narcotic Drugs is the international treaty against illicit drug manufacture and trafficking that forms the...

Pharmacokinetics

Codeine is considered a prodrug, since it is metabolised in vivo to the primary active compounds morphine and codeine-6-glucuronide.^[6][7] 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 dependence-liability than morphine.^[8] 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. A prodrug is a pharmacological substance (drug) which is administered in an inactive (or significantly less active) form. ... In vivo (Latin for (with)in the living). ... This article is about the drug. ... Hydromorphone is a drug developed in Germany in the 1920s and introduced to the mass market beginning in 1926. ... Drug addiction, or dependency is the compulsive use of drugs, to the point where the user has no effective choice but to continue use. ...

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. Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from two of the naturally occurring opiates, codeine and thebaine. ... Not to be confused with oxytocin. ... Increased doses of the drug do not produce increased effects after a certain point, or ceiling. ...

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^[9] 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.^[10] 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. Cytochrome P450 Oxidase (CYP2E1) Cytochrome P450 oxidase (commonly abbreviated CYP) is a generic term for a large number of related, but distinct, oxidative enzymes (EC 1. ... Cytochrome P450 2D6 (CYP2D6), a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. ... Cytochrome P450 3A4 (abbreviated CYP3A4) (EC 1. ... UGT2B7 (UDP-Glucuronosyltransferase-2B7) is a phase II metabolism isoenzyme found to be active in the liver, kidneys, epithelial cells of the lower gastrointestinal tract and also has been reported in the brain. ...

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 inhibitors, 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. SSRI redirects here; for other uses, see SSRI (disambiguation). ... Prozac redirects here. ... Citalopram is an antidepressant drug used to treat depression associated with mood disorders. ... Rifampicin (INN) (IPA: ) or rifampin (USAN) is a bacteriocidal antibiotic drug of the rifamycin group. ... Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid hormones. ...

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.

Pharmacology

Main article: Opioid receptor

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. To meet Wikipedias quality standards, this article may require cleanup. ... A prodrug is a pharmacological substance (drug) which is administered in an inactive (or significantly less active) form. ... This article is about the drug. ... Cytochrome P450 2D6 (CYP2D6), a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. ...

Adverse effects

Common adverse drug reactions associated with the use of codeine include euphoria, itching, nausea, vomiting, drowsiness, dry mouth, miosis, orthostatic hypotension, urinary retention and constipation.^[11] Euphoria (Greek ) is a medically recognized emotional state related to happiness. ... An itch (Latin: pruritus) is a sensation felt on an area of skin that makes a person or animal want to scratch it. ... For other uses, see Nausea (disambiguation). ... Heaving redirects here. ... Somnolence (or drowsiness, or hypersomnia) is a state of near-sleep, a strong desire for sleep, or sleeping unusually long periods. ... Xerostomia is the medical term for a dry mouth due to a lack of saliva. ... Miosis should not be confused with meiosis, the cellular division process involved in sexual reproduction. ... Orthostatic hypotension (also known as postural hypotension, orthostatic intolerance and, colloquially, as head rush or a dizzy spell) is a sudden fall in blood pressure, typically greater than 20/10 mm Hg, that occurs when a person assumes a standing position, usually after a prolonged period of rest. ... Urinary retention also known as ischuria is a lack of ability to urinate. ... Constipation or irregularity, is a condition of the digestive system where a person (or animal) experiences hard feces that are difficult to egest; it may be extremely painful, and in severe cases (fecal impaction) lead to symptoms of bowel obstruction. ...

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. In medicine, hypoventilation exists when ventilation is inadequate to perform gas exchange. ...

Another side effect commonly noticed is the lack of sexual drive and increased complications in erectile dysfunction.^[12]

Codeine has also been known to interact negatively with some psychiatric medications such as reboxetine and venlafaxine.^[13] Psychiatry is a branch of medicine that studies and treats mental and emotional disorders (see mental illness). ... This article does not cite any references or sources. ... Reboxetine is an antidepressant drug used in the treatment of clinical depression, panic disorder and ADD/ADHD. Its mesilate ( methanesulfonate) salt is sold under tradenames including Edronax®, Norebox®, Prolift®, Solvex® or Vestra®. Reboxetine has two chiral centers, but it only exists as two enantiomers, (R,R)-(-)- and (S,S)-(+)-reboxetine. ... Venlafaxine (Effexor) is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class first introduced by Wyeth in 1993. ...

Recreational use

It has been suggested that Purple_drank be merged into this article or section. (Discuss)

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. Image File history File links Mergefrom. ... Purple Drank is an illegal recreational drink popular amongst the hip-hop community of the Southern United States. ... Recreational drug use is the use of psychoactive drugs for recreational rather than medical or spiritual purposes, although the distinction is not always clear. ...

Codeine is the opioid which causes the most itching 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.

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. It has been suggested that this article or section be merged with hypnotic. ... Glutethimide is a hypnotic sedative that was introduced in 1954 as a safe alternative to barbiturates to treat insomnia. ... Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and by the brand names of Synalgos DC, Panlor DC, Panlor SS, SS Bron, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine, Didrate, Dihydrin, Hydrocodin, Nadeine, Novicodin, Rapacodin, Fortuss, Dico, and DF-118 amongst others, is a semi-synthetic opioid... Hydrocodone or dihydrocodeinone is a semi-synthetic opioid derived from two of the naturally occurring opiates, codeine and thebaine. ... Carisoprodol is a centrally-acting skeletal muscle relaxant whose active metabolite is meprobamate. ... Hydroxyzine (pronounced ) is a first-generation antihistamine, of the piperazine class that is an H1 receptor antagonist. ... Diphenhydramine hydrochloride (trade name Benadryl as produced by Johnson & Johnson, or Dimedrol outside the U.S. & Canada. ... Orphenadrine (Norflex®, Disipal®, Banflex®, Flexon® and others) is an anticholinergic and NMDA receptor antagonist [1]drug belonging to the ethanolamine class of antihistamines. ... Categories: Stub | Antihistamines ... Dexbrompheniramine maleate is an antihistamine used to treat allergic conditions such as hay fever or urticaria. ... Chlorphenamine (INN) or chlorpheniramine (USAN, former BAN), commonly marketed as its salt chlorphenamine maleate (CPM), is first-generation antihistamine used in the prevention of the symptoms of allergic conditions such as rhinitis and urticaria. ... Dexchlorpheniramine maleate (Polaramine®, Schering) is an antihistamine used to treat allergic conditions such as hay fever or urticaria. ... Carbinoxamine is an antihistamine. ... Tripelennamine (INN, also known as pyribenzamine) is a first generation pyridine antipruritic and antihistamine in the ethylenediamine class. ...

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.

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. Promethazine is a first-generation H1 receptor antagonist antihistamine and antiemetic medication. ... Cimetidine (INN) (IPA: ) is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. ...

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.

In some countries codeine has easy availability over the counter or on 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 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. Over-the-counter (OTC) drugs are medicines that may be sold without a prescription, in contrast to prescription drugs. ... A medical prescription ) is an order (often in written form) by a qualified health care professional to a pharmacist or other therapist for a treatment to be provided to their patient. ... Look up euphoria, euphoric in Wiktionary, the free dictionary. ... Cold water extraction is the process whereby a substance is extracted from a mixture via cold water. ...

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)). Hydroxyzine (pronounced ) is a first-generation antihistamine, of the piperazine class that is an H1 receptor antagonist. ... Naproxen (INN) (IPA: ) is a non-steroidal anti-inflammatory drug (NSAID) commonly used for the reduction of mild to moderate pain, fever, inflammation and stiffness caused by conditions such as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, injury (like fractures), menstrual cramps, tendonitis, bursitis, and the treatment of primary...

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 betwixt doses.

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.^{[citation needed]} A heroin addict may use codeine to ward off the effects of a withdrawal.^[14] Withdrawal, also known as withdrawal syndrome, refers to the characteristic signs and symptoms that appear when a drug that causes physical dependence is regularly used for a long time and then suddenly discontinued or decreased in dosage. ...

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. 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.^[15] Promethazine is a first-generation H1 receptor antagonist antihistamine and antiemetic medication. ... Purple Drank is an illegal recreational drink popular amongst the hip-hop community of the Southern United States. ... Southern rap (or Dirty South hip-hop) is a type of hip hop music that emerged in the late-1990s as a popular force from cities such as New Orleans, Miami, Atlanta, Memphis, Houston, and Dallas. ... Houston redirects here. ... Sprite is a clear soda, lemon-lime flavored, caffeine free soft drink, produced by the Coca-Cola Company. ... Originally called Backyard Posse, Triple 6 Mafia were a group of US rap musicians from Memphis, TN. The group had many members (including Gangsta Blac, Gangsta Boo, Lord Infamous, Koopsta Knicca & chief producers Juicy J and DJ Paul) and are best known for their gruesome lyrics, extolling drugs, pornography, and... Paul Slayton, (born March 11, 1981)[1] better known by his stage name Paul Wall, is a rapper and DJ, promoter and jeweller, originally one half of Houston hip-hop group The Color Changin Click. ...

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 hemorrhaging, particularly gastrointestinal hemorrhage. Paracetamol (INN) (IPA: ) or acetaminophen (USAN), is the active metabolite of phenacetin, a so-called coal tar analgesic. ... Hepatotoxicity (from hepatic toxicity) implies chemical-driven liver damage. ... Paracetamol (INN) (IPA: ) or acetaminophen (USAN), is the active metabolite of phenacetin, a so-called coal tar analgesic. ... The liver is the largest internal organ in the human body, and is an organ present in vertebrates and some other animals. ... Coated 200 mg ibuprofen tablets Ibuprofen (INN) (IPA: ) (from the earlier and no longer correct nomenclature iso-butyl-propanoic-phenolic acid) is a non-steroidal anti-inflammatory drug (NSAID) originally marketed as Brufen, and since then under various other trademarks (see tradenames section), most notably Advil. ... The kidneys are the organs that filter wastes (such as urea) from the blood and excrete them, along with water, as urine. ... In anatomy, the stomach is a bean-shaped hollow muscular organ of the gastrointestinal tract involved in the second phase of digestion, following mastication. ... For other uses, see Nausea (disambiguation). ... This article is about the drug. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... For the Physics term GUT, please refer to Grand unification theory The gastrointestinal or digestive tract, also referred to as the GI tract or the alimentary canal or the gut, is the system of organs within multicellular animals which takes in food, digests it to extract energy and nutrients, and...

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.^[16] Pyridine is a chemical compound with the formula C5H5N. It is a liquid with a distinctively putrid odour. ... In pathology, a carcinogen is any substance or agent that promotes cancer. ...

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