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. 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 They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug 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 system is maintained by the National Center for Biotechnology Information (NCBI a component 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 a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 364 g/mol
Pharmacokinetic data
Bioavailability	~90% Oral
Metabolism	Hepatic, via CYP2D6 (Cytochrome P450 2D6)[1]
Half life	2. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The liver is a vital organ in the human body and is 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 The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity 5–3 hours
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status	Controlled (S8)(AU) Schedule I(CA) Class B(UK) Schedule II(US)
Routes	oral, intra-rectally, SC, IM

Codeine (INN) or methylmorphine is an opiate used for its analgesic, antitussive and antidiarrheal properties. Excretion is the process of eliminating waste products of Metabolism and other non-useful materials 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 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 a topic outline on this subject see List of basic Australia topics. The Controlled Drugs and Substances Act is Canada 's federal drug control statute Country to "Dominion of Canada" or "Canadian Federation" or anything else please read the Talk Page The Misuse of Drugs Act 1971 (c38 is an Act of Parliament, by which the United Kingdom aims to control the possession and supply of numerous drugs The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located 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 The United States of America —commonly referred to as the In Pharmacology and Toxicology, a route The subcutaneous tissue or subcutis is the layer of Loose connective tissue directly underlying the Dermis. Intramuscular injection is the injection of a substance directly into a Muscle. An International Nonproprietary Name ( INN; also known as rINN, for recommended International Nonproprietary Name or pINN for proposed For other uses see Opiate (disambiguation, or for the class of drugs see Opioid. A cough medicine is a medicinal drug used to treat Coughing and related conditions An anti-diarrheal drug is any Medication which provides symptomatic relief for diarrhea. 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. An opioid is a chemical Substance that has a Morphine -like action in the body 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.

Codeine is an alkaloid found in opium and other poppy saps like Papaver bracteatum the Iranian poppy. This article is about the chemical compounds alkaloids For the Pharmaceutical company in the Republic of Macedonia see Alkaloid (company. Opium is a Narcotic formed from the Latex (ie sap released by lacerating (or "scoring" the immature seed pods of opium poppies ( It was first isolated in 1830 in France by Jean-Pierre Robiquet, in concentrations ranging from 0. This article is about the country For a topic outline on this subject see List of basic France topics. Pierre Jean Robiquet ( January 13, 1780 &ndash April 1840) was a French Chemist. 3 to 3. 0 percent. In Mathematics, a percentage is a way of expressing a number as a Fraction of 100 ( per cent meaning "per hundred" While codeine can be extracted from opium, most codeine is synthesized from morphine through the process of O-methylation. Medical uses Morphine can be used as an analgesic in hospital settings to relieve pain in Myocardial infarction pain in 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. The War on Drugs is a prohibition campaign undertaken by the United States government with the assistance of participating countries intended to reduce the Illegal 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. 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). Salicylic acid (from the Latin word for the willow tree Salix, from whose bark it can be obtained is a Beta hydroxy acid (BHA with the formula Barbiturates are drugs that act as central nervous system Depressants and by virtue of this they produce a wide spectrum of effects from mild Sedation Codeine citrate, nitrate, picrate, acetate, hydrobromide and others are occasionally encountered on the pharmaceutical market and in research.

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. 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, Nicocodeine ( Lyopect Tusscodin) is an Opiate derivative closely related to Dihydrocodeine and the codeine analogue of Nicomorphine developed as a Oxycodone is an Opioid Analgesic Medication synthesized from Thebaine. 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. Heterocodeine (6-methylmorphine is an Opiate derivative the 6- Methyl Ether of Morphine, and a structural Isomer 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. Ethylmorphine (also known as codethyline, Dionine®, and ethyl morphine) is a drug in the class of both Opiates (representing a minor synthetic k. a. codethyline (Dionine) and benzylmorphine (Peronine). Benzylmorphine ( Peronine) is a Semi-synthetic opiate Narcotic introduced to the international market in 1897 and that of the United States very shortly While having no narcotic effects of its own, the important opioid precursor thebaine differs from codeine only slightly in structure. Parameters work only in their own section When a parameter is not needed please leave it empty when a parameter is wrong just clear Pseudocodeine and some other similar alkaloids not currently used in medicine are found in trace amounts in opium as well.

Contents 1 Indications 2 Controlled substance 3 Pharmacokinetics 4 Pharmacology 5 Adverse effects 6 Recreational use 7 References

Indications

Approved indications for codeine include:

• Cough, though its efficacy in low dose over the counter formulations has been disputed. In Medicine, a cough ( Latin: tussis) is a sudden and often repetitively occurring defence Reflex which helps to clear the large breathing passages Over-the-counter (OTC drugs are medicines that may be sold without a prescription, in contrast to Prescription drugs The name "over-the-counter" ^[2]
• Diarrhea
• Mild to severe pain
• Irritable bowel syndrome

Codeine is sometimes marketed in combination preparations with the analgesic, acetaminophen (paracetamol), as co-codamol, paracod, panadeine, 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. In Medicine, diarrhea, also spelled diarrhoea (see spelling differences) is frequent loose or liquid Bowel movements Acute diarrhea Pain, in the sense of physical pain, is a typical sensory experience that may be described as the unpleasant awareness of a noxious stimulus or bodily harm In Gastroenterology, irritable bowel syndrome ( IBS) is a Functional bowel disorder characterized by mild to severe Abdominal pain, discomfort Paracetamol ( INN) (ˌpærəˈsiːtəmɒl -ˈsɛtə- or acetaminophen ( USAN) is a widely-used Analgesic and Antipyretic Medication Paracetamol ( INN) (ˌpærəˈsiːtəmɒl -ˈsɛtə- or acetaminophen ( USAN) is a widely-used Analgesic and Antipyretic Medication Co-codamol ( BAN) is a non- Proprietary name used to denote a Compound analgesic, a combination of Codeine phosphate and Paracetamol Co-codamol ( BAN) is a non- Proprietary name used to denote a Compound analgesic, a combination of Codeine phosphate and Paracetamol Co-codamol ( BAN) is a non- Proprietary name used to denote a Compound analgesic, a combination of Codeine phosphate and Paracetamol Aspirin, or acetylsalicylic acid (ASA (əˌsɛtɨlsælɨˌsɪlɨk ˈæsɨd is a Salicylate drug, often used as an Analgesic to relieve Aspirin, or acetylsalicylic acid (ASA (əˌsɛtɨlsælɨˌsɪlɨk ˈæsɨd is a Salicylate drug, often used as an Analgesic to relieve Co-codaprin ( BAN) is a non-proprietary name used to denote a Compound analgesic, a combination of Codeine phosphate with Aspirin. Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAID s or NAID s, are drugs with Analgesic, Antipyretic and in higher Anti-inflammatory refers to the property of a substance or treatment that reduces Inflammation. Ibuprofen ( INN) (ˌaɪbjuːˈpɹəʊfɛn (from the now outdated nomenclature i so- bu tyl- pro panoic- phen olic acid is a Non-steroidal Nurofen is the brand name of a range of pain-relief medication made by Reckitt Benckiser (The nurofen brand was acquired following Reckitt Benckiser's acquisition of Boots These combinations provide greater pain relief than either agent alone (drug synergy). Synergy (from the Greek el-Latn syn-ergo, el συνεργός meaning working together is the term used to describe a situation where the final outcome 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).

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, The United Kingdom, Romania, Canada and many other countries, codeine is regulated. For a topic outline on this subject see List of basic Australia topics. New Zealand is an Island country in the south-western Pacific Ocean comprising two main landmasses (the North Island and the South Island The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located Romania ( dated: Rumania, Roumania Country to "Dominion of Canada" or "Canadian Federation" or anything else please read the Talk Page 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.

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. Aspirin, or acetylsalicylic acid (ASA (əˌsɛtɨlsælɨˌsɪlɨk ˈæsɨd is a Salicylate drug, often used as an Analgesic to relieve Caffeine is a bitter white crystalline Xanthine Alkaloid that acts as a Psychoactive Stimulant Drug and a mild Diuretic Paracetamol ( INN) (ˌpærəˈsiːtəmɒl -ˈsɛtə- or acetaminophen ( USAN) is a widely-used Analgesic and Antipyretic Medication 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. Synergy (from the Greek el-Latn syn-ergo, el συνεργός meaning working together is the term used to describe a situation where the final outcome ^[3]

Codeine is listed under the Betäubungsmittelgesetz in Germany and the similarly-named narcotics & controlled substances law in Switzerland. Germany, officially the Federal Republic of Germany ( ˈbʊndəsʁepuˌbliːk ˈdɔʏtʃlant is a Country in Central Europe. Switzerland (English pronunciation; Schweiz Swiss German: Schwyz or Schwiiz Suisse Svizzera Svizra officially the Swiss Confederation In Austria, the drug is listed under the Suchtmittelgesetz in categories corresponding to their classification under the Single Convention on Narcotic Drugs. Austria (Österreich ( officially the Republic of Austria (Republik Österreich Dispensing of products containing codeine and similar drugs (dihydrocodeine, nicocodeine, benzylmorphine, ethylmorphine &c. Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and by the brand names of Synalgos DC, Panlor DC, ) 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.

In Hong Kong, codeine is regulated under Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance. Hong Kong ( officially the Hong Kong Special Administrative Region, is a territory located on China 's south coast on the Pearl River Delta, and borders Hong Kong ( officially the Hong Kong Special Administrative Region, is a territory located on China 's south coast on the Pearl River Delta, and borders 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.

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 formulations are prescription only medicines, with the exception of co-codamol 8/500 tablets where 8mg of codeine phosphate is combined with 500mg paracetamol which is available as a pharmacy supervised medicine. The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located This applies as well to Nurofen Plus, which contains 200mg Ibuprofen with 12. Ibuprofen ( INN) (ˌaɪbjuːˈpɹəʊfɛn (from the now outdated nomenclature i so- bu tyl- pro panoic- phen olic acid is a Non-steroidal 8mg Codeine per tablet. Intramuscular injection of codeine is a controlled drug under the Misuse of Drugs Act 1971. Intramuscular injection is the injection of a substance directly into a Muscle. The Misuse of Drugs Act 1971 (c38 is an Act of Parliament, by which the United Kingdom aims to control the possession and supply of numerous drugs

In the United States, codeine is regulated by the Controlled Substances Act. The United States of America —commonly referred to as the 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 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. Paracetamol ( INN) (ˌpærəˈsiːtəmɒl -ˈsɛtə- or acetaminophen ( USAN) is a widely-used Analgesic and Antipyretic Medication 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. Ethylmorphine (also known as codethyline, Dionine®, and ethyl morphine) is a drug in the class of both Opiates (representing a minor synthetic Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and by the brand names of Synalgos DC, Panlor DC, 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. Paregoric, or Camphorated Tincture of Opium, also known as tinctura opii camphorata, is a Medication known for its Antidiarrheal Hydrocodone or dihydrocodeinone is a semi-synthetic Opioid derived from two of the naturally occurring Opiates Codeine and Thebaine Diphenoxylate ( Lomotil® Co-phenotrope and others is an Opioid agonist used for the treatment of Diarrhoea that acts by slowing intestinal contractions Pethidine ( INN) or meperidine ( USAN) (commonly referred to as Demerol but also referred to as isonipecaine lidol pethanol piridosal Algil Alodan

Codeine is also available outside the United States as an over-the-counter drug in liquid cough-relief formulations. Over-the-counter (OTC drugs are medicines that may be sold without a prescription, in contrast to Prescription drugs The name "over-the-counter" Internationally, codeine is a Schedule II drug under the Single Convention on Narcotic Drugs. The Single Convention on Narcotic Drugs is an international Treaty to prohibit production and supply of specific (nominally Narcotic) Drugs and of drugs ^[5]

Pharmacokinetics

Codeine is considered a prodrug, since it is metabolised in vivo to the primary active compounds morphine and codeine-6-glucuronide. A prodrug is a pharmacological substance ( drug) that is administered in an inactive (or significantly less active form In vivo ( Latin: within the living means that which takes place inside an organism. Medical uses Morphine can be used as an analgesic in hospital settings to relieve pain in Myocardial infarction pain in ^[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%). Norcodeine is an Opiate analogue that is the N-demethylated derivative of Codeine. Hydromorphone, a more common synonym for dihydromorphinone hydrochloride (trade names Palladone IR, Palladone SR, Dilaudid and numerous others It is less potent than morphine and has a correspondingly lower dependence-liability than morphine. Drug addiction is widely considered a pathological state. The disorder of addiction involves the progression of acute Drug use to the development of drug-seeking ^[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.

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. Hydrocodone or dihydrocodeinone is a semi-synthetic Opioid derived from two of the naturally occurring Opiates Codeine and Thebaine Oxycodone is an Opioid Analgesic Medication synthesized from Thebaine. Because codeine needs to be metabolized to an active form, there is a ceiling effect around 400-450 mg. In Pharmacology, the term ceiling effect refers to the property of increasing doses of a given medication to have progressively smaller incremental effect (an example of This low ceiling further contributes to codeine being less addictive than the other opiates.

The conversion of codeine to morphine occurs in the liver and is catalysed by the cytochrome P450 enzyme CYP2D6. Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of Hemoproteins found in all Domains 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 CYP3A4 produces norcodeine and UGT2B7 conjugates codeine, norcodeine and morphine to the corresponding 3- and 6- glucuronides. Cytochrome P450 3A4 (abbreviated CYP3A4) ( a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism UGT2B7 (UDP-Glucuronosyltransferase-2B7 is a phase II Metabolism isoenzyme found to be active in the Liver, Kidneys epithelial cells 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.

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). Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders Citalopram is an Antidepressant drug used to treat major depression associated with Mood disorders It is also used on occasion in the treatment Other drugs, such as rifampicin and dexamethasone, induce expression of CYP450 isozymes and thus increase the rate of metabolism. Rifampicin ( INN) (rɪˈfæmpəsɪn or rifampin ( USAN) is a Bactericidal Antibiotic drug of the Rifamycin group Dexamethasone is a potent synthetic member of the glucocorticoid class of Steroid Hormones It acts as an Anti-inflammatory and immunosuppressant

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. Opioid receptors are a group of G-protein coupled receptors with Opioids as Ligands The Endogenous Opioids are Dynorphins A prodrug is a pharmacological substance ( drug) that is administered in an inactive (or significantly less active form Medical uses Morphine can be used as an analgesic in hospital settings to relieve pain in Myocardial infarction pain in 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 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.

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. Euphoria is a medically recognized emotional state related to Pleasure and Happiness. Itch ( Latin: pruritus) is an unpleasant Sensation that evokes the desire or Reflex to scratch Nausea ( Latin: Nausea, Greek:, " Sea-sickness " also called wamble) is the sensation of unease and discomfort Vomiting (also called throwing up, emesis) is the forceful expulsion of the contents of one's Stomach through the Mouth and sometimes the Somnolence (or " drowsiness " is a state of near- Sleep, a strong desire for sleep or sleeping for unusually long periods (c Xerostomia is the medical term for a dry mouth due to a lack of Saliva. Miosis is Constriction of the Pupil of the Eye. This is a normal response to an increase in light but can also be associated with certain Pathological Orthostatic hypotension (also known as postural hypotension, and colloquially as head rush or a dizzy spell) is a form of Hypotension in which Urinary retention also known as ischuria is a lack of ability to Urinate. Constipation, costiveness, or irregularity, is a condition of the Digestive system in which a person (or animal experiences hard Feces that ^[11]

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. In Medicine, hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate ( hypo means "below" to perform needed This depression is dose-related and is the mechanism for the potentially fatal consequences of overdose.

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. Psychiatry is a medical specialty which exists to study, prevent, and treat Mental disorders in Humans Psychiatric Medication, also referred to as medicine, can be loosely defined as any substance intended for use in the diagnosis cure mitigation treatment or prevention of disease Reboxetine is an Antidepressant drug used in the treatment of Clinical depression, Panic disorder and ADD/ADHD, developed by Pharmacia (now Venlafaxine (Effexor Efexor is an Antidepressant of the Serotonin-norepinephrine reuptake inhibitor (SNRI class first introduced by Wyeth in 1993 ^[12]

Some people may also have an allergic reaction to codeine, which may cause severe allergic reactions such as the swelling of skin and rashes. ^[12]

Recreational use

Codeine can be used as a recreational drug. Recreational drug use is the use of Psychoactive drugs for Recreational purposes rather than for work, medical or spiritual purposes However, it has much less abuse potential than some other opiates or opioids, such as oxycodone and hydrocodone. When taken for recreational use, codeine is commonly referred to as "cilly" (pronounced like silly) or "loopy c" because of the euphoric effect it causes. Codeine is also known as juice (when in cough syrup form), school boy, codys (when in tablet form), little c, T1s, T2s, T3s, and T4s.

Codeine can cause itching for a large 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 (when two Doriden tablets are taken with four tablets of Tylenol With Codeine No. A sedative, or more specifically a sedative-hypnotic, is a substance that depresses the Central nervous system (CNS resulting in calmness relaxation sleepiness Glutethimide is a hypnotic Sedative that was introduced in 1954 as a safe alternative to Barbiturates to treat Insomnia. 4]]) a "six-pack". Like dihydrocodeine and hydrocodone, codeine is also mixed with carisoprodol to intensify its effect. Dihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and by the brand names of Synalgos DC, Panlor DC, 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. For potentiation and control of itching in both clinical and recreational settings, codeine and its derivatives are often combined with antihistamines, including hydroxyzine, diphenhydramine, orphenadrine, brompheniramine, dexbrompheniramine, chlorpheniramine, dexchlorpheniramine, carbinoxamine, bromdiphenhydramine, and tripelennamine. Hydroxyzine (haɪˈdrɒksɨziːn is a first-generation antihistamine of the Piperazine class that is an H1 receptor antagonist Pharmacological action Diphenhydramine (dye fen hye' dra meen works by blocking the effect of histamine at H1 receptor sites Orphenadrine (sold under the Brand names Norflex Mephenamin Disipal Banflex Flexon Biorphen Brocasipal and others is an Anticholinergic Drug of Brompheniramine (also known as Bromfed, Dimetapp, Bromfenex, and Dimetane) is an Antihistamine drug of the Propylamine 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 Dexchlorpheniramine maleate (Polaramine Schering) is an Antihistamine used to treat allergic conditions such as Hay fever or Urticaria Carbinoxamine is an H1 class Antihistamine. It was first launched in the United States by the McNeil Corporation under the brand name Clistin Tripelennamine ( INN, also known as pyribenzamine) is a first generation Pyridine Antipruritic and Antihistamine in the Ethylenediamine

Some opioid-potentiator combinations that use this knowledge are narcotic cough syrup and ginger ale; codeine, dihydrocodeine, and hydrocodone; similar tablets or liquids with the green label Alka Seltzer Cold Medicine; and the opioids above with naproxen and cyclobenzaprine with caffeine. 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.

It is also worthy to note that mood can effect the high associated with the drug, as the mindset that it won't do anything can lead to a sudden euphoric and energizing experience and, conversely, anticipation for euphoria can lead to disappointment.

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. Promethazine is a first-generation H1 receptor antagonist Antihistamine and Antiemetic medication 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. Cimetidine ( INN) (sɨˈmɛtɨdiːn/ /saɪ- is a histamine H2-receptor antagonist that inhibits the production of acid in the Stomach. Mixing opioids with depressant medications such as those above is certainly not without risks of its own.

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). Over-the-counter (OTC drugs are medicines that may be sold without a prescription, in contrast to Prescription drugs The name "over-the-counter" A prescription (℞ is a health-care program implemented by a Physician or other medical practitioner in the form of instructions that govern the plan of care for an individual 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. Cold water extraction (CWE 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. Hydroxyzine (haɪˈdrɒksɨziːn is a first-generation antihistamine of the Piperazine class that is an H1 receptor antagonist Naproxen ( INN) (nəˈprɒksən is a Non-steroidal anti-inflammatory drug (NSAID commonly used for the reduction of moderate to severe Pain, Fever 32–33 of fourth edition (2000)).

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.

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. This article is about the country For a topic outline on this subject see List of basic France topics. A heroin addict may use codeine to ward off the effects of a withdrawal. Withdrawal, also known as withdrawal/abstinence syndrome, refers to the characteristic signs and symptoms that appear when a drug that causes Physical dependence is ^[13]

Codeine is also available in conjunction with the anti-nausea medication promethazine in the form of a syrup. Promethazine is a first-generation H1 receptor antagonist Antihistamine and Antiemetic medication 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. Purple drank is a Slang term for a Recreational drug popular in the hip-hop community of the Southern United States. Southern hip hop is a form of American hip hop music that emerged from a club oriented vibe in the late-1990s as a popular force from cities including but not limited to Sprite is a clear soda Lemon-lime Flavored caffeine free Soft drink, produced by The Coca-Cola Company. 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". Three 6 Mafia (formerly Triple 6 Mafia) is an Academy-Award winning American Rap group originating from Memphis, Tennessee Paul Slayton, better known by his Stage name Paul Wall, was born March 11, 1981. 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. ^[14]

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. The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located Ireland (pronounced /ˈaɾlənd/ Éire) is the third largest island in Europe, and the twentieth-largest island in the world For a topic outline on this subject see List of basic Australia topics. New Zealand is an Island country in the south-western Pacific Ocean comprising two main landmasses (the North Island and the South Island Country to "Dominion of Canada" or "Canadian Federation" or anything else please read the Talk Page Paracetamol ( INN) (ˌpærəˈsiːtəmɒl -ˈsɛtə- or acetaminophen ( USAN) is a widely-used Analgesic and Antipyretic Medication In doing so, users run the serious risk of hepatotoxicity associated with large doses of paracetamol. Drug metabolism in liver The human body identifies almost all drugs as foreign substances (i 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) (ˌpærəˈsiːtəmɒl -ˈsɛtə- or acetaminophen ( USAN) is a widely-used Analgesic and Antipyretic Medication The liver is a vital organ in the human body and is present in Vertebrates and some other animals Ibuprofen ( INN) (ˌaɪbjuːˈpɹəʊfɛn (from the now outdated nomenclature i so- bu tyl- pro panoic- phen olic acid is a Non-steroidal The kidneys are complicated organs that have numerous biological roles In Human anatomy, the stomach is a J-shaped hollow muscular organ of the Gastrointestinal tract involved in the second phase of Digestion, following Nausea ( Latin: Nausea, Greek:, " Sea-sickness " also called wamble) is the sensation of unease and discomfort Aspirin, or acetylsalicylic acid (ASA (əˌsɛtɨlsælɨˌsɪlɨk ˈæsɨd is a Salicylate drug, often used as an Analgesic to relieve Bleeding, technically known as hemorrhaging / haemorrhaging (see American and British spelling differences) is the loss of Blood from

Codeine is also demethylated by reaction with pyridine to illicitly synthesize morphine. Pyridine is a Chemical compound with the formula C5[[Hydrogen H5]] N. Pyridine is toxic and carcinogenic, so morphine illicitly produced in this manner (and potentially contaminated with pyridine) may be particularly harmful. The term carcinogen refers to any substance Radionuclide or radiation that is an agent directly involved in the promotion of Cancer or in the fatation of its propagation ^[15]

References

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