| Description | Codein phosphate and hydrochloride caused contactdermatitis in a worker in the production of opiumalkaloids. Codeine bitartrate caused contact dermatitisin a worker in the production of concentrated poppystraw. Codeine was a sensitizer in a laboratory workerat an opiate-manufacturing pharmaceutical company,also sensitive to the baine. |
| Description | Codeine (CRM) (Item No. ISO60140) is a certified reference material categorized as an opioid. Like other opioid analgesics, codeine is commonly abused. Codeine is regulated as a Schedule II compound in the United States. Codeine (CRM) (Item No. ISO60140) is provided as a DEA exempt preparation. This product is intended for research and forensic applications. |
| Chemical Properties | White Solid |
| Chemical Properties | Codeine, also known as methylmorphine, C18H21NO3· H2O, is a colorless white crystalline substance, slightly soluble in water, soluble in alcohol and chloroform, effloresces slowly in dry air. |
| Uses | Codeine is derived from opium by extraction or by the methylation of morphine. For medical use, codeine is usually offered as the dichloride, phosphate, or sulfate. Codeine is habit forming. Codeine is known to exacerbate urticaria (familiarly known as hives). Since codeine is incorporated in numerous prescription medicines for headache, heartburn, fatigue, coughing, and relief of aches and pains, persons with a history of urticaria should make this fact known to their physician. Codeine is sometimes used in cases of acute pericarditis to relieve severe chest pains in early phases of disease. Codeine is sometimes used in drug therapy of renal (kidney) diseases. |
| Uses | Codeine is used in medicine for its narcoticanalgesic action. It is used as a sedative incough mixtures. Codeine occurs in opiumfrom 0.7% to 2.5%. It is prepared frommorphine by methylating the phenolic OHgroup of the morphine. It is also obtained byextraction of opium. |
| Uses | Present in opium from 0.7% to 2.5%, depending on the source. Weak narcotic analgesic, perhaps due to conversion to morphine, with minimal hypnotic properties; potent antitussive.Controlled substance (opiate) |
| Definition | ChEBI: A morphinane alkaloid found in the opium poppy, Papaver somniferum var. album; has analgesic, anti-tussive and anti-diarrhoeal properties. |
| Definition | codeine: An alkaloid C18H21NO3found in opium. It is structurally similarto morphine, from which it isproduced, and is used in the form ofthe sulphate or phosphate as apainkiller and cough medicine.Codeine is converted into morphinein the liver. It is used to some extentas a recreational drug. In the UK it isa class B drug but can be obtained incomposite over-the-counter preparationsin which it has a low concentrationand is combined with paracetamolor ibuprofen. See also opioids. |
| Brand name | Algisedal;Codol;Diarrest;Novacetol;Sedarene. |
| World Health Organization (WHO) | Codeine, which has antitussive, opioid analgesic and antidianhoealactivity, was first extracted from opium in 1832 and has since been widely used inmedicine. The development of dependence and its potential for abuse resulted inthe control af the substance under Schedule II of the 1961 Single Convention onNarcotic Drugs. Preparations containing codeine remain widely available and areincluded in the WHO Model List of Essential Drugs.(Reference: (WHTAC1) The Use of Essential Drugs, 2nd Report of the WHO ExpertCommittee, 722, , 1985) |
| Biological Functions | Like morphine, codeine is a naturally occurring opioidfound in the poppy plant. Codeine is indicated for thetreatment of mild to moderate pain and for its antitussiveeffects. It is widely used as an opioid antitussive becauseat antitussive doses it has few side effects and hasexcellent oral bioavailability. Codeine is metabolized inpart to morphine, which is believed to account for itsanalgesic effect. It is one of the most commonly usedopioids in combination with nonopioids for the relief ofpain. The administration of 30 mg of codeine in combinationwith aspirin is equivalent in analgesic effect tothe administration of 65 mg of codeine. The combinationof the drugs has the advantage of reducing the amount of opioid required for pain relief and abolitionof the pain via two distinct mechanisms, inhibition ofprostanoid synthesis and opioid inhibition of nociceptivetransmission. When given alone, orally administeredcodeine has about one-tenth to one-fifth the potencyof morphine for the relief of pain. In addition, IVcodeine has a greater tendency to release histamine andproduce vasodilation and hypotension than does morphine.Thus, the use of IV codeine is rare. Codeine israrely addictive and produces little euphoria. |
| General Description | Codeine is an alkaloid that occurs naturally in opium, butthe amount present is usually too small to be of commercialimportance. Consequently, most commercial codeine is preparedfrom morphine by methylating the phenolic OHgroup. It occurs as levorotatory, colorless, efflorescent crystals,or as a white crystalline powder. It is light sensitive.Codeine is a monoacidic base and readily forms salts withacids, with the most important being the sulfate and thephosphate. The acetate and methylbromide derivatives havebeen used to a limited extent in cough preparations.The general pharmacological action of codeine is similarto that of morphine, but it does not possess the sameanalgesic potency. |
| General Description | Colorless to white crystalline solid or white powder. Sublimes at 284°F. Odorless. Bitter taste. pH (saturated aqueous solution) 9.8. |
| Air & Water Reactions | CODEINE is light sensitive and sensitive to prolonged exposure to air. Insoluble in water. |
| Reactivity Profile | CODEINE is incompatible with bromides, iodides and salts of heavy metals. . CODEINE is an amine. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides. |
| Hazard | Habit-forming narcotic, sale legallyrestricted. |
| Health Hazard | The toxic effects due to codeine are similarbut less toxic than those of morphineand other opium alkaloids. An overdosecan cause respiratory failure. It is a weakdepressant of the central nervous system.It also exhibits stimulant action. Toxicsymptoms from high dosages may includedrowsiness, sleep, tremors, excitement, andhallucinations. It may also produce gastricpains and constipation. An oral LD50 value in rats is 427 mg/kg. The habit-forming effectsof codeine are lower than those associatedwith morphine.
Nagamatsu and coworkers (1985) havereported in vitro formation of codeinonefrom codeine by rat or guinea pig liverhomogenate. Codeinone may be a metabolicintermediate in the presence of nicotinamideadenine dinucleotide (NAD). Its acute toxicityin mice was determined to be 30 timeshigher than that of codeine. |
| Fire Hazard | CODEINE is combustible. |
| Contact allergens | Codeine has been reported as an occupational sensitizerin workers in the production of opium alkaloids.Codeine has been responsible for fixed drug eruptionsor generalized dermatitis. Cross-sensitivity is expectedto morphine. |
| Pharmacology | Codeine is a constituent of opium. Up to 10% of a dose of codeine ismetabolised by the hepatic microsomal enzyme CYP2D6 to morphine, whichcontributes significantly to its analgesic effect. The rest is metabolised in theliver to norcodeine and then conjugated to produce glucuronide conjugatesof codeine, norcodeine and morphine. Codeine is considerably less potentthan morphine. A round 8% of Western Europeans are deficient in theCYP2D6 enzyme and may not experience adequate analgesia with codeine.S imilarly, with super-metabolisers, there may be problems with opioidtoxicity; particular care is needed in the breastfeeding mother as morphine istransferred in milk. Codeine can cause significant histamine release, andintravenous administration should be avoided. It has marked antitussiveeffects and also causes significant constipation. It is often combined withparacetamol. |
| Purification Methods | Codeine crystallises from water or aqueous EtOH. Dry it at 80o. Evaporation of a CHCl3 extract gives a colourless glass which crystallises on scratching. It crystallises from H2O as the monohydrate, m 157-158.5o, and has [] D -136o (c 2.8, EtOH). The hydrobromide crystallises in needles from H2O, and effervesces at 151-160o, solidifies and remelts with extensive decomposition at 273-278o. It sublimes at 100o/0.03mm. [Gates J Am Chem Soc 75 4340 1953, Dauben et al. J Org Chem 44 1567 1979, Beilstein 27 II 136, 27 III/IV 2228.] |
| References | [1] E E CODD. Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception.[J]. Journal of Pharmacology and Experimental Therapeutics, 1995, 274 3: 1263-1270. |
