- Pholcodine
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Pholcodine 
Systematic (IUPAC) name 7,8-didehydro- 4,5α-epoxy- 17-methyl- 3- [2- (morpholin- 4- yl) ethoxy] morphinan- 6α-ol Clinical data AHFS/Drugs.com International Drug Names Pregnancy cat. A(AU) Legal status ? (UK) Schedule I (US) Dependence liability Low Routes Oral Pharmacokinetic data Bioavailability Maximum plasma conc. attained 4-8 hours after oral dose. Protein binding 23.5% Metabolism Hepatic Half-life 32-43 hours; volume of distribution is 36-49L/kg. Excretion Renal Identifiers CAS number 509-67-1 
ATC code R05DA08 PubChem CID 5311356 DrugBank ? ChemSpider 4470854 
UNII LPP64AWZ7L KEGG D07385 ChEBI CHEBI:53579 Chemical data Formula C23H30N2O4 Mol. mass 398.55 g/mol SMILES eMolecules & PubChem - InChI=1S/C23H30N2O4/c1-24-7-6-23-16-3-4-18(26)22(23)29-21-19(5-2-15(20(21)23)14-17(16)24)28-13-10-25-8-11-27-12-9-25/h2-5,16-18,22,26H,6-14H2,1H3/t16-,17+,18-,22-,23-/m0/s1
Key:GPFAJKDEDBRFOS-FKQDBXSBSA-N
(what is this?) (verify)Pholcodine is a drug which is an opioid cough suppressant (antitussive). It helps suppress unproductive coughs and also has a mild sedative effect, but has little or no analgesic effects. It is also known as morpholinylethylmorphine.
Pholcodine is found in certain cough lozenges.[1] However, in the UK, the preparation is almost exclusively an oral solution, typically 5 mg / 5 ml. Adult dosage is 5-10ml up to 3-4 times daily.[2] Pholcodine now largely replaces the previously more common codeine linctus, as it has a much lower potential for dependence.
Pholcodine is a Schedule I drug in the US. It is also a class B substance in the United Kingdom although can be purchased over-the-counter in most UK pharmacies.
Contents
Mechanism of action
Pholcodine is readily absorbed from the gastrointestinal tract and freely crosses the blood-brain barrier. It acts primarily on the central nervous system (CNS), causing depression of the cough reflex, partly by a direct effect on the cough centre in the medulla. It is metabolized in the liver and its action may be prolonged in individuals with hepatic insufficiency (i.e. liver problems). Its use is therefore contraindicated in patients with liver disease, while care is advised in patients with hepatic impairement.
Metabolism and excretion
Pholcodine is slowly biotransformed in the body via oxidation and conjugation to a series of metabolites that are eliminated primarily in the urine. With an average half-life of approximately 2.3 days, steady-state in someone taking the drug chronically would not be reached for nearly 2 weeks. Nearly one-half of a single dose is eventually excreted as free or conjugated parent drug. The most important urinary metabolite is conjugated morphine, which may be detectable for days or weeks after the last dose. This could trigger a positive result for opiates in a urine drug testing program.[3][4]
Side effects
Side effects are rare and may include dizziness and gastrointestinal disturbances such as nausea or vomiting.
Adverse effects such as constipation, drowsiness, excitation, ataxia and respiratory depression have been reported occasionally or after large doses.
A Norwegian cough-syrup containing pholcodine "Tuxi" has been withdrawn from the market because it caused increased levels of IgE-antibodies, regardless of an actual allergy to the drug. This is believed to increase the risk of anaphylaxis to neuromuscular blocking agents used during anaesthesia.
See also
References
- ^ inovapharma.com
- ^ BNF (2007). British National Formulary 54. BMJ Publishing Group Ltd., RPS Publishing, London. Page 175.
- ^ Maurer HH, Fritz CF. Toxicological detection of pholcodine and its metabolites in urine and hair using radio immunoassay, fluorescence polarisation immunoassay, enzyme immunoassay, and gas chromatography-mass spectrometry. Int. J. Legal Med. 104: 43-46, 1990.
- ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1258-1260.
External links
- Australian Therapeutic Goods Admission document on Pholcodine (Rich Text Format)
Cough and cold preparations (R05) Expectorants Mucolytics Acetylcysteine • Ambroxol • Bromhexine • Carbocisteine • Domiodol • Dornase alfa • Eprazinone • Erdosteine • Letosteine • Mesna • Neltenexine • Sobrerol • Stepronin • TioproninCough suppressants Acetyldihydrocodeine • Benzylmorphine • Codeine • Dextromethorphan • Diacetylmorphine • Dihydrocodeine • Dimemorfan • Droxypropine • Ethylmorphine • Hydrocodone • Hydromorphone • Isoaminile • Laudanum • Levomethadone • Levopropoxyphene • Methadone • Nicocodeine • Nicodicodeine • Normethadone • Noscapine • Pholcodine • Thebacon • Tipepidine • ZipeprolOtherBenzonatate • Benproperine • Bibenzonium bromide • Butamirate • Clobutinol • Clofedanol • Cloperastine • Diphenhydramine • Dibunate • Dimethoxanate • Dropropizine • Fedrilate • Glaucine • Levodropropizine • Meprotixol • Morclofone • Nepinalone • Oxolamine • Oxeladin • Pentoxyverine • Pipazetate • Prenoxdiazine • PiperidioneCategories:- Semisynthetic opioids
- Antitussives
- Morphinans
- Morpholines
- Phenol ethers
- Alcohols
- InChI=1S/C23H30N2O4/c1-24-7-6-23-16-3-4-18(26)22(23)29-21-19(5-2-15(20(21)23)14-17(16)24)28-13-10-25-8-11-27-12-9-25/h2-5,16-18,22,26H,6-14H2,1H3/t16-,17+,18-,22-,23-/m0/s1
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