Pholcodine

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Pholcodine
Pholcodine.svg
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 Controlled (S8) (AU) Class B (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 N
ATC code R05DA08
PubChem CID 5311356
DrugBank ?
ChemSpider 4470854 YesY
UNII LPP64AWZ7L YesY
KEGG D07385 YesY
ChEBI CHEBI:53579 YesY
Chemical data
Formula C23H30N2O4 
Mol. mass 398.55 g/mol
 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.

Mechanism of action[edit]

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 impairment.

Metabolism and excretion[edit]

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[edit]

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[edit]

References[edit]

  1. ^ inovapharma.com
  2. ^ BNF (2007). British National Formulary 54. BMJ Publishing Group Ltd., RPS Publishing, London. Page 175.
  3. ^ 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.
  4. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1258-1260.

External links[edit]