Pholcodine

Pholcodine

Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy category	AU: A
Dependence liability	Low
Routes of administration	Oral
ATC code	R05DA08 (WHO)
Legal status
Legal status	UK: Class B US: Schedule I
Pharmacokinetic data
Bioavailability	Maximum plasma conc. attained 4-8 hours after oral dose.
Protein binding	23.5%
Metabolism	Hepatic
Elimination half-life	32-43 hours; volume of distribution is 36-49L/kg.
Excretion	Renal
Identifiers
IUPAC name 7,8-didehydro- 4,5α-epoxy- 17-methyl- 3- [2- (morpholin- 4- yl) ethoxy] morphinan- 6α-ol
CAS Number	509-67-1 N
PubChem CID	5311356
DrugBank	? N
ChemSpider	4470854 Y
UNII	LPP64AWZ7L
KEGG	D07385 Y
ChEBI	CHEBI:53579 Y
CompTox Dashboard (EPA)	DTXSID70198923
ECHA InfoCard	100.007.367
Chemical and physical data
Formula	C23H30N2O4
Molar mass	398.55 g/mol g·mol−1
3D model (JSmol)	Interactive image
SMILES O(c5ccc4c1c5O[C@H]3[C@@H](O)\C=C/[C@H]2[C@H](N(C)CC[C@@]123)C4)CCN6CCOCC6
InChI 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 Y Key:GPFAJKDEDBRFOS-FKQDBXSBSA-N Y
NY (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. 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. 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

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

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.

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

• Dextromethorphan
• Codeine
• Hydrocodone

External links

• Australian Therapeutic Goods Admission document on Pholcodine (Rich Text Format)