Editing Dihydrocodeine (section)

== Pharmacology ==
Dihydrocodeine exerts its analgesic action through affinity to predominantly [[μ-opioid receptor]] and to lesser extent to [[κ-opioid receptor]] and [[δ-opioid receptor]]. 30 mg of [[Subcutaneous administration|subcutaneous]] dihydrocodeine is equianalgesic to 10 mg of morphine.<ref name=":2" /> Another source states that dihydrocodeine is twice as strong as codeine<ref>{{Cite web |title=Equivalence table (in French) |url=https://www.chu-toulouse.fr/IMG/pdf/12_table_conversion_palier_ii_et_iii_v5-2.pdf |url-status=dead |archive-url=https://web.archive.org/web/20130201212249/https://www.chu-toulouse.fr/IMG/pdf/12_table_conversion_palier_ii_et_iii_v5-2.pdf |archive-date=1 February 2013 |access-date=12 April 2018}}</ref><ref name=":2" /> and the metabolite dihydromorphine is likewise twice as strong as morphine.<ref name=":2" /> 

Dihydrocodeine (DHC) is ''O''-demethylated into [[dihydromorphine]] (DHM) by [[CYP2D6]] and ''N''-demethylated into nordihydrocodeine (NDHC) by [[CYP3A4]], summarily yielding nordihydromorphine (NDHM). Dihydrocodeine and its metabolites [[Glucuronidation|form 3- and 6-glucuronides]]. Due to the multidirectional metabolism, as opposed to [[tramadol]] and [[codeine]], CYP2D6 activity probably does not influence DHC analgesia. The analgesia is likely achieved by the action of DHC itself, as well as DHC-6-G.<ref name=":2" /> DHC appears not to differ between [[Poor metaboliser|poor]] and [[Extensive metabolizer|extensive metabolizers]] in terms of its pain threshold and pupillary reaction effect in spite of major variation in DHM blood levels.<ref>{{cite journal | vauthors = Schmidt H, Vormfelde SV, Walchner-Bonjean M, Klinder K, Freudenthaler S, Gleiter CH, Gundert-Remy U, Skopp G, Aderjan R, Fuhr U | title = The role of active metabolites in dihydrocodeine effects | journal = International Journal of Clinical Pharmacology and Therapeutics | volume = 41 | issue = 3 | pages = 95–106 | date = March 2003 | doi = 10.5414/cpp41095 | pmid = 12665158 | url = https://www.openagrar.de/receive/bimport_mods_00000213 | url-access = subscription }}</ref> 

DHC-6-G is half as potent as DHC. DHM and DHM-6-G display the highest affinity to μ-opioid receptors, being 70 times as potent as DHC, whereas other metabolites display lesser affinity. DHM-6-G has similar potency as DHM, while DHM-3-G is considerably weaker. Action on δ-opioid receptor is 5-50 weaker compared to μ with the exception of DHC-6-G being twice as strong as DHC. 6-glucuronides possess lesser affinity towards κ-opioid receptors, albeit the affinity of DHC is comparable to codeine, DHM and morphine.<ref name=":2" /> 

The primary compounds responsible for analgesia are DHC and DHC-6-G. Although some of the metabolites are far more potent, the concentration of NDHM and NDHM-6-G in urine were minimal, suggesting no significant role in pain relief.<ref name="IntJClinPharmacolTher2003-Schmidt">{{cite journal  |vauthors=Schmidt H, Vormfelde SV, Walchner-Bonjean M, Klinder K, Freudenthaler S, Gleiter CH, Gundert-Remy U, Skopp G, Aderjan R, Fuhr U |date=March 2003 |title=The role of active metabolites in dihydrocodeine effects |journal=International Journal of Clinical Pharmacology and Therapeutics |volume=41 |issue=3 |pages=95–106 |doi=10.5414/cpp41095 |pmid=12665158}}</ref><ref name=":2" /> 

After oral absorption, the drug is absorbed relatively rapidly with mean peak concentration at 1.7 hours. The mean half-life is 4 hours. The mean bioavailability of orally administered drug is 21%. Metabolite concentrations are high in relation to the parent drug, suggesting extensive [[First pass effect|first-pass metabolism]].<ref>{{cite journal | vauthors = Rowell FJ, Seymour RA, Rawlins MD | title = Pharmacokinetics of intravenous and oral dihydrocodeine and its acid metabolites | journal = European Journal of Clinical Pharmacology | volume = 25 | issue = 3 | pages = 419–424 | date = 1983-05-01 | pmid = 6628531 | doi = 10.1007/BF01037958 }}</ref> Dihydrocodeine tablets may possess an extended-release mechanism, lowering peak concentrations and increasing duration of action.<ref name=":2" />