Dihydrocodeine

From Drug Information

Dihydrocodeine is a semi-synthetic opioid developed in 1908 in Germany based on codeine and morphine. It was first marketed in 1911.[1] It is 2 times stronger than the original codeine,[2] and 1/6 times than the oral morphine.[3] Usually prescribed for pain relief or antitussive. If it is prescribed for pain relief, usually they use XR which lasts for 12 hours, giving them 60mg per dose, and 60-120mg per day. [4] If it is for cough, they usually use 10mg per dose, and 3 doses per day. [5] But they use tablets combined with things like Paracetamol, Methylephedrine, Guaifenesin, Chlorpheniramine, or Caffeine.

[6]

semi-synthetic opioid
Chemical name: Morphinan-6-ol,

4,5-epoxy-3-metoxy-17-metyl-, (5α,6α)-

Chemical Formula: C18-H23-N-O3
Molecule weight: 301
Routes of administration: oral has to be the most good way to take Dihydrocodeine. About the prodrug oral vs other route, please go to the hyperlinked document
Oral bioactivity: 21% (range 12-34;rathers between person’s activity of CYP2D6). [7] It can be more active when it takes together with grapefruit
Oral Dose of recreational use
Dosage Levels
20-50mg Minimal
50-100mg Light
100-150mg Common
150-200mg Strong
200-400mg+ Heavy
Pharmacological Profile
Onset 45-55 minutes
Comeup 40-50 minutes
Peak 2-2.5 hours
Offset 3-4 hours
Total Duration 7-8 hours
Half-life 3.3-4.5 hours

[8]

Chemical

Pharmacology

Normally, we take dihydrocodeine orally. As it is an opioid, it has opioid effects, and most of dihydrocodeine’s opioid receptor effect is on to µ-opioid receptors. [9] It is twice stronger than codeine, and 1/6 times of morphine orally. [10] Dihydrocodeine is a famous prodrug that metabolizes in the liver, especially through the CYP2D6 enzyme. But also, it activates in CYP3A4. Through CYP2D6, dihydrocodeine is O-methylated into dihydromorphine, which is 1.3 times stronger than the original morphine. But less than 10% of the dihydrocodeine converts to dihydromorphine [11], and other metabolism is known as a meaningless opioid receptor. Even dihydrocodeine itself is an opioid receptor, but is so weak which the article says “It has been suggested that dihydrocodeine have little analgesic effect their own, but rather function as prodrugs” [12] Substances metabolised by CYP3A4 is nordihydrocodeine, demethylated dehydrocodeine, which is also not a good receptor in opioid. Also through UGT in the liver, Dihydrocodeine metabolises form 3- and 6-glucuronides. This is the most metabolation, which can be 85% of the whole metabolation. UGT 2B7 is known as the most responsible for DHC-6-Glucuronide formation. [13]

The effect of the dihydrocodeine has differed by person because of genetic polymorphism. 5-10% of white people and some more percentage of Asian people has low metabolism in CYP2D6, which is a very big variable of dihydrocodeine as a drug. [14] Because CYP2D6 metabolism is almost all of this drug’s effect, CYP2D6 inhibitors such as Fluoxetin, Paroxetine, Bupropion, Quinidine makes dihydrocodeine’s effect weaker. [15]

Because of these lots of variables, many sources say different strengths about dihydrocodeine and dihydromorphine. But the interesting part of the dihydrocodeine is, there could be more potent of DHC-6-Glucuronide formation in opioid receptors. There is recent research using Quinidine and injecting dihydrocodeine, and seeing how they feel. [16] [17] In these two studies, they are still saying that dihydromorphine conversion is the most important metabolization. But [18] in this research, they said the theoretical medical action could not really act in the real case. In this research, they say DHC-6-Glucuronide formation could have more potential than we think. I look forward to further research.


Different routes of taking dihydrocodeine

As I said, dihydrocodeine is a prodrug, which needs to be metabolized through the liver first. But as I said, recently many scientists think that dihydrocodeine itself or other metabolized substances could be a good potent opioid.

When you take dihydrocodeine in the other way, such as nasel, sublingual, intravessel, rectal, it bypasses the first-pass metabolism, and dihydrocodeine just strikes the brain. After the blood vessels through the liver, part of the dihydrocodeine will have the metabolization but the rate will be way lower than oral.

But in early study of dihydrocodeine, there was a study about subcutaneous injection of dihydrocodeine.[19] It was a very old way and just it say is how the patient felt, but still, it says morphine is 3-4 times stronger than dihydrocodeine when jt is subcutaneous.

Maybe, taking dihydrocodeine in a different route could be a good way. But it could also be dangerous and hard to control the doses.

Medical Use

Substance Effects

Desired Effects

Euphoria

Pain Relief

Sedation

Cough suppression

Side Effects

Itchiness - This is because of opioid’s histamine increase, so we can use cetrezine for this.

Hard to breath - This could be more hard to breath when you take with benzodiazepine or DPH

Constipation

Difficulty urinating

Pupil constriction

Decrease sexual desire

Decrease eating desire

Orgasm suppression

Harm, Tocity, social problem of Dihydrocodeine

Combinations with other substances

Good Combinations

Bad Combinations

History

References

  1. ↑ Stolerman, I. P. (Ed.). (2010). *Encyclopedia of Psychopharmacology*. Springer-Verlag Berlin Heidelberg.
  2. ↑ Sobczak, Ł., & Goryński, K. (2020). Pharmacological Aspects of Over-the-Counter Opioid Drugs Misuse. *Table 2.3*. PMC7504308
  3. ↑ Leppert, W. (2010). Dihydrocodeine as an opioid analgesic for the treatment of moderate to severe chronic pain. *Current Drug Metabolism*, 11(6), pp. 515-520. PMID: 20540693
  4. ↑ 약학정보원. (n.d.). drug_cd=A11A0410A0051 디코데서방정 의약품 정보. 약학정보원 의약품상세정보.
  5. ↑ 약학정보원. (n.d.). 코푸정 의약품 정보. 약학정보원 의약품상세정보, Medication information of SS Bron from Japan.
  6. ↑ photo of the chemical structure is from wikipedia, [1]
  7. ↑ Rowell, F. J., Seymour, R. A., & Rawlins, M. D. (1983). Pharmacokinetics of intravenous and oral dihydrocodeine and its acid metabolites. *European Journal of Clinical Pharmacology*, 25(3), pp. 419–424.
  8. ↑ Rowell, F. J., Seymour, R. A., & Rawlins, M. D. (1983). Pharmacokinetics of intravenous and oral dihydrocodeine and its acid metabolites. *European Journal of Clinical Pharmacology*, 25(3), 419–424.
  9. ↑ Sobczak, Ł., & Goryński, K. (2020). Pharmacological Aspects of Over-the-Counter Opioid Drugs Misuse. *Table 2.1*. PMC7504308
  10. ↑ Leppert, W. (2010). Dihydrocodeine as an opioid analgesic for the treatment of moderate to severe chronic pain. *Current Drug Metabolism*, 11(6), pp. 515-520. PMID: 20540693
  11. ↑ Webb, J. A., Rostami-Hodjegan, A., Abdul-Manap, R., Hofmann, U., Mikus, G., & Kamali, F. (2001). Contribution of dihydrocodeine and dihydromorphine to analgesia following dihydrocodeine administration in man: a PK–PD modelling analysis. *British Journal of Clinical Pharmacology*, 52(6), pp. 619–628. DOI: 10.1046/j.0306-5251.2001.01414.x
  12. ↑ Wilder-Smith, C. H., Hufschmid, E., & Thormann, W. (1998). The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolizers. *British Journal of Clinical Pharmacology*, 45(6), 575–581. PMC1873649
  13. ↑ Armstrong, S. C., & Cozza, K. L. (2003). Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part II. *Psychosomatics*, 44(6), 518–525. DOI: 10.1176/appi.psy.44.6.518
  14. ↑ Wilder-Smith, C. H., Hufschmid, E., & Thormann, W. (1998). The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolizers. British Journal of Clinical Pharmacology, 45(6), pp. 575–581 PMC1873649
  15. ↑ Wilder-Smith, C. H., Hufschmid, E., & Thormann, W. (1998). The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolizers. British Journal of Clinical Pharmacology, 45(6), 575–581. PMC1873649
  16. ↑ Wilder-Smith, C. H., Hufschmid, E., & Thormann, W. (1998). The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine: a cross-over study with extensive and quinidine-induced poor metabolizers. British Journal of Clinical Pharmacology, 45(6), 575–581. PMC1873649
  17. ↑ Webb, J. A., Rostami-Hodjegan, A., Abdul-Manap, R., Hofmann, U., Mikus, G., & Kamali, F. (2001). Contribution of dihydrocodeine and dihydromorphine to analgesia following dihydrocodeine administration in man: a PK–PD modelling analysis. British Journal of Clinical Pharmacology, 52(4), 35–43. DOI: 10.1046/j.0306-5251.2001.01414.x
  18. ↑ Armstrong, S. C., & Cozza, K. L. (2003). Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part II. *Psychosomatics*, 44(6), 518–525. DOI: 10.1176/appi.psy.44.6.518
  19. ↑ Gravenstein, J. S., Smith, G. M., Sphire, R. D., Isaacs, J. P., & Beecher, H. K. (1956). Dihydrocodeine. New England Journal of Medicine, 254(19), 877–885. DOI: 10.1056/NEJM195605102541901
Retrieved from "http://druginfowiki.com/index.php?title=Dihydrocodeine&oldid=138"