Why is methadone used


MethadoneDrug groupsOpioidsMethadone is a pain reliever from the group of opioids that is used to treat pain and as a substitute for heroin withdrawal therapy. The effects are based on the binding to the µ- and κ-opioid receptors. In addition, methadone has an antagonistic effect on the NMDA receptor. The dose is determined individually. Methadone differs from other opioids in that it has a much longer duration of action and the slower influx in the brain. Possible undesirable side effects include nausea, vomiting, respiratory depression, constipation, and itching.

synonyms: methadonum, methadoni hydrochloridum, methadone hydrochloride

Products

Methadone is available in the form of tablets, as an injection solution and oral solution (e.g. Ketalgin®, Methadon Streuli®). Methadone solutions are also prepared as magistral formulas in pharmacies.

Structure and properties

Methadone (C.21H27NO, Mr = 309.45 g / mol) is a synthetically produced derivative of pethidine, which is itself a derivative of atropine. It is chiral and exists as a racemate, a mixture composed of the D and an L isomer. Levomethadone (L-methadone) is predominantly active. In medicinal products, methadone is usually present as methadone hydrochloride, a white, crystalline powder that is soluble in water.

Effects

Methadone (ATC N07BC02) has pain-relieving, cough-relieving, calming, respiratory-depressive, slightly constipating, miotic and emetic properties. The effects are based on the binding to opioid receptors, mainly to the µ- and κ-receptors in the central nervous system, the affinity to the µ-receptors being much higher than that to the κ-receptors.

Methadone differs from other opioids in that it has additional, non-competitive antagonistic activity on the NMDA receptor. NMDA is responsible for central pain transmission and plays an important role in the development of opioid tolerance and resistance.

Indications Dosage

According to the medicinal product information. Methadone has a variable half-life. It is normally around 24 hours and therefore administration once a day is usually sufficient. Due to the inter-individual variable pharmacokinetics, the dose must be set individually for each individual patient. If it is not taken into account in the dosage, it can lead to accumulation and thus to methadone poisoning, which can lead to respiratory failure and death. As a solution for addicts, methadone is usually diluted or stained with syrup or juice, which prevents an injection.

Contraindications
  • Over-sensitivity
  • pregnancy and breast feeding period
  • Chronic respiratory failure
  • Inflammation of the pancreas
  • Severe hepatic and renal insufficiency
  • Methadone should also not be given to patients with acute alcohol intoxication.

The complete precautionary measures can be found in the medicinal product information sheet.

Interactions

Methadone is mainly metabolized in the liver. Above all, CYP3A4 plays an important role, which methadone via N-Demethylation metabolized to EDDP, an inactive metabolite. Other enzymes involved in the biotransformation are CYP2D6, 2B6 and 1A2. Since many drugs are substrates, inducers, or inhibitors of CYP3A4, numerous interactions are possible.

The simultaneous administration of MAO inhibitors and methadone can cause a fatal drop in blood pressure and, in the worst case, put the patient into a coma. A stronger depressant effect can be expected with centrally depressant substances such as alcohol and sleeping pills.

unwanted effects

The most common adverse effects include nausea, vomiting, respiratory depression, constipation, sweating, dizziness, dry mouth, itching, drowsiness, sedation, euphoria, and dysphoria.

A rare and serious undesirable effect is the increase in the QT interval, which can lead to abnormal heart rhythms. The most common reason for QT prolongation to occur is concomitant use of other QT prolonging drugs or cocaine use.

Methadone and heroin addiction

See under methadone substitution

literature
  • Pharmaceutical product information (CH, D, USA)
  • Berkowitz B.A. The relationship of pharmacokinetics to pharmacological activity: morphine, methadone and naloxone. Clin Pharmacokinet, 1976, 1 (3), 219-30 Pubmed
  • Bruera E., Sweeney C. Methadone use in cancer patients with pain: a review. J Palliat Med, 2002, 5 (1), 127-38 Pubmed
  • Corkery J.M., Schifano F., Ghodse A.H., Oyefeso A. The effects of methadone and its role in fatalities. Hum Psychopharmacol, 2004, 19 (8), 565-76 Pubmed
  • Eap C.B., Buclin T., Baumann P. Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Clin Pharmacokinet, 2002, 41 (14), 1153-93 Pubmed
  • Ferrari A., Coccia C.P., Bertolini A., Sternieri E. Methadone - metabolism, pharmacokinetics and interactions. Pharmacol Res, 2004, 50 (6), 551-9 Pubmed
  • Inturrisi C.E. Pharmacology of methadone and its isomers. Minerva Anestesiol, 2005, 71 (7-8), 435-7 Pubmed
  • Hunt J. Actions and side effects of methadone. Dtsch Med Wochenschr, 1990, 115 (14), 552-5 Pubmed
  • Medicine textbooks
  • Li Y., Kantelip J.P., Gerritsen-van Schieveen P., Danavi S. Interindividual variability of methadone response: impact of genetic polymorphism. Mol Diagn Ther, 2008, 12 (2), 109-24 Pubmed
  • Sim S.K. Methadone. Can Med Assoc J, 1973, 109 (7), 615-9 Pubmed
  • Sticherling C., Schaer B.A., Ammann P., Maeder M., Osswald S. Methadone-induced Torsade de pointes tachycardias. Swiss Med Wkly, 2005, 135 (19-20), 282-5 Pubmed
Author and Review

Conflicts of Interest: None / Independent. The author (SG) has no relationships with the manufacturers and is not involved in the sale of the products mentioned. Internal review: AV.

Peer review: Norman Ott, pharmacist, hospital pharmacy at Basel University Hospital

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This article was last changed on 3/14/2021.
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