| Indication |
For the treatment of dry cough, drug withdrawal syndrome, opioid type drug dependence, and pain. |
| Pharmacodynamics |
Methadone is a synthetic opioid analgesic with multiple actions
quantitatively similar to those at morphine, the most prominent of which
involve the central nervous system and organs composed of smooth
muscle. However, Methadone is more active and more toxic than morphine.
Methadone is indicated for relief of severe pain, for detoxification
treatment of narcotic addiction, and for temporary maintenance treatment
of narcotic addiction. The principal actions of therapeutic value are
analgesia and sedation and detoxification or temporary maintenance in
narcotic addiction. The Methadone abstinence syndrome, although
qualitatively similar to that of morphine, differs in that the onset is
slower, the course is more prolonged, and the symptoms are less severe. |
| Mechanism of action |
Methadone is a mu-agonist; a synthetic opioid analgesic with
multiple actions qualitatively similar to those of morphine, the most
prominent of which involves the central nervous system and organs
composed of smooth muscle. The principal therapeutic uses for methadone
are for analgesia and for detoxification or maintenance in opioid
addiction. The methadone abstinence syndrome, although qualitatively
similar to that of morphine, differs in that the onset is slower, the
course is more prolonged, and the symptoms are less severe. Some data
also indicate that methadone acts as an antagonist at the
N-methyl-D-aspartate (NMDA) receptor. The contribution of NMDA receptor
antagonism to methadone's efficacy is unknown. Other NMDA receptor
antagonists have been shown to produce neurotoxic effects in animals. |
| Absorption |
Well absorbed following oral administration. The bioavailability of methadone ranges between 36 to 100%. |
| Volume of distribution |
|
| Protein binding |
In plasma, methadone is predominantly bound to α1-acid glycoprotein (85% to 90%). |
| Metabolism |
Hepatic. Cytochrome P450 enzymes, primarily CYP3A4, CYP2B6, and
CYP2C19 and to a lesser extent CYP2C9 and CYP2D6, are responsible for
conversion of methadone to EDDP and other inactive metabolites, which
are excreted mainly in the urine. |
| Route of elimination |
The elimination of methadone is mediated by extensive biotransformation, followed by renal and fecal excretion.
Unmetabolized methadone and its metabolites are excreted in urine to a variable degree. |
| Half life |
24-36 hours |
| Clearance |
|
| Toxicity |
In severe overdosage, particularly by the intravenous route, apnea, circulatory collapse, cardiac arrest, and death may occur. |
