Methadone

[SH4:p116]

 

Usage

• Analgesia in the setting of chronic pain syndrome
• Suppression of withdrawal symptoms
• Analgesia, post-operative

Structure

Synthetic opioid agonist

Pharmacodynamics

• Low abuse potential

Side effects

• Similar side-effect profile as morphine
• Sedative and euphoric actions are less than morphine
• Miosis is less prominent
  * Addicts can develop complete tolerance to miosis produced by methadone

Pharmacokinetics

Absorption

• Highly effective by the oral route

Metabolism

• Metabolised in liver
  --> Inactive metabolites
  --> Excreted in urine and bile

Elimination

• Small amount of methadone is excreted unchanged in urine.
• Prolonged elimination half-time = 35 hours

Clinical

Administration

• Methandone 20mg IV produces postoperative analgesia lasting more than 24 hours

Opioid withdrawal

• Used for suppression of withdrawal symptoms in physically dependent persons (e.g. heroin addicts)
  * Efficient oral absorption
  * Prompt onset of action
  * Prolonged duration of action
• Methadone can be substituted for morphine in addicts at about 1/4 the dosage.
• Controlled withdrawal from opioids using methadone is
  * Milder
  * Less acute

Treatment of chronic pain

• Methadone has been advocated as an alternative to slow-release formulations for treatment of chronic pain due to low abuse potential.
• Main disadvantage is prolonged and unpredictable half-time
  --> Risk of accumulation and prolonged respiratory depression