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methadone

methadone

Introduction

  • an opioid agonist which is well absorbed orally with a long half-life allowing once daily dosing
  • developed in Germany during world war II as a synthetic alternative to morphine as morphine was hard to obtain
  • introduced in Australia for Rx of heroin dependence in 1964
  • pts attend a clinic or pharmacy each day to be given a supervised dose
  • detoxification is not required for pts starting methadone
  • psychosocial interventions are an important adjunct
  • as many as 85% will stay on methadone for 12mths & most require Rx for at least 2 yrs
  • pts retained in Rx on a larger dose & for a longer duration generally achieve better results
  • optimal dose is 60-100mg/day
  • important Rx factors include optimal dosing & the morale of clinic staff
  • programs are not available in the NT

Pharmacology

  • mu opioid receptor agonist
  • NMDA receptor antagonist actions thought to decrease tolerance
  • large Vd 4L/kg as widely distributed to tissues which prolongs its half life as it gets secondarily re-distributed
  • eliminated mainly by widespread metabolism to metabolites which, along with some methadone, is excreted in urine
    • CYP3A4 inducers increase metabolism
      • eg carbamazepine and phenytoin
    • CYP3A4 inhibitors reduce metabolism and increase clinical effect
      • eg. fluconazole, macrolides, antiretrovirals
  • half life is extremely variable:
    • opiate naive patients have much longer half lives of up to 59hrs
    • most patients have half lives of around 30hrs

Adverse effects

  • constipation
  • sedation
  • diaphoresis
  • methadone overdose - resp. depression, coma, non-cardiogenic pulmonary oedema, etc
  • prolonged QTc and increased frequency of syncope related to the hERG K+ channel 1)
    • patients with significantly prolonged QTc should probably be switched to buprenorphine
methadone.txt · Last modified: 2019/01/11 01:35 by wh