Methadone drug tolerance

Methadone is extensively used in opioid withdrawal and maintenance programs (see Drug tolerance in this monograph), and has been safely used for this purpose in pregnancy, with only mild effects on the offspring (41). However, fetal exposure to methadone in utero can cause a neonatal abstinence syndrome after delivery. 

Methadone is extensively used in opioid withdrawal and maintenance programs (see Drug tolerance in this... 

Cross-tolerance A condition where an individual who is tolerant to the pharmacological effects of one member of a drug family also shows tolerance to other members of that family. Cross-dependence allows drug substitution during detoxification (e.g., methadone for heroin or clomethiazole for ethanol), so reducing the severity and potential danger of withdrawal symptoms. 

Unnecessary detoxification with drugs should be avoided if possible (e.g., if symptoms are tolerable). Heroin withdrawal reaches a peak within 36 to 72 hours, and methadone withdrawal peak is reached at 72 hours. 

The treatment of opioid abuse and dependence aims also at preventing the social complications of abuse, especially infections linked to parenteral administration (HIV and HepB). It relies on the use of substimtive drugs that can be either pure agonists, or partial agonist-antagonists (methadone, buprenor-phine, naltrexone), with the objective of limiting receptor desensitization and the development of tolerance. Any success in the treatment of opiate dependence may stem as much from the re-establishment of healthcare contact and social reinsertion as from any treatment induced decrease in the abuse behaviour itself. 

The patient who uses methadone long-term may develop a tolerance to the drug s analgesic effect and physical dependence. 

Methadone is widely used in the treatment of opioid abuse. Tolerance and physical dependence develop more slowly with methadone than with morphine. The withdrawal signs and symptoms occurring after abrupt discontinuance of methadone are milder, although more prolonged, than those of morphine. These properties make methadone a useful drug for detoxification and for maintenance of the chronic relapsing heroin addict. 

Cross-tolerance occurs between all opiates that act primarily via the mu receptors. This is the basis of the methadone substitution therapy which is commonly used to withdraw people who are dependent on heroin or morphine methadone is used because of its relatively long half-life (about 12 hours) and its ease of administration in an oral form. Cross-tolerance does not occur between the opiates and other classes of dependence-producing drugs such as the barbiturates, alcohol or the amphetamines, which act through different mechanisms. 

Methadone maintenance treatment is considered to be a medically safe treatment with relatively few and minimal adverse effects. However, the danger of serious adverse effects and death with the increasing use of methadone as maintenance therapy in drug addicts has been highlighted. It must be emphasized that a daily maintenance dose of 50-100 mg is toxic in a non-tolerant adult and as little as 10 mg can be fatal in a child. There is an increasing number of reports of the deaths of children of mothers on maintenance therapy from inadvertent ingestion. 

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