Long-term effects beyond the neonatal period, however, are not su

Long-term effects beyond the neonatal period, however, are not sufficiently studied. Agonist maintenance: methadone Pioneering work by Dole and Nyswander in the 1960s55-57 provided the initial scientific basis for using the long-acting opioid agonist methadone for maintenance. Numerous studies since then58-62 have demonstrated that methadone maintenance of opioid addicts substantially reduces mortality and morbidity, the risk of new human immunodeficiency virus Inhibitors,research,lifescience,medical (HIV) infection, criminal activity, and illicit opioid

use, especially when used with enhanced ancillary services.63 Unfortunately, many programs do not provide these services, both because of decreased technical support government funding and increased private ownership. In the US, there are over 240 000 individuals maintained on methadone, while in some other countries, eg, Russia, government opposition Inhibitors,research,lifescience,medical to agonist maintenance prevents its use, even when high HIV rates exist. Federal regulations With a few exceptions, methadone may only be dispensed for opioid detoxification or maintenance treatment by opioid treatment programs certified by the Substance Abuse and Mental Health Administration (SAMHSA) and approved by the appropriate state

agency. Inhibitors,research,lifescience,medical Depending on criteria such as continued illicit drug use and employment, an increasing number of takehome doses is permitted, up to a maximum of a 1 -month supply after 2 years or longer. Pharmacology While heroin is short-acting and relatively ineffective orally, methadone is a long-acting, and orally effective, opioid. It is excreted primarily Inhibitors,research,lifescience,medical in the urine and is an agonist at li and 8 opiate receptors. Methadone is primarily metabolized through cytochrome P450 (CYP) enzymes, predominantly involving the CYP3A4 pathway. Drugs that increase the P450 enzymes, such as the retroviral agents for treating HIV, may increase methadone metabolism and lead to withdrawal symptoms, even in stable maintained patients. In Inhibitors,research,lifescience,medical contrast, drugs that inhibit these enzymes, such

as some selective serotonin selleck chemicals llc reuptake inhibitor (SSRI) antidepressants, may increase methadone levels and sedation.64-68 Effects are more likely early in treatment before plasma levels have stabilized.69 Physicians using methadone are advised to consult tables of drug interactions for complete listings. Dosing Methadone’s plasma GSK-3 half-life, once stabilized, averages 24 to 36 hours70 with a range of 13 to 50 hours, making it a useful once-daily maintenance medication compared with morphine or heroin. However, up to 10 days may be needed for such a steady state and before that, new patients, either in maintenance or given methadone for analgesia, are at risk of fatal overdose.8,71 Doses should not exceed 40 mg/day the first day of dosing or be increased over the next 2 weeks by more than 5 to 10 mg every 2 to 3 days.

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