The effects of methadone and its role in fatalities

Abstract

Methadone is a synthetic opioid, used both as an analgesic in severe pain relief and now mainly in the treatment of opiate dependence. Such use of the drug has increased as its advantages have become widely recognized. There are undesirable outcomes from its greater use, including a substantial market in diverted methadone and a high number of deaths where the drug has been implicated. It is important to understand how and why methadone causes death so that such fatalities can be minimized, and to disseminate such information. This paper presents an overview of the chief effects of methadone on the human body, considering its metabolism, drug interactions and tolerance. The principal mechanisms by which methadone causes death are discussed: respiratory depression, aspiration of vomit, pulmonary oedema, bronchopneumonia, cardiac problems and renal failure. Many such deaths are preventable, if drug interactions and polydrug use are avoided, its longer period of metabolism and individuals' tolerance levels are considered. It is hoped that this paper will (a) help guide health professionals in their management and treatment of patients participating in methadone treatment programmes, and (b) provide some basic information for those dealing with individuals who have consumed methadone.

Resting-state Abnormalities in Heroin-dependent Individuals

“…Furthermore, methadone in the initial phase of methadone replacement therapy has been shown to be slowlymetabolized (Corkery et al, 2004). More specifically, according to Wolff et al (2000) the median elimination half-life of methadone has been found to be diminished more than 60% when the addict has reached a steadystate methadone level.…”

Methadone Deaths: Risk Factors in Pain and Addicted Populations

“…It takes 2-4 hours to achieve peak plasma levels. 15 Methadone is metabolized primarily in the liver into inactive metabolites by the P450, CYP 3A4 enzymes that are also used by several QTc prolonging medications. 16,17 Methadone is a weak inhibitor of the 3A4 system and a minor weak substrate of 2C89, 2C19 and 2D6.…”

“…Thus, individuals prescribed methadone for pain generally experience relief for 4-8 hours, but methadone remains pharmacologically active for much longer periods, potentially leading to toxicity. 15 Although individuals receiving MMT typically take methadone only once daily, 8 its pharmacologic properties may interact with relatively rapid titration regimens to cause increases in serum levels in opioid dependent patients.…”

“…Individuals differ significantly in how long it takes for methadone to achieve steady state and maximum effect, and it may take seven days or longer to realize full therapeutic actions. 15 Meanwhile, strong cravings to use opioids may persist and elicit in patients a sense of urgency to increase the dose or resort to street heroin. Drinking heavily or using benzodiazepines may also result in accidental overdoses.…”

“…In MMT settings, patients are required to attend daily appointments, during which methadone ingestion and clinical status can be monitored and dosage adjusted accordingly. 8 Because 30 mg of methadone can cause fatal respiratory depression in opioid-naïve individuals, consensus now exists that methadone induction protocols should initiate doses under 30 mg. 15 Most guidelines propose increases of 5-10 mg every 3-5 days, until cravings are reduced and, if taken, euphorigenic effects of illicit opioids are blocked. 8 Although these guidelines exist, empirical data demonstrating doseresponse relationships and safe dosing levels in these contexts are lacking.…”