Related Experiment Video
Updated: Jul 12, 2026
09:16
A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration
Published on: January 22, 2016
Methadone toxicity causing death in ten subjects starting on a methadone maintenance program
O H Drummer1, K Opeskin, M Syrjanen
1Victorian Institute of Forensic Pathology, South Melbourne, Australia.
The American Journal of Forensic Medicine and Pathology
|December 1, 1992
Summary
Deaths occurred in patients starting methadone maintenance therapy, a treatment for opioid addiction. High initial doses and lack of tolerance were identified as key risk factors in the early days of treatment.
Area of Science:
- Pharmacology
- Toxicology
- Public Health
Background:
- Methadone maintenance therapy (MMT) is a cornerstone treatment for opioid use disorder.
- MMT aims to reduce illicit opioid use and associated harms.
- Prior to this study, deaths directly linked to the initiation of MMT were not well-documented.
Observation:
- This study reports the deaths of 10 individuals within days of commencing MMT under general practitioner care.
- Autopsies and comprehensive toxicological analyses were performed on all deceased subjects.
- Key findings included the presence of chronic persistent hepatitis in all subjects and bronchopneumonia in five.
Findings:
- The mean starting dose of methadone was 53 mg, with a mean final dose of 57 mg.
- Death occurred after a mean of 3 days on the program, with a mean blood methadone concentration of 2.1 mumol/L.
- Six subjects had other substances detected, including alcohol, benzodiazepines, and morphine; causes of death were attributed to methadone toxicity, sometimes compounded by bronchopneumonia.
Implications:
- Initiating methadone maintenance therapy carries significant risks in the initial treatment phase.
- High starting doses of methadone, especially in individuals without prior opioid tolerance, can be dangerous.
- Clinical vigilance and careful dose titration are crucial during the early days of MMT to prevent fatal outcomes.
Related Concept Videos
01:15Opioid Analgesics: Synthetic and Semisynthetic Opioids
Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...
01:00Drug Toxicity: Overview
Drug toxicity quantifies the harm a compound causes to an organism, varying by dose and potentially impacting whole systems or specific organs like the liver. Toxic reactions may arise from venomous insect or spider bites, with effects ranging from mild symptoms to severe outcomes such as brain damage or death. Common forms of acute poisoning include ethanol intoxication and overdose of pain or fever medications, with substances like GHB and heroin being particularly lethal at doses close to...
01:24Drug Toxicity: Risk factors
Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
01:24Drug Toxicity: Dose-Dependent Reactions
Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...
01:16Drug toxicity: Idiosyncratic Reactions
Idiosyncratic drug reactions represent abnormal chemical responses that vary significantly among individuals, ranging from extreme sensitivity to low doses to insensitivity to high doses. These reactions often occur due to the drug's covalent binding with serum proteins, forming a foreign hapten that triggers an immunotoxicological response. The variability in drug reactions has a strong pharmacogenetic foundation, with genetic differences crucial in how individuals metabolize drugs. For...
01:30Drug toxicity: Drug–Drug Interaction
Drug–drug interactions can precipitate toxicity through multiple mechanisms. Absorption interactions alter how drugs enter the body, exemplified when ranitidine increases the absorption of basic drugs, while cholestyramine decreases the levels of propranolol. Protein binding interactions occur when drugs share the same binding sites on plasma proteins. Drugs like aspirin and warfarin, when bound in excess, can lead to increased free drug concentrations, enhancing the potential for...