High Risk Of Overdose Research Articles

THE TIME HAS COME FOR NEW, MORE PRECISE GUIDELINES IN THE TREATMENT OF HIGH RISK ACUTE CORONARY SYNDROMES WITH HEPARIN

Background The aim of this analysis was to define the risk factors associated with the problematic dose titration of unfractionated heparin (UFH) in high-risk non-ST-segment elevation acute coronary syndrome (NSTE ACS) patients. Methods and Results The study group comprised 267 patients with high-risk NSTE ACS managed with an early invasive strategy and treated with the recommended dose of UFH. The subsequent dose was adjusted after measurement of activated partial thromboplastin time (aPTT), using the nomogram. The goal for aPTT was 1.5-2.5-fold of the control value. At 6 h after starting therapy 29% of patients had a therapeutic initial aPTT value; half of them were over-anticoagulated, and 22% were undertreated. By continuing therapy, the proportion of optimally treated patients increased; after 12 h of treatment 40% of patients reached the therapeutic dose, and 58% after 24 h. Undertreatment was a problem in ≤65-year-old men. Women and older patients have a higher risk of overdose. The patients with a therapeutic dose of UFH had the lowest occurrence of major ischemic adverse events. Conclusions Expert consensus on more precise dose guidelines for UFH is needed. The dose needs to be not only weight, but also age and sex, adjusted. (Circ J 2008; 72: 1674 - 1679)

Providing Naloxone to Substance Users for Secondary Administration to Reduce Overdose Mortality in New York City

Overdose on illicit drugs is a substantial and grow ing public health problem. In New York City (NYC) between 1990 and 2001, overdose deaths increased by 48%, from 541 to 799 fatalities; in contrast, homicides decreased by 71%, from 2,081 to 609 during this same time period.1 Certain populations are at particularly high risk of overdose: among users of single-adult homeless shelters in NYC, overdose morbidity and mortality markedly exceeds rates in the general popu lation.2 Overdose has been identified as a primary cause of excess mortality among substance users with acquired immunodeficiency syndrome (AIDS) in NYC.3 A substantial increase in overdose risk has been identi

Linkage with Methadone Treatment Upon Release from Incarceration

Injection drug users (IDUs) are at increased risk for HIV, viral hepatitis, and tuberculosis, and making up more than a quarter of the incarcerated population in the United States. Methadone maintenance treatment of opiate addiction is highly effective at reducing drug use, drug-related criminal activity, and risk of HIV transmission. Recently released inmates are at particularly high risk for overdose and disease transmission. Linkage to methadone treatment immediately upon release from incarceration is a promising opportunity to combat disease transmission, facilitate reentry into the community, and reduce recidivism.

Opiate replacement therapy at time of release from incarceration: Project MOD, a pilot program

Approximately 7 million people in the United States are in jail, in prison, or on probation or parole, many as a result of drug-related offenses. Individuals who use opiates account for a significant minority of this population. Methadone maintenance treatment (MMT) of opiate addiction is highly effective in reducing drug use, drug-related criminal activity, and risk of human immunodeficiency virus transmission. Recently released inmates are at particularly high risk for overdose and disease transmission. Project MOD (Managing Opioid Dependency) provides services to eliminate logistical and financial barriers to MMT entry immediately on release from incarceration. Such programs provide a promising opportunity to facilitate reentry into the community, combat disease transmission, and reduce recidivism.

Influence of glutethimide on rat brain mononucleotides by sub-chronic codeine treatment.

It was investigated the in vivo effect of glutethimide on the intracellular neuroadaptation characteristic for m-opioid receptor tolerance induced by chronic codeine treatment and reflected by increased levels of adenylyl cyclase (AC) and cAMP-dependent protein kinase (PKA). AC activity was appreciated by cyclic-AMP (cAMP) formation, the levels of adenine and guanine nucleotides in brain extracts being assayed using a high performance liquid chromatographic method. The concomitant chronic administration of codeine and glutethimide resulted in a pronounced and long-lasting energetic depletion of the neurons, consistent with the high risk of overdose, and increase of cAMP's stable metabolite, 5'-AMP. This increase is persistent even after withdrawal and suggests an interference with the adenylyl cyclase system involved in the development of tolerance of opioid receptor and in relapse and provides a possible explanation of addiction and fast increase of doses observed in humans abusing this combination.

Mechanisms of fatal opioid overdose

There has been increasing recognition of the problem of fatal opioid overdose. This review examines the pharmacological basis of respiratory depression following opioid administration. Respiration is controlled principally through medullary respiratory centres with peripheral input from chemoreceptors and other sources. Opioids produce inhibition at the chemoreceptors via mu opioid receptors and in the medulla via mu and delta receptors. While there are a number of neurotransmitters mediating the control of respiration, glutamate and GABA are the major excitatory and inhibitory neurotransmitters, respectively. This explains the potential for interaction of opioids with benzodiazepines and alcohol: both benzodiazepines and alcohol facilitate the inhibitory effect of GABA at the GABAA receptor, while alcohol also decreases the excitatory effect of glutamate at NMDA receptors. Heroin and methadone are the major opioids implicated in fatal overdose. Heroin has three metabolites with opioid activity. Variation in the formation of these metabolites due to genetic factors and the use of other drugs could explain differential sensitivity to overdose. Metabolites of methadone contribute little to its action. However, variation in rate of metabolism due to genetic factors and other drugs used can modify methadone concentration and hence overdose risk. The degree of tolerance also determines risk. Tolerance to respiratory depression is less than complete, and may be slower than tolerance to euphoric and other effects. One consequence of this may be a relatively high risk of overdose among experienced opioid users. While agonist administration modifies receptor function, changes (usually in the opposite direction) also result from use of antagonists. The potential for supersensitivity to opioids following a period of administration of antagonists such as naltrexone warrants further investigation. While our understanding of the pharmacological basis of opioid-related respiratory depression has advanced, better understanding of the role of heroin metabolites, the metabolism of methadone, drug interactions and tolerance would all be of considerable value in knowing how best to respond to this problem.

THE 1998 JAMES RANKIN ORATION: Reducing the toll of opioid overdose deaths in Australia

AbstractOpioid overdose mortality among young adults in Australia has increased consistently over the past several decades. Among Australian adults aged 15–44 years, the number of these deaths has increased from six in 1964 to 600 in 1997. The rate (per million adults in this age group) increased 55‐fold, from 1.3 in 1964 to 71.5 in 1997. The proportion of all deaths in adults in this age group caused by opioid overdose increased from 0.1% in 1964 to 7.3% in 1997. The magnitude of the increase makes it unlikely to be an artefact of changes in diagnosis, especially as similar increases have also been observed in other countries. These trends are also consistent with historical information which indicates that illicit heroin use first came to police attention in Sydney and Melbourne in the late 1960s. There is an urgent need to implement and evaluate a variety of measures to reduce the unacceptable toll of opioid overdose deaths among young Australians. These include: peer education about the risks of polydrug use and overdose after resuming opioid use after periods of abstinence, and attracting more dependent users into opioid maintenance treatment. Measures are also needed to improve responses to overdose by encouraging witnesses to call ambulances, training drug users in CPR, and trialling distribution of the opiate antagonist naloxone to users at high risk of overdose.

Lidocaine overdose

Physicians who prescribe viscous lidocaine preparations should be aware of the adverse effects and the high risk for overdose in pediatric patients. Owing to altered pharmacokinetics (increased absorption, decreased clearance, and prolonged half-life), doses that are innocuous for adults may present a significant potential toxic hazard in children. Lidocaine should not be used to treat painful mouth lesions in children until further safety data are available. Benzocaine may be considered as a safe alternative to lidocaine. Its low incidence of side effects makes it a safer choice for infants and children. If no other choices are appropriate, then very specific instructions should be given to parents. The amount, frequency, maximum daily dose, and mode of administration should be clearly communicated (eg, cotton pledget to individual lesions, one-half dropper to each cheek every four hours, or 20 minutes before meals). They should never be prescribed on a "PRN" basis.

Heroin-Overdose Deaths in Atlanta

Heroin-overdose mortality in Atlanta increased from 0.4/100,000 population in 1970 to 1.9/100,000 in 1971. Eight persons, most of whom were young black men, died in one 11-day period. Concurrently, 12 heroin-overdose survivors were hospitalized. Both groups in this epidemic reportedly had little or no tolerance for large doses of heroin. Heroin content in consumer packages increased from an average of 8.4 mg per package before, to 12.8 mg per package during the epidemic. Heroin content varied from 3.3 to 33.3 mg of heroin per package during this period, although there was great variation in other months as well. The lack of dose standardization may be one important factor in heroin mortality, placing those who have been abstaining and novice heroin users at particularly high risk of overdose. (JAMA228:319-322, 1974)