Opioids toxicity

Opioid toxicity IV, IM, Subcutaneous 0.4-2 mg q2-3min as needed. May repeat q20-60min. 

Nielsen S, Dietze P, Lee N, Dunlop A Taylor D (2007). Concurrent buprenorphine and benzodiazepines use and self-reported opioid toxicity in opioid substitution treatment. Addiction, 102, 616-22... 

Madadi P et al Pharmacogenetics of neonatal opioid toxicity following maternal use of codeine during breastfeeding A case control study. Clin Pharmacol Ther 2009 85 31. [PMID 18719619]... 

An interaction of itraconazole with fentanyl has been reported in a 67-year-old man with cancer on a stable dose of transdermal fentanyl 50 micrograms/hour (88). He took itraconazole 200 mg bd for oropharyngeal candidiasis, and 24 hours later developed signs of opioid toxicity, which was reversed by withdrawal of fentanyl and replacement with short-acting opioids. 

The episode of unconsciousness was attributed to opioid toxicity in a patient in whom autonomic dysfunction may already have been present. It was suggested that opioid analgesics should be used with caution in patients with Guillain-Barre syndrome, because of the risk of hypotension consequent on autonomic dysfunction. 

Accumulation of morphine-6-glucuronide is a risk factor for opioid toxicity during morphine treatment. However, it does not occur in all patients with renal insufficiency, which is the most common reason for accumulation of morphine-6-glucuronide this suggests that other risk factors can contribute to morphine-6-glucuronide toxicity. 

Clinical effects of CYP2D6 and OPRMl variants on opioid toxicity and efficacy... 

Acute opioid toxicity may result from clinical overdosage, accidental overdosage in addicts, or attempts at suicide. Occasionally, a delayed type of toxicity may occur from the injection of an opioid into dulled skin areas or in patients with low blood pressure and shock. The drug is not fully absorbed, and therefore, a subsequent dose may be given. When normal circulation is restored, an excessive amount may be absorbed suddenly. It is difficult to define the exact amount of any opioid that is toxic or lethal to humans. In nontolerant individuals, serious toxicity may follow the oral ingestion of 40-60 mg of methadone. A normal, pain-free adult is not likely to die after oral doses of morphine of <120 mg or to have serious toxicity with <30 mg parenteraUy. 

Some patients may experience prolonged and increased alfentanil effects if they are given fluconazole or voriconazole. In vitro data surest itraconazole and ketoconazole may interact similarly. Intravenous fentanyl does not appear to interact with itraconazole in healthy subjects, but one case of possible opioid toxicity from transdermal fentanyl has been reported. 

In a study in 13 healthy subjects receiving methadone, tenofovir 300 mg daily for 2 weeks did not alter the pharmacokinetics of methadone, and no symptoms of opioid toxicity or opioid withdrawal were detected. ... 

Finally, caregivers must recognize that, unlike non-selective antagonists, methynaltrexone will not reverse excessive sedation, respiratory depression, and other symptoms associated with central opioid toxicity. 

F. Bektas, C. Eken and V. Sayrac, Opioid toxicity as a result of oral/ transmucosal administration of transdermal fentanyl patch, Eur. J. Emerg. Med., 2009, 16, 344-345. 

Opioid toxicity causing coma or respiratory depression. It is possibly of use in kolokol-1 poisoning. 

Anxiety disorders are common in the population of opioid-addicted individuals however, treatment studies are lacking. It is uncertain whether the frequency of anxiety disorders contributes to high rates of illicit use of benzodiazepines, which is common in methadone maintenance programs (Ross and Darke 2000). Increased toxicity has been observed when benzodiazepines are co-administered with some opioids (Borron et al. 2002 Caplehorn and Drummer 2002). Although there is an interesting report of clonazepam maintenance treatment for methadone maintenance patients who abuse benzodiazepines, further studies are needed (Bleich et al. 2002). Unfortunately, buspirone, which has low abuse liability, was not effective in an anxiety treatment study in opioid-dependent subjects (McRae et al. 2004). Current clinical practice is to prescribe SSRIs or other antidepressants that have antianxiety actions for these patients. Carefully controlled benzodiazepine prescribing is advocated by some practitioners. 

Lotsch J, Zimmermann M, Darimont J, et al Does the Al 18G polymorphism at the mu-opioid receptor gene protect against morphine-6-glucuronide toxicity Anesthesiology 97 814-819, 2002... 

Opiate drug exposure has a significant impact on HIV infection as well as progression to HIV-associated dementia. On a cellular level it is comprehendible that drugs of abuse such as opioids would reduce the threshold for neurotoxicity such that a marginally toxic insult would now be exacerbated and lead to cell death or injury... 

Influencing the efficacy or potency of chemicals is a strategy used by the pharmaceutical industry as part of the drug discovery process that can be incorporated into designing safer industrial chemicals. Efficacy is the maximal effect, either therapeutic or toxic, that a chemical can achieve. Potency is a measure of the amount of a substance that is needed to attain a given response level. Opioid analgesics are examples of where structural modifications have been used to establish a relationship between structure and activity. ... 

Severe pain should be treated with an opioid such as morphine, hydromorphone, methadone, or fentanyl. Moderate pain can be treated effectively in most cases with a weak opioid such as codeine or hydrocodone, usually in combination with acetaminophen. Meperidine should be avoided owing to its relatively short analgesic effect and its toxic metabolite, normeperidine. Normeperidine may accumulate with repeated dosing and can lead to central nervous system side effects including seizures. 

The perhaps most important and easily ignored cause of secondary dysmotility is the drug-induced toxic type. Pharmaceuticals are important to consider, in particular those with anticholinergic and/or opioid properties [177]. In individuals with reduced reserve capacity of the gut, either due to concomitant disease or age, such drugs may... 

Naloxone is a pure opioid antagonist that binds competitively to opioid receptors but does not produce an analgesic response. It is used to reverse the toxic effects of agonist and agonist-antagonist opioids. 

Naloxone (Narcan). Naloxone, like naltrexone, is a potent opioid receptor blocker. Its primary use has been to reverse opiate toxicity after an overdose. However, some physicians have found it is also useful for a process known as rapid opiate detoxification. Although opiate withdrawal is not life threatening, it can be extremely unpleasant. Most opiate addicts are fearful of the withdrawal symptoms therefore, it usually requires a slow, deliberate detoxification to keep the withdrawal symptoms in check. Rapid opiate detoxification is an alternative approach that keeps the taper and detoxification as brief as possible. In this approach, naloxone is used in conjunction with general anesthesia or a nonopiate sedative such as the benzodiazepine mid-... 

E does not present the risk of toxicity in non-opioid dependent adults... 

Methadone is an opioid analgesic that is available for oral and parenteral administration. It is used in severe pain, in palliative care and as an adjunct in the management of opioid dependence. Compared with morphine, it is less sedating and has a longer duration of action. It may lead to addiction and can still cause toxicity when used in adults with non-opioid dependency. Because of the long duration of action, in overdosage, patients need to be monitored for long periods. 

Tramadol is an opioid analgesic and when given to patients who are also receiving imipramine (a tricyclic antidepressant), there is an increased risk of central nervous system toxicity. The risk of occurrence of sedation is increased. 

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