Fentanyl toxicity

Fentanyl transdermal delivery systems (FTDS) use an unsealed multilaminate system containing a solid matrix, in which fentanyl is embedded instead of the reservoir designed in the TTS. FTDS is not to be recommended for routine postoperative pain treatment, even though it has a faster onset of action (4—6 hours) after cases of fentanyl toxicity, especially respiratory depression. FTDS has not been investigated adequately in chronic pain and is not expected to be superior to the TTS technique. 

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. 

Percutaneous patches are used in small animals. Fentanyl is a drug used for pain control and is quite effective. Unfortunately, it is quite toxic to animals and young children if accidentally ingested. 

Drugs metabolized by CYP that interact with cimetidine include, but are not limited to, the following lidocaine, quinidine, midazolam, triazolam, nifedipine, verapamil, and fentanyl (4). In each instance, inhibition of CYP by cimetidine results in reduced metabolic clearance and increases in serum concentrations of the other drug, which can lead to the expected toxicity and adverse experiences characteristic of the other drug. 

This situation became particularly acute with respect to the development of illicit analogs of fentanyl to derive heroin substitutes. Fentanyl is a synthetic opioid, a p-receptor agonist, and is about 100-200 times more potent than morphine as an analgesic. As with other narcotic analgesics, respiratory depression is the most significant acute toxic effect of the fentanyl derivatives. Fentanyl analogs can be 80-1000... 

Dihydromorphine (79) has been converted via its 6-tosylate into 6-deoxy-6-azidodihydroisomorphine (89).°86) This derivative is a remarkably potent analgesic (300 times morphine in the rat and 50 times morphine in humans) and was reported to be less toxic than either morphine or fentanyl with a low PDC in monkeys. In humans, however, an abstinence syndrome087 189 and ability to substitute for morphine090 was reported. 

PHENYTOIN ANALGESICS-OPIOIDS 1.1 efficacy of fentanyl and methadone 2. Risk of pethidine toxicity 1. t hepatic metabolism of fentanyl and methadone, and possibly an effect at the opioid receptor 2. Phenytoin induces metabolism of pethidine, which causes t levels of a neurotoxic metabolite 1. Be aware that the dose of fentanyl and methadone may need to be t 2. Co-administer with caution the effect may be 1 by administering pethidine intravenously... 

OPIOIDS ANTICANCER AND IMMUNOMODULATING DRUGS - CYTOTOXICS 1. Imatinib may cause t plasma concentrations, with a risk of toxic effects of codeine, dextromethorphan, hydroxycodone, methadone, morphine, oxycodone, pethidine and tramadol 2. Unpredictable reactions may occur associated with hypotension and respiratory depression when procarbazine is co-administered with alfentanil, fentanyl, sufentanil or morphine... 

CANNABIS ANALGESICS - OPIOIDS -alfentanil, fentanyl, methadone, codeine, dextromethorphan Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index Induction or inhibition of CYP3A4-mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes... 

AMPHETAMINES ANALGESICS-OPIOIDS-alfentanil, fentanyl, propoxyphene t plasma concentrations of amphetamine, with risk of toxic effects Due to inhibition of CYP2D6-mediated metabolism of amphetamine Avoid concurrent use... 

Gardner-Nix J. Caregiver toxicity from transdermal fentanyl. J Pain Symptom Manage 2001 21(6) 447-8. 

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. 

Fentanyl produces excitatory effects in cats, pigs, and horses. Its effects on dogs mimic its human toxicity. Naloxone can be administered to animals. 

Fentanyl overdose leads to the classic triad of symptoms consistent with the opioid intoxication syndrome miosis, respiratory depression, and CNS depression. Additional toxic effects of fentanyl include bradycardia, hypotension, decreased gastrointestinal motility, euphoria, and acute lung injury. 

The toxic effects of illicit fentanyl derivatives include rapid onset respiratory and central nervous system depression. Patients often present comatose and apneic. Other signs and symptoms consistent with opioid intoxication such as bradycardia, hypotension, miosis, and decreased gastrointestinal motility also occur. 

It exhibits a profile of pharmacological action very much identical to morphine, and differs exceptionally on two accounts, namely flrst-it does not cause emesis secondly, it does not release histamine. Its safety measure in frequency cases has not yet been fully understood. It is observed to cross the placental barrier therefore, its usage during labour may ultimately give rise to respiratory depression in the newly bom infant. However, Fentanyl s transient action after the parenteral administration is caused solely on account of redistribution, rather than to "metabolism" or "excretion". Hence, longer usage of this drug may cause in accumulation and toxicities. 

The drug exhibits relatively low therapeutic potency, medium extrapyradimal toxicity, high sedative effect, and above all high hypotensive action. However, it is most frequently employed in the form of its combination [Innovar ] along with the narcotic agent fentanyl [Sublimaze ] preanaesthetically. 

Fentanyl s short duration of action after parenteral dose is caused by redistribution rather than by metabolism or excretion. Repeated doses of fentanyl can result in accumulation and toxicities. Elderly patients usually are more sensitive to fentanyl and require lower doses. 

II. Toxic dose. The toxic dose varies widely depending on the specific compound, the route and rate of administration, and the tolerance to the effects of the drug as a result of chronic use. Some newer fentanyl derivatives have a potency up to 2000 times that of morphine. 

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