エトルフィン

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

/HUMAN EXPOSURE STUDIES/ The effects of etorphine, a potent morphine-like drug, were qualitatively and quantitatively compared to those of morphine. In nondependent subjects, etorphine in doses of 0.025, 0.050, and 0.100 mg produced pupillary constriction and morphine-like subjective effects and euphoria. Etorphine was 500 times as potent as morphine, with a very rapid onset and short duration of action. In morphine-dependent subjects, etorphine suppressed abstinence but for a shorter period than morphine. These studies indicate that in man etorphine is a morphine-like drug with a high abuse potential.

/CASE REPORTS/ ... A case of voluntary self-injection with Large Animal Immobilon, a veterinary anesthesia product containing etorphine, a very strong opioid, and acepromazine, a phenothiazine. This resulted in cardiorespiratory arrest and the need for sustained hemodynamic support after resuscitation. Large Animal Immobilon is used under specific conditions only, mainly in zoo and wildlife medicine. Primary toxicological analysis, although guided by the presumed toxin, could only detect a metabolite of acepromazine in the urine. Further analysis was able to show some traces of etorphine.

/CASE REPORTS/ In a forensic case involving Immobilon /commerical formulation/, the etorphine concentrations measured in postmortem femoral vein and heart blood specimens were 14.5 and 23.5 ug/L, respectively. No etorphine was detected in the urine.

/ALTERNATIVE and IN VITRO TESTS/ The present study was undertaken to compare the neurotoxic effects of three etorphine-like opiates (etorphine, dihydroetorphine, and another derivative of oripavine) and heroin with their ability to activate opiate receptors in human neuroblastoma cell line SK-N-SH as well as in two other neuronal cell lines. Neurotoxicity was measured by using [3H]-thymidine incorporation analysis, cell viability measurement and Cytosensor microphysiometry. It was found that, in spite of the very similar molecular structures of these opiates, they displayed significant differences in cytotoxicity, with etorphine and another derivative of oripavine possessing high potency but dihydroetorphine and heroin little effect. However, neurotoxic potency of the opiates was not directly correlated to their ability to activate opioid receptors, as determined by [35S]-guanylyl-5'-O-(gamma-tho)-triphosphate binding assay. These findings provide clear evidence of differential neurotoxicity of etorphine-like opiates, and suggest that the neurotoxicity is not closely related to the molecular configuration required as opioid receptor agonist but is probably associated with the presence of a double bond in the structure.

For more Human Toxicity Excerpts (Complete) data for ETORPHINE (6 total), please visit the HSDB record page.

/LABORATORY ANIMALS: Acute Exposure/ The results of a preliminary evaluation of etorphine/methotrimeprazine ('Small Animal Immobilon') and midazolam in rats and mice are reported, and this regimen is compared to fentanyl/fluanisone/midazolam in mice. In rats, a surgical plane of anesthesia with good muscle relaxation was produced, but blood gas analysis showed the presence of severe hypoxia, hypercapnia and acidosis. In mice etorphine/methotrimeprazine/midazolam and fentanyl/fluanisone/midazolam produced adequate anesthesia, but blood gas analysis showed severe respiratory depression with both regimens. Since etorphine/methotrimeprazine/midazolam produced severe respiratory depression in rats and mice it is suggested that this regimen is used with caution. Administration of supplemental oxygen would seem advisable when using either etorphine/methotrimeprazine/midazolam or fentanyl/fluanisone/midazolam in rats and mice.

/LABORATORY ANIMALS: Neurotoxicity/ One hundred forty-two rats given intracerebral microinjections of 1 microgram of etorphine hydrochloride were observed for subsequent analgesia (flinch-jump technique) and catatonia (bar test). Neuroanatomical specificity of effect was demonstrated to the extent that behavioral effects did not result from injections into areas of low opiate receptor binding affinity, such as medial cerebral cortex and hippocampus, nor were positive results obtained from injections into fiber bundles, such as the corpus callosum and internal capsule. Positive results were obtained in a large number of areas, ranging from brain stem to telencephalon. Injections eliciting analgesia without catatonia were limited in number (9 animals) and were widely scattered throughout neuroanatomical loci. Microinjection more frequently elicited catatonia only (29 animals), and site of injection was limited to posterior cerebral cortex, posterior amygdala, dorsal reticular formation, and cerebral aqueduct. Dual behavioral effects were elicited in 28 of the animals and occurred most frequently upon injection into the periaqueductal gray, inferior colliculus, and cerebral aqueduct. (Injection into cerebral aqueduct produced 50% catatonia only and 50% dual effects). The study suggests that opiate-elicited analgesia and catatonia may be neuroanatomically distinct phenomena.

/LABORATORY ANIMALS: Neurotoxicity/ This study has examined the relationship between the effects of opioids on the internalization of mu opioid receptors (MORs) and the morphology of dendritic spines. Several opioids (morphine, etorphine, DAMGO or methadone) were applied to cultured /rat/ hippocampal neurons. Live imaging and biochemical techniques were used to examine the dynamic changes in MOR internalization and spine morphology. This study reveals that MOR internalization can regulate opioid-induced morphological changes in dendritic spines: (1) Chronic treatment with morphine, which induced minimal receptor internalization, caused collapse of dendritic spines. In contrast, "internalizing" opioids such as DAMGO and etorphine induced the emergence of new spines. It reveals that opioid-induced changes in spines vary greatly depending on how the applied opioid agonist affects MOR internalization. (2) The blockade of receptor internalization by dominant negative mutant of dynamin, K44E, reversed the effects of DAMGO and etorphine. It indicates that receptor internalization is necessary for the distinct effects of DAMGO and etorphine on spines. (3) In neurons that were cultured from MOR knock-out mice and had been co-transfected with DsRed and MOR-GFP, morphine caused collapse of spines whereas DAMGO induced emergence of new spines, indicating that opioids can alter the structure of spines via postsynaptic MORs. (4) Methadone at a low concentration induced minimal internalization and had effects that were similar to morphine. At a high concentration, methadone induced robust internalization and had effects that are opposite to morphine. The concentration-dependent opioid-induced changes in dendritic spines might also contribute to the variation in the effects of individual opioids.

While data specific to etorphine were not located(SRC, 2008), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through soils(1).

Emergency and supportive measures: Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. Treat coma, seizures, hypotension, and noncardiogenic pulmonary edema if they occur. /Opiates and opioids/

Specific drugs and antidotes: Naloxone is a specific opioid antagonist with no agonist properties of its own; large doses may be given safely. ... Caution: The duration of effect of naloxone (1-2 hours) is shorter than that of many opioids. Therefore, do not release a patient who has awakened after naloxone treatment until at least 3-4 hours has passed since the last dose of naloxone. In general, if naloxone was required to reverse opioid-induced coma, it is safer to admit the patient for at least 6-12 hours of observation. Nalmefene is an opioid antagonist with a longer duration of effect (3-5 hours). ... /Opiates and opioids/

Decontamination. Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. ... /Opiates and opioids/

Enhanced elimination. Because of the very large volumes of distribution of the opioids and the availability of an effective antidotal treatment, there is no role for enhanced elimination procedures. /Opiates and opioids/

For more Antidote and Emergency Treatment (Complete) data for ETORPHINE (7 total), please visit the HSDB record page.

/DEA/ Schedule I shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. Unless specifically excepted or unless listed in another schedule, any of the following opium derivatives, its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation. Etorphine (except hydrochloride salt) (DEA Code Number: 9056) is included on this list.

/DEA/ Schedule II shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. Unless specifically excepted or unless listed in another schedule, any of the following substances whether produced directly or indirectly by extraction from substances of vegetable origin, or independently by means of chemical synthesis, or by a combination of extraction and chemical synthesis: (1) Opium and opiate, and any salt, compound, derivative, or preparation of opium or opiate excluding apomorphine, thebaine-derived butorphanol, dextrorphan, nalbuphine, nalmefene, naloxone, and naltrexone, and their respective salts, but including the following. Etorphine hydrochloride (DEA Code Number: 9059) is included on this list. /Etorphine hydrochloride/

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Etorphine hydrochloride is included on this list. /Etorphine hydrochloride/

Implantation or injectable dosage form new animal drugs. Etorphine hydrochloride injection. ... Conditions of use. (1) The drug is used for the immobilization of wild and exotic animals. (2) It is administered intramuscularly by hand syringe or syringe dart at a suitable dosage level depending upon the species. (3) Do not use the drug unless diprenorphine hydrochloride injection, veterinary, as provided for in section 522.723, is available for use in reversing the effects of etorphine hydrochloride injection, veterinary. (4) For use in wild or exotic animals only. Do not use in domestic food-producing animals. Do not use 30 days before, or during, the hunting season in free-ranging wild animals that might be used for food. (5) Federal law restricts this drug to use by or on the order of a licensed veterinarian. Distribution is restricted to veterinarians engaged in zoo and exotic animal practice, wildlife management programs, and researchers. /Etorphine Hydrochloride/

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Etorphine hydrochloride is included on this list. /Etorphine Hydrochloride/

This is a /DEA/ Schedule I controlled substance.

This is a /DEA/ Schedule II controlled substance. /Etorphine hydrochloride/

Therapeutic Category (VET): Used to immobilize large animals.

In many animals, etorphine has an analgesic potency as much as 1000 times that of morphine; in humans the ratio is 400:1. This drug is used in veterinary practice as a potent tranquilizing analgesic for large animals.

The drug is used for the immobilization of wild and exotic animals. /Etorphine Hydrochloride/

For veterinary use, etorphine is usually available in its commercial formulation as Immobilon, when in combination with acepromazine or methotrimeprazine.

Immobilon /Hydrochloride in combination with acepomazine/