2014 opioids eastern or ems conference
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  • In the terminology of the United States Drug Enforcement Administration, diversion is the use of prescription drugs for recreational purposes. The term comes from the "diverting" of the drugs from their original purposes. The Drug Enforcement Administration employs Diversion Investigators to address these problems.
  • Opioid receptors are a group of G protein-coupled receptors with opioids as ligands.[1][2][3] The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins andnociceptin. The opioid receptors are ~40% identical to somatostatin receptors (SSTRs). Opiate receptors are distributed widely in the brain, and are found in the spinal cord anddigestive tract.NOMENCLATURE OF OPIOID RECEPTORSThe nomenclature for the opioid receptors remains controversial. A 1996 review and proposal for a novel nomenclature [11] based on guidelines from NC-IUPHAR has not been widely accepted by the research community. The 1996 proposal recommended replacement of the terms, μ, δ, and κ with the terms OP3, OP1, and OP2, respectively. However, in the three years or more since the publication of this recommendation, almost all papers referring to opioid receptors have continued to use the well-established Greek symbol nomenclature. Many in the field have voiced their concerns that the original Greek symbol nomenclature is now so established that introduction of an alternative nomenclature is both inappropriate and confusing. It is argued that elimination of this well-established terminology will lead to impaired access to, and reduced citation of, the large body of research literature already published on the structure and properties of opioid receptors.THE OPIOID RECEPTOR FAMILYThe very well-defined pattern of structure-activity relationships for agonism and antagonism and the absolute stereochemistry requirements for opiate-like analgesic activity induced Beckett and Casy and others to propose receptors for opiate drugs long before the presence of endogenous ligands for these receptors was established [1,39]. An established pharmacological convention defined actions as 'opioid' when the actions resembled those produced by a prototypic opiate drug such as morphine and were antagonised by naloxone [26]. This convention continues to have wide acceptance. The term "opiate" is now used to describe drugs derived from the opium poppy Papaversomniferum including morphine and codeine, and other semisynthetic drugs derived from these alkaloids or from thebaine. The term is also used to describe the pharmacological properties of a wide range of synthetic drugs with similar pharmacology, but is not used to describe the endogenous peptides with affinity for the receptors activated by morphine and other opiate drugs. These are called "opioid" peptides since they resemble opiates in their affinities for one or more of the OP receptors. Following the convention established by NC-IUPHAR, the receptors themselves are also called "opioid", since they are the primary targets for the endogenous opioid peptides. Early studies established that the opioid peptide receptors are heterogeneous. Measures of antagonist affinities against various opioid agonists in different systems resulted in unambiguous evidence for heterogeneity of receptor types, and the eventual definition of the μ, δ and κ receptor types [26,30]. This pharmacological classification was later confirmed when three mRNAs for the three receptor types were cloned and characterized [7,12,21,47]. Subsequently, the structures of the gene for the μ receptor [32,45], and later for the δ- and κ- receptors were elucidated.The OP receptorsSeveral abbreviations for the opioid receptor family name have been used; with the simple abbreviation, OR (for opioid receptor), receiving widespread use after the cloning of the receptors in the early 1990s. Unfortunately, this abbreviation is inconsistent with NC-IUPHAR guidelines (the inclusion of 'R' leads too readily to the tautology 'OR receptor' - opioid receptor receptor). Cognisant of these concerns, NC-IUPHAR proposed the abbreviation, OP, as a convenient and unique descriptor for the opioid peptide receptor family [11]. We continue to support this proposal (Table 1).The NOP receptorThe discovery of the ORL1/LC132 receptor [4,33] has significantly complicated the nomenclature for this family of structurally related receptors. The only known endogenous ligand for this receptor has two names, nociceptin or orphanin FQ, given by the two groups that independently discovered the peptide [31,40]. Neither name is ideal for the peptide and neither name is accepted by all groups publishing in this area. Many authors abbreviate the peptide as N/OFQ; this abbreviation is used here. The structure of the N/OFQ receptor indicates that it has evolved as part of the OP receptor family. Sequence comparisons with μ, κ, and δ receptors, and with other similar G protein-coupled receptors (e.g. of the SOM receptor family), indicate that the N/OFQ receptor is more closely related to OP receptors than to other types of G protein-coupled receptors [3]. Additionally, agonists at N/OFQ receptors induce activation of the same set of transduction pathways activated by μ, κ, and δ receptors (see data tables), and the endogenous ligand, N/OFQ, shares considerable sequence homology with dynorphin A and, to a lesser extent, with the enkephalins. Thus, the N/OFQ receptor and its endogenous ligand are closely related in an evolutionary sense to the μ, κ, and δ receptors.Despite this evidence of evolutionary and functional homology, the N/OFQ receptor is not an opioid receptor from a pharmacological perspective. The effects of activation of this receptor are not obviously 'opiate-like' with respect to pain perception. The N/OFQ receptor has negligible affinity for naloxone and for most other antagonists at μ, κ or δ receptors. The N/OFQ receptor is, however, expressed in many functional systems in which endogenous opioids play a regulatory role. Although the functions of N/OFQ are not yet fully understood, regulatory functions for N/OFQ parallel to but not identical to those of the endogenous opioid peptides seem very probable. Despite these functional differences, the subcommittee finds the structural relationship between the N/OFQ receptor and μ, δ and κ receptors compelling. Given the evidence, we suggest this receptor be considered a non-opioid branch of the OP family of receptors and propose the abbreviation, NOP (Table 1).THE μ OR MOP RECEPTORThe μ receptor was originally defined and characterised pharmacologically by Martin, Kosterlitz and their colleagues on the basis of its high affinity for, and sensitivity to, morphine [26,30]. The endogenous opioids, [Met5]-enkephalin, [Leu5]-enkephalin, extended forms of [Met5]-enkephalin including metorphamide and BAM-18, β-endorphin, and truncated forms of dynorphin (e.g. dynorphin-(1-9) and shorter dynorphin peptides), also have affinities for μ receptors that are consistent with a possible role for each of these peptides as natural ligands for this receptor type, although these endogenous peptides are not selective for μ receptors. Two putative natural ligands, endomorphin-1 and -2, that appear to mediate their effects exclusively through the μ opioid receptor, also have been reported to be present in brain [49] although no gene, precursor protein, or other mechanism for their endogenous synthesis has been identified.Potent and selective agonists and antagonists for the μ receptor have been developed and these have greatly helped in the characterization of the receptors [27,37]. The μ receptors are distributed throughout the neuraxis. The highest μ receptor densities are found in the thalamus, caudate putamen, neocortex, nucleus accumbens, amygdala, interpeduncular complex, and inferior and superior colliculi [29]. The μ receptors, as well as δ and κ receptors, are also present in the superficial layers of the dorsal horn of spinal cord [2]. A moderate density of μ receptors is found in periaqueductal gray and raphé nuclei [16]. These brain regions have a well-established role in pain and analgesia. Other physiological functions regulated by μ receptors include respiratory and cardiovascular functions, intestinal transit, feeding, mood, thermoregulation, hormone secretion and immune functions [11]. Recent studies have demonstrated that μ receptor distribution in mouse brain is similar to that in rat, with some notable quantitative differences. For example, μ receptors are higher in the hypothalamus in mouse than in rat, but the opposite is true in the hippocampus [22]. THE δ OR DOP RECEPTORThe δ opioid receptor was defined using the mouse vas deferens preparation and the enkephalins are generally considered the preferred endogenous ligands [26]. Several agonists and antagonists with high affinity and selectivity at δ receptors have been synthesised [41]. The δ receptors are discretely distributed in the central nervous system (CNS), with a prominent gradient of receptor density from high levels in forebrain structures to relatively low levels in most hindbrain regions. The highest densities are found in olfactory bulb, neocortex, caudate putamen, nucleus accumbens, and amygdala [29]. The thalamus and hypothalamus have a moderate density of δ receptors; in more caudal regions the interpeduncular nucleus and pontine nuclei show high binding in rat, but much lower levels in mouse [22]. In the spinal cord, δ receptors are present in dorsal horn where they play a role in mediating the analgesic effects of δ agonists. The functional roles of δ receptors are less clearly established than for μ receptors; in addition to analgesia, δ receptors may have a role in gastrointestinal motility, mood and behaviour as well as in cardiovascular regulation [40].THE κ OR KOP RECEPTORThe κ opioid receptor was first proposed on the basis of in vivo studies in dogs with ketocyclazocine and related drugs [30]. Subsequent studies have confirmed the presence of this receptor type in other species including guinea pig, a species that was preferred for many of the early studies on kappa opioid receptors [6]. Dynorphins A and B and α-neoendorphin appear to be the endogenous ligands for opioid κ receptors [13], although shorter peptides derived from prodynorphin have comparable affinities at μ and κ receptors. Synthetic compounds (both agonists and antagonists) with selective activity at κ receptors are available (see data tables and [41]). The κ receptors are located predominantly in the cerebral cortex, nucleus accumbens, claustrum and hypothalamus of rat and mouse [22,29], and have been implicated in the regulation of nociception, diuresis, feeding, neuroendocrine and immune system functions [11].THE RECEPTOR FOR N/OFQ: THE NOP RECEPTORThe NOP receptor was originally identified by homology cloning as an orphan opioid receptor like clone, ORL1 or LY132 [4,33]. Natural and synthetic opiate drugs, and the opioid receptor antagonists, naloxone, naltrexone, naltrindole and nor-binaltorphimine are also without significant affinity. Non-peptide drugs related to etorphine and diprenorphine have very low but measurable affinity for the NOP receptor. NOP receptors are present at relatively high density in selected regions of rat cortex, anterior olfactory nucleus, lateral septum, ventral forebrain, hippocampus, hypothalamus, amygdala, substantianigra, ventral tegmental area, locus coeruleus, brain stem nuclei and in the dorsal horn of spinal cord [35]. They are also found in immune system cells. This diffuse distribution suggests a role for N/OFQ in many functions including motor and aggressive behaviours, reinforcement and reward, nociception, the stress response, and control of autonomic and immune functions.OTHER RECEPTORSIn the 1976 studies of Martin et al. [30], which first offered evidence of the heterogeneity of opioid receptors, another receptor type, the σ (sigma; for SKF10047) receptor was also proposed as a form of opioid receptor. Subsequent studies have shown that naloxone does not act as an antagonist at this receptor [28]. A sigma receptor that does not display the seven transmembrane domain (7TM) structure typical of G protein-coupled receptors has recently been cloned [15] and shown to be expressed in the nervous system [42]. There is also evidence for heterogeneity among sigma receptors. However, the sigma receptors defined to date are no longer regarded as members of the OP receptor family.1. Beckett AH, Casy AF. (1954) Synthetic analgesics: stereochemical considerations. J. Pharm. Pharmacol., 6: 986-999. [PMID:13212680]2. Besse D, Lombard MC, Zajac JM, Roques BP, Besson JM. (1990) Pre- and postsynaptic distribution of mu, delta and kappa opioid receptors in the superficial layers of the cervical dorsal horn of the rat spinal cord. Brain Res., 521: 15-22. [PMID:2169958]3. Birgul N, Weise C, Kreienkampf H-J, Richter D. (1999) Reverse Physiology in drosophila: identification of a novel allatostatin-like neuropeptide and its cognate receptor structurally related to the mammalian somatostatin/galanin/opioid receptor family. EMBO J., 18: 5892-5900. [PMID:10545101]4. Bunzow JR, Saez C, Mortrud M, Bouvier C, Williams JT, Low M, Grandy DK. (1994) Molecular cloning and tissue distribution of a putative member of the rat opioid receptor gene family that is not μ, δ or κ opioid receptor type. FEBS Lett., 347: 284-288. [PMID:8034019]5. Calo G, Guerrini R, Bigoni R, Rizzi A, Marzola G, Okawa H, Bianchi C, Lambert DG, Salvadori S, Regoli D. (2000) Characterization of [Nphe1]nociceptin(1-13)NH2, a new selective nociceptin receptor antagonist. Br. J. Pharmacol., 129: 1183-1193. [PMID:10725267]6. Chavkin C, James IF, Goldstein A. (1982) Dynorphin is a specific endogenous ligand of the kappa opioid receptor. Science, 215: 413-415. [PMID:6120570]7. Chen Y, Mestek A, Liu J, Hurley JA, Yu L. (1993) Molecular cloning and expression of a mu-opioid receptor from rat brain. Mol. Pharmacol., 44: 8-12. [PMID:8393525]8. Connor M, Vaughan CW, Allen RS, Christie MJ. (1999) Nociceptin, Phe1ψ-nociceptin113, nocistatin and prepronociceptin154181effects on calcium channel currents and a potassium current in rat locus coeruleusin vitro. Br. J. Pharmacol., 128: 1779-1787. [PMID:10588934]9. Cox BM, Goldstein A, Li CH. (1976) Opioid activity of a peptide,β-lipotropin-(61-91), derived fromβ-lipotropin. Proc. Natl. Acad. Sci. U.S.A., 73: 1821-1823. [PMID:1064855]10. Cvejic S, Devi L. (1997) Dimerization of theδopioid receptor: implication for a role in receptor internalization. J. Biol. Chem., 272: 26959-26964. [PMID:9341132]11. Dhawan BN, Cesselin F, Raghubir R, Reisine T, Bradley PB, Portoghese PS, Hamon M. (1996) International Union of Pharmacology. XII. Classification for opioid receptors. Pharmacol. Rev., 48: 567-592. [PMID:8981566]12. 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U.S.A., 70: 1947-1949. [PMID:4516196]44. Terenius L. (1973) Stereospecific interaction between narcotic analgesics and a synaptic plasma membrane fraction of rat cerebral cortex. ActaPharmacol. Toxicol., 32: 317-320. [PMID:4801733]45. Wang JB, Johnson PS, Persico AM, Hawkins AL, Griffin CA, Uhl GR. (1994) Human μ opiate receptor cDNA and genomic clones, pharmacologic characterization and chromosomal assignment. FEBS Lett., 338: 217-222. [PMID:7905839]46. Wuster M, Schulz R, Herz A. (1979) Specificity of opioids towards the mu-,delta-and epsilon-opiate receptors. Neurosci. Lett., 15: 193-198. [PMID:231238]47. Yasuda K, Raynor K, Kong H, Breder CD, Takeda J, Reisine T, Bell GI. (1993) Cloning and functional comparison of κ and δ opioid receptors from mouse brain. Proc. Natl. Acad. Sci. U.S.A., 90: 6736-6740. [PMID:8393575]48. Zachariou V, Georgescu D, Sanchez N, Rahman Z, DiLeone R, Berton O, Neve RL, Sim-Selley LJ, Selley DE, Gold SJ, Nestler EJ. (2003) Essential role for RGS9 in opiate action. ProcNatlAcadSci U S A, 100: 13656-13661. [PMID:14595021]49. Zadina JE, Hackler L, Ge LJ, Kastin AB. (1997) A potent and selective endogenous agonist for the μ-opiate receptor. Nature, 386: 499-502. [PMID:9087409]50. Zagon IS, Gibo DM, McLaughlin PJ. (1991) Zeta, a growth-related opioid receptor in developing rat cerebellum: identification and characterization.Brain Res., 551: 28-35. [PMID:1655161]51. Zagon IS, Verderame MDF, Allen SS, McLaughlin PJ. (1999) Cloning, sequencing, expression and function of a cDNA encoding a receptor for the opioid growth factor, [Met(5)]enkephalin. Brain Res., 849: 147-154. [PMID:10592296]52. Zaratin PF, Petrone G, Sbacchi M, Garnier M, Fossati C, Petrillo P, Ronzoni S, Giardina GA, Scheideler MA. (2004) Modification of nociception and morphine tolerance by the selective opiate receptor-like orphan receptor antagonist (-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol (SB-612111). J PharmacolExpTher, 308: 454-461. [PMID:14593080]To cite this family introduction, please use the following:Brian M. Cox, Anna Borsodi, GirolamoCaló, Charles Chavkin, MacDonald J. Christie, Olivier Civelli, Lakshmi A. Devi, Christopher Evans, Graeme Henderson, Volker Höllt, Brigitte Kieffer, Ian Kitchen, Mary-Jeanne Kreek, Lee-Yuan Liu-Chen, Jean-Claude Meunier, Philip S. Portoghese, Toni S. Shippenberg, Eric J. Simon, Lawrence Toll, John R. Traynor, Hiroshi Ueda, Yung H. Wong.Opioid receptors, introduction. Last modified on 13/10/2009. Accessed on 06/02/2014. 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  • There are four major subtypes of opioid receptors:[12]ReceptorSubtypesLocation[13][14]Function[13][14]delta (δ)DOROP1 (I)δ1, δ2brainpontine nucleiamygdalaolfactory bulbsdeep cortexperipheral sensory neuronsanalgesiaantidepressant effectsConvulsant effectsphysical dependencePerhaps of mu-opioid receptor-mediated respiratory depressionkappa (κ)KOROP2 (I)κ1, κ2, κ3brainhypothalamusperiaqueductal grayclaustrumspinal cordsubstantiagelatinosaperipheral sensory neuronsanalgesiaanticonvulsant effectsdissociative & deliriant effectsDiuresisdysphoriamiosisneuroprotectionsedationmu (μ)MOROP3 (I)μ1, μ2, μ3braincortex (laminae III and IV)thalamusstriosomesperiaqueductal grayrostral ventromedial medullaspinal cordsubstantiagelatinosaperipheral sensory neuronsintestinal tractμ1:analgesiaphysical dependenceμ2:respiratory depressionmiosiseuphoriareduced GI motilityphysical dependenceμ3:possible vasodilationNociceptin receptorNOPOP4ORL1braincortexamygdalahippocampusseptal nucleihabenulahypothalamusspinal cordanxietydepressionappetitedevelopment of tolerance to μ agonists
  • Morphine (INN) (/ˈmɔrfiːn/) (sold under nearly a hundred trade names) is an opioid analgesic drug, a recreational drug, and the main psychoactive chemical in opium. In clinical medicine, morphine is regarded as the gold standard, or benchmark, of analgesics used to relieve intense pain and suffering.[2] Like other opioids, such as oxycodone, hydromorphone, and diacetylmorphine (heroin), morphine acts directly on the central nervous system (CNS) to relieve pain.Morphine has a high potential for addiction; tolerance and psychological dependence develop rapidly, although physiologicaldependence may take several months to develop. Tolerance to respiratory depression and euphoria develops more rapidly than tolerance to analgesia, and many chronic pain patients are therefore maintained on a stable dose for years. However, its effects can also reverse fairly rapidly, worsening pain through hyperalgesia.Morphine is the most abundant opiate found in opium, the dried latex from unripe seedpods of Papaversomniferum (the opium poppy). Morphine was the first active ingredient purified from a plant source. It is one of at least fifty alkaloids of several different types present in opium, poppy straw concentrate, and other poppy derivatives. The primary source of morphine is chemical extraction from opium.Morphine was first isolated in 1804 by Friedrich Sertürner, which is generally believed to be the first ever isolation of a natural plantalkaloid in history. Sertürner began distributing it in 1817, and Merck began marketing it commercially in 1827. At the time, Merck was a single small chemists' shop. Morphine was more widely used after the invention of the hypodermic needle in 1857. Sertürner originally named the substance morphium after the Greek god of dreams, Morpheus (Greek: Μορφεύς), for its tendency to cause sleep.[3]
  • Hydrocodone is a semi-synthetic opioid derived from codeine. Hydrocodone is used orally as a narcoticanalgesic and antitussive (cough medicine), often in combination with paracetamol (acetaminophen) or ibuprofen.[1] Hydrocodone is prescribed predominantly in the United States. The International Narcotics Control Board reported 99% of the worldwide supply in 2007 was consumed in the United States.[2]
  •  The bioavailability of oral administration of oxycodone averages 60–87%, with rectal administration yielding the same results; intranasal varies between individuals with a mean of 46%
  • Hydromorphone, a more common synonym for dihydromorphinone (not to be confused by dihydromorphine, which is a different derivative of the morphine family), commonly a hydrochloride (brand names Palladone, Dilaudid, and numerous others) is a very potent centrally acting analgesic drug of the opioid class. It is a derivative of morphine; to be specific, a hydrogenated ketone thereof, and it can be said that hydromorphone is to morphine as hydrocodone is to codeine and, therefore, a semi-synthetic drug. It is in medical terms an opioid analgesic and in legal terms a narcotic. Hydromorphone is commonly used in the hospital setting, mostly intravenously (IV) because its bioavailability orally, rectally, and intranasally is very low. Sublingual administration is usually superior to swallowing for bioavailability and effects.Hydromorphone is much more soluble in water than morphine and therefore hydromorphone solutions can be produced to deliver the drug in a smaller volume of water. The hydrochloride salt is soluble in three parts of water whereas a gramme of morphine hydrochloride dissolves in 16 ml of water; for all common purposes the pure powder for hospital use can be used to produce solutions of virtually arbitrary concentration. When the powder has appeared on the street, this very small volume of powder needed for a dose means that overdoses are likely for those who mistake it for heroin or other powdered narcotics, especially those that have been cut or stepped on already.Very small quantities of hydromorphone are detected in assays of opium on rare occasions; it appears to be produced by the plant under circumstances and by processes which are not understood at this time and may include the action of bacteria. A similar process and/or other metabolic processes in the plant may very well be responsible for the very low quantities of hydrocodone also found on rare occasions in opium and alkaloid mixtures derivedherefrom; dihydrocodeine, oxymorphol, oxycodone, oxymorphone, metopon and possibly other derivatives of morphine and/or hydromorphone also are found in trace amounts in opium.Hydromorphone, a semi-synthetic μ-opioid agonist, is a hydrogenated ketone of morphine and shares the pharmacologic properties typical of opioid analgesics. Hydromorphone and related opioids produce their major effects on the central nervous system andgastrointestinal tract. These include analgesia, drowsiness, mental clouding, changes in mood, euphoria or dysphoria, respiratory depression, cough suppression, decreased gastrointestinal motility, nausea, vomiting, increased cerebrospinal fluid pressure, increasedbiliary pressure, pinpoint constriction of the pupils, increased parasympathetic activity and transient hyperglycemia.The chemical modification of the morphine molecule to produce hydromorphone results in a drug with higher lipid solubility and ability to cross the blood–brain barrier and, therefore, more rapid and complete central nervous system penetration. The results show hydromorphone to be somewhat faster-acting and about eight to ten times more potent than morphine and about three to five times more potent than heroin on a per milligram basis.[citation needed] The effective morphine to hydromorphone conversion ratio can vary from patient to patient by a significant amount with relative levels of some liver enzymes being the main cause; the normal human range appears to be of 4-8:1. It is not uncommon, for example, for the 2-mg tablet to have an effect similar to that of 30 mg of morphine sulfate or a similar morphine preparation, whereas other patients may need 8 mg for similar effect.Patients with kidney problems must exercise caution when dosing hydromorphone. In those with renal impairment, the half-life of hydromorphone can increase to as much as 40 hours. This could cause an excess buildup of the drug in the body, and result in fatality. The typical half-life of intravenous hydromorphone is 2.3 hours.[4] Peak plasma levels usually occur between 30 and 60 minutes after oral dosing.[5]
  • Despite being a moreLike other lipid-soluble drugs, the pharmacodynamics of fentanyl are poorly understood. The manufacturers acknowledge that there are no data on the pharmacodynamics of fentanyl in elderly, cachectic, or debilitated patients, frequently the type of patient for whom transdermal fentanyl is being used. This may explain the increasing number of reports ofrespiratory depression events since the late 1970s.[19][20][21][22][23][24][25] In 2006 the U.S. Food and Drug Administration (FDA) began investigating several respiratory deaths, but doctors in the United Kingdom were not warned of the risks with fentanyl until September 2008.[26] The FDA reported in April 2012 that young children had died or become seriously ill from accidental exposure to a fentanyl skin patch.[27]The precise reason for sudden respiratory depression is unclear, but there are several hypotheses:Saturation of the body fat compartment in patients with rapid and profound body fat loss (patients with cancer, cardiac or infection-induced cachexia can lose 80% of their body fat).Early carbon dioxide retention causing cutaneous vasodilatation (releasing more fentanyl), together with acidosis, which reduces protein binding of fentanyl, releasing yet more fentanyl.Reduced sedation, losing a useful early warning sign of opioid toxicity and resulting in levels closer to respiratory-depressant levels. potent analgesic, fentanyl tends to induce less nausea, as well as less histamine-mediated itching, in relation to morphine.[“Stone Chest Syndrome”
  • Krokodil is a home cooked, desomorphine-based mixture of codeine and other ingredients such as gasoline, paint thinner, hydrochloric acid, iodine and red phosphorous scraped from the striking pads on matchboxes that is injected directly into the vein. It gets its name from the rough, scaly, alligator-like texture of the user’s skin.Most damage results from Vascular /damage and subsequent tissue necrosis. Blood vessels burst, the surrounding tissue dies. Gangrene sets in and blackened flesh falls from the bone. The life expectancy of a krokodil addict is one to three years (IN Russia)
  • It is important to mention that other causes for altered mental status should be ruled out. Use ofa glucometer, complete assessment, scene assessment, and detailed interview of any bystandersshould be performed before being lead .down a primrose path.. A common mnemonic toremember differential diagnosis is A E I O U, T I P S:• A - alcohol, alcohol withdrawal, and anoxia• E . epilepsy and other neurological disorders• I - insulin (Hyper or Hypo-glycemia)• O- overdose (Poly-pharmacy?)• U - uremia, underdose of current medications.• T- trauma• I - infection• P - psychiatric• S . stroke, shock states
  • NarcanOpioid Antagonists drugs have long been considered the standard of care for opioid overdoses.The two most common are naloxone (Narcan) and nalmefene (Revex). Both are pure opioidantagonist with no agonist properties. Nalmefene has a significantly longer half-life thannaloxone, but is also more expensive. Therefore the overwhelming number of EMS systems andER.s use naloxone in the emergent setting. While namefene was originally designed for opiatetoxicity, it has been used with significant success in the chronic treatment of alcoholism andother addictions., Because of its almost exclusive use in EMS, this article will primarily focuson naloxone.Naloxone is a pure opioid antagonist with no appreciable agonist properties. It, like morphine,has its strongest affinity for mu receptors, although it inhibits kappa and delta receptors as well.It has no effect on sigma receptors. It competitively binds to these receptors, meaning it will.kick off. opioids with a weaker bond. It is commonly believed that some of the syntheticopiates (such as fentanyl, methadone, oxycodone, and dilauded) have a stronger bond with theirrespective receptor sites and may take higher than normal amounts of naloxone to have anappreciable effect. Naloxone will typically last 30-45 minutes, after which the patient may resedate.Naloxone can be administered intravenously (bolus or infusion), subcutaneously,intramuscularly, sublingual and buccally, intranasally, and via an endotracheal tube (althoughthis no longer encouraged).It should be noted that a response to (or failure to respond) naloxone is not considered a reliablediagnostic tool in determining if a patient has consumed opoiods.
  • Resuscitation. 2010 Jan;81(1):42-6. doi: 10.1016/j.resuscitation.2009.09.016. Epub 2009 Nov 13.Naloxone in cardiac arrest with suspected opioid overdoses.Saybolt MD1, Alter SM, Dos Santos F, Calello DP, Rynn KO, Nelson DA, Merlin MA.Author informationAbstractINTRODUCTION:Naloxone's use in cardiac arrest has been of recent interest, stimulated by conflicting results in both human case reports and animal studies demonstrating antiarrhythmic and positive ionotropic effects. We hypothesized that naloxone administration during cardiac arrest, in suspected opioid overdosed patients, is associated with a change in cardiac rhythm.METHODS:From a database of 32,544 advanced life support (ALS) emergency medical dispatches between January 2003 and December 2007, a retrospective chart review was completed of patients receiving naloxone in cardiac arrest. Forty-two patients in non-traumatic cardiac arrest were identified. Each patient received naloxone because of suspicion by a paramedic of acute opioid use.RESULTS:Fifteen of the 36 (42%) (95% confidence interval [CI]: 26-58) patients in cardiac arrest who received naloxone in the pre-hospital setting had an improvement in electrocardiogram (EKG) rhythm. Of the participants who responded to naloxone, 47% (95% CI: 21-72) (19% [95% CI: 7-32] of all study subjects) demonstrated EKG rhythm changes immediately following the administration of naloxone.DISCUSSION:Although we cannot support the routine use of naloxone during cardiac arrest, we recommend its administration with any suspicion of opioid use. Due to low rates of return of spontaneous circulation and survival during cardiac arrest, any potential intervention leading to rhythm improvement is a reasonable treatment modality.Copyright 2009 Elsevier Ireland Ltd. All rights reserved.PMID: 19913979 [PubMed - indexed for MEDLINE]
  • Acute morphine along with and other opioid withdrawal proceeds through a number of stages. Other opioids differ in the intensity and length of each, and weak opioids and mixed agonist-antagonists may have acute withdrawal syndromes that do not reach the highest level. As commonly cited[by whom?], they are:Stage I: Six to fourteen hours after last dose: Drug craving, anxiety, irritability, perspiration, and mild to moderate dysphoria.Stage II: Fourteen to eighteen hours after last dose: Yawning, heavy perspiration, mild depression, lacrimation, crying, running nose, dysphoria, also intensification of the above symptoms. "yen sleep" (a waking trance-like state)[clarification needed]Stage III: Sixteen to twenty-four hours after last dose: Rhinorrhea (runny nose) and increase in other of the above, dilated pupils, piloerection (goose bumps - giving the name 'cold turkey'), muscle twitches, hot flashes, cold flashes, aching bones and muscles, loss of appetite and the beginning of intestinal cramping.Stage IV: Twenty-four to thirty-six hours after last dose: Increase in all of the above including severe cramping and involuntary leg movements ("kicking the habit" also calledrestless leg syndrome), loose stool, insomnia, elevation of blood pressure, moderate elevation in body temperature, increase in frequency of breathing and tidal volume,tachycardia (elevated pulse), restlessness, nauseaStage V: Thirty-six to seventy-two hours after last dose: Increase in the above, fetal position, vomiting, free and frequent liquid diarrhea, which sometimes can accelerate the time of passage of food from mouth to out of system to an hour or less, weight loss of two to five kilos per 24 hours, increased white cell count and other blood changes.Stage VI: After completion of above: Recovery of appetite and normal bowel function, beginning of transition to post-acute and chronic symptoms that are mainly psychological but that may also include increased sensitivity to pain, hypertension, colitis or other gastrointestinal afflictions related to motility, and problems with weight control in either direction.
  • Manfredi PL, Ribeiro S, Chandler SW, Payne R.. "Inappropriate use of naloxone in cancerpatients with pain.." J Pain Symptom Manage. 11(2)(1996): 131-134.Schwartz JA, Koenigsberg MD, "Naloxone-induced pulmonary edema." Ann Emerg Med 11(1987): 1294-6.Osterwalder JJ. Naloxone for intoxications with intravenous heroin and heroin mixtures:harmless or hazardous? A prospective clinical study. J ToxicolClinToxicol 34 (1996): 409-416Cuss FM, Colaço CB, & Baron JH Cardiac arrest after reversal of effects of opiates withnaloxone. Br Med J, 288(1984): 363-364
  • A naloxone infusion may be useful over prolonged patient contact times to reduce the incidenceof adverse effects, re-sedation, and maintain naloxone.s effects though a more evenadministration than a simple re-bolus. Infusions have also proved useful with the more potentopioids. There are several naloxone infusions recommended, however many of these are notindividualized to the patient. There is a recommended infusion (presented below) that isrelatively simple, and individualized to the patient. This infusion is not common in EMSsystems, but is relatively easy to prepare.Infusion**:• Give the loading dose of naloxone according to protocol. Repeat as protocol allowsuntil desired effect.• Mix the total effective dose of naloxone in 100 cc. Infuse over 1 hour (approx90 gtt/min or 1.5 drops/sec)• Rebolus naloxone 15-20 minutes at half the effective dose.• Monitor closely for over sedation and titrate infusion for effect.
  • Opioid withdrawal in pregnant patients. There is good evidence that the fetus may be moresusceptible to withdrawal symptoms than the mother. In the mother, the initial signs of opioidwithdrawal progress to increasingly painful physical symptoms (including uterine contractions,as noted above). There is some evidence that the use of opioid antagonist in an opioiddependant pregnant patient may result in intera-uterine death of the fetus due to acutewithdrawal. Therefore the use of naloxone should be approached with caution in thepregnant patient, and only used after a thorough risk-benefit assessment. It should only beused on those with severe respiratory depression. When used, the smallest effective dosepossible should be administered.
  • ..If a cancer patient treated with opioids is experiencing clinically significant respiratorydepression, The immediate administration of naloxone is an appropriate therapeutic anddiagnostic modality.However, the more common clinical presentation is that of a sedated and altered patientwithout sign of respiratory depression, who is taking opioids, but has other potential causes forthe abnormal mental status. The rush to make a rapid diagnosis of opioid overdose should betempered by the concern for causing severe withdrawal symptoms and pain...It is generally unwise to treat these patients with am opioid antagonist unless life threateningrespiratory depression is a reasonable concern.."Inappropriate use of naloxone in cancer patients with pain.." J Pain Symptom Manage. 11(2)(1996): 131-134. EMS should consider diluting 0.4-0.5 mg of naloxone in 10 cc, and slowly administering 0.5 ccboluses (0.025 mg)* every 2 minutes until desired effects are seen.

2014 opioids eastern or ems conference 2014 opioids eastern or ems conference Presentation Transcript

  • Opioids: Old Friends and New EASTERN OREGON EMS CONFERENCE
  • "Among the remedies which it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium." -THOMAS SYDENHAM (1624 -1689)
  • Objectives Discuss the basic pharmacology of opioids Discuss the epidemiology of illicit opioid use Describe common treatment modalities Describe treatment variations for uncommon presentations Describe common pitfalls in the emergency care of opioid overdoses
  • Who am I? Steve Cole croaker260@gmail.com Ada County Paramedics for 15 years EMS for 23 (and counting) years
  • Disclaimer I have no financial conflicts of interest This presentation is not a substitute for basic clinical judgment. Follow your protocols!
  • Educatingstarted….. Before we get Yourself…. Doing your own research… Knowing where to look Staying up to date
  • EMS Textbooks SUCK!
  • http://www.samhsa.gov/data/DAWN.aspx Hundreds of Metropolitan/Suburban Hospitals and Coroners/ME offices across the US. A DAWN case is any ED visit or death related to recent drug use. The criteria for inclusion in DAWN are intentionally broad and simple, with few exceptions Thousands of drugs of all types are included in DAWN. These include: ◦ ◦ ◦ ◦ ◦ ◦ Illegal drugs of abuse; Prescription and over-the-counter medications; Dietary supplements; Non-pharmaceutical inhalants; Alcohol in combination with other drugs (adults and children) Alcohol alone (age < 21).
  • Epidemiology Opioids of all types are a significant cause of ED visit (approximately 35%) ◦ ◦ ◦ ◦ Heroin accounts for approximately 9% of opioid related visits Heroin has resulted in a 67% increase of ED related visits from 2004 though 2011 Illicit use of pharmaceutical opioids accounts for about 26% Oxycodone containing products had a 158% increase from 2004 through 2011 Source: 2011 DAWN statistics
  • What is Diversion? Diversion is the use of prescribed substances (Opioids are just one drug class that is often diverted) for illicit or recreational use. How are Drugs Diverted? ◦ ◦ ◦ ◦ ◦ ◦ Hospice/Home Health Care Visitors Family Health Care providers Public Safety Workers Professional Patients.
  • Opioids: What are we talking about? Illicit vs. Legal? Synthetic vs. naturally occurring opioids? Clinical vs Recreational use?
  • The Opium Poppy Use/Abuse goes back At least to 4000 BC The poppy contains numerous opioid alkaloids The most common Opioid Alkaloids are: ◦ ◦ ◦ ◦ Morphine (1-10%) Codeine Thebaine Oripavine
  • Opioid Receptors Source: http://www.iuphar-db.org/DATABASE/FamilyIntroductionForward?familyId=50
  • Opioid Receptors (Continued) μ (MU) receptors: ◦ Located in the CNS (Brain/Spinal Cord) AND the digestive tract. ◦ CNS depression ◦ Analgesia ◦ ↓ GI Motility (Constipation) ◦ ↑ Euphoria ⱪ (Kappa) Receptors: ◦ Located in CNS ◦ Analgesia, Dissascoiation ◦ DYSphoria,
  • What is a Toxidrome? syn·drome (ⱪ sinⱪdrōm /) tox·i·drome (ⱪ täksiⱪdrōm /) noun noun 1. a group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms. 1. a group of signs and symptoms constituting the basis for a diagnosis of poisoning. In other words: A toxidrome is a “syndrome” that specifically relates to a specific toxin Be cautious, many syndromes/toxidromes are subtle and overlap their symptoms. Thorough assessment is essential
  • Opioid Toxidrome The Opiate Toxidrome consists of: ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ Altered mental status Miosis* Unresponsiveness Shallow respirations Slow respiratory rate Decreased bowel sounds Hypothermia Hypotension* * these symptoms are very subjective, and may not be present in polypharmacy overdoses. KEY POINT: Miosis and Hypotension are not definitive for ruling in or ruling out a opioid overdose.
  • Methods of use: Shooting Skin Popping Muscle Popping Chasing the dragon Freebasing Dirty Hit Tea ◦ With Grapefruit Juice Tincture ◦ Laudanum and Perigoric
  • So why do people overdose? IV opioid use Poly-pharmacy Overdose Returning to opioid use from abstinence ◦ Jail? ◦ Detox? The Weekend Warrior Using opioids alone New supply of Drug
  • Types of Opioids
  • Opium The raw Latex (sap) of the poppy plant Source: http://www.aaronhuey.com/#/editorial-archive/afghanistan-drugwar/Opium_032
  • Morphine Naturally occurring in raw opium ◦ First isolated in 1804 ◦ First IV opioid in 1857 The gold standard by which other opioids are judged Potent Respiratory / CNS depressant “Equipotent” euphoria to Heroin, though slower onset. Intermediate Duration (3-6 hours) Many “ER” (extended release) formulations
  • Codeine, Hydrocodone Codeine naturally occurs in the poppy plant Hydrocodone is a semi-synthetic derivative of codeine. Often taken as a oral tablet or an elixir ◦ Often co-ingested with an NSAID (such as APAP, Motrin or ASA) ◦ Norco, Vicodin
  • Heroin Black Tar China White Speed Ball Homicide, Buick, super Buick, twilight sleep
  • Old verses New
  • Oxycontin/Oxycodone Oxycodone is Another semi-synthetic Derived from Thebaine Roughly twice as potent as Morphine Also More potent than Hydrocodone Most often available in Tablet form ◦ Like Hydrocodone, Often co-ingested with an NSAID (such as APAP, Morin or ASA) ◦ Percocet Extended release versions known as Oxycodone ◦ “Oxy”
  • Oxycontin /Oxycodone Time released capsules, some may have more than 100 mg Often crushed and snorted, eliminating the “time release” May be crushed, diluted, and injected like traditional heroin Becoming much more common
  • Methadone Synthetic opioid Comparable with Oxycontin and Dilaudid. Longer acting than most other Analgesic ◦ Typically 4-8 hours Like other prescription opiates, WIDELY Available One study showed of 18 methadone related deaths: ◦ Less than ½ were prescribed methadone ◦ Only three were prescribed methadone through a methadone tx program
  • Dilaudid Hydromorphone Semi-Synthetic Opioid ◦ Technically found in small quantities in the poppy plant ◦ Synthesized in 1924 directly from Morphine Very potent analgesic Very Euphoric Very potent CNS/ Respiratory Depressant Faster acting than Morphine (similar to Heroin for rate of onset) ◦ 10 times more potent than Morphine ◦ 5 times more potent than Heroin
  • Fentanyl Citrate Very common medically, Increasingly common recreational abuse ◦ Difficult to detect on standard drug assays ◦ Purely Synthetic Potent Analgesic ◦ 80-100 times potency of Morphine Low Euphoric properties Moderate respiratory/CNS depressant Both pharmaceutical and illicitly prepared Rapid Onset, short Duration Comes in multiple formulations ◦ Typically IV/IM ◦ Oral (lollypops) ◦ Transdermal (Duragesic)
  • Duragesic Fentanyl Citrate Synthetic opioid Transdermal Absorption Used in chronic pain patients 100 times the potency of morphine Commonly Used for chronic pain Easily Acquired Easily abused
  • Duragesic- methods of abuse Almost 70 fold increase in use from 1995-2002 (DAWN) Rate of use is increasing. Street price between $10-100/PATCH Methods of abuse ◦ Topical ◦ Injected – increased Mortality (Woodall et al, 2007) ◦ Chewed Oral Conversion ◦ ◦ ◦ ◦ ◦ ◦ Up to 50% may be lost in conversion, so it is often frozen first. Preservatives may cause liver problems 25 ug/hr = 2.5 mg avail 50 ug/hr = 5 mg avail 75 ug/hr = 7.5 mg avail 100 ug/hr = 10 mg avail
  • Krocodil
  • Krocodil Desomorphine ◦ ◦ ◦ ◦ Synthetic Opioid , first described in 1932 Clandestinely produced and derived from Codeine in a method similar to Methamphetamine production (Relatively) new trend in Eastern Europe/Western Asia Since early 2000’s Incidence is more directly related to Heroin use than Prescription opioid use Important note: Huge difference in pharmaceutical Desomophine and illicit “Krocodil” ◦ Actual Krocodil is only 5-20% opioid Fast Acting (similar to Heroin) Short Duration Strong analgesic, Strong Euphoric ◦ 8-10 times analgesia of Morphine, no data on other properties Potent sedative but Low respiratory depressant
  • Krocodil in the US? Much hype, few questions Production and availability directly tied to availability of pre-cursers (Codiene) ◦ Typically $30-50 of product will render about $500 of end product (European/Western Asia Reports) Predictions (also known as educated guesses): ◦ ◦ ◦ ◦ ◦ Much hype, most likely will fizzle out Predominantly an IV drug market Will be misbranded as heroin and mixed with heroin Will be most common in the users of Black Tar and Low end heroin out of Mexico We will not see the extensive morbidity and mortality patterns seen in the former USSR due to the differences in health care and social safety nets as well as differences in Opioid use/abuse demographics ◦ Will still see some (rare) dramatic cases in the homeless/forgotten populations
  • Much Hype, Little actual Bite to this Krocodil
  • Poly-Opioid Mixes Increasingly common practice of mixing one type of opioid (typically Heroin) with another , more potent opioid. ◦ This increases the “potency” (increasing profit) without increasing the “purity” (i.e. the cost) ◦ Retains the eurphoric effects of some opioids while getting the heavier nod of others.
  • Treatment
  • REMEMBER: Opioid overdoses are AMS calls first, opioid overdoses last • A - alcohol, alcohol withdrawal, and anoxia • E . epilepsy and other neurological disorders • I - insulin (Hyper or Hypo-glycemia) • O- overdose (Poly-pharmacy?) • U - uremia, underdose of current medications. • T- trauma • I - infection • P - psychiatric • S . stroke, shock states
  • Important note: According to DAWN Data: ◦ About 18% of opioid related cases will also have alcohol. ◦ This is about 137% more common now than 10 years ago. ◦ About 10% of opioid related cases will also involve another pharmaceutical or illicit substance ◦ This is about 84% more common today than 10 years ago Why?
  • Treatment In order to treat an opioid patient we need to understand HOW opioids kill… Primary Causes of Mortality: ◦ Respiratory failure ◦ Airway Failure Secondary Causes of Mortality ◦ ◦ ◦ ◦ Aspiration (Rarely) hypothermia and hypotension Situational Factors MIS-TREATMENT by providers
  • Effect Potential Respiratory Effect of Certain Opioids (i.e. Heroin, Dilaudid) Potential Respiratory Effect of Other Opioids (i.e. Morphine, Methadone) Threshold of Respiratory Arrest/Failure NOTE: Sufficient quantities of ANY opioid may induce respiratory compromise! Time
  • Narcan (Naloxone) Narcan is a Competitive Opioid Antagonist ◦ Synthetic, derived from Thebain since the 1960’s ◦ Competitive means it will KICK OFF Opioids from receptors Predominantly works on μ (MU) receptors ◦ Minimal effects on other opioid receptors It will NOT work on other CNS depressants (with few exceptions) Clinical effects last 20-45 minutes depending on circumstances ◦ Most opioids last longer (exception IV fentanyl) Some studies on use in Septic Shock and other situations
  • Narcan (Naloxone) Ventilation/stimulation first Slow admin of Narcan, just enough to make them breath ◦ ABSOLUTELY NO PUNATIVE ADMINISTRATION!!! Adult: ◦ IV, SL: 0.1-2 mg PRN to a max of 10 mg.* ◦ IN/IM/ETT, IV in cardiac arrest: 2 mg. Pediatrics: ◦ 0.01-0.05 mg/kg IV, IO, IM, SubQ, ET. Repeat PRN. ◦ MAX 2 mg/dose High doses may be needed if drug is synthetic Watch for re-sedation due to Narcan’s short duration (about 20-30 minutes)
  • KEY POINT: It should be noted that a response to (or failure to respond) naloxone is not considered a reliable diagnostic tool in determining if a patient has consumed opoiods. Failure to respond to a total dose of 10 mg of naloxone usually indicates: ◦ That poisoning is not due to opioids (or opioids alone); ◦Or that hypoxic brain damage has occurred. ◦Or that the AMS is not opioid related at all ◦ (A-E-I-O-U-T-I-P-S)
  • Narcan in Cardiac Arrest Poorly studied but very reasonable In one AHA study: ◦ ◦ ◦ ◦ ◦ ◦ Small study , 36 patients Asytole and PEA were predominant rhythm. Down times varied but were typically extended. 42% of cardiac arrest patients with a suspected opioid etiology showed improvement in EKG rhythm s/p Narcan administration 27% had ROSC by arrival at ER 1% had survival to discharge. “…Although we cannot support the routine use of naloxone during cardiac arrest, we recommend its administration with any suspicion of opioid use. Due to low rates of return of spontaneous circulation and survival during cardiac arrest, any potential intervention leading to rhythm improvement is a reasonable treatment modality.” Why? ◦ Inhibits the adverse effects of the opioids in cardiac arrest, specifically hypotension ◦ Narcan may cause a endogenous sympathetic response (i.e. release of endogenous epinephrine) in the opioid addicted patient ◦ May have indirect, poorly understood antiarrhythmic effects Source : Resuscitation. 2010 Jan;81(1):42-6. doi: 10.1016/j.resuscitation.2009.09.016. Epub 2009 Nov 13. Naloxone in cardiac arrest with suspected opioid overdoses. Saybolt MD1, Alter SM, Dos Santos F, Calello DP, Rynn KO, Nelson DA, Merlin MA.
  • Smaller doses of Narcan? “The short time between naloxone administration and the occurrence of complications, as well as the type of complications, are strong evidence of a causal link. In 1000 clinically diagnosed intoxications with heroin or heroin mixtures, from 4 to 30 serious complications can be expected. “ “…Development of ventricular tachycardia or fibrillation; atrial fibrillation; asystole; pulmonary edema; convulsions; vomiting; and violent behavior within ten minutes after parenteral administration of naloxone.” “Such a high incidence of complications is unacceptable and could theoretically be reduced by artificial respiration with a bag valve device (hyperventilation) as well as by administering naloxone in minimal divided doses, injected slowly.” Source: ◦ Osterwalder JJ. “Naloxonefor intoxications with intravenous heroin and heroin mixtures: harmless or hazardous? A prospective clinical study.” J Toxicol Clin Toxicol 34 (1996): 409-416 ◦ Cuss FM, Colaço CB, & Baron JH Cardiac arrest after reversal of effects of opiates with naloxone. Br Med J, 288(1984): 363-364
  • Narcan Infusions? Narcan infusions are a MAINTANANCE therapy, ideal for LONG transports (20-30 minutes or greater) Many different methods/compositions/protocols Administer NARCAN as normal to achieve respiratory and airway stability Mix the TOTAL effective dose in 100 cc (or 250 cc) NS Set rate to infuse over 1 hour ◦ 100 cc Bag: 90 gtts a minute ( 1.5 gtt/sec) ◦ 250 cc Bag: 250 gtts a minute (4 gtts / sec) If re-sedation occurs: ◦ Evaluate for other causes ◦ Titrate upward for effect ◦ Rebolus IV Narcan
  • LAYPERSON/ BLS Narcan?
  • Thoughts IM clinically safer than IN ◦ Both should be an option Protocols/Training should mandate BVM/Airway Management first
  • NARCAN Treat & Release Criteria ◦ Criteria: ◦ The patient can mobilize as usual; ◦ The patient has an oxygen saturation on room air of >92%; 3) have a respiratory rate >10 breaths/min and <20 breaths/min; ◦ The patient has a temperature of >35.0°C and <37.5°C; ◦ The patient has a heart rate >50 beats/min and <100 beats/min; and ◦ The patient has a Glasgow Coma Scale score of 15. ◦ Follow up with IM (or SQ) Narcan References: ◦ Christenson J, Etherington J, Grafstein E, et al. Early discharge of patients with presumed opioid overdose: development of a clinical prediction rule. Acad Emerg Med 2000;7(10);1110-18. ◦ Wanger K, Brough L, MacMillan I, et al. Intravenous vs subcutaneous naloxone for out-of-hospital management of presumed opioid overdose. Acad Emerg Med 1998;5(4);293-9.
  • When to avoid Narcan all together Semi- Awake patients Pregnancy Aspiration POLY PHARM OD’s
  • It is generally unwise to treat these patients with an opioid antagonist unless life threatening respiratory depression is a reasonable concern.. "Inappropriate use of naloxone in cancer patients with pain.." J Pain Symptom Manage. 11(2)(1996): 131-134. Source: http://www.elephantjournal.com/2013/10/love-it-all-a-husbands-farewell-to-his-dying-wife-photos/
  • In the End Stay up to date Don’t believe the Hype Overdose patients are AMS patients first, opioid overdoses last CORRECT HYPOXIA, ACIDOSIS , HYPERCARBIA BEFORE NARCAN When giving Narcan: SLOW and LOW (Slow Push and Low Doses repeated) ◦ Goal is airway and respiratory correction, not to wake them up
  • Questions? Source: http://paindr.com/wp-content/uploads/2013/04/Poppy-smiley-157x195.jpg