opioid intoxication foroud shahbazi pharmd. introduction opioid analgesic overdose is a preventable...
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OPIOID INTOXICATIONForoud shahbazi PharmD
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Introduction
• Opioid analgesic overdose is a preventable and potentially lethal
condition that results from prescribing practices, inadequate
understanding on the patient's part of the risks of medication misuse,
errors in drug administration, and pharmaceutical abuse
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Opioid classification
1. Opioid refers to natural and synthetic substances with morphine-like activity.
2. Opiate: alkaloid compounds extracted from opium, including morphine, heroin,
codeine, and semisynthetic derivatives of the poppy plant
3. Endorphins are endogenous peptides that produce pain relief
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Opioid classification
4) Prescription opioids
5) "Designer" opioids are synthetic derivatives of opioids created in makeshift
laboratories and include 3-methylfentanyl (Moscow theater hostage crisis of
2002), α-fentanyl (“China White”), desomorphine (“krokodil”), and other
agents, such as MPTP.
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Krocodil
• Desomorphine
• It has been used commercially in Switzerland under the brand name Permonid®
• Is a l-receptor agonist and synthetic derivative of morphine
• Desomorphine with morphine in patients with cancer, a 1:10 dosing ratio of
desomorphine to morphine was used
• Shorter duration of action
• After 3 weeks of desomorphine use, the patients experienced withdrawal
symptoms if the drug was withheld for as little as 4 hours
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PHARMACOLOGY
• Mechanism of action and pharmacokinetics — Three types of receptors have been identified: mu
(µ), kappa (k), and delta (δ); most opioids interact with more than one type.
• An opioid-receptor-like 1 (ORL-1) receptor or “orphan” receptor has also been described.
• The primary sites of opioid action are the limbic system, thalamus, and hypothalamus
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Half-life
Mayo Clin Proc. 2009;84(7):602-612
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Potency
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EPIDEMIOLOGY
• Opioid abuse is a major international public health problem with up to 22 million
people using opium or heroin worldwide
• Mortality
• Increase rate opioid abuse
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Volkow ND et al. N Engl J Med 2014;370:2063-2066.
Opioid Sales, Admissions for Opioid-Abuse Treatment, and Deaths Due to Opioid Overdose in the United States, 1999–2010.
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Methadone ????
• In studies by the US Centers for Disease Control and Prevention (CDC) from 1999-2010,
methadone accounted for 4.5-18.5% of narcotics sold in the United States and was involved in
31% of opioid deaths in the 13 states involved in the study.
• In addition, CDC analysis of data collected from 2004-2009 revealed a significant increase in the
nonmedical use of methadone alone or in combination with other drugs
J Forensic Sci. 2011;56:1072-5MMWR Morb Mortal Wkly Rep. 2012 ;61:493-7.
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Toxicokinetics of OpioidAnalgesics• The pharmacokinetics of particular opioid analgesic agents are often irrelevant in
overdose • Bezoars formation after ingestions• No linear dose elimination (zero order elimination)•
N Engl J Med 2012;367:146-55.
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N Engl J Med 2012;367:146-55.
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CLINICAL MANIFESTATIONS
• The diagnosis of opioid overdose is based upon the history and physical examination
• Family members, EMS
• Ingestion time, quantity, and co-ingestants are important aspects of the history and should be ascertained.
• Naloxone test
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Clinical features
• Apnea, stupor, and miosis suggests the diagnosis of opioid toxicity, all of these findings are not
consistently present.
• The sine qua non of opioid intoxication is respiratory depression.
• A respiratory rate of 12 breaths per minute or less in a patient who is not in physiologic sleep strongly suggests acute
opioid intoxication, particularly when accompanied by miosis or stupor.
• Miosis?
• Polysubstance ingestions may produce normally reactive or mydriatic pupils, as can poisoning from
meperidine, propoxyphene, or tramadol
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• Failure of oxygenation and non cardiogenic pulmonary edema
• Cardiovascular (bradycardia, hypotension, QT prolongation
• Seizure (IV fentanyl administration, the prolonged use of meperidine, and large ingestions of tramadol
• Gastrointestinal
• Muscle rigidity and rhabdomyolysis
•
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Toxicities of specific agents
• Buprenorphine – Partial opioid agonist, may induce withdrawal in opioid-dependent patients
• Dextromethorphan – Serotonin syndrome,
• Fentanyl – Very short acting
• Hydrocodone – Often combined with acetaminophen
• Meperidine – Seizure, serotonin syndrome (in combination with other agents)
• Methadone – Very long-acting; QTc prolongation, Torsades de Pointes
• Oxycodone – Often combined with acetaminophen; possible QTc interval prolongation
• Propoxyphene – QRS prolongation, seizure
• Tramadol – Seizure
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DIFFERENTIAL DIAGNOSIS
• CLONIDINE: miosis and obtundation, bradycardia, and hypotension are more prominent than in
patients with opioid intoxication
• ETHANOL: intoxication produces little to no miosis and no change in bowel sounds
• THE SEDATIVE-HYPNOTIC AGENTS: much less respiratory depression than the opioids,
(PO). Pupils are typically not pinpoint and ataxia may be a prominent feature in children.
• BACLOFEN: can cause coma, bradycardia, and hypotension after ingestion in children and
adolescents. Miosis is typically not present
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LABORATORY EVALUATION AND ANCILLARY STUDIES
• Glucose monitoring
• Pulse oximetry
• ABG
• Serum acetaminophen concentration
• Serum ethanol levels
• Serum CPK in prolonged immobilization
• Urine toxicologic screens should NOT be routinely obtained.
• Phenytoin when indicated
• Rapid pregnancy test
• Chest radiograph
• Electrocardiography
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First step, pre-hospital care
• Respiratory stabilization
• If advanced life support (ALS) is available, intravenous naloxone may be given to reduce respiratory depression
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Hospital
• Airway control and adequate oxygenation remain the primary intervention if not already established by EMS
• If occult trauma is suspected, implement cervical spine immobilization
• Administer naloxone for significant central nervous system (CNS) and/or respiratory depression• The usual dose administered by EMS is between 0.4 and 2 mg in the adult and 0.1 mg/kg in
the child or infant• To avoid precipitous withdrawal use lower dose especially in patients suspected of taking
another CNS depressant(s) (eg, benzodiazepines, tricyclic antidepressants, ethanol
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• Role of activated charcoal
• Should be reserved for patients who present within 1 hour after ingestion;
• Offers no benefit outside this time frame and complicates visualization of airway anatomy during orotracheal
intubation
• Whole-bowel irrigation can be considered for removal of ingested drug packets in body packers,
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N Engl J Med 2012;367:146-155.
Decision Tree for Managing Opioid Analgesic Overdose in Adults.
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Naloxone
• Is a competitive mu opioid–receptor antagonist that reverses all signs of opioid
intoxication.
• It is active when the parenteral, intranasal, or pulmonary route of administration is used
• Negligible bioavailability after oral administration
• In patients with opioid dependence, plasma levels of naloxone are initially lower?
• Onset of action 2min, Duration 20-90min
• Dosing protocols
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N Engl J Med 2012;367:146-155.
Naloxone Dosing.
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Continue
• If no response after 8-10 mg?
• Buprenorphine and naloxone: dose response ?
• Once the respiratory rate improves after the administration of naloxone, the
patient should be observed for 4 to 6 hours before discharge is considered
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Thanks for your attention