Transcript Opioid intoxication

OPIOID INTOXICATION
Foroud shahbazi PharmD
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
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
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.
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
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
Half-life
Mayo Clin Proc. 2009;84(7):602-612
Potency
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
Opioid Sales, Admissions for Opioid-Abuse Treatment, and Deaths Due to
Opioid Overdose in the United States, 1999–2010.
Volkow ND et al. N Engl J Med 2014;370:2063-2066.
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;56:1072-5
MMWR Morb Mortal Wkly Rep. 2012 ;61:493-7.
Toxicokinetics of Opioid
Analgesics
• The pharmacokinetics of particular opioid analgesic agents are often irrelevant in
overdose
• Bezoars formation after ingestions
• No linear dose elimination (zero order elimination)
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N Engl J Med 2012;367:146-55.
N Engl J Med 2012;367:146-55.
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
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
• 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
•
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
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
LABORATORY EVALUATION AND ANCILLARY STUDIES
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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
First step, pre-hospital care
• Respiratory stabilization
• If advanced life support (ALS) is available, intravenous naloxone may be given to reduce
respiratory depression
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
• 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,
Decision Tree for Managing Opioid Analgesic Overdose in Adults.
N Engl J Med 2012;367:146-155.
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
Naloxone Dosing.
N Engl J Med 2012;367:146-155.
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
Thanks for your attention