MORPHINE TOXICITYJoey Tabula,MDInternal Medicine
Objectives
To present a case of multidrug toxicity with focus on morphine toxicity
To discuss pharmacologic and toxicologic effects of morphine
To discuss the management of morphine toxicity
General Data
CASE DELETED IN SLIDESHARE
Present Working Impression
Substance abuse to morphine, diazepam, methamphetamine, nicotine Poisoning by morphine, diazepam, methamphetamine
Acute respiratory failure, resolving Encephalopathy, resolved Distributive shock, resolved Ischemic acute tubular necrosis, resolving Ischemic hepatitis, resolving Rhabdomyolysis Acute bilateral globus pallidus infarcts Possible fall resulting to trauma to the cervical spine (quadriplegia)
Complicated UTI Hypertension
Toxidrome: Narcotics and opiates
Coma Desaturation
Hypotension Pinpoint pupils
Morphine and Diazepam
Toxidrome History
Drug Testing (bedside and
semiquantitative)
Manifestations
Morphine• Coma• Respiratory
depression• Hypotension• Pinpoint pupils• Bronchial
hypersecretion
Diazepam• Coma• Bronchial
hypersecretion• Nystagmus• Hypothermia
MAP• Coma• Mydriasis• Tremors• Hyperpyrexia• Hypertension• Flushing
Drug interactions
Diazepam + Morphine increase side effects such as dizziness, drowsiness, and
difficulty concentrating No interactions with Methamphetamine
Opioids
psychoactive analgesic drugs for pain relief and palliative care
addictive potential controlled prescriptions
needed to avoid misuse and dependence
Opioid receptor transduction mechanisms
Opioid receptor subtypes
Euphoria
Clinical Effects of Opioids
Morphine
isolated between 1803 and 1805 by Friedrich Sertürner first isolation of an active ingredient from a plant Sertürner originally named the substance morphium after
the Greek god of dreams, Morpheus, for its tendency to cause sleep.
Duration of effect of oral opiates
Onset and Duration of Action in Therapeutic Dosing and Overdose of Selected Opioid Analgesic Agents
Boyer, 2012
Opioid LipophilicityLipophilic
Hydrophilic
SufentanilBuprenorphine FentanylMethadoneHydromorphoneHydrocodoneMorphineCodeinePropoxyphene
Opioid “Liking” Phenomenon
Higher
Lower
OxycodoneHydromorphoneLevorphanolHydrocodoneMethadoneMorphineFentanylOxymorphoneCodeineTapentadolTramadolBuprenorphine
Opioid acute withdrawal syndrome symptoms
Cardiac disorders TachycardiaGastrointestinal disorders Diarrhea Nausea VomitingGeneral disorders and administration site conditions Asthenia Chills Pain PyrexiaInvestigations Blood pressure increased
Nervous system disorders TremorPsychiatric disorders Nervousness RestlessnessRespiratory, thoracic and mediastinal disorders Rhinorrhea Sneezing YawningSkin and subcutaneous tissue disorders Hyperhidrosis Piloerection
Cooked Morphine
It is common for many injecting drug users to prepare injections from tablets that are designed for oral administration
Cigarette filter + Commercial syringe filter
Pulmonary embolism
Pulmonary granulomas
Pulmonary edema Emphysema Pulmonary fibrosis Hypertension
Naloxone
competitive antagonist to opioids in the central nervous system
approved as a prescription medication in the US since 1971
generally devoid of activity unless opioids are present in a person
Naloxone: mechanism of action
Goal of naloxone is not necessarily
complete arousal but adequate spontaneous ventilation.
Adverse effects after naloxone in reversal of opioid depression
Cardiac disorders Cardiac arrest Tachycardia Ventricular fibrillation Ventricular tachycardiaGastrointestinal disorders Nausea VomitingInvestigations Blood pressure increased
Nervous system disorders Convulsion TremorPsychiatric disorders Withdrawal syndromeRespiratory, thoracic and mediastinal disorders Pulmonary edemaSkin and subcutaneous tissue disorders Hyperhidrosis
Five-step process first responder on suspected opioid overdose
1. Check for signs of opioid overdose (unconscious and unarousable, slow or absent breathing, pale, clammy skin, slow or no heart beat).
2. Call EMS to access immediate medical attention.3. Administer naloxone.4. Rescue breathe if patient not breathing.5. Stay with the person and monitor their response until emergency medical
assistance arrives. After 5 minutes, repeat the naloxone dose if person is not awakening or breathing well enough. A repeat dose may be needed 30–90 minutes later if sedation and respiratory depression recur.
Wermeling, 2015
Naloxone spray
spraying naloxone injection into the nasal cavity as a needle-free means of administering naloxone, thus reducing the risk of needle stick injury
Barton et al, 2002
Naloxone at home
Overdose training and take-home naloxone for opiate users: prospective cohort study of impact on knowledge and attitudes and subsequent management of overdose (Strang J, 2015) 239 opiate users Pre-training and post-training questionnaire on overdose
management 3-month follow-up, re-interviewed 18 overdoses Naloxone used in 12 occasions, successful reversal 1 death in 6 overdoses where naloxone was not used
Case Reports
Morphine-induced cardiogenic shock in a 44-year old woman (Feeney C, et al 2011)
Morphine-induced constipation treated with methylnatrexone (Feeney KT, et al 2012)
Morphine-induced muscle rigidity in a 2-day old term neonate (van der Lee R, et al 2009)
Morphine-induced rhabdomyolysis and hyperkalemia (Feldman R, et al 2001)
Near-fatal intoxication in a 46-year old depressed woman reversed with naloxone (Westerling D, et al 1998)
Three-pronged Treatment: prioritization
Morphine
Naloxone
Thank you!