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!