Morphine toxicity was presented as a case of multidrug toxicity involving morphine, diazepam and methamphetamine. Morphine can cause coma, respiratory depression, hypotension and pinpoint pupils while diazepam and methamphetamine interactions were also discussed. Naloxone is used to reverse morphine toxicity by competitively binding opioid receptors. Proper administration of naloxone and monitoring for withdrawal symptoms after reversal are important for management of morphine overdoses.
2. 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
8. Drug interactions
Diazepam + Morphine
increase side effects such as dizziness, drowsiness, and
difficulty concentrating
No interactions with Methamphetamine
9. Opioids
psychoactive analgesic drugs for pain relief and palliative
care
addictive potential
controlled prescriptions
needed to avoid misuse and dependence
16. 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.
24. 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
26. Goal of naloxone
is not necessarily
complete arousal but
adequate spontaneous ventilation.
27. Adverse effects after naloxone in reversal
of opioid depression
Cardiac disorders
Cardiac arrest
Tachycardia
Ventricular fibrillation
Ventricular tachycardia
Gastrointestinal disorders
Nausea
Vomiting
Investigations
Blood pressure increased
Nervous system disorders
Convulsion
Tremor
Psychiatric disorders
Withdrawal syndrome
Respiratory, thoracic and mediastinal
disorders
Pulmonary edema
Skin and subcutaneous tissue disorders
Hyperhidrosis
28. 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
29. 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
30. 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
31. 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)
Opioid-receptor signal transduction mechanisms. Upon binding of an opioid agonist to an opioid receptor, the respective G protein is activated. G proteins may (A) reduce the capacity of adenylate cyclase to produce cyclic adenosine monophosphate (cAMP); (B) close calcium channels that reduce the signal to release neurotransmitters; (C) open potassium channels and hyperpolarize the cell, which indirectly reduces cell activity. Each mechanism has been found coupled to each receptor subtype, depending on location of the receptor (pre-/postsynaptic), and the neuron within the brain. Note that α2 receptors (D) mediate similar effects, using a different G protein (Gz). NT = n
Mesolimbic system
Smaller particles (< 3-4 μm) can pass through capillaries and remain in the circulation until sequestered by the mononuclear phagocytic system, mainly in the liver and spleen
Unfiltered tablet extracts contained tens of millions of particles with a range in sizes from < 5 μm to > 400 μm. Cigarette filters removed most of the larger particles (> 50 μm) but the smaller particles remained. Commercial syringe filters (0.45 and 0.22 μm) produced a dramatic reduction in particles
. It facilitates the release of the Neurotransmitters Dopamine, Serotonin, and noradrenaline from parasynaptic storage sites in CNS nerve terminals. This is the most dominant mechanism of action. 2. Meth binds to the monoamine oxidase within these neurones to prevent the degradation of each neurotransmitter, thus preventing them from dissipating, leaving free dopamine in the nerve terminals. 3. By binding to the neurotransmitter re-uptake transponder, it can reverse it`s effects, causing it to transport more neurotransmitters out of the nerve terminal rather than storing the free neurotransmitters inside their storage vesicles.
