OPIOID TOXICITY
Neeraj Ojha
Yuvraj Kalathoki
Om Acharya

INTRODUCTION
Opioids are substances that act on opioid receptors to
produce morphine-like effects.
Medically they are primarily used for pain relief, including
anesthesia.[ Other medical uses include suppression of
diarrhea, replacement therapy for opioid use disorder,
reversing opioid overdose, suppressing cough, as well as for
executions in the United States.

Contd.
Opioid are potent respiratory depressants.Opium is latex
obtained from Papaver somniferum.It is an alkaloid .
An opioid overdose is toxicity due to excessive opioids.
Examples of opioids include morphine, heroin, fentanyl,
tramadol, and methadone. Symptoms include insufficient
breathing, small pupils, and unconsciousness. Onset of
symptoms depends in part on the route by which the opioids
are taken.

Mechanism of action of opioids
Opioids produce their actions at a cellular level by activating
opioid receptors. These receptors are distributed throughout
the central nervous system (CNS) with high concentrations in
the nuclei of tractus solitarius, peri-aqueductal grey area
(PAG);
High densities of opioid receptors known as mu ,delta and
kappa are found in the dorsal horn horn of spinal cord and
higher CNS centres.

Contd.
Most currently used opioid receptors act mainly at mu -opioid
receptors.Morphine acts at kappa receptors of the substancia
granulosa of spinal cord and decrease the release of
substance p which modulates pain perception in the spinal
cord .

MOA of toxicity
User ingests opioids that attaches to receptors in the brain
responsible for breathing and suppress respiratory drive.
User’s breathing slows and the user becomes unresponsive
with respiratory depression and hypoxia;
Lack of oxygen (oxygen starvation) affects vital organs,
including the heart and brain, leading to organ damage,
coma, and death • Within 3-5 minutes without oxygen, brain
damage starts to occur.

Clinical features /symptoms
1. Respiratory depression
2. Stupor
3. Miosis
4. Hypothermia
5. Drowsiness
6. Euphoria
7. Rhabdomyolysis
8. Myoglobinuric renal failure

Treatment and management
Patients with apnea need a pharmacologic or mechanical stimulus
in order to breathe;
In patients lacking spontaneous respirations, orotracheal intubation
is preferred. If advanced life support (ALS) is available, intravenous
naloxone (Narcan) may be given to reduce respiratory depression.
Alternate routes of naloxone administration include intraosseusly,
intramuscularly, intranasally, or via endotracheal tube

ANTIDOTE
Naloxone ,the antidote for opioid overdose, is a competitive
mu opioid -receptor antagonist that reverses all signs of
opioid intoxication;
The onset of action less than 2 minutes when naloxone is
administered intravenously ,and its apparent duration of
action is 20-90 minutes;
It is active when the parenteral ,intranasal or pulmonary

Contd.
route of administration is used but has negligible
bioavailability when administered orally because of extensive
first pass metabolism .

CASE STUDY
A 28-year-old male was admitted to an inpatient medically supervised withdrawal
facility in Vancouver, Canada, for management of comorbid opioid and stimulant
use disorders. Hewas not in contact with his family and had a history of
homelessness. Before admission, the patient was living in a shelter and supported
by income assistance. His past medical history was significant for
schizoaffectivedisorder,whichwas treated by a psychiatrist with medications
including olanzapine, quetiapine, lorazepam, and trazodone. The patient was both
HIV and hepatitis C negative. He had a history of attending inpatient medically
supervised withdrawal on numerous previous occasions. He had a brief 2-week
period of methadone maintenance therapy 2 months before, up to a maximum
daily dose of 50mg, which he had abruptly discontinued for unclear reasons. The
patient had never previously been prescribed buprenorphine/naloxone treatment.

Contd.
● Subjective details:
Male
28 yrs old
Country:Canada

Objective details:
● Signs of opioid withdrawal, including frequent yawning,
piloerection, and dilated pupils at 6 mm diameter;
● Pulse=0
● Needle was found in the right antecubital fossa when the
person was found;
● His urine drug screen on arrival at the hospital was
positive for opiates and amphetamines;
● Brain magnetic resonance imaging was consistent with
severe anoxic brain injury;

Assessment/Diagnosis:
● So, the patient was diagnosed on the day after admission
of various symptoms related to opioid toxicity;
● Patient had a return of spontaneous respiration after the
administration of naloxone IM;
● The patient failed to regain consciousness after several
days in the ICU.

Planning:
 A plan for buprenorphine/naloxone taper was initiated to manage the
acute symptoms of opioid withdrawal;
 An initial dose of buprenorphine/naloxone 8 mg/ 2 mg was to be
tapered by 2/0.5 mg daily to discontinuation over 4 days;
 The patient was also prescribed trazodone, clonidine, quetiapine, and
dimenhydrinate as needed to treat any residual opioid withdrawal
symptoms;
 The patient was discharged from the facility back to a shelter after
completion of the 4-day buprenorphine/naloxone taper;
 After discussion with the family, a decision was made to transfer the
patient to a palliative care unit, and the patient died 20 days in unit.

Discussion:
● Risk factors for fatal overdose like this one include co-
ingestion of CNS depressants such as BZDs, and alcohol,
use of illicit opioids, particularly by injection, past nonfatal
overdose, and recent periods of abstinence from opioids.