OPIOID TOXICITY AND WITHDRAWAL

1. OPIOIDS TOXICITY
BY DR.SHAKEEL
PGY1

2. OPIATES: Alkaloid found as a natural product in Papaver somniferum (Poppy)-
unripened seedpods.
NARCOTIC: Broader group of agents and is predominantly used by law
enforcement to designate a variety of controlled substances with abuse or addictive.
It induces sleep.
OPIOIDS: Medications that relieve pain. It applies to all natural, semi-synthetic and
synthetic agents.

3. Natural (opiates) Heroin
Codeine
Morphine
Semi-synthetic Buprenorphine
Hydrocodone
Hydromorphone
Oxycodone
Oxymorphone
Synthetic Diphenoxylate
Fentanyl
Meperidine
Methadone
Pentazocine
Propoxyphene
Tramadol
Classification

4. Pharmacological Action
• Actions of opioids involve many organ systems, incl. the central nervous
system (CNS), Peripheral nervous system (PNS), CVS, Respiratory system, and
gastrointestinal system, and cause characteristic clinical effects.
• Goals: Sedation and analgesia.
1. μ-receptors Analgesia, Sedation, Miosis, Respiratory depression, Cough suppression,
Euphoria, Decreased GI motility.
2. κ-receptors Analgesia, Sedation, Miosis, Decreased intestinal motility, Dysphoria,
Hallucinations
3. δ-receptors Analgesia, some antidepressant effect, Dysphoria, Supraspinal and spinal
analgesia

5. Drug µ Receptor κ Receptor ∂ Receptor
Morphine - +++ ++ +
Fentanyl - +++ +
Codein - + + +
Buprenorphine- +
Methadone - ++
Naloxone - --- - - -
Pentazocine - - ++ +

6. • Oral, parenteral, nasal, rectal, transdermal depending upon the lipid solubility.
• Heroin is usually abused through IV and S/C routes, but also absorbed after
nasal administration because it is lipid soluble.
• Opioid toxicity is less pronounced but more prolonged with ingestion than with
parenteral administration. Absorption of opioids after ingestion occurs in the
small intestine. However, because of delayed gastric emptying, absorption and
clinical effects of toxicity may be prolonged after overdose.
• All opioids undergo hepatic metabolism (first-pass hepatic metabolism) and renal
elimination, and variations in hepatic and renal function
are important because metabolite activity may contribute
to clinical effects and toxicity.
Routes of administration and Metabolism

8. Opioid Toxicity
• Nervous System:
-Direct CNS depression
-Respiratory depression – hypoxia
-Seizures
-Hypertonicity Mepiridine & propoxyphene
-Myoclonus
-Dysphoria
-Psychosis
-Spongiform leukoencephalopathy- Heroin preparation on aluminium foil –
‘chasing the dragon’
-Serotonin syndrome - Meperidine, methadone, tramadol - clinical triad of
mental status changes, autonomic instability, and neuromuscular changes

9. .
• Ophthalmologic
-Stimulation of μ- receptors in the Edinger-Westphal nuclei of the third nerve
usually results in miosis.
• Otologic
-Sensorineural hearing loss
• Cardiovascular system
-Hypotension and bradycardia
-Propoxyphene – Na+ channel blocker – acts as Class A antiarrhythmic agent –
prolong QRS complex
-Methadone – QTc prolongation
• Respiratory System
-Decrease respiratory rate and tidal volume
-Bronchospasm (rare but severe)

10. • Gastrointestinal system
-Nausea and vomiting
-Delayed gastric emptying – may lead to Ileus
• Other systems:
-Urinary retention from urethral sphincter spasm and decreased detrusor tone
-Pruritus, flushing, and urticarial
-Hypoglycemia
-Hypothermia

11. Diagnosis
History and physical examination
ABG
ECG
Chest X-ray
Urine tox screen
Differentials
Clonidine toxicity
Valproic acid toxicity
Sedative-hypnotic agents

12. Treatment
• ABC
• IV Fluids
• Single-dose activated charcoal, 1 gram/kg PO, should be administered if
the opioid ingestion occurred within the hour.
• Naloxone is a pure competitive antagonist at all opioid receptors, with
particular affinity for μ-receptors, therefore fully reverses all the effects of
opioid. Onset – 1-2 min, duration – 30-90 min.
• Nalmefene - opioid antagonist with a long half-life (8-11 hours) and
duration of clinical effect

14. Opioid Withdrawal
• Downregulation of opioid receptors occurs with long-term use of opioids. Abrupt cessation of
opioid use does not allow time for upregulation of receptors and results in increased neuronal
firing and the opioid withdrawal syndrome.
Onset: within hours Onset: 12 h Onset: 24–36 h
Peak effects: 36–72 h Peak effects: 72 h Peak effects: 72 h
Anxiety Irritability Insomnia
Yawning Tremor Muscle spasms
Drug craving Piloerection Abdominal pain
Lacrimation Mydriasis Nausea, vomiting
Rhinorrhea diarrhea
Diaphoresis
Myalgias
• Methadone - a long-acting opioid, provides opioid replacement to treat or to prevent
withdrawal - 20 mg orally or 10 mg IM, onset – 30-60 min
• Clonidine (central alpha2-agonist) - 0.1 mg orally, repeated every 30-60min

15. A 25-year-old man is carried into the ED by two of his friends who
state that he is not breathing. The patient has a history of heroin abuse. His
vital signs are BP 115/70 mm Hg, HR 99 beats per minute, temperature
98.9°F, RR 3 breaths per minute and O2 saturation 87% on room air. You
notice fresh needle marks and miotic pupils. You begin bag-valve-mask
ventilation and his O2 saturation increases to 99%. Which of the following
is the most appropriate next step in management?
a. Continue bag-mask-ventilation until he breathes on his own
b. Administration of naloxone
c. Administration of flumazenil
d. Place a nasogastric tube and administer activated charcoal
e. Place a nasogastric tube and administer syrup of ipecac
Question 1

16. A 30-year-old man is brought to the ED by police officers. The
patient is agitated, vomiting, and complaining of body aches. He states that
he is withdrawing from his medication. His vital signs are BP 160/85 mm Hg,
RR 20 breaths per minute, HR 107 beats per minute, and temperature
99.7°F. On exam he is diaphoretic, has rhinorrhea, piloerection, and hyperactive
bowel sounds. Which of the following substances is this patient most
likely withdrawing from?
a. Ethanol
b. Cocaine
c. Nicotine
d. Methadone
e. Clonidine
Question 2