Opioid Overdose

Question 1

Opioid vs Opiate

Answer 1

Opioid
- Any synthetic or semi-synthetic drug derived from the opium poppy (e.g. fentanyl and oxycodone).

Opiate
- A naturally occurring alkaloid drug derived from the opium poppy (e.g. morphine and codeine).

Question 1

What receptors are opioid receptors?

Answer 1

G-coupled proteins

Question 2

Where is the highest concentration of opioid receptors?

Answer 2

In the CNS
but some exist in PNS

Question 3

What are the main receptor subtypes for opioids?

Answer 3

Mu receptors
Kappa receptors
Delta receptors

Question 4

What does activation of all opioid receptors produce?

Answer 4

Analgesic effects

Question 5

What are the side effects of opioid receptor activation?

Answer 5

Respiratory depression

Reduced consciousness

Miosis (constricted pupils)

Higher cortical processing effects eg. euphoria and dependence.

Question 6

What is the physiological effect of Mu receptors?

Answer 6

• Most abundant
• Hve the highest affinity for morphine
• Produce the most potent analgesic effects
• Activat mesolimbic dopaminergic system which is also responsible for euphoria, respiratory depression and constipation associated with opioid use.

Question 7

What is the physiological effect of Kappa receptors?

Answer 7

• Produce less analgesia than mu receptors.
• A/w reduced consciousness, respiratory depression, dependence and dysphoria.

Question 8

What is the physiological effect of Delta receptors?

Answer 8

thought to be involved in the psychological effects of opioids including dysphoria

Question 9

What determines the strength of an opioid drug?

Answer 9

Ability to act as an agonist against the mu receptor

Question 10

Examples of weak and strong opioids and their routes

Answer 10

Weak - codeine (oral), tramadol (oral, IV)

Strong - morphine (oral, IV, SC), fentanyl (IV, transdermal), Methadone (oral), Heroin (IV)

Question 11

What are RF’s the different subgroups of OD?

Answer 11

Recreational Drug Use:
- IVDU

Intentional OD:
- Self-harm or suicide attempt
- Less commonly to harm someone else in a person’s care, by purposefully administrating more than the prescribed dose

Unintentional OD:
- Chronic pain or palliative care patients
- Elderly, more likely if starting a new opioid, changing a dose or starting a new interacting medication
- Children (safeguarding issue)
- Starting a new opioid, especially in the opioid naïve
- A therapeutic error by incorrect prescription or incorrect dose/form/agent administration
- Hepatic or renal impairment: opioid may not be metabolised fully or can accumulate to toxic levels
CYP2D6 gene duplication carriers causing ultra-fast metabolism of codeine into its active metabolite, morphine, into potentially toxic concentrations

Question 12

What are clinical features of an opioid OD?

Answer 12

• Decreased level of consciousness
• N +/- V
• Constipation
• Pruritis
• Tiredness and increased somnolence
• Confusion (especially in the elderly)

These sx can also represent SE’s!!

Question 13

What should be elicited in the history?

Answer 13

Drug history:
- What opioids patient is taking and compare this to their prescription.
- Review all sources of opioid prescription.

Past medical history:
- Assess RF’s for unintentional overdose (e.g. renal impairment)
- Psychiatric history: previous episodes of overdose and/or self-harm.

Question 14

What is the classical toxidrome of an opioid overdose?

Answer 14

Triad:

reduced consciousness
respiratory depression
miosis

Question 15

ABCDE findings in opioid OD?

Answer 15

A
- decreased consciousness
- airway obstruction
- committing + decreased consciousness = hazard!

B
- Respiratory depression - bradypnoea, hypoxia, respiratory arrest.
- Low RR

C
- bradycardia
- Opioids (esp IV) cause vasodilation and hypotension

D
- Miosis (pinpoint pupils)

E
- track marks on arm
- Chronic pain or EOL pt: syringe driver or fentanyl patch
- May be drug paraphernalia around them/in pockets/hidden in clothing such as dirty needles.

Question 16

Below 8 intubate

Answer 16

patients with a GCS score less than 8, of any cause, are unable to protect their own airway, therefore, are at risk of obstructing it. They may require emergency intubation if the problem cannot be corrected quickly.

Question 17

What are DD’s of opioid OD?

Answer 17

Hypoglycaemia
Post-octal status
OD with other depressants
Head injury or intracranial pathology
CO2 narcosis

Question 18

What investigations may be done and why? What may they show?

Answer 18

• Obs
• ABG - type 2 resp failure and acidosis
• Glucose - rule out hypoglycaemia
• FBC - baseline
• U&E - check if pt unknowingly accumulating opioids
• LFTs - if pt can metabolise opioid load effectively
• Paracetamol levels - rule out mixed OD
• CT Head - if level of consciousness doesn’t improve

Question 19

How is an opioid OD managed?

Answer 19

• Remove source
• Monitor
• ABCDE

Naloxone
- Competitive opioid receptor antagonist
- IV, IM, SC, intranasal, oral
- Commonly administered in repeat IV boluses titrated to effect
- IV has most rapid onset of action and easy ability to titrate

Question 20

When is the oral route of Naloxone used?

Answer 20

oral route is used in the treatment of opioid-induced constipation

Question 21

Can naloxone be used diagnostically?

Answer 21

Yes

can be used as a diagnostic tool in the unconscious patient where the cause of loss of consciousness is unclear.

A response to naloxone, represented by an improvement in the GCS score, miosis and respiratory rate, indicates the presence of opioid overdose.

Alternative diagnoses should be considered if there is no response to naloxone.

Question 22

What is the half-life of naloxone?

Answer 22

60-90 minutes

Half life of opioids is longer

Question 23

When may different routes and methods of naloxone administration be used?

Answer 23

IVDU
- Risk that once OD has been reversed (or partially reversed), these patients will abscond only to relapse into a coma as the antagonist effect of the naloxone wears off and the effects of the opioids re-emerge.
- Simultaneous intramuscular (IM) dose of naloxone may be administered with the IV dose to reduce likelihood of this occurring.

Chronic pain or palliative care patients:
- Not desirable to fully reverse the effects of the opioids in this group of patients as it can cause significant distress and pain.
- Naloxone should be administered in small aliquots, titrating the dose to reverse the toxidrome without reversing all the desirable analgesic effects.

High opioid load:
- Sometimes patients have such a high opioid load (e.g. a large overdose, reduced renal excretion) that it is difficult to manage with intermittent boluses of naloxone.
- These patients may be commenced on a naloxone infusion until they have cleared adequate amounts of opiate from their system.

Question 24

How is opioid OD managed long term?

Answer 24

Intentional OD:
- Mental health assessment
- Psych services
- Of children at home, involve social services

Unintentional ODL
- Review medication regime
- Educate pt on risks of opiate OD
- If using recreational drugs - refer to local drug cessation service

Question 25

What are complications of an opioid OD?

Answer 25

Untreated + significant OD –> death secondary to respiratory depression

Acute lung injury following heroin OD - presents with ARDS

Question 26

What is the most common SE of naloxone tx?

Answer 26

Acute withdrawal syndrome and N+V